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Genetic Epilepsy v0.2228 TAOK1 Elena Savva gene: TAOK1 was added
gene: TAOK1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TAOK1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TAOK1 were set to Developmental delay with or without intellectual impairment or behavioral abnormalities MIM#619575
Review for gene: TAOK1 was set to RED
Added comment: No reports found of patients with seizures/epilepsy.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2228 TAOK1 Elena Savva gene: TAOK1 was added
gene: TAOK1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TAOK1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TAOK1 were set to Developmental delay with or without intellectual impairment or behavioral abnormalities MIM#619575
Review for gene: TAOK1 was set to RED
Added comment: No reports found of patients with seizures/epilepsy.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2227 TANC2 Elena Savva Marked gene: TANC2 as ready
Genetic Epilepsy v0.2227 TANC2 Elena Savva Gene: tanc2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2227 TANC2 Elena Savva Classified gene: TANC2 as Green List (high evidence)
Genetic Epilepsy v0.2227 TANC2 Elena Savva Gene: tanc2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2226 TANC2 Elena Savva gene: TANC2 was added
gene: TANC2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TANC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TANC2 were set to PMID: 31616000
Phenotypes for gene: TANC2 were set to Intellectual developmental disorder with autistic features and language delay, with or without seizures MIM#618906
Review for gene: TANC2 was set to GREEN
Added comment: PMID: 31616000 - 11/20 individuals had either a formal diagnosis of epilepsy (nā€‰=ā€‰9) or suffered from recurrent seizures (nā€‰=ā€‰2).
Sources: Literature
Genetic Epilepsy v0.2225 TAF1C Elena Savva Marked gene: TAF1C as ready
Intellectual disability syndromic and non-syndromic v0.5695 TAF1C Elena Savva Phenotypes for gene: TAF1C were changed from Global developmental delay; Intellectual disability; Spasticity; Strabismus; Seizures; Abnormality of nervous system morphology to Neurodevelopmental disorder (MONDO#0700092), TAF1C-related
Genetic Epilepsy v0.2225 TAF1C Elena Savva Gene: taf1c has been classified as Red List (Low Evidence).
Mendeliome v1.1529 TAF1C Elena Savva Phenotypes for gene: TAF1C were changed from Global developmental delay; Intellectual disability; Spasticity; Strabismus; Seizures; Abnormality of nervous system morphology to Neurodevelopmental disorder (MONDO#0700092), TAF1C-related
Genetic Epilepsy v0.2225 TAF1C Elena Savva gene: TAF1C was added
gene: TAF1C was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TAF1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAF1C were set to 32779182
Phenotypes for gene: TAF1C were set to Neurodevelopmental disorder (MONDO#0700092), TAF1C-related
Review for gene: TAF1C was set to RED
Added comment: Knuutinen et al (2020 - PMID: 32779182) report on 2 individuals from 2 consanguineous families, homozygous for TAF1C missense variants. Both presented with an early onset neurological phenotype with severe global DD, ID (2/2 - moderate and profound), spasticity (2/2), ophthalmic findings (strabismus 2/2, nystagmus 1/2). Epilepsy, abnormal brain MRI (cerebral and cerebellar atrophy and white matter hyperintensities) as well and additional findings were reported in one (always the same individual).

NO hom PTCs in gnomAD v4
Sources: Literature
Genetic Epilepsy v0.2224 SYNE1 Elena Savva Marked gene: SYNE1 as ready
Genetic Epilepsy v0.2224 SYNE1 Elena Savva Gene: syne1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2224 SYNE1 Elena Savva gene: SYNE1 was added
gene: SYNE1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SYNE1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SYNE1 were set to PMID: 31703138; 37096302; 30573412
Phenotypes for gene: SYNE1 were set to Arthrogryposis multiplex congenita 3, myogenic type MIM#618484; Emery-Dreifuss muscular dystrophy 4, autosomal dominant MIM#612998; Spinocerebellar ataxia, autosomal recessive 8 MIM#610743
Review for gene: SYNE1 was set to RED
Added comment: PMID: 31703138 - PTC in a child featuring infantile epilepsy and developmental disorder, inherited from a father with a history of convulsions in infancy

PMID: 37096302;30573412 - review, no reports noted of patients with seizures/epilepsy.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2223 SUMF1 Elena Savva Marked gene: SUMF1 as ready
Genetic Epilepsy v0.2223 SUMF1 Elena Savva Gene: sumf1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2223 SUMF1 Elena Savva gene: SUMF1 was added
gene: SUMF1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SUMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUMF1 were set to 36980153; 36959582
Phenotypes for gene: SUMF1 were set to Multiple sulfatase deficiency MIM#272200
Review for gene: SUMF1 was set to RED
Added comment: PMID: 36980153 - review, no patients described with seizures/epilepsy

PMID: 36959582 - review, no patients described with seizures/epilepsy. Single proband in the study reported to have intractable epilepsy during sleep EEG study

Gene was listed in the Oliver list
Sources: Literature
Mendeliome v1.1528 SMC3 Bryony Thompson reviewed gene: SMC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38297832; Phenotypes: Cornelia de Lange syndrome MONDO:0016033; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Genetic Epilepsy v0.2222 SRCAP Elena Savva Classified gene: SRCAP as Amber List (moderate evidence)
Genetic Epilepsy v0.2222 SRCAP Elena Savva Gene: srcap has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2222 SRCAP Elena Savva Marked gene: SRCAP as ready
Genetic Epilepsy v0.2222 SRCAP Elena Savva Gene: srcap has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2222 SRCAP Elena Savva Classified gene: SRCAP as Amber List (moderate evidence)
Genetic Epilepsy v0.2222 SRCAP Elena Savva Gene: srcap has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2221 SRCAP Elena Savva gene: SRCAP was added
gene: SRCAP was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SRCAP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SRCAP were set to 23193612; 23621943
Phenotypes for gene: SRCAP were set to Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities MIM#619595; Floating-Harbor syndrome MIM#136140
Review for gene: SRCAP was set to AMBER
Added comment: OMIM: Seizures listed as a rare trait for both conditions

GeneReviews: Seizures have been observed in seven of 73 individuals.

PMID: 23621943: review, 6/52 patients reported with seizures
Sources: Literature
Genetic Epilepsy v0.2220 SOX11 Elena Savva Mode of pathogenicity for gene: SOX11 was changed from None to None
Genetic Epilepsy v0.2219 SOX11 Elena Savva Marked gene: SOX11 as ready
Genetic Epilepsy v0.2219 SOX11 Elena Savva Gene: sox11 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2219 SOX11 Elena Savva gene: SOX11 was added
gene: SOX11 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SOX11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SOX11 were set to Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism MIM#615866
Review for gene: SOX11 was set to RED
Added comment: No reports found of patients with seizures/epilepsy.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2218 SON Elena Savva Classified gene: SON as Green List (high evidence)
Genetic Epilepsy v0.2218 SON Elena Savva Gene: son has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2217 SON Elena Savva Classified gene: SON as Green List (high evidence)
Genetic Epilepsy v0.2217 SON Elena Savva Gene: son has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2217 SON Elena Savva Classified gene: SON as Green List (high evidence)
Genetic Epilepsy v0.2217 SON Elena Savva Gene: son has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2216 SON Elena Savva Marked gene: SON as ready
Genetic Epilepsy v0.2216 SON Elena Savva Gene: son has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2216 SON Elena Savva gene: SON was added
gene: SON was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SON was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SON were set to PMID: 37488749; 27545680
Phenotypes for gene: SON were set to ZTTK syndrome MIM#617140
Review for gene: SON was set to GREEN
Added comment: Seizures (in some patients) noted in OMIM

PMID: 37488749 - review of 79 patients, seizures not described

PMID: 27545680 - 11 of 20 individuals developed seizures and/or epilepsy with an age of onset ranging from 1 to 6 years
Sources: Literature
Cardiomyopathy_Paediatric v0.178 CASZ1 Ivan Macciocca gene: CASZ1 was added
gene: CASZ1 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CASZ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CASZ1 were set to PMID: 28099117; 36293425; 31268246
Phenotypes for gene: CASZ1 were set to dilated cardiomyopathy, left ventricular non compaction
Penetrance for gene: CASZ1 were set to unknown
Review for gene: CASZ1 was set to GREEN
Added comment: rare cause of paeditric onsent DCM.
at least 3 papers report LoF variants, 2 of which each report a novel de novo frameshift variant in children diagnosed with DCM less than 1 and who died at 11 mths ( PMID: 31268246; Guo 2019) and 22mths (PMID: 36293425, Orlova 2022). Another paper (PMID: 28099117, Qiu 2017) reported a nonsense variant that segregated with DCM in a family in an AD fashion (full text not available).
Sources: Literature
Genetic Epilepsy v0.2215 BET1 Zornitza Stark Phenotypes for gene: BET1 were changed from Muscular dystrophy MONDO:0020121 to Muscular dystrophy, congenital, with rapid progression, MIM# 254100
Genetic Epilepsy v0.2214 BET1 Zornitza Stark edited their review of gene: BET1: Changed phenotypes: Muscular dystrophy, congenital, with rapid progression, MIM# 254100
Muscular dystrophy and myopathy_Paediatric v1.11 BET1 Zornitza Stark Phenotypes for gene: BET1 were changed from Muscular dystrophy; Epilepsy to Muscular dystrophy, congenital, with rapid progression, MIM# 254100
Muscular dystrophy and myopathy_Paediatric v1.10 BET1 Zornitza Stark edited their review of gene: BET1: Changed phenotypes: Muscular dystrophy, congenital, with rapid progression, MIM# 254100
Mendeliome v1.1528 BET1 Zornitza Stark Phenotypes for gene: BET1 were changed from Muscular dystrophy, MONDO:0019950, BET1-related; Epilepsy to Muscular dystrophy, congenital, with rapid progression, MIM# 254100
Mendeliome v1.1527 BET1 Zornitza Stark edited their review of gene: BET1: Changed phenotypes: Muscular dystrophy, congenital, with rapid progression, MIM# 254100
Intellectual disability syndromic and non-syndromic v0.5694 CSTF2 Zornitza Stark Phenotypes for gene: CSTF2 were changed from Intellectual disability to Intellectual developmental disorder, X-linked 113, MIM# 301116
Intellectual disability syndromic and non-syndromic v0.5693 CSTF2 Zornitza Stark edited their review of gene: CSTF2: Changed phenotypes: Intellectual developmental disorder, X-linked 113, MIM# 301116
Mendeliome v1.1527 CSTF2 Zornitza Stark Phenotypes for gene: CSTF2 were changed from Intellectual disability to Intellectual developmental disorder, X-linked 113, MIM# 301116
Mendeliome v1.1526 CSTF2 Zornitza Stark edited their review of gene: CSTF2: Changed phenotypes: Intellectual developmental disorder, X-linked 113, MIM# 301116
Hypertrophic cardiomyopathy v0.176 TTR Zornitza Stark Tag treatable tag was added to gene: TTR.
Mendeliome v1.1526 TTR Zornitza Stark Tag treatable tag was added to gene: TTR.
Fetal anomalies v1.188 NARS Zornitza Stark Marked gene: NARS as ready
Fetal anomalies v1.188 NARS Zornitza Stark Gene: nars has been classified as Green List (High Evidence).
Fetal anomalies v1.188 NARS Zornitza Stark Classified gene: NARS as Green List (high evidence)
Fetal anomalies v1.188 NARS Zornitza Stark Gene: nars has been classified as Green List (High Evidence).
Congenital Heart Defect v0.412 DLG5 Zornitza Stark Marked gene: DLG5 as ready
Congenital Heart Defect v0.412 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.412 DLG5 Zornitza Stark Classified gene: DLG5 as Green List (high evidence)
Congenital Heart Defect v0.412 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.411 DLG5 Zornitza Stark gene: DLG5 was added
gene: DLG5 was added to Congenital Heart Defect. Sources: Expert list
Mode of inheritance for gene: DLG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLG5 were set to 32631816
Phenotypes for gene: DLG5 were set to Yuksel-Vogel-Bauer syndrome, MIM#620703
Review for gene: DLG5 was set to GREEN
Added comment: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations.
Sources: Expert list
Renal Ciliopathies and Nephronophthisis v1.22 DLG5 Zornitza Stark Marked gene: DLG5 as ready
Renal Ciliopathies and Nephronophthisis v1.22 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v1.22 DLG5 Zornitza Stark Classified gene: DLG5 as Green List (high evidence)
Renal Ciliopathies and Nephronophthisis v1.22 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v1.21 DLG5 Zornitza Stark gene: DLG5 was added
gene: DLG5 was added to Renal Ciliopathies and Nephronophthisis. Sources: Expert Review
Mode of inheritance for gene: DLG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLG5 were set to 32631816
Phenotypes for gene: DLG5 were set to Yuksel-Vogel-Bauer syndrome, MIM#620703
Review for gene: DLG5 was set to GREEN
Added comment: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations.
Sources: Expert Review
Hydrocephalus_Ventriculomegaly v0.123 DLG5 Zornitza Stark Marked gene: DLG5 as ready
Hydrocephalus_Ventriculomegaly v0.123 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.123 DLG5 Zornitza Stark Classified gene: DLG5 as Green List (high evidence)
Hydrocephalus_Ventriculomegaly v0.123 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.122 DLG5 Zornitza Stark gene: DLG5 was added
gene: DLG5 was added to Hydrocephalus_Ventriculomegaly. Sources: Expert Review
Mode of inheritance for gene: DLG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLG5 were set to 32631816
Phenotypes for gene: DLG5 were set to Yuksel-Vogel-Bauer syndrome, MIM#620703
Review for gene: DLG5 was set to GREEN
Added comment: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations.
Sources: Expert Review
Fetal anomalies v1.187 DLG5 Zornitza Stark Marked gene: DLG5 as ready
Fetal anomalies v1.187 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Fetal anomalies v1.187 DLG5 Zornitza Stark Classified gene: DLG5 as Green List (high evidence)
Fetal anomalies v1.187 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Fetal anomalies v1.186 DLG5 Zornitza Stark gene: DLG5 was added
gene: DLG5 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: DLG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLG5 were set to 32631816
Phenotypes for gene: DLG5 were set to Yuksel-Vogel-Bauer syndrome, MIM#620703
Review for gene: DLG5 was set to GREEN
Added comment: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations.
Sources: Expert Review
Mendeliome v1.1526 DLG5 Zornitza Stark Phenotypes for gene: DLG5 were changed from Ciliopathy, MONDO:0016044, DLG5-related; Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations to Yuksel-Vogel-Bauer syndrome, MIM#620703
Mendeliome v1.1525 DLG5 Zornitza Stark edited their review of gene: DLG5: Changed phenotypes: Yuksel-Vogel-Bauer syndrome, MIM#620703
Mendeliome v1.1525 DLG5 Zornitza Stark changed review comment from: Four unrelated families reported, supportive Xenopus animal model data.
Sources: Literature; to: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations.
Sources: Literature
Ciliopathies v1.48 DLG5 Zornitza Stark Phenotypes for gene: DLG5 were changed from Ciliopathy, MONDO:0016044, DLG5-related; Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations to Yuksel-Vogel-Bauer syndrome, MIM#620703
Ciliopathies v1.47 DLG5 Zornitza Stark edited their review of gene: DLG5: Changed phenotypes: Yuksel-Vogel-Bauer syndrome, MIM#620703
Ciliopathies v1.47 DLG5 Zornitza Stark changed review comment from: Four unrelated families reported, supportive Xenopus animal model data.
Sources: Literature; to: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5693 ASCC3 Zornitza Stark Marked gene: ASCC3 as ready
Intellectual disability syndromic and non-syndromic v0.5693 ASCC3 Zornitza Stark Gene: ascc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5693 ASCC3 Zornitza Stark Classified gene: ASCC3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5693 ASCC3 Zornitza Stark Gene: ascc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5692 ASCC3 Zornitza Stark gene: ASCC3 was added
gene: ASCC3 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: ASCC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASCC3 were set to 21937992; 35047834
Phenotypes for gene: ASCC3 were set to Intellectual developmental disorder, autosomal recessive 81, MIM# 620700
Review for gene: ASCC3 was set to GREEN
Added comment: Combined neuromuscular and neurobehavioral phenotype.

11 individuals from 7 unrelated families with homozygous (missense) or compound heterozygous variants (missense with a presumed LoF variant or 2 missense, no biallelic LoF) with a neurologic phenotype that ranges from severe developmental delay to muscle fatigue
Sources: Expert Review
Muscular dystrophy and myopathy_Paediatric v1.10 ASCC3 Zornitza Stark Phenotypes for gene: ASCC3 were changed from Congenital Myopathy (MONDO:0019952); Neuromuscular Symptoms to Intellectual developmental disorder, autosomal recessive 81, MIM# 620700
Muscular dystrophy and myopathy_Paediatric v1.9 ASCC3 Zornitza Stark Publications for gene: ASCC3 were set to 35047834
Muscular dystrophy and myopathy_Paediatric v1.8 ASCC3 Zornitza Stark reviewed gene: ASCC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 35047834; Phenotypes: Intellectual developmental disorder, autosomal recessive 81, MIM# 620700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1525 ASCC3 Zornitza Stark Phenotypes for gene: ASCC3 were changed from Neuromuscular syndrome; congenital myopathy to Intellectual developmental disorder, autosomal recessive 81, MIM# 620700
Mendeliome v1.1524 ASCC3 Zornitza Stark Publications for gene: ASCC3 were set to 21937992; https://doi.org/10.1016/j.xhgg.2021.100024
Mendeliome v1.1523 ASCC3 Zornitza Stark reviewed gene: ASCC3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 81, MIM# 620700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5691 GIGYF1 Zornitza Stark Phenotypes for gene: GIGYF1 were changed from Autism, Intellectual disability, GIGYF1-related (MONDO#0001071) to Autism spectrum disorder (MONDO:0005258), GIGYF1-related
Mendeliome v1.1523 GIGYF1 Zornitza Stark Phenotypes for gene: GIGYF1 were changed from Autism, Intellectual disability, GIGYF1-related (MONDO#0001071) to Autism spectrum disorder (MONDO:0005258), GIGYF1-related
Intellectual disability syndromic and non-syndromic v0.5690 SYN1 Zornitza Stark Mode of inheritance for gene: SYN1 was changed from BIALLELIC, autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.2214 SNAP29 Elena Savva Marked gene: SNAP29 as ready
Genetic Epilepsy v0.2214 SNAP29 Elena Savva Gene: snap29 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2214 SNAP29 Elena Savva Classified gene: SNAP29 as Green List (high evidence)
Genetic Epilepsy v0.2214 SNAP29 Elena Savva Gene: snap29 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2213 SNAP29 Elena Savva gene: SNAP29 was added
gene: SNAP29 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SNAP29 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNAP29 were set to PMID: 33977139
Phenotypes for gene: SNAP29 were set to Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome MIM#609528
Review for gene: SNAP29 was set to GREEN
Added comment: Seizures (in some patients) noted in OMIM

PMID: 33977139 - cohort of 6 probands, seizures detected in 3/6. Paper reviews previous reports, notes seizures in another cohort of 7/19
Sources: Literature
Genetic Epilepsy v0.2212 SMARCE1 Elena Savva Marked gene: SMARCE1 as ready
Genetic Epilepsy v0.2212 SMARCE1 Elena Savva Gene: smarce1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2212 SMARCE1 Elena Savva gene: SMARCE1 was added
gene: SMARCE1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SMARCE1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SMARCE1 were set to PMID: 30548424
Phenotypes for gene: SMARCE1 were set to Coffin-Siris syndrome 5 MIM#616938
Review for gene: SMARCE1 was set to RED
Added comment: PMID: 30548424 - Proband with a de novo splice variant (proven to result in inframe exon skipping), presented with seizures, hypotonia, GDD, ataxia etc.

No other literature showing SNVs in this gene and epilepsy/seizures. Gene was listed in the Oliver review
Sources: Literature
Genetic Epilepsy v0.2211 SLC19A3 Elena Savva Marked gene: SLC19A3 as ready
Genetic Epilepsy v0.2211 SLC19A3 Elena Savva Gene: slc19a3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2211 SLC19A3 Elena Savva Classified gene: SLC19A3 as Green List (high evidence)
Genetic Epilepsy v0.2211 SLC19A3 Elena Savva Gene: slc19a3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2210 SLC19A3 Elena Savva gene: SLC19A3 was added
gene: SLC19A3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SLC19A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC19A3 were set to PMID: 37670342; 23269594; 26863430
Phenotypes for gene: SLC19A3 were set to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2) MIM#607483
Review for gene: SLC19A3 was set to GREEN
Added comment: Seizures noted in OMIM

PMID: 37670342 - 1/21 probands had absence seizure on Depakene. Hom missense but many families in this paper had the same variant (likely founder).

PMID: 23269594 - 8/10 patients had acute-subacute onset consisting of ataxia, seizures, and encephalopathy. All probands had the same recurring missense described in PMID: 37670342.

PMID: 26863430 - two siblings with early-onset encephalopathy dystonia and epilepsy,
Sources: Literature
Genetic Epilepsy v0.2209 SHANK3 Elena Savva Marked gene: SHANK3 as ready
Genetic Epilepsy v0.2209 SHANK3 Elena Savva Gene: shank3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2209 SHANK3 Elena Savva Classified gene: SHANK3 as Green List (high evidence)
Genetic Epilepsy v0.2209 SHANK3 Elena Savva Gene: shank3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2209 SHANK3 Elena Savva Classified gene: SHANK3 as Green List (high evidence)
Genetic Epilepsy v0.2209 SHANK3 Elena Savva Gene: shank3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2208 SHANK3 Elena Savva gene: SHANK3 was added
gene: SHANK3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SHANK3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SHANK3 were set to PMID: 37655421
Phenotypes for gene: SHANK3 were set to Phelan-McDermid syndrome MIM#606232
Review for gene: SHANK3 was set to GREEN
Added comment: Seizures listed in OMIM, SHANK3 is often involved in a 22q13.3 deletion

PMID: 37655421 - Proband with a PTC, presenting with epileptic seizures, impaired speech development

PMID: 36967043 - large review, considered patients who had the 22q13.3 deletion as well as SNVs. Prevalence of epilepsy ranged from 17-70% in one study, 27% in another study and 41% in another. Seizure type was highly variable, ranging from atypical absent, tonic, atonic, tonic-clonic and myoclonic.
Sources: Literature
Genetic Epilepsy v0.2207 SERAC1 Elena Savva Marked gene: SERAC1 as ready
Genetic Epilepsy v0.2207 SERAC1 Elena Savva Gene: serac1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2207 SERAC1 Elena Savva Classified gene: SERAC1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2207 SERAC1 Elena Savva Gene: serac1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2206 SERAC1 Elena Savva gene: SERAC1 was added
gene: SERAC1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SERAC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERAC1 were set to PMID: 27186703; 24997715
Phenotypes for gene: SERAC1 were set to 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome MIM#614739
Review for gene: SERAC1 was set to AMBER
Added comment: Seizures (less common) listed in OMIM

PMID: 27186703 - two sibling patients who presented with 3-methylglutaconic acid and 3-methylglutaric aciduria, microcephaly, growth retardation, dysmorphic features, severe sensorineural deafness, progressive spasticity, dystonia, seizures and basal ganglia involvement.

PMID: 24997715 - Proband with biallelic PTCs, presented with 3-methylglutaconic aciduria, sensorineural hearing loss, encephalopathy, and Leigh-like pattern on MRI, as well as developmental delay and developmental regression, bilateral optic nerve atrophy, microcephaly, and myoclonic epilepsy.

GeneReviews - 38% of patients have seizures (febrile, myoclonic)
Sources: Literature
Mendeliome v1.1522 HNRNPC Zornitza Stark Phenotypes for gene: HNRNPC were changed from Neurodevelopmental disorder (MONDO:0700092), HNRNPC-related to Intellectual developmental disorder-74, MIM#620688
Mendeliome v1.1521 HNRNPC Zornitza Stark edited their review of gene: HNRNPC: Changed phenotypes: intellectual developmental disorder-74, MIM#620688
Intellectual disability syndromic and non-syndromic v0.5689 HNRNPC Zornitza Stark Phenotypes for gene: HNRNPC were changed from Neurodevelopmental disorder (MONDO:0700092), HNRNPC-related to intellectual developmental disorder-74, MIM#620688
Intellectual disability syndromic and non-syndromic v0.5688 HNRNPC Zornitza Stark edited their review of gene: HNRNPC: Changed phenotypes: intellectual developmental disorder-74, MIM#620688
Genetic Epilepsy v0.2205 SCN10A Elena Savva Marked gene: SCN10A as ready
Genetic Epilepsy v0.2205 SCN10A Elena Savva Gene: scn10a has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2205 SCN10A Elena Savva gene: SCN10A was added
gene: SCN10A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SCN10A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCN10A were set to PMID: 28078312
Phenotypes for gene: SCN10A were set to Episodic pain syndrome, familial, 2 MIM#615551; Neurodevelopmental disorder (MONDO#0700092), SCN10A-related
Review for gene: SCN10A was set to RED
Added comment: PMID: 28078312 - three families (2x biallelic missense, hom PTC).
- family 1 had progressive neuromuscular disease, severe cognitive impairment, muscle weakness, upper motor neuron lesion, anhydrosis, facial dysmorphism, and recurrent seizures
- family 2 had neonatal hypotonia, bradycardia, and recurrent seizures
- family 3 had febrile infection-related epilepsy syndrome (FIRES)
- Additional 5 probands reported with biallelic missense and Lennoxā€“Gastaut syndrome, epilepsy databases and autism databases
- Het carriers of PTC were NOT affected, but LOF is NOT a known mechanism of AD disease

Red for biallelic disease - none of the missense had functional studies to support pathogenicity. More evidence needed.
Sources: Literature
Genetic Epilepsy v0.2204 SACS Elena Savva Classified gene: SACS as Amber List (moderate evidence)
Genetic Epilepsy v0.2204 SACS Elena Savva Gene: sacs has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2203 SACS Elena Savva Classified gene: SACS as Amber List (moderate evidence)
Genetic Epilepsy v0.2203 SACS Elena Savva Gene: sacs has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2202 SACS Elena Savva Marked gene: SACS as ready
Genetic Epilepsy v0.2202 SACS Elena Savva Gene: sacs has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2202 SACS Elena Savva gene: SACS was added
gene: SACS was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SACS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SACS were set to PMID: 27871429; 35386405
Phenotypes for gene: SACS were set to Spastic ataxia, Charlevoix-Saguenay type MIM#270550
Review for gene: SACS was set to AMBER
Added comment: PMID: 27871429 - two consanguinous families (8 affecteds) with homozygous PTCs. Epilepsy observed for all 4/4 members of a single family. Authors note seizures may be present in 10% of SACS patients

PMID: 35386405 - Review of chinese patients, found 4/27 patients had epilepsy (one was questionable)
Sources: Literature
Genetic Epilepsy v0.2201 TMEM5 Elena Savva Marked gene: TMEM5 as ready
Genetic Epilepsy v0.2201 TMEM5 Elena Savva Gene: tmem5 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2201 TMEM5 Elena Savva gene: TMEM5 was added
gene: TMEM5 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TMEM5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM5 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10 MIM#615041
Review for gene: TMEM5 was set to RED
Added comment: Alt, gene name RXYLT1

No literature showing SNVs in this gene and epilepsy/seizures. Gene was listed in the Oliver review
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5688 WDR44 Zornitza Stark Marked gene: WDR44 as ready
Intellectual disability syndromic and non-syndromic v0.5688 WDR44 Zornitza Stark Gene: wdr44 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5688 WDR44 Zornitza Stark Classified gene: WDR44 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5688 WDR44 Zornitza Stark Gene: wdr44 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5687 WDR44 Zornitza Stark gene: WDR44 was added
gene: WDR44 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WDR44 were set to 38191484
Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related
Review for gene: WDR44 was set to GREEN
Added comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Mendeliome v1.1521 RIC1 Zornitza Stark Phenotypes for gene: RIC1 were changed from Cleft lip; cataract; tooth abnormality; intellectual disability; facial dysmorphism; ADHD to Cleft lip/palate MONDO:0016044, RIC1-related; Cleft lip; cataract; tooth abnormality; intellectual disability; facial dysmorphism; ADHD
Mendeliome v1.1520 RIC1 Zornitza Stark Publications for gene: RIC1 were set to 31932796
Mendeliome v1.1519 RIC1 Zornitza Stark Mode of inheritance for gene: RIC1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1518 RIC1 Zornitza Stark Classified gene: RIC1 as Green List (high evidence)
Mendeliome v1.1518 RIC1 Zornitza Stark Gene: ric1 has been classified as Green List (High Evidence).
Fetal anomalies v1.185 MYMK Zornitza Stark Deleted their comment
Fetal anomalies v1.185 MYMK Zornitza Stark Classified gene: MYMK as Green List (high evidence)
Fetal anomalies v1.185 MYMK Zornitza Stark Gene: mymk has been classified as Green List (High Evidence).
Fetal anomalies v1.184 MYMK Zornitza Stark edited their review of gene: MYMK: Added comment: Cleft palate, micrognathia, microcephaly, talipes are features detectable on fetal ultrasound.; Changed rating: GREEN
Clefting disorders v0.249 MYMK Zornitza Stark Marked gene: MYMK as ready
Clefting disorders v0.249 MYMK Zornitza Stark Gene: mymk has been classified as Green List (High Evidence).
Clefting disorders v0.249 MYMK Zornitza Stark Phenotypes for gene: MYMK were changed from Carey-Fineman-Ziter syndrome 254940 to Carey-Fineman-Ziter syndrome, MIM# 254940
Clefting disorders v0.248 MYMK Zornitza Stark reviewed gene: MYMK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Carey-Fineman-Ziter syndrome, MIM# 254940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting disorders v0.248 FBXO11 Zornitza Stark Marked gene: FBXO11 as ready
Clefting disorders v0.248 FBXO11 Zornitza Stark Gene: fbxo11 has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.248 FBXO11 Zornitza Stark reviewed gene: FBXO11: Rating: AMBER; Mode of pathogenicity: None; Publications: 30057029; Phenotypes: intellectual developmental disorder with dysmorphic facies and behavioral abnormalities, MIM# 618089; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting disorders v0.248 FOXP2 Zornitza Stark Marked gene: FOXP2 as ready
Clefting disorders v0.248 FOXP2 Zornitza Stark Gene: foxp2 has been classified as Red List (Low Evidence).
Clefting disorders v0.248 FOXP2 Zornitza Stark Phenotypes for gene: FOXP2 were changed from Speech-language disorder-1, 602081 to Speech-language disorder-1, MIM# 602081
Clefting disorders v0.247 FOXP2 Zornitza Stark Classified gene: FOXP2 as Red List (low evidence)
Clefting disorders v0.247 FOXP2 Zornitza Stark Gene: foxp2 has been classified as Red List (Low Evidence).
Clefting disorders v0.246 FOXP2 Zornitza Stark reviewed gene: FOXP2: Rating: RED; Mode of pathogenicity: None; Publications: 36328423; Phenotypes: Speech-language disorder-1, MIM# 602081; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5686 ACACA Zornitza Stark Marked gene: ACACA as ready
Intellectual disability syndromic and non-syndromic v0.5686 ACACA Zornitza Stark Gene: acaca has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5686 ACACA Zornitza Stark Classified gene: ACACA as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5686 ACACA Zornitza Stark Gene: acaca has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5685 ACACA Zornitza Stark gene: ACACA was added
gene: ACACA was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ACACA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACACA were set to 34552920; 10677481; 16717184; 36709796
Phenotypes for gene: ACACA were set to Acetyl-CoA carboxylase deficiency, MIM# 613933
Review for gene: ACACA was set to AMBER
Added comment: Two families with molecular testing, missense variants, supportive functional data.
Sources: Literature
Mendeliome v1.1517 ACACA Zornitza Stark Classified gene: ACACA as Amber List (moderate evidence)
Mendeliome v1.1517 ACACA Zornitza Stark Gene: acaca has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1516 ACACA Zornitza Stark reviewed gene: ACACA: Rating: AMBER; Mode of pathogenicity: None; Publications: 36709796; Phenotypes: Acetyl-CoA carboxylase deficiency, MIM# 613933; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.38 ANO1 Zornitza Stark Phenotypes for gene: ANO1 were changed from Moyamoya disease, MONDO:0016820, ANO1 related to Moyamoya disease 7, MIM# 620687
Cerebral vascular malformations v0.37 ANO1 Zornitza Stark reviewed gene: ANO1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Moyamoya disease 7, MIM# 620687; Mode of inheritance: None
Stroke v1.15 ANO1 Zornitza Stark Phenotypes for gene: ANO1 were changed from moyamoya; cerebral arteriopathy; stroke; MONDO:0016820 to Moyamoya disease 7, MIM# 620687
Stroke v1.14 ANO1 Zornitza Stark reviewed gene: ANO1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Moyamoya disease 7, MIM# 620687; Mode of inheritance: None
Mendeliome v1.1516 ANO1 Zornitza Stark Phenotypes for gene: ANO1 were changed from Intestinal dysmotility syndrome, MIM# 620045; Moyamoya disease, MONDO:0016820, ANO1 related to Intestinal dysmotility syndrome, MIM# 620045; Moyamoya disease 7, MIM# 620687
Mendeliome v1.1515 ANO1 Zornitza Stark edited their review of gene: ANO1: Changed phenotypes: Intestinal dysmotility syndrome, MIM# 620045, Moyamoya disease 7, MIM# 620687
Proteinuria v0.222 NUP160 Zornitza Stark Classified gene: NUP160 as Green List (high evidence)
Proteinuria v0.222 NUP160 Zornitza Stark Gene: nup160 has been classified as Green List (High Evidence).
Proteinuria v0.221 NUP160 Zornitza Stark Deleted their comment
Proteinuria v0.221 NUP160 Zornitza Stark edited their review of gene: NUP160: Changed rating: GREEN
Proteinuria v0.221 NUP160 Zornitza Stark commented on gene: NUP160: PMID: 30910934 1 x patient with familial steroid-resistant nephrotic syndrome (SRNS) and FSGS carried novel compound-heterozygous variants in NUP160 (R1173X and E803K).

Silencing of Drosophila NUP160 specifically in nephrocytes (fly renal cells) led to functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure. These defects were completely rescued by the expression of the wild-type human NUP160 gene in nephrocytes.

PMID: 30179222 1 x family (2 sibs) with compound het variants E803K and Arg910X. 1 Sib had SRNS and FSGS, the other had proteinuria.

PMID: 33456446 1 x family (2 sibs) with SRNS and chronic kidney disease. Homozygous for NUP160 c.1179+5G>A, confirmed by RT-PCR to cause abnormal splicing [r.1102_1179del;p.(Phe368_Gln393del)]. These individuals also had additional neurological features of intellectual disability and epilepsy.

PMID: 38224683 Generated a podocyte-specific Nup160 knockout (Nup160podKO) mouse model using CRISPR/Cas9 and Cre/loxP technologies. They showed that Nup160podKO mice develop typical signs of NS.
Proteinuria v0.221 NUP160 Zornitza Stark edited their review of gene: NUP160: Added comment: PMID: 30910934 1 x patient with familial steroid-resistant nephrotic syndrome (SRNS) and FSGS carried novel compound-heterozygous variants in NUP160 (R1173X and E803K).

Silencing of Drosophila NUP160 specifically in nephrocytes (fly renal cells) led to functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure. These defects were completely rescued by the expression of the wild-type human NUP160 gene in nephrocytes.

PMID: 30179222 1 x family (2 sibs) with compound het variants E803K and Arg910X. 1 Sib had SRNS and FSGS, the other had proteinuria.

PMID: 33456446 1 x family (2 sibs) with SRNS and chronic kidney disease. Homozygous for NUP160 c.1179+5G>A, confirmed by RT-PCR to cause abnormal splicing [r.1102_1179del;p.(Phe368_Gln393del)]. These individuals also had additional neurological features of intellectual disability and epilepsy.

PMID: 38224683 Generated a podocyte-specific Nup160 knockout (Nup160podKO) mouse model using CRISPR/Cas9 and Cre/loxP technologies. They showed that Nup160podKO mice develop typical signs of NS.; Changed publications: 30910934, 30179222, 33456446, 38224683
Mendeliome v1.1515 NUP160 Zornitza Stark Publications for gene: NUP160 were set to 30179222
Mendeliome v1.1514 NUP160 Zornitza Stark Classified gene: NUP160 as Green List (high evidence)
Mendeliome v1.1514 NUP160 Zornitza Stark Gene: nup160 has been classified as Green List (High Evidence).
Mendeliome v1.1513 NUP160 Melanie Marty changed review comment from: PMID: 30910934 1 x patient with familial steroid-resistant nephrotic syndrome (SRNS) and FSGS carried novel compound-heterozygous variants in NUP160 (R1173X and E803K). Silencing of Drosophila NUP160 specifically in nephrocytes (fly renal cells) led to functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure. These defects were completely rescued by the expression of the wild-type human NUP160 gene in nephrocytes.

PMID: 30179222 1 x family (2 sibs) with compound het variants E803K and Arg910X. 1 Sib had SRNS and FSGS, the other had proteinuria.

PMID: 33456446 1 x family (2 sibs) with steroid-resistant nephrotic syndrome and chronic kidney disease. Homozygous for NUP160 c.1179+5G>A, confirmed by RT-PCR to cause abnormal splicing [r.1102_1179del;p.(Phe368_Gln393del)]. These individuals also had additional neurological features of intellectual disability and epilepsy.

PMID: 38224683 Generated a podocyte-specific Nup160 knockout (Nup160podKO) mouse mode using CRISPR/Cas9 and Cre/loxP technologies. They showed that Nup160podKO mice develop typical signs of NS.; to: PMID: 30910934 1 x patient with familial steroid-resistant nephrotic syndrome (SRNS) and FSGS carried novel compound-heterozygous variants in NUP160 (R1173X and E803K). Silencing of Drosophila NUP160 specifically in nephrocytes (fly renal cells) led to functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure. These defects were completely rescued by the expression of the wild-type human NUP160 gene in nephrocytes.

PMID: 30179222 1 x family (2 sibs) with compound het variants E803K and Arg910X. 1 Sib had SRNS and FSGS, the other had proteinuria.

PMID: 33456446 1 x family (2 sibs) with SRNS and chronic kidney disease. Homozygous for NUP160 c.1179+5G>A, confirmed by RT-PCR to cause abnormal splicing [r.1102_1179del;p.(Phe368_Gln393del)]. These individuals also had additional neurological features of intellectual disability and epilepsy.

PMID: 38224683 Generated a podocyte-specific Nup160 knockout (Nup160podKO) mouse model using CRISPR/Cas9 and Cre/loxP technologies. They showed that Nup160podKO mice develop typical signs of NS.
Mendeliome v1.1513 NUP160 Melanie Marty reviewed gene: NUP160: Rating: GREEN; Mode of pathogenicity: None; Publications: 30910934, 30179222, 33456446, 38224683; Phenotypes: Steroid-resistant nephrotic syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5684 SP9 Zornitza Stark Marked gene: SP9 as ready
Intellectual disability syndromic and non-syndromic v0.5684 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5684 SP9 Zornitza Stark Classified gene: SP9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5684 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5683 SP9 Suliman Khan gene: SP9 was added
gene: SP9 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SP9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SP9 were set to PMID: 38288683
Phenotypes for gene: SP9 were set to neurodevelopmental disorder MONDO:0700092
Review for gene: SP9 was set to GREEN
Added comment: PMID: 38288683: reported 5 unrelated patients with de novo heterozygous variants (missense and PTV) in SP9 gene. In silico and in vitro studies suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants. Patients with loss-of-function variants had ID, ASD, and epilepsy, whereas missense variants in the second C2H2 binding domain result in hypomorphic and neomorphic DNA binding functions that cause severe epileptic encephalopathy. The author suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants.
Sources: Literature
Mendeliome v1.1513 SP9 Zornitza Stark Marked gene: SP9 as ready
Mendeliome v1.1513 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Mendeliome v1.1513 SP9 Suliman Khan commented on gene: SP9: PMID: 38288683: reported 5 unrelated patients with de novo heterozygous variants (missense and PTV) in SP9 gene. In silico and in vitro studies suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants. Patients with loss-of-function variants had ID, ASD, and epilepsy, whereas missense variants in the second C2H2 binding domain result in hypomorphic and neomorphic DNA binding functions that cause severe epileptic encephalopathy. The author suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants.
Mendeliome v1.1513 SP9 Zornitza Stark Phenotypes for gene: SP9 were changed from neurodevelopmental disorder MONDO:0700092 to neurodevelopmental disorder MONDO:0700092, SP9-related
Mendeliome v1.1512 SP9 Zornitza Stark Classified gene: SP9 as Green List (high evidence)
Mendeliome v1.1512 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.134 WDR44 Seb Lunke Marked gene: WDR44 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.134 WDR44 Seb Lunke Added comment: Comment when marking as ready: GoF mentioned but not well supported.
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.134 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.134 WDR44 Seb Lunke Classified gene: WDR44 as Green List (high evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.134 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Mendeliome v1.1511 SP9 Suliman Khan gene: SP9 was added
gene: SP9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SP9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SP9 were set to PMID: 38288683
Phenotypes for gene: SP9 were set to neurodevelopmental disorder MONDO:0700092
Review for gene: SP9 was set to GREEN
Added comment: Sources: Literature
Genetic Epilepsy v0.2200 SP9 Zornitza Stark Marked gene: SP9 as ready
Genetic Epilepsy v0.2200 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2200 SP9 Zornitza Stark Phenotypes for gene: SP9 were changed from neurodevelopmental disorder MONDO:0700092 to neurodevelopmental disorder MONDO:0700092, SP9-related
Genetic Epilepsy v0.2199 SP9 Zornitza Stark Classified gene: SP9 as Green List (high evidence)
Genetic Epilepsy v0.2199 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2198 SP9 Suliman Khan gene: SP9 was added
gene: SP9 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SP9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SP9 were set to PMID: 38288683
Phenotypes for gene: SP9 were set to neurodevelopmental disorder MONDO:0700092
Penetrance for gene: SP9 were set to Incomplete
Review for gene: SP9 was set to GREEN
Added comment: PMID: 38288683: reported 5 unrelated patients with de novo heterozygous variants (missense and PTV) in SP9 gene. In silico and in vitro studies suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants. Patients with loss-of-function variants had ID, ASD, and epilepsy, whereas missense variants in the second C2H2 binding domain result in hypomorphic and neomorphic DNA binding functions that cause severe epileptic encephalopathy. The author suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants.
Sources: Literature
Mendeliome v1.1511 MEI4 Lisa Norbart edited their review of gene: MEI4: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1511 MEI4 Lisa Norbart changed review comment from: PMID: 38252283 - 5x compound heterozygous missense variants and 1x homozygous missense variant seen in five individuals across 4 unrelated families affected with female infertility characterised by preimplantation embryonic arrest. Includes one family with two affected sisters with the same compound heterozygous variants. 2/4 families showed inheritance, parental data not available for other two families. Homozygous variant in the consanguineous family appears with a more severe phenotype.

In vitro evidence shows variants reduced the interactions between MEI4 and DNA, but no effects on protein levels. In vivo knock-out mouse model showed female mice were infertile, characterised by developmental defects during oogenesis.
Sources: Literature; to: PMID: 38252283 - 5x compound heterozygous missense variants and 1x homozygous missense variant seen in five individuals across 4 unrelated families affected with female infertility characterised by preimplantation embryonic arrest. Includes one family with two affected sisters with the same compound heterozygous variants. 2/4 families showed inheritance, parental data not available for other two families. Homozygous variant in the consanguineous family appears with a more severe phenotype.

In vitro evidence shows variants reduced the interactions between MEI4 and DNA, but no effects on protein levels. In vivo knock-out mouse model showed female mice were infertile, characterised by developmental defects during oogenesis.
Sources: Literature
Genetic Epilepsy v0.2198 CCDC88C Rylee Peters reviewed gene: CCDC88C: Rating: AMBER; Mode of pathogenicity: None; Publications: 38173219; Phenotypes: monogenic epilepsy MONDO:0015653, CCDC88C-related; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.1511 CCDC88C Rylee Peters reviewed gene: CCDC88C: Rating: AMBER; Mode of pathogenicity: None; Publications: 38173219; Phenotypes: monogenic epilepsy MONDO:0015653, CCDC88C-related; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.1511 RHOXF1 Zornitza Stark Marked gene: RHOXF1 as ready
Mendeliome v1.1511 RHOXF1 Zornitza Stark Gene: rhoxf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1511 RHOXF1 Zornitza Stark Classified gene: RHOXF1 as Amber List (moderate evidence)
Mendeliome v1.1511 RHOXF1 Zornitza Stark Gene: rhoxf1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.184 CELSR1 Chern Lim edited their review of gene: CELSR1: Changed rating: GREEN
Hydrops fetalis v0.308 CELSR1 Chern Lim edited their review of gene: CELSR1: Changed rating: GREEN
Mendeliome v1.1510 MEI4 Zornitza Stark Marked gene: MEI4 as ready
Mendeliome v1.1510 MEI4 Zornitza Stark Gene: mei4 has been classified as Green List (High Evidence).
Mendeliome v1.1510 RHOXF1 Chris Ciotta gene: RHOXF1 was added
gene: RHOXF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RHOXF1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RHOXF1 were set to PMID: 38258527
Phenotypes for gene: RHOXF1 were set to Spermatogenic failure, MONDO:0004983, RHOXF1-related
Review for gene: RHOXF1 was set to AMBER
Added comment: In a cohort of 1,201 men from China with oligozoospermia and azoospermia, hemizygous RHOXF1 variants were identified in 4 unrelated individuals.

Three of these variants were missense variants (V130M, A91V & A156V), all were absent from gnomAD (including version 4) and had deleterious in silicos.

The one other variant was a nonsense variant (R160X) which is predicted to escape NMD and truncate the protein. This is seen in gnomAD version 4 in 1 heterozygote female, and absent in other versions.

In vitro functional evidence for these variants was provided, the V130M, A156V and R160X mutants demonstrated impaired protein localisation with an increase in the protein in the cytoplasm and impaired nuclear entry, the A91V mutant protein did not share these localisation defects.

Further, The V130M mutant protein decreased DMRT1 promotor activity, DMRT1 is considered essential for testicular development and spermatogenesis. However, the R160X variant demonstrated increased activation, three times higher than WT. The two other missense variants had no effect.
Sources: Literature
Mendeliome v1.1510 PRDM6 Elena Savva Marked gene: PRDM6 as ready
Mendeliome v1.1510 PRDM6 Elena Savva Gene: prdm6 has been classified as Green List (High Evidence).
Mendeliome v1.1510 PRDM6 Elena Savva Classified gene: PRDM6 as Green List (high evidence)
Mendeliome v1.1510 PRDM6 Elena Savva Gene: prdm6 has been classified as Green List (High Evidence).
Mendeliome v1.1509 PRDM6 Elena Savva gene: PRDM6 was added
gene: PRDM6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRDM6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRDM6 were set to 38071433; 27716515; 27181681
Phenotypes for gene: PRDM6 were set to Patent ductus arteriosus 3 MIM#617039
Review for gene: PRDM6 was set to GREEN
Added comment: Gene is established for patent ductus arteriosus. Only missense reported but supported by functional studies suggesting LOF.

PMID: 38071433 - Two families (3 affected, 6 affected) with patent ductus arteriosus with/without additional coarctation of the aorta. Family 1 had a missense, family 2 had a PTC - both regarded as VUSs

Additional papers PMID: 27716515;27181681 describe nonsyndromic patent ductus arteriosus for the first time
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.133 WDR44 Andrew Fennell gene: WDR44 was added
gene: WDR44 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic. Sources: Literature
Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WDR44 were set to PMID: 38191484
Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related
Review for gene: WDR44 was set to GREEN
Added comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction.
3 patients had renal anomalies including 1 with unilateral cystic kidney disease; and nephritis, and kidney hypoplasia resulting in renal failure in two patients.
All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Mendeliome v1.1508 MEI4 Zornitza Stark Classified gene: MEI4 as Green List (high evidence)
Mendeliome v1.1508 MEI4 Zornitza Stark Gene: mei4 has been classified as Green List (High Evidence).
Mendeliome v1.1507 MEI4 Lisa Norbart gene: MEI4 was added
gene: MEI4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MEI4 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: MEI4 were set to 38252283
Phenotypes for gene: MEI4 were set to Infertility disorder, MONDO:0005047, MEI4-related
Review for gene: MEI4 was set to GREEN
Added comment: PMID: 38252283 - 5x compound heterozygous missense variants and 1x homozygous missense variant seen in five individuals across 4 unrelated families affected with female infertility characterised by preimplantation embryonic arrest. Includes one family with two affected sisters with the same compound heterozygous variants. 2/4 families showed inheritance, parental data not available for other two families. Homozygous variant in the consanguineous family appears with a more severe phenotype.

In vitro evidence shows variants reduced the interactions between MEI4 and DNA, but no effects on protein levels. In vivo knock-out mouse model showed female mice were infertile, characterised by developmental defects during oogenesis.
Sources: Literature
Hydrops fetalis v0.308 CELSR1 Ain Roesley Phenotypes for gene: CELSR1 were changed from Lymphatic malformation 9, MIM# 619319 to Lymphatic malformation 9, MIM# 619319
Hydrops fetalis v0.307 CELSR1 Ain Roesley changed review comment from: Comment on phenotypes: Presentation of hydrod is a phenotypic expansion on Lymphatic malformation; to: Comment on phenotypes: Presentation of hydrops is a phenotypic expansion on Lymphatic malformation
Hydrops fetalis v0.307 CELSR1 Ain Roesley Marked gene: CELSR1 as ready
Hydrops fetalis v0.307 CELSR1 Ain Roesley Gene: celsr1 has been classified as Green List (High Evidence).
Hydrops fetalis v0.307 CELSR1 Ain Roesley Added comment: Comment on phenotypes: Presentation of hydrod is a phenotypic expansion on Lymphatic malformation
Hydrops fetalis v0.307 CELSR1 Ain Roesley Phenotypes for gene: CELSR1 were changed from hydrops fetalis (MONDO:0015193), CELSR1-related to Lymphatic malformation 9, MIM# 619319
Mendeliome v1.1507 WDR44 Seb Lunke Marked gene: WDR44 as ready
Mendeliome v1.1507 WDR44 Seb Lunke Added comment: Comment when marking as ready: GoF mentioned but not well established.
Mendeliome v1.1507 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Hydrops fetalis v0.306 CELSR1 Ain Roesley Classified gene: CELSR1 as Green List (high evidence)
Hydrops fetalis v0.306 CELSR1 Ain Roesley Gene: celsr1 has been classified as Green List (High Evidence).
Mendeliome v1.1507 WDR44 Seb Lunke Classified gene: WDR44 as Green List (high evidence)
Mendeliome v1.1507 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Fetal anomalies v1.184 PIEZO1 Naomi Baker reviewed gene: PIEZO1: Rating: RED; Mode of pathogenicity: None; Publications: PMID:38184690; Phenotypes: Prune belly syndrome (MONDO:0007032), PIEZO1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.184 WDR44 Seb Lunke Marked gene: WDR44 as ready
Fetal anomalies v1.184 WDR44 Seb Lunke Added comment: Comment when marking as ready: GoF mentioned but not well established.
Fetal anomalies v1.184 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Fetal anomalies v1.184 CELSR1 Ain Roesley Publications for gene: CELSR1 were set to 31215153; 31403174; 26855770
Fetal anomalies v1.184 WDR44 Seb Lunke Classified gene: WDR44 as Green List (high evidence)
Fetal anomalies v1.184 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Fetal anomalies v1.183 CELSR1 Ain Roesley Classified gene: CELSR1 as Green List (high evidence)
Fetal anomalies v1.183 CELSR1 Ain Roesley Gene: celsr1 has been classified as Green List (High Evidence).
Mendeliome v1.1506 WDR44 Andrew Fennell gene: WDR44 was added
gene: WDR44 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WDR44 were set to PMID: 38191484
Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related
Review for gene: WDR44 was set to GREEN
Added comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Fetal anomalies v1.182 WDR44 Andrew Fennell gene: WDR44 was added
gene: WDR44 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WDR44 were set to PMID: 38191484
Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related
Review for gene: WDR44 was set to GREEN
Added comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Macular Dystrophy/Stargardt Disease v0.44 SAMD7 Zornitza Stark Marked gene: SAMD7 as ready
Macular Dystrophy/Stargardt Disease v0.44 SAMD7 Zornitza Stark Gene: samd7 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v0.44 SAMD7 Zornitza Stark Classified gene: SAMD7 as Green List (high evidence)
Macular Dystrophy/Stargardt Disease v0.44 SAMD7 Zornitza Stark Gene: samd7 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.86 SH2B3 Ain Roesley Marked gene: SH2B3 as ready
Bone Marrow Failure v1.86 SH2B3 Ain Roesley Gene: sh2b3 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.86 SH2B3 Ain Roesley Classified gene: SH2B3 as Green List (high evidence)
Bone Marrow Failure v1.86 SH2B3 Ain Roesley Gene: sh2b3 has been classified as Green List (High Evidence).
Mendeliome v1.1506 SAMD7 Zornitza Stark Marked gene: SAMD7 as ready
Mendeliome v1.1506 SAMD7 Zornitza Stark Gene: samd7 has been classified as Green List (High Evidence).
Ciliopathies v1.47 WDR44 Seb Lunke Marked gene: WDR44 as ready
Ciliopathies v1.47 WDR44 Seb Lunke Added comment: Comment when marking as ready: GoF mentioned but not well supported.
Ciliopathies v1.47 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Mendeliome v1.1506 SAMD7 Zornitza Stark Classified gene: SAMD7 as Green List (high evidence)
Mendeliome v1.1506 SAMD7 Zornitza Stark Gene: samd7 has been classified as Green List (High Evidence).
Ciliopathies v1.47 WDR44 Seb Lunke Classified gene: WDR44 as Green List (high evidence)
Ciliopathies v1.47 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.85 SH2B3 Ain Roesley gene: SH2B3 was added
gene: SH2B3 was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: SH2B3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SH2B3 were set to 37206266; 23908464; 38152053; 37206266; 38152053
Phenotypes for gene: SH2B3 were set to Predisposition to haematological malignancies; Myeloproliferation and multi-organ autoimmunity; juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related
Review for gene: SH2B3 was set to GREEN
gene: SH2B3 was marked as current diagnostic
Added comment: PMID:37206266
2x families
- hom missense variant Val402Met:
functional performed on patient's fibroblasts demonstrated increased basal pSTAT5, pSTAT3 and increased pJAK2 + pSTAT5 after stimulation with IL-3, GH, GM-CSF and EPO

- hom fs Arg148Profs*40
functional performed in zebrafish demonstrated increased number of macrophages and thrombocytes

PMID:23908464;
1 fam with 2 affecteds with dev delay + autoimmunity + (1x) ALL, hom for Asp231Gly fs*3

PMID:38152053;
JMML cohort - 2x hom missense + 2x het PTCs
Sources: Literature
Fetal anomalies v1.182 CELSR1 Chern Lim reviewed gene: CELSR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 38272662; Phenotypes: hydrops fetalis (MONDO:0015193), CELSR1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hydrops fetalis v0.305 CELSR1 Chern Lim gene: CELSR1 was added
gene: CELSR1 was added to Hydrops fetalis. Sources: Literature
Mode of inheritance for gene: CELSR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CELSR1 were set to 38272662
Phenotypes for gene: CELSR1 were set to hydrops fetalis (MONDO:0015193), CELSR1-related
Review for gene: CELSR1 was set to AMBER
gene: CELSR1 was marked as current diagnostic
Added comment: PMID: 38272662:
- Het de novo missense variants in two unrelated cases of fetal pleural effusions leading to severe fetal hydrops - Cys1318Tyr, Cys1349Arg.
- Both variants lie within the same protein domain.
- Functional studies performed for only one of the variants, p.(Cys1318Tyr): the variant affected CELSR1 protein cell membrane localisation compared with wild-type CELSR1 protein in both a plasmid-based overexpression system and the patient fibroblast cells. Bulk RNA-seq of RNA samples extracted from the proband and the motherā€™s fibroblast cells demonstrated that in the proband mRNA samples, the amount of CELSR1 mRNA was significantly decreased.
- No functional testing was performed on the p.(Cys1349Arg) variant.
Sources: Literature
Mendeliome v1.1505 SH2B3 Ain Roesley Phenotypes for gene: SH2B3 were changed from Predisposition to haematological malignancies to Predisposition to haematological malignancies; Myeloproliferation and multi-organ autoimmunity; juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related
Mendeliome v1.1504 SH2B3 Ain Roesley Publications for gene: SH2B3 were set to 26457647; 23908464; 31102422; 31173385
Mendeliome v1.1503 SH2B3 Ain Roesley Mode of inheritance for gene: SH2B3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ciliopathies v1.46 WDR44 Andrew Fennell changed review comment from: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recaptulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature; to: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Ciliopathies v1.46 WDR44 Andrew Fennell gene: WDR44 was added
gene: WDR44 was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WDR44 were set to PMID: 38191484
Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related
Review for gene: WDR44 was set to GREEN
Added comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recaptulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Mendeliome v1.1502 SH2B3 Ain Roesley Deleted their comment
Mendeliome v1.1502 SH2B3 Ain Roesley commented on gene: SH2B3: PMID:37206266
2x families
- hom missense variant Val402Met:
functional performed on patient's fibroblasts demonstrated increased basal pSTAT5, pSTAT3 and increased pJAK2 + pSTAT5 after stimulation with IL-3, GH, GM-CSF and EPO

- hom fs Arg148Profs*40
functional performed in zebrafish demonstrated increased number of macrophages and thrombocytes

PMID:23908464;
1 fam with 2 affecteds with dev delay + autoimmunity + (1x) ALL, hom for Asp231Gly fs*3

PMID:38152053;
JMML cohort - 2x hom missense + 2x het PTCs
Mendeliome v1.1502 SH2B3 Ain Roesley reviewed gene: SH2B3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37206266, 23908464, 38152053; Phenotypes: Myeloproliferation and multi-organ autoimmunity, juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1502 SAMD7 Paul De Fazio gene: SAMD7 was added
gene: SAMD7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SAMD7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SAMD7 were set to 38272031
Phenotypes for gene: SAMD7 were set to Macular dystrophy, retinal, SAMD7-related MONDO:0031166
Review for gene: SAMD7 was set to GREEN
gene: SAMD7 was marked as current diagnostic
Added comment: Five biallelic variants were identified in eight individuals from six families with macular dystrophy with or without cone dysfunction. Three families were consanguineous. Mean age at first presentation was 34.8 years, range 14 to 51.

Four variants affected splicing, while one missense variant impaired the repressive activity of SAMD7. All functional work was performed using in vitro assays.
Sources: Literature
Macular Dystrophy/Stargardt Disease v0.43 SAMD7 Paul De Fazio gene: SAMD7 was added
gene: SAMD7 was added to Macular Dystrophy/Stargardt Disease. Sources: Literature
Mode of inheritance for gene: SAMD7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SAMD7 were set to 38272031
Phenotypes for gene: SAMD7 were set to Macular dystrophy, retinal, SAMD7-related MONDO:0031166
Review for gene: SAMD7 was set to GREEN
gene: SAMD7 was marked as current diagnostic
Added comment: Five biallelic variants were identified in eight individuals from six families with macular dystrophy with or without cone dysfunction. Three families were consanguineous. Mean age at first presentation was 34.8 years, range 14 to 51.

Four variants affected splicing, while one missense variant impaired the repressive activity of SAMD7. All functional work was performed using in vitro assays.
Sources: Literature
Genetic Epilepsy v0.2198 CAMK2D Elena Savva Classified gene: CAMK2D as Amber List (moderate evidence)
Genetic Epilepsy v0.2198 CAMK2D Elena Savva Gene: camk2d has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2198 CAMK2D Elena Savva Classified gene: CAMK2D as Amber List (moderate evidence)
Genetic Epilepsy v0.2198 CAMK2D Elena Savva Gene: camk2d has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2197 CAMK2D Elena Savva Marked gene: CAMK2D as ready
Genetic Epilepsy v0.2197 CAMK2D Elena Savva Gene: camk2d has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2197 CAMK2D Elena Savva gene: CAMK2D was added
gene: CAMK2D was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CAMK2D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAMK2D were set to 38272033
Phenotypes for gene: CAMK2D were set to Neurodevelopmental disorder (MONDO#0700092), CAMK2D-related
Review for gene: CAMK2D was set to AMBER
Added comment: PMID: 38272033
- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old
- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological
- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5)
Sources: Literature
Cardiomyopathy_Paediatric v0.178 CAMK2D Elena Savva Marked gene: CAMK2D as ready
Cardiomyopathy_Paediatric v0.178 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Mendeliome v1.1502 CAMK2D Elena Savva Marked gene: CAMK2D as ready
Mendeliome v1.1502 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.178 CAMK2D Elena Savva Classified gene: CAMK2D as Green List (high evidence)
Cardiomyopathy_Paediatric v0.178 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Mendeliome v1.1502 CAMK2D Elena Savva Classified gene: CAMK2D as Green List (high evidence)
Mendeliome v1.1502 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.177 CAMK2D Elena Savva changed review comment from: PMID: 38272033
- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old
- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological
- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5)
Sources: Literature; to: PMID: 38272033
- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old
- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological
- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5)
Sources: Literature
Mendeliome v1.1501 CAMK2D Elena Savva gene: CAMK2D was added
gene: CAMK2D was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CAMK2D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAMK2D were set to 38272033
Phenotypes for gene: CAMK2D were set to Neurodevelopmental disorder (MONDO#0700092), CAMK2D-related
Added comment: PMID: 38272033
- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old
- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological
- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5)
Sources: Literature
Cardiomyopathy_Paediatric v0.177 CAMK2D Elena Savva gene: CAMK2D was added
gene: CAMK2D was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CAMK2D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAMK2D were set to 38272033
Phenotypes for gene: CAMK2D were set to Neurodevelopmental disorder (MONDO#0700092), CAMK2D-related
Review for gene: CAMK2D was set to GREEN
Added comment: PMID: 38272033
- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old
- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological
- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5)
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5683 CAMK2D Elena Savva Marked gene: CAMK2D as ready
Intellectual disability syndromic and non-syndromic v0.5683 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5683 CAMK2D Elena Savva Classified gene: CAMK2D as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5683 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5682 CAMK2D Elena Savva gene: CAMK2D was added
gene: CAMK2D was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CAMK2D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAMK2D were set to PMID: 38272033
Phenotypes for gene: CAMK2D were set to Neurodevelopmental disorder (MONDO#0700092), CAMK2D-related
Review for gene: CAMK2D was set to GREEN
Added comment: PMID: 38272033
- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old
- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological
- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5)
Sources: Literature
Mendeliome v1.1500 ERG Zornitza Stark Phenotypes for gene: ERG were changed from Lymphatic malformation 14, MIM# 620602 to Lymphatic malformation 14, MIM# 620602; Myelodysplasia syndrome, MONDO:0018881, ERG-related
Bone Marrow Failure v1.84 ERG Zornitza Stark Phenotypes for gene: ERG were changed from https://ash.confex.com/ash/2023/webprogram/Paper191986.html to Myelodysplasia syndrome, MONDO:0018881, ERG-related
Bone Marrow Failure v1.83 ERG Zornitza Stark Publications for gene: ERG were set to
Bone Marrow Failure v1.82 ERG Zornitza Stark edited their review of gene: ERG: Changed phenotypes: Myelodysplasia syndrome, MONDO:0018881, ERG-related
Mendeliome v1.1499 ERG Zornitza Stark edited their review of gene: ERG: Changed rating: AMBER; Changed publications: s://ash.confex.com/ash/2023/webprogram/Paper191986.html; Changed phenotypes: Myelodysplasia syndrome, MONDO:0018881, ERG-related; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bone Marrow Failure v1.82 ERG Zornitza Stark edited their review of gene: ERG: Changed publications: https://ash.confex.com/ash/2023/webprogram/Paper191986.html
Bone Marrow Failure v1.82 ERG Zornitza Stark changed review comment from: Conference abstract:

15 heterozygous variants in the ERG gene, 13 of which are missense and 2 truncating variants, in 17 individuals with cytopenia and/or HM (mainly myeloid) or lympheedema. Onset of hematological symptoms ranged from birth to 38 years for truncating and constrained ETS domain variants.
Sources: Literature; to: Conference abstract:

15 heterozygous variants in the ERG gene, 13 of which are missense and 2 truncating variants, in 17 individuals with cytopenia and/or HM (mainly myeloid) or lymphoedema. Onset of hematological symptoms ranged from birth to 38 years for truncating and constrained ETS domain variants.
Sources: Literature
Bone Marrow Failure v1.82 ERG Zornitza Stark Marked gene: ERG as ready
Bone Marrow Failure v1.82 ERG Zornitza Stark Gene: erg has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.82 ERG Zornitza Stark Classified gene: ERG as Amber List (moderate evidence)
Bone Marrow Failure v1.82 ERG Zornitza Stark Gene: erg has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.81 ERG Zornitza Stark gene: ERG was added
gene: ERG was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: ERG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ERG were set to https://ash.confex.com/ash/2023/webprogram/Paper191986.html
Review for gene: ERG was set to AMBER
Added comment: Conference abstract:

15 heterozygous variants in the ERG gene, 13 of which are missense and 2 truncating variants, in 17 individuals with cytopenia and/or HM (mainly myeloid) or lympheedema. Onset of hematological symptoms ranged from birth to 38 years for truncating and constrained ETS domain variants.
Sources: Literature
Mendeliome v1.1499 RBMX Zornitza Stark Phenotypes for gene: RBMX were changed from Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238 to Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238; Gustavson syndrome, MIM# 309555
Mendeliome v1.1498 RBMX Zornitza Stark Publications for gene: RBMX were set to 25256757; 34260915
Mendeliome v1.1497 RBMX Zornitza Stark edited their review of gene: RBMX: Added comment: PMID 37277488: In-frame deletion reported in a large multiplex Swedish family; Changed publications: 25256757, 34260915, 37277488; Changed phenotypes: Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238, Gustavson syndrome, MIM# 309555
Intellectual disability syndromic and non-syndromic v0.5681 RBMX Zornitza Stark Phenotypes for gene: RBMX were changed from Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238 to Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238; Gustavson syndrome, MIM# 309555
Intellectual disability syndromic and non-syndromic v0.5680 RBMX Zornitza Stark Publications for gene: RBMX were set to 25256757; 34260915
Intellectual disability syndromic and non-syndromic v0.5679 RBMX Zornitza Stark edited their review of gene: RBMX: Added comment: PMID 37277488: In-frame deletion reported in a large multiplex Swedish family; Changed publications: 25256757, 34260915, 37277488; Changed phenotypes: Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238, Gustavson syndrome, MIM# 309555
Genetic Epilepsy v0.2196 LMX1B Elena Savva Marked gene: LMX1B as ready
Genetic Epilepsy v0.2196 LMX1B Elena Savva Gene: lmx1b has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2196 LMX1B Elena Savva gene: LMX1B was added
gene: LMX1B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: LMX1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: LMX1B were set to Focal segmental glomerulosclerosis 10 MIM#256020; Nail-patella syndrome MIM#161200
Review for gene: LMX1B was set to RED
Added comment: GeneReviews - Epilepsy was reported in 6% of affected individuals in one large study [Sweeney et al 2003].

No new literature describing SNVs in this gene and epilepsy/seizures.

Gene was listed on Oliver's list
Sources: Literature
Genetic Epilepsy v0.2195 LMNB2 Elena Savva gene: LMNB2 was added
gene: LMNB2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: LMNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LMNB2 were set to PMID: 33783721; 25954030; 34466237
Phenotypes for gene: LMNB2 were set to ?Epilepsy, progressive myoclonic, 9 MIM#616540
Review for gene: LMNB2 was set to AMBER
Added comment: PMID: 33783721 - hom missense p.(Arg158Trp) in a proband with Progressive myoclonus epilepsies. No functional studies to validate the missense variant

PMID: 25954030 - hom missense p.(His157Tyr) in a proband with Progressive myoclonus epilepsies. In vitro assembly analysis of mutant lamin B2 protein revealed a distinct defect in the assembly of the highly ordered fibrous arrays typically formed by wild-type lamin B2, variant segregated in the affected sister

PMID: 34466237 - Hom missense p.(Arg158Leu) in a 5yo boy with progressive wide-based ataxic gait and intractable myoclonic seizure. All unaffected relatives (13) were het or wildtype

Association to epilepsy is amber and biallelic
Seizures noted as a rare feature of dominant disease in OMIM
Sources: Literature
Genetic Epilepsy v0.2194 L2HGDH Elena Savva Classified gene: L2HGDH as Green List (high evidence)
Genetic Epilepsy v0.2194 L2HGDH Elena Savva Gene: l2hgdh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2193 L2HGDH Elena Savva Classified gene: L2HGDH as Green List (high evidence)
Genetic Epilepsy v0.2193 L2HGDH Elena Savva Gene: l2hgdh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2192 L2HGDH Elena Savva Marked gene: L2HGDH as ready
Genetic Epilepsy v0.2192 L2HGDH Elena Savva Gene: l2hgdh has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2192 L2HGDH Elena Savva gene: L2HGDH was added
gene: L2HGDH was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: L2HGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: L2HGDH were set to PMID: 37113859
Phenotypes for gene: L2HGDH were set to L-2-hydroxyglutaric aciduria MIM#236792
Review for gene: L2HGDH was set to GREEN
Added comment: PMID: 37113859 - two sisters with a hom PTC, features included delayed milestones, both had generalised tonic clonic seizures associated with fever in childhood. Reviews literature, notes seizures observed in 26% of patients
Sources: Literature
Genetic Epilepsy v0.2191 KRIT1 Elena Savva Classified gene: KRIT1 as Green List (high evidence)
Genetic Epilepsy v0.2191 KRIT1 Elena Savva Gene: krit1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2191 KRIT1 Elena Savva Classified gene: KRIT1 as Green List (high evidence)
Genetic Epilepsy v0.2191 KRIT1 Elena Savva Gene: krit1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2190 KRIT1 Elena Savva Marked gene: KRIT1 as ready
Genetic Epilepsy v0.2190 KRIT1 Elena Savva Gene: krit1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2190 KRIT1 Elena Savva gene: KRIT1 was added
gene: KRIT1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KRIT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KRIT1 were set to 35836010; 35444609
Phenotypes for gene: KRIT1 were set to Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations MIM#116860; Cavernous malformations of CNS and retina MIM#116860; Cerebral cavernous malformations-1 MIM#116860
Review for gene: KRIT1 was set to GREEN
Added comment: Seizures noted as a feature in OMIM

PMID: 35836010 - proband presenting with seizures, nausea and vomiting, tachycardia, and bulging fontanelles

PMID: 35444609 - Family with CCM, segregated extensively. Only a single relative had seizures, but infrequently. Review, notes ~60% of individuals with cavernous hemangioma will experience seizures

GeneReviews - "The cumulative incidence of childhood seizures is ~20% (~60% by age 80 yrs)."
Sources: Literature
Genetic Epilepsy v0.2189 KMT2B Elena Savva Marked gene: KMT2B as ready
Genetic Epilepsy v0.2189 KMT2B Elena Savva Gene: kmt2b has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2189 KMT2B Elena Savva gene: KMT2B was added
gene: KMT2B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KMT2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KMT2B were set to PMID: 34477219; 37309110
Phenotypes for gene: KMT2B were set to Dystonia 28, childhood-onset MIM#617284; Intellectual developmental disorder, autosomal dominant 68 MIM#619934
Review for gene: KMT2B was set to RED
Added comment: PMID: 34477219 - Single 30yo patient with a canonical splice variant resulting in inframe exon 8 skipping. Presented with adult-onset cerebellar ataxia, minor dystonia, neuropathy and seizure

PMID: 37309110 - large review study, no patients specified to have seizures/epilepsy

Gene was listed in the Oliver review
Sources: Literature
Genetic Epilepsy v0.2188 KMT2A Elena Savva Classified gene: KMT2A as Green List (high evidence)
Genetic Epilepsy v0.2188 KMT2A Elena Savva Gene: kmt2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2188 KMT2A Elena Savva Classified gene: KMT2A as Green List (high evidence)
Genetic Epilepsy v0.2188 KMT2A Elena Savva Gene: kmt2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2187 KMT2A Elena Savva Marked gene: KMT2A as ready
Genetic Epilepsy v0.2187 KMT2A Elena Savva Gene: kmt2a has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2187 KMT2A Elena Savva gene: KMT2A was added
gene: KMT2A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KMT2A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KMT2A were set to PMID: 37075569
Phenotypes for gene: KMT2A were set to Wiedemann-Steiner syndrome MIM#605130
Review for gene: KMT2A was set to GREEN
Added comment: OMIM notes seizures were observed in a single patient

PMID: 37075569 - couldnt access paper, but abstract notes five patients with DEE, where epilepsy ranged from drug resistant to self-limited. Reviews literature and notes 33 patients with epilepsy, but limited clinical details.
Sources: Literature
Mendeliome v1.1497 MCTS1 Zornitza Stark Phenotypes for gene: MCTS1 were changed from Inherited susceptibility to mycobacterial diseases, MONDO:0019146, MCTS1-related to Immunodeficiency 118, mycobacteriosis, MIM# 301115
Mendeliome v1.1496 MCTS1 Zornitza Stark edited their review of gene: MCTS1: Changed phenotypes: Immunodeficiency 118, mycobacteriosis, MIM# 301115
Hereditary Neuropathy v1.10 PLA2G16 Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573), PLA2G16-related to Lipodystrophy, familial partial, type 9, MIM# 620683
Intellectual disability syndromic and non-syndromic v0.5679 PLA2G16 Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573), PLA2G16-related to Lipodystrophy, familial partial, type 9, MIM# 620683
Mendeliome v1.1496 PLA2G16 Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573), PLA2G16-related to Lipodystrophy, familial partial, type 9, MIM# 620683
Lipodystrophy_Lipoatrophy v1.14 PLA2G16 Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573), PLA2G16-related to Lipodystrophy, familial partial, type 9, MIM# 620683
Lipodystrophy_Lipoatrophy v1.13 PLA2G16 Zornitza Stark edited their review of gene: PLA2G16: Changed rating: GREEN; Changed phenotypes: Lipodystrophy, familial partial, type 9, MIM# 620683; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2186 KDM6A Elena Savva Marked gene: KDM6A as ready
Genetic Epilepsy v0.2186 KDM6A Elena Savva Gene: kdm6a has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2186 KDM6A Elena Savva gene: KDM6A was added
gene: KDM6A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KDM6A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: KDM6A were set to PMID: 28442529
Phenotypes for gene: KDM6A were set to Kabuki syndrome 2 MIM#300867
Review for gene: KDM6A was set to RED
Added comment: PMID: 28442529 - describes generalized epilepsy with febrile seizures plus in a family with a co-segregating SCN1A variant. Proband had GEFS+, dysmorphic facial features, short stature, developmental delay, and intellectual disability.

Gene was on the Oliver list
Sources: Literature
Genetic Epilepsy v0.2185 KDM5A Elena Savva Marked gene: KDM5A as ready
Genetic Epilepsy v0.2185 KDM5A Elena Savva Gene: kdm5a has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2185 KDM5A Elena Savva gene: KDM5A was added
gene: KDM5A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KDM5A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: KDM5A were set to PMID: 34210021
Phenotypes for gene: KDM5A were set to Neurodevelopmental disorder MONDO:0700092, KDM5A-related
Review for gene: KDM5A was set to RED
Added comment: PMID: 34210021 - large multigene deletion in a family with ID, epilepsy and schizophrenia. This gene and CACNA1C were considered the best candidates.

No evidence of SNVs in this gene causing epilepsy. This gene was on the Oliver list
Sources: Literature
Mendeliome v1.1495 KDM5A Elena Savva Phenotypes for gene: KDM5A were changed from autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 to autism spectrum disorder, MONDO:0005258; Neurodevelopmental disorder MONDO:0700092, KDM5A-related
Genetic Epilepsy v0.2184 KATNB1 Elena Savva gene: KATNB1 was added
gene: KATNB1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KATNB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KATNB1 were set to PMID: 26640080
Phenotypes for gene: KATNB1 were set to Lissencephaly 6, with microcephaly MIM#616212
Review for gene: KATNB1 was set to RED
Added comment: PMID: 26640080 - Proband with congenital microcephaly, lissencephaly, short stature, polysyndactyly, and dental abnormalities. Seizures developed by 6mo, had a homozygous canonical splice deletion

PMID: 31484711 - describes patients with seizures (epilepsy was documented in 69%) from a cohort with subcortical heterotopic gray matter malformations, but unclear which were specific for this gene
Sources: Literature
Genetic Epilepsy v0.2183 KAT6A Elena Savva Marked gene: KAT6A as ready
Genetic Epilepsy v0.2183 KAT6A Elena Savva Gene: kat6a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2183 KAT6A Elena Savva Classified gene: KAT6A as Green List (high evidence)
Genetic Epilepsy v0.2183 KAT6A Elena Savva Gene: kat6a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2182 KAT6A Elena Savva gene: KAT6A was added
gene: KAT6A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KAT6A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KAT6A were set to PMID: 34748993
Phenotypes for gene: KAT6A were set to Arboleda-Tham syndrome MIM#616268
Review for gene: KAT6A was set to GREEN
Added comment: PMID: 34748993 - 2 new probands with KAT6A syndrome and epilepsy.
Proband 1 - Epilepsy onset was at 3 months of age when daily right hemiclonic seizures appeared in sleep. Had a de novo missense, previously reported as pathogenic.
Proband 2 - Seizures onset was at 5 months with daily clusters of symmetric spasms characterized by flexion of the arms, extension of the legs and eyesā€™ rolling. Had a de novo PTC

Paper then reviews literature, notes 17/90 probands had epilepsy
Sources: Literature
Genetic Epilepsy v0.2181 KANSL1 Elena Savva Classified gene: KANSL1 as Green List (high evidence)
Genetic Epilepsy v0.2181 KANSL1 Elena Savva Gene: kansl1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2180 KANSL1 Elena Savva Marked gene: KANSL1 as ready
Genetic Epilepsy v0.2180 KANSL1 Elena Savva Gene: kansl1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2180 KANSL1 Elena Savva gene: KANSL1 was added
gene: KANSL1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KANSL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KANSL1 were set to PMID: 28440867
Phenotypes for gene: KANSL1 were set to Koolen-De Vries syndrome MIM#610443
Review for gene: KANSL1 was set to GREEN
Added comment: GeneReviews: describes seizures/epilepsy as a less common trait, where OMIM notes its in 50% of cases.

PMID: 28440867 - Median age at seizure onset was 3.5 years, and 9 of 22 had refractory seizures 2 years after onset. Focal impaired awareness seizures were the most frequent seizure type occurring in 20 of 31, usually with prominent autonomic features.
Sources: Literature
Genetic Epilepsy v0.2179 JMJD1C Elena Savva Classified gene: JMJD1C as Amber List (moderate evidence)
Genetic Epilepsy v0.2179 JMJD1C Elena Savva Gene: jmjd1c has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2178 JMJD1C Elena Savva Classified gene: JMJD1C as Amber List (moderate evidence)
Genetic Epilepsy v0.2178 JMJD1C Elena Savva Gene: jmjd1c has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2177 JMJD1C Elena Savva Marked gene: JMJD1C as ready
Genetic Epilepsy v0.2177 JMJD1C Elena Savva Gene: jmjd1c has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2177 JMJD1C Elena Savva gene: JMJD1C was added
gene: JMJD1C was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: JMJD1C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: JMJD1C were set to PMID: 32996679; 26181491; 31954878
Phenotypes for gene: JMJD1C were set to Intellectual disability (MONDO#0001071), JMJD1C-related
Review for gene: JMJD1C was set to AMBER
Added comment: PMID: 32996679 - de novo synonymous variant resulting in a 21bp deletion, who had learning disability and myoclonic epilepsy (onset 10yo).
Paper reviews prev reports, notes only 1/19 other patients with seizures (p.P163L)

PMID: 26181491 - de novo p.P163L (same as above), in a proband with gait dyspraxia, hand-washing stereotype, learning impairment, teeth grinding, air swallowing, kyphoscoliosis, and tonic epilepsy. Functional studies support missense pathogenicity.

PMID: 31954878 - 2/7 patients with de novo variants with ASD, ID and seizures. One proband had a de novo missense (p.V117I), another a PTC (p.P109Lfs*3) of unknown inheritance
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5678 JMJD1C Elena Savva Phenotypes for gene: JMJD1C were changed from Intellectual disability to Intellectual disability (MONDO#0001071), JMJD1C-related
Mendeliome v1.1494 JMJD1C Elena Savva Phenotypes for gene: JMJD1C were changed from Intellectual disability to Intellectual disability (MONDO#0001071), JMJD1C-related
Genetic Epilepsy v0.2176 JARID2 Elena Savva gene: JARID2 was added
gene: JARID2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: JARID2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: JARID2 were set to PMID: 22480366
Phenotypes for gene: JARID2 were set to Developmental delay with variable intellectual disability and dysmorphic facies MIM#620098
Review for gene: JARID2 was set to RED
Added comment: PMID: 22480366 - part of a larger multigene deletion, where a patient had seizures.

No patients with seizures reported with SNVs, but on the Oliver list as a gene to be considered.
Sources: Literature
Genetic Epilepsy v0.2175 ITGB4 Elena Savva Marked gene: ITGB4 as ready
Genetic Epilepsy v0.2175 ITGB4 Elena Savva Gene: itgb4 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2175 ITGB4 Elena Savva gene: ITGB4 was added
gene: ITGB4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ITGB4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ITGB4 were set to Epidermolysis bullosa, junctional 5A, intermediate MIM#619816; Epidermolysis bullosa, junctional 5B, with pyloric atresia MIM#226730
Review for gene: ITGB4 was set to RED
Added comment: No reports of seizures/epilepsy in probands with biallelic variants in this gene
Sources: Literature
Genetic Epilepsy v0.2174 INTS8 Elena Savva Marked gene: INTS8 as ready
Genetic Epilepsy v0.2174 INTS8 Elena Savva Gene: ints8 has been classified as Red List (Low Evidence).
Red cell disorders v1.24 PKLR Zornitza Stark Mode of inheritance for gene: PKLR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Red cell disorders v1.23 PKLR Zornitza Stark edited their review of gene: PKLR: Added comment: Only single family for the mono-allelic condition.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5677 CRELD1 Zornitza Stark Marked gene: CRELD1 as ready
Intellectual disability syndromic and non-syndromic v0.5677 CRELD1 Zornitza Stark Gene: creld1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5677 CRELD1 Zornitza Stark Classified gene: CRELD1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5677 CRELD1 Zornitza Stark Gene: creld1 has been classified as Green List (High Evidence).
Mendeliome v1.1493 MEIOB Zornitza Stark Phenotypes for gene: MEIOB were changed from Spermatogenic failure 22 MIM#617706; primary ovarian insufficiency to Spermatogenic failure 22 MIM#617706; Premature ovarian failure 23, MIM# 620686
Mendeliome v1.1492 MEIOB Zornitza Stark Publications for gene: MEIOB were set to 34794894; 24068956; 31000419; 28206990
Mendeliome v1.1491 MEIOB Zornitza Stark reviewed gene: MEIOB: Rating: GREEN; Mode of pathogenicity: None; Publications: 35991565, 34392356, 31000419; Phenotypes: Premature ovarian failure 23, MIM# 620686; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2174 INTS8 Elena Savva gene: INTS8 was added
gene: INTS8 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: INTS8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: INTS8 were set to ?Neurodevelopmental disorder with cerebellar hypoplasia and spasticity MIM#618572
Review for gene: INTS8 was set to RED
Added comment: No published evidence associating this gene and epilepsy
Sources: Literature
Genetic Epilepsy v0.2173 IBA57 Elena Savva Marked gene: IBA57 as ready
Genetic Epilepsy v0.2173 IBA57 Elena Savva Gene: iba57 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2173 IBA57 Elena Savva gene: IBA57 was added
gene: IBA57 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: IBA57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IBA57 were set to PMID: 30258207
Phenotypes for gene: IBA57 were set to Multiple mitochondrial dysfunctions syndrome 3 MIM#615330
Review for gene: IBA57 was set to RED
Added comment: PMID: 30258207 - girl with developmental regression and spastic quadriplegia. Brain MRI at 8 months showed cerebral white matter involvement, periventricular rarefaction, and corpus callosum involvement. She developed febrile seizures at the age of 18 months.
Chet missense pair found, no functional studies to support pathogenicity
Sources: Literature
Genetic Epilepsy v0.2172 IARS2 Elena Savva Marked gene: IARS2 as ready
Genetic Epilepsy v0.2172 IARS2 Elena Savva Gene: iars2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2172 IARS2 Elena Savva gene: IARS2 was added
gene: IARS2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: IARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IARS2 were set to PMID: 30041933
Phenotypes for gene: IARS2 were set to Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia MIM#616007
Review for gene: IARS2 was set to RED
Added comment: PMID: 30041933 - Japanese sibling pair presented with Leigh syndrome and infantile spasms. The siblings were identified with compound heterozygous missense mutations p.[(Phe227Ser)];[(Arg817His)]. No functional studies to support the pathogenicity of the missense variants
Sources: Literature
Gastrointestinal neuromuscular disease v1.24 OPA3 Bryony Thompson Marked gene: OPA3 as ready
Gastrointestinal neuromuscular disease v1.24 OPA3 Bryony Thompson Gene: opa3 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v1.24 OPA3 Bryony Thompson Classified gene: OPA3 as Green List (high evidence)
Gastrointestinal neuromuscular disease v1.24 OPA3 Bryony Thompson Gene: opa3 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v1.23 OPA3 Bryony Thompson gene: OPA3 was added
gene: OPA3 was added to Gastrointestinal neuromuscular disease. Sources: Literature
Mode of inheritance for gene: OPA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OPA3 were set to 31119193
Phenotypes for gene: OPA3 were set to Optic atrophy 3 MONDO:0008133
Mode of pathogenicity for gene: OPA3 was set to Other
Review for gene: OPA3 was set to GREEN
gene: OPA3 was marked as current diagnostic
Added comment: 11 of the 12 affected individuals from 3 families with OPA3 missense (p.Met8Thr, & p.Gln105Glu) had possible or confirmed gastrointestinal dysmotility symptoms as a feature of the condition. Haploinsufficiency is not expected to be the mechanism of disease. Gain of function or dominant negative effect have been suggested mechanisms of disease.
Sources: Literature
Mitochondrial disease v0.915 OPA3 Bryony Thompson Marked gene: OPA3 as ready
Mitochondrial disease v0.915 OPA3 Bryony Thompson Gene: opa3 has been classified as Green List (High Evidence).
Hereditary Neuropathy v1.9 OPA3 Bryony Thompson Marked gene: OPA3 as ready
Hereditary Neuropathy v1.9 OPA3 Bryony Thompson Gene: opa3 has been classified as Green List (High Evidence).
Hereditary Neuropathy v1.9 OPA3 Bryony Thompson Classified gene: OPA3 as Green List (high evidence)
Hereditary Neuropathy v1.9 OPA3 Bryony Thompson Gene: opa3 has been classified as Green List (High Evidence).
Hereditary Neuropathy v1.8 OPA3 Bryony Thompson gene: OPA3 was added
gene: OPA3 was added to Hereditary Neuropathy - complex. Sources: Literature
Mode of inheritance for gene: OPA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OPA3 were set to 31119193; 28050599
Phenotypes for gene: OPA3 were set to Optic atrophy 3 MONDO:0008133
Mode of pathogenicity for gene: OPA3 was set to Other
Review for gene: OPA3 was set to GREEN
gene: OPA3 was marked as current diagnostic
Added comment: Peripheral neuropathy has been reported in multiple individuals with ADOA associated with OPA3. Haploinsufficiency is not expected to be the mechanism of disease. Gain of function or dominant negative effect have been suggested mechanisms of disease.
PMID: 31119193 - 9 of the 12 affected individuals from 3 families with OPA3 missense (p.Met8Thr, & p.Gln105Glu) had a possible or confirmed peripheral neuropathy. Was presenting feature in a single case.
PMID: 28050599 - de novo c.235C>G p.(Leu79Val) identified in a woman who presented with cataracts, optic atrophy, lipodystrophy/lipoatrophy, and peripheral neuropathy.
Sources: Literature
Mitochondrial disease v0.915 OPA3 Bryony Thompson Phenotypes for gene: OPA3 were changed from to 3-methylglutaconic aciduria, type III (MGA3) (MIM#258501), AR; Optic atrophy 3 with cataract (MIM#165300), AD
Mitochondrial disease v0.914 OPA3 Bryony Thompson Publications for gene: OPA3 were set to
Mitochondrial disease v0.913 OPA3 Bryony Thompson Mode of inheritance for gene: OPA3 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Early-onset Parkinson disease v0.265 OPA3 Bryony Thompson Marked gene: OPA3 as ready
Early-onset Parkinson disease v0.265 OPA3 Bryony Thompson Gene: opa3 has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.265 OPA3 Bryony Thompson Classified gene: OPA3 as Red List (low evidence)
Early-onset Parkinson disease v0.265 OPA3 Bryony Thompson Gene: opa3 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2171 DHX16 Zornitza Stark Marked gene: DHX16 as ready
Genetic Epilepsy v0.2171 DHX16 Zornitza Stark Gene: dhx16 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2171 DHX16 Zornitza Stark Classified gene: DHX16 as Green List (high evidence)
Genetic Epilepsy v0.2171 DHX16 Zornitza Stark Gene: dhx16 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2170 DOHH Zornitza Stark Marked gene: DOHH as ready
Genetic Epilepsy v0.2170 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2170 DOHH Zornitza Stark Classified gene: DOHH as Green List (high evidence)
Genetic Epilepsy v0.2170 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2169 ECHS1 Zornitza Stark Marked gene: ECHS1 as ready
Genetic Epilepsy v0.2169 ECHS1 Zornitza Stark Gene: echs1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2169 ECHS1 Zornitza Stark Phenotypes for gene: ECHS1 were changed from Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, MIM# 616277; Leigh syndrome MONDO:0009723; cerebral palsy MONDO:0006497; paroxysmal dystonia MONDO:0016058 to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, MIM# 616277
Genetic Epilepsy v0.2168 ECHS1 Zornitza Stark Classified gene: ECHS1 as Green List (high evidence)
Genetic Epilepsy v0.2168 ECHS1 Zornitza Stark Gene: echs1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2167 EED Zornitza Stark Marked gene: EED as ready
Genetic Epilepsy v0.2167 EED Zornitza Stark Gene: eed has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2167 EED Zornitza Stark Classified gene: EED as Red List (low evidence)
Genetic Epilepsy v0.2167 EED Zornitza Stark Gene: eed has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2166 ECM1 Zornitza Stark Phenotypes for gene: ECM1 were changed from Urbach-Wiethe disease, MIM# 247100 to Urbach-Wiethe disease, MIM# 247100
Genetic Epilepsy v0.2166 ECM1 Zornitza Stark Marked gene: ECM1 as ready
Genetic Epilepsy v0.2166 ECM1 Zornitza Stark Gene: ecm1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2166 ECM1 Zornitza Stark Phenotypes for gene: ECM1 were changed from to Urbach-Wiethe disease, MIM# 247100
Genetic Epilepsy v0.2165 ECM1 Zornitza Stark Classified gene: ECM1 as Green List (high evidence)
Genetic Epilepsy v0.2165 ECM1 Zornitza Stark Gene: ecm1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2164 ECM1 Zornitza Stark reviewed gene: ECM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Urbach-Wiethe disease, MIM# 247100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2164 KARS Zornitza Stark Marked gene: KARS as ready
Genetic Epilepsy v0.2164 KARS Zornitza Stark Gene: kars has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2164 KARS Zornitza Stark Phenotypes for gene: KARS were changed from to Leukoencephalopathy, progressive, infantile-onset, with or without deafness MIM#619147
Genetic Epilepsy v0.2163 KARS Zornitza Stark Publications for gene: KARS were set to
Genetic Epilepsy v0.2162 KARS Zornitza Stark Mode of inheritance for gene: KARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1491 NEPRO Zornitza Stark Publications for gene: NEPRO were set to 26633546; 29620724; 31250547
Mendeliome v1.1490 NEPRO Zornitza Stark Classified gene: NEPRO as Green List (high evidence)
Mendeliome v1.1490 NEPRO Zornitza Stark Gene: nepro has been classified as Green List (High Evidence).
Mendeliome v1.1489 NEPRO Zornitza Stark reviewed gene: NEPRO: Rating: GREEN; Mode of pathogenicity: None; Publications: 37294112; Phenotypes: Anauxetic dysplasia 3, MIM618853; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.262 NEPRO Zornitza Stark Marked gene: NEPRO as ready
Skeletal dysplasia v0.262 NEPRO Zornitza Stark Gene: nepro has been classified as Green List (High Evidence).
Skeletal dysplasia v0.262 NEPRO Zornitza Stark Publications for gene: NEPRO were set to 26633546; 29620724; 31250547
Skeletal dysplasia v0.261 NEPRO Zornitza Stark Classified gene: NEPRO as Green List (high evidence)
Skeletal dysplasia v0.261 NEPRO Zornitza Stark Gene: nepro has been classified as Green List (High Evidence).
Stroke v1.14 JAM3 Zornitza Stark Marked gene: JAM3 as ready
Stroke v1.14 JAM3 Zornitza Stark Gene: jam3 has been classified as Green List (High Evidence).
Stroke v1.14 JAM3 Zornitza Stark Classified gene: JAM3 as Green List (high evidence)
Stroke v1.14 JAM3 Zornitza Stark Gene: jam3 has been classified as Green List (High Evidence).
Stroke v1.13 JAM3 Zornitza Stark gene: JAM3 was added
gene: JAM3 was added to Stroke. Sources: Expert Review
Mode of inheritance for gene: JAM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JAM3 were set to 23255084; 21109224
Phenotypes for gene: JAM3 were set to Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, MIM# 613730
Review for gene: JAM3 was set to GREEN
Added comment: Autosomal recessive disorder with a distinctive phenotype comprising haemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts. Affected individuals have a catastrophic neurologic clinical course resulting in death in infancy.

Four unrelated families reported.
Sources: Expert Review
Aortopathy_Connective Tissue Disorders v1.80 COL12A1 Elena Savva Publications for gene: COL12A1 were set to 28306229; 31273343; 24334604
Aortopathy_Connective Tissue Disorders v1.79 COL12A1 Elena Savva reviewed gene: COL12A1: Rating: ; Mode of pathogenicity: None; Publications: 37458870, 37353357; Phenotypes: ; Mode of inheritance: None
Cerebral vascular malformations v0.37 RNF213 Zornitza Stark Marked gene: RNF213 as ready
Cerebral vascular malformations v0.37 RNF213 Zornitza Stark Gene: rnf213 has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.37 RNF213 Zornitza Stark Phenotypes for gene: RNF213 were changed from {Moyamoya disease 2, susceptibility to} to susceptibility to Moyamoya disease 2, (MIM# 607151)
Cerebral vascular malformations v0.36 RNF213 Zornitza Stark Publications for gene: RNF213 were set to 21048783
Cerebral vascular malformations v0.35 RNF213 Zornitza Stark Mode of inheritance for gene: RNF213 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1489 RNF213 Zornitza Stark Publications for gene: RNF213 were set to
Mendeliome v1.1488 RNF213 Zornitza Stark Mode of inheritance for gene: RNF213 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.410 MYOCD Zornitza Stark Classified gene: MYOCD as Amber List (moderate evidence)
Congenital Heart Defect v0.410 MYOCD Zornitza Stark Gene: myocd has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.409 MYOCD Zornitza Stark edited their review of gene: MYOCD: Added comment: Single family with bi-allelic disease reported, which seems to be more severe expression of the mono-allelic disease, hence the Amber (rather than Red) rating.; Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.5676 POLR1A Zornitza Stark Phenotypes for gene: POLR1A were changed from Acrofacial dysostosis, Cincinnati type MIM#616462 to Acrofacial dysostosis, Cincinnati type MIM#616462; Leukodystrophy, hypomyelinating, 27, MIM# 620675
Leukodystrophy v0.304 POLR1A Zornitza Stark changed review comment from: Further two unrelated patients reported.; to: Further two unrelated patients reported but overall two homozygous missense variants only.
Leukodystrophy v0.304 POLR1A Zornitza Stark edited their review of gene: POLR1A: Changed rating: AMBER
Leukodystrophy v0.304 POLR1A Zornitza Stark Classified gene: POLR1A as Amber List (moderate evidence)
Leukodystrophy v0.304 POLR1A Zornitza Stark Gene: polr1a has been classified as Amber List (Moderate Evidence).
Leukodystrophy v0.303 POLR1A Zornitza Stark Classified gene: POLR1A as Green List (high evidence)
Leukodystrophy v0.303 POLR1A Zornitza Stark Gene: polr1a has been classified as Green List (High Evidence).
Leukodystrophy v0.302 POLR1A Zornitza Stark edited their review of gene: POLR1A: Added comment: Further two unrelated patients reported.; Changed rating: GREEN; Changed publications: 36917474
Intellectual disability syndromic and non-syndromic v0.5675 POLR1A Zornitza Stark Mode of inheritance for gene: POLR1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5674 POLR1A Zornitza Stark reviewed gene: POLR1A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukodystrophy, hypomyelinating, 27, MIM# 620675; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy v0.302 POLR1A Zornitza Stark Phenotypes for gene: POLR1A were changed from Leukodystrophy MONDO:0019046, POLR1A related to Leukodystrophy, hypomyelinating, 27, MIM# 620675
Leukodystrophy v0.301 POLR1A Zornitza Stark reviewed gene: POLR1A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukodystrophy, hypomyelinating, 27, MIM# 620675; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1487 POLR1A Zornitza Stark Phenotypes for gene: POLR1A were changed from Acrofacial dysostosis, Cincinnati type, (MIM#616462); Leukodystrophy MONDO:0019046, POLR1A-related to Leukodystrophy, hypomyelinating, 27, MIM# 620675; Acrofacial dysostosis, Cincinnati type, (MIM#616462)
Mendeliome v1.1486 POLR1A Zornitza Stark edited their review of gene: POLR1A: Changed phenotypes: Leukodystrophy, hypomyelinating, 27, MIM# 620675, Acrofacial dysostosis, Cincinnati type, (MIM#616462)
Mendeliome v1.1486 PCYT1A Zornitza Stark Phenotypes for gene: PCYT1A were changed from Spondylometaphyseal dysplasia with cone-rod dystrophy, MIM# 608940; Congenital lipodystrophy to Spondylometaphyseal dysplasia with cone-rod dystrophy, MIM# 608940; Lipodystrophy, congenital generalized, type 5, MIM# 620680
Mendeliome v1.1485 PCYT1A Zornitza Stark edited their review of gene: PCYT1A: Changed phenotypes: Spondylometaphyseal dysplasia with cone-rod dystrophy, MIM# 608940, Lipodystrophy, congenital generalized, type 5, MIM# 620680
Lipodystrophy_Lipoatrophy v1.13 PCYT1A Zornitza Stark Phenotypes for gene: PCYT1A were changed from Congenital lipodystrophy; fatty liver disease to Lipodystrophy, congenital generalized, type 5, MIM# 620680
Lipodystrophy_Lipoatrophy v1.12 PCYT1A Zornitza Stark edited their review of gene: PCYT1A: Changed phenotypes: Lipodystrophy, congenital generalized, type 5, MIM# 620680
Optic Atrophy v1.27 SPG7 Elena Savva commented on gene: SPG7: PMID: 32548275 - fs reported in AD optic atrophy where in NMD-predicted regions of the protein, were either isolated cases (1 proband) or segregated in a single family (2 affected).
**Several families with missense variants had more extensive segregation within families, and one was de novo - this is in ANOTHER gene, NOT SPG7
Intellectual disability syndromic and non-syndromic v0.5674 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971 to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Intellectual disability syndromic and non-syndromic v0.5673 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971 to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Genetic Epilepsy v0.2161 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971 to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Intellectual disability syndromic and non-syndromic v0.5673 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Neurodevelopmental disorder, MONDO:0700092, ATP6V0A1-related to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Genetic Epilepsy v0.2161 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Neurodevelopmental disorder, MONDO:0700092, ATP6V0A1-associated to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Mendeliome v1.1485 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Neurodevelopmental disorder MONDO:0700092, ATP6V0A1-associated to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Ataxia v1.18 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Neurodevelopmental disorder, MONDO:0700092, ATP6V0A1-associated to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Skeletal dysplasia v0.260 NEPRO Achchuthan Shanmugasundram reviewed gene: NEPRO: Rating: GREEN; Mode of pathogenicity: None; Publications: 37294112; Phenotypes: Anauxetic dysplasia 3, OMIM:618853; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1484 TREX1 Zornitza Stark Mode of inheritance for gene: TREX1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2160 EIF2AK2 Zornitza Stark Marked gene: EIF2AK2 as ready
Genetic Epilepsy v0.2160 EIF2AK2 Zornitza Stark Gene: eif2ak2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2160 EIF2AK2 Zornitza Stark Classified gene: EIF2AK2 as Green List (high evidence)
Genetic Epilepsy v0.2160 EIF2AK2 Zornitza Stark Gene: eif2ak2 has been classified as Green List (High Evidence).
Neurodegeneration with brain iron accumulation v0.31 FTH1 Zornitza Stark Phenotypes for gene: FTH1 were changed from Neuroferritinopathy (MONDO:0011638) to Neurodegeneration with brain iron accumulation 9, MIM# 620669
Neurodegeneration with brain iron accumulation v0.30 FTH1 Zornitza Stark reviewed gene: FTH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with brain iron accumulation 9, MIM# 620669; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Regression v0.542 FTH1 Zornitza Stark Phenotypes for gene: FTH1 were changed from Neuroferritinopathy (MONDO:0011638) to Neurodegeneration with brain iron accumulation 9, MIM# 620669
Regression v0.541 FTH1 Zornitza Stark reviewed gene: FTH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with brain iron accumulation 9, MIM# 620669; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1483 FTH1 Zornitza Stark Phenotypes for gene: FTH1 were changed from Hemochromatosis, type 5, MIM# 615517; Neuroferritinopathy (MONDO:0011638) to Hemochromatosis, type 5, MIM# 615517; Neurodegeneration with brain iron accumulation 9, MIM# 620669
Cerebellar and Pontocerebellar Hypoplasia v1.64 FTH1 Zornitza Stark Phenotypes for gene: FTH1 were changed from Neuroferritinopathy (MONDO:0011638) to Neurodegeneration with brain iron accumulation 9, MIM# 620669
Cerebellar and Pontocerebellar Hypoplasia v1.63 FTH1 Zornitza Stark reviewed gene: FTH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with brain iron accumulation 9, MIM# 620669; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1482 IRF1 Zornitza Stark Phenotypes for gene: IRF1 were changed from Inherited susceptibility to mycobacterial disease, MONDO:0019146, IRF1-related to Immunodeficiency 117, mycobacteriosis, autosomal recessive, MIM# 620668
Mendeliome v1.1481 IRF1 Zornitza Stark edited their review of gene: IRF1: Changed phenotypes: Immunodeficiency 117, mycobacteriosis, autosomal recessive, MIM# 620668
Ataxia v1.17 COQ4 Zornitza Stark edited their review of gene: COQ4: Added comment: PMIDs 36047608;38014483;38013626: more than 10 families reported with more limited spastic ataxia phenotype, onset from infancy to adulthood.; Changed publications: 30225196, 33704555, 30847826, 36047608, 38014483, 38013626; Changed phenotypes: Coenzyme Q10 deficiency, primary, 7, MIM# 616276, Spastic ataxia 10, autosomal recessive, MIM# 620666
Mitochondrial disease v0.912 COQ4 Zornitza Stark Phenotypes for gene: COQ4 were changed from Coenzyme Q10 deficiency, primary, 7, MIM# 616276 to Coenzyme Q10 deficiency, primary, 7, MIM# 616276; Spastic ataxia 10, autosomal recessive, MIM# 620666
Mitochondrial disease v0.911 COQ4 Zornitza Stark Publications for gene: COQ4 were set to 25658047; 26185144; 33704555
Mitochondrial disease v0.910 COQ4 Zornitza Stark edited their review of gene: COQ4: Added comment: PMIDs 36047608;38014483;38013626: more than 10 families reported with more limited spastic ataxia phenotype, onset from infancy to adulthood.; Changed publications: 25658047, 26185144, 33704555, 36047608, 38014483, 38013626; Changed phenotypes: Coenzyme Q10 deficiency, primary, 7, MIM# 616276, Spastic ataxia 10, autosomal recessive, MIM# 620666
Mendeliome v1.1481 COQ4 Zornitza Stark Phenotypes for gene: COQ4 were changed from Coenzyme Q10 deficiency, primary, 7, MIM# 616276 to Coenzyme Q10 deficiency, primary, 7, MIM# 616276; Spastic ataxia 10, autosomal recessive, MIM# 620666
Mendeliome v1.1480 COQ4 Zornitza Stark Publications for gene: COQ4 were set to 25658047; 26185144; 33704555
Mendeliome v1.1479 COQ4 Zornitza Stark edited their review of gene: COQ4: Added comment: PMIDs 36047608;38014483;38013626: more than 10 families reported with more limited spastic ataxia phenotype, onset from infancy to adulthood.; Changed publications: 25658047, 26185144, 33704555, 36047608, 38014483, 38013626; Changed phenotypes: Coenzyme Q10 deficiency, primary, 7, MIM# 616276, Spastic ataxia 10, autosomal recessive, MIM# 620666
Mendeliome v1.1479 SEC61A1 Zornitza Stark Phenotypes for gene: SEC61A1 were changed from Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Hypogammaglobulinaemia; Neutropaenia to Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Immunodeficiency, common variable, 15, MIM# 620670; Neutropenia, severe congenital, 11, autosomal dominant, MIM# 620674
Mendeliome v1.1478 SEC61A1 Zornitza Stark Publications for gene: SEC61A1 were set to 27392076; 32325141; 28782633
Mendeliome v1.1477 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Added comment: PMID 32325141: single individual with de novo missense and phenotype primarily characterised by severe neutropenia.; Changed publications: 27392076, 32325141, 28782633, 32325141
Mendeliome v1.1477 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Changed phenotypes: Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056, Immunodeficiency, common variable, 15, MIM# 620670, Neutropenia, severe congenital, 11, autosomal dominant, MIM# 620674
Phagocyte Defects v1.25 SEC61A1 Zornitza Stark Phenotypes for gene: SEC61A1 were changed from Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Hypogammaglobulinaemia; Neutropaenia to Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Neutropenia, severe congenital, 11, autosomal dominant, MIM# 620674; Immunodeficiency, common variable, 15, MIM# 620670
Phagocyte Defects v1.24 SEC61A1 Zornitza Stark Classified gene: SEC61A1 as Green List (high evidence)
Phagocyte Defects v1.24 SEC61A1 Zornitza Stark Gene: sec61a1 has been classified as Green List (High Evidence).
Phagocyte Defects v1.23 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Changed rating: GREEN
Phagocyte Defects v1.23 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Added comment: PMID 32325141: single individual with de novo missense and phenotype primarily characterised by severe neutropenia.

PMID 28782633: 11 individuals with primarily CVID phenotype, including neutropenia.; Changed publications: 27392076, 32325141, 28782633, 32325141; Changed phenotypes: Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056, Neutropenia, severe congenital, 11, autosomal dominant, MIM# 620674, Immunodeficiency, common variable, 15, MIM# 620670
Mendeliome v1.1477 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Changed phenotypes: Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056, Immunodeficiency, common variable, 15, MIM# 620670
Predominantly Antibody Deficiency v0.132 SEC61A1 Zornitza Stark Phenotypes for gene: SEC61A1 were changed from Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Hypogammaglobulinaemia; Severe recurrent respiratory tract infections to Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Immunodeficiency, common variable, 15, MIM# 620670
Predominantly Antibody Deficiency v0.131 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Changed phenotypes: Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056, Immunodeficiency, common variable, 15, MIM# 620670
Genetic Epilepsy v0.2159 KPNA7 Elena Savva Phenotypes for gene: KPNA7 were changed from severe neurodevelopmental defects; epilepsy to Neurodevelopmental disorder (MONDO#0700092), KPNA7-related
Mendeliome v1.1477 KPNA7 Elena Savva Phenotypes for gene: KPNA7 were changed from Oocyte/zygote/embryo maturation arrest 17, MIM# 620319; Neurodevelopmental disorder to Oocyte/zygote/embryo maturation arrest 17, MIM# 620319; Neurodevelopmental disorder (MONDO#0700092), KPNA7-related
Genetic Epilepsy v0.2158 KIF4A Elena Savva Publications for gene: KIF4A were set to 24812067; 34346154
Genetic Epilepsy v0.2158 KIF4A Elena Savva Classified gene: KIF4A as Amber List (moderate evidence)
Genetic Epilepsy v0.2158 KIF4A Elena Savva Gene: kif4a has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2157 KIF4A Elena Savva reviewed gene: KIF4A: Rating: ; Mode of pathogenicity: None; Publications: PMID: 36482480, 24812067, 34346154; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.5672 KIF4A Elena Savva Phenotypes for gene: KIF4A were changed from Mental retardation, X-linked 100, MIM# 300923 to Intellectual developmental disorder, X-linked 100 MIM#300923
Mendeliome v1.1476 KIF4A Elena Savva Phenotypes for gene: KIF4A were changed from Mental retardation, X-linked 100, MIM# 300923; Taurodontism, microdontia, and dens invaginatus (MIM#313490) to Intellectual developmental disorder, X-linked 100 MIM#300923; Taurodontism, microdontia, and dens invaginatus MIM#313490
Hydrocephalus_Ventriculomegaly v0.121 KIF4A Elena Savva Phenotypes for gene: KIF4A were changed from Mental retardation, X-linked 100, MIM# 300923 to Intellectual developmental disorder, X-linked 100 MIM#300923
Genetic Epilepsy v0.2157 KIF4A Elena Savva Phenotypes for gene: KIF4A were changed from Mental retardation, X-linked 100, MIM# 300923 to Intellectual developmental disorder, X-linked 100 MIM#300923
Genetic Epilepsy v0.2156 KIF1BP Elena Savva Classified gene: KIF1BP as Red List (low evidence)
Genetic Epilepsy v0.2156 KIF1BP Elena Savva Gene: kif1bp has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2155 KIF1BP Elena Savva reviewed gene: KIF1BP: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 28277559; Phenotypes: Goldberg-Shprintzen megacolon syndrome, MIM#609460; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5671 KCTD13 Elena Savva Mode of inheritance for gene: KCTD13 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2155 KCTD13 Elena Savva Mode of inheritance for gene: KCTD13 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.1475 KCTD13 Elena Savva Mode of inheritance for gene: KCTD13 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.5670 KCTD13 Elena Savva Phenotypes for gene: KCTD13 were changed from Intellectual disability to Neurodevelopmental disorder (MONDO#0700092), KCTD13-related
Genetic Epilepsy v0.2154 KCTD13 Elena Savva Phenotypes for gene: KCTD13 were changed from Neurodevelopmental disorder (MONDO#0700092), KCTD13-related to Neurodevelopmental disorder (MONDO#0700092), KCTD13-related
Genetic Epilepsy v0.2154 KCTD13 Elena Savva Phenotypes for gene: KCTD13 were changed from to Neurodevelopmental disorder (MONDO#0700092), KCTD13-related
Mendeliome v1.1474 KCTD13 Elena Savva Phenotypes for gene: KCTD13 were changed from Intellectual disability; seizures to Neurodevelopmental disorder (MONDO#0700092), KCTD13-related
Hypertrichosis syndromes v0.46 KCNN3 Elena Savva Classified gene: KCNN3 as Amber List (moderate evidence)
Hypertrichosis syndromes v0.46 KCNN3 Elena Savva Gene: kcnn3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5669 KCNN3 Elena Savva Phenotypes for gene: KCNN3 were changed from Zimmermann-Laband syndrome 3; OMIM# 618658 to Zimmermann-Laband syndrome 3 MIM#618658
Hypertrichosis syndromes v0.45 KCNN3 Elena Savva Marked gene: KCNN3 as ready
Hypertrichosis syndromes v0.45 KCNN3 Elena Savva Gene: kcnn3 has been classified as Red List (Low Evidence).
Hypertrichosis syndromes v0.45 KCNN3 Elena Savva gene: KCNN3 was added
gene: KCNN3 was added to Hypertrichosis syndromes. Sources: Literature
Mode of inheritance for gene: KCNN3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCNN3 were set to 34907639
Phenotypes for gene: KCNN3 were set to Zimmermann-Laband syndrome 3 MIM#618658
Review for gene: KCNN3 was set to AMBER
Added comment: PMID: 34907639 - literature review of previous ZLS patients, describes hypertrichosis as mild/moderate on trunk and limbs (3/7), or synophrys (4/7) in all patients
Sources: Literature
Mendeliome v1.1473 KCNN3 Elena Savva Phenotypes for gene: KCNN3 were changed from Zimmermann-Laband syndrome 3; OMIM# 618658 to Zimmermann-Laband syndrome 3; MIM#618658
Genetic Epilepsy v0.2153 KCNN3 Elena Savva Phenotypes for gene: KCNN3 were changed from Zimmermann-Laband syndrome to Zimmermann-Laband syndrome 3 MIM#618658
Genetic Epilepsy v0.2153 KCNN3 Elena Savva Publications for gene: KCNN3 were set to PMID: 33594261
Genetic Epilepsy v0.2152 KCNN3 Elena Savva reviewed gene: KCNN3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34907639; Phenotypes: Zimmermann-Laband syndrome 3 MIM#618658; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2152 KCNAB3 Elena Savva Publications for gene: KCNAB3 were set to PMID: 32990398
Mendeliome v1.1472 KCNAB3 Elena Savva Publications for gene: KCNAB3 were set to PMID: 32990398
Genetic Epilepsy v0.2151 KCNAB3 Elena Savva reviewed gene: KCNAB3: Rating: RED; Mode of pathogenicity: None; Publications: 37396552, 32990398, 36345448; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), KCNAB3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.1471 KCNAB3 Elena Savva reviewed gene: KCNAB3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 37396552, 32990398, 36345448; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), KCNAB3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2151 KCNAB3 Elena Savva Phenotypes for gene: KCNAB3 were changed from febrile seizures; afebrile seizure; genetic epilepsy with febrile seizures plus to Neurodevelopmental disorder (MONDO#0700092), KCNAB3-related
Mendeliome v1.1471 KCNAB3 Elena Savva Phenotypes for gene: KCNAB3 were changed from febrile seizures; afebrile seizure; genetic epilepsy with febrile seizures plus to Neurodevelopmental disorder (MONDO#0700092), KCNAB3-related
Genetic Epilepsy v0.2150 KARS Elena Savva reviewed gene: KARS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33942428; Phenotypes: Leukoencephalopathy, progressive, infantile-onset, with or without deafness MIM#619147; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5668 JAKMIP1 Elena Savva Phenotypes for gene: JAKMIP1 were changed from Intellectual disability; Seizures to Neurodevelopmental disorder (MONDO#0700092), JAKMIP1-related
Genetic Epilepsy v0.2150 JAKMIP1 Elena Savva Phenotypes for gene: JAKMIP1 were changed from Intellectual disability; Seizures to Neurodevelopmental disorder (MONDO#0700092), JAKMIP1-related
Mendeliome v1.1470 JAKMIP1 Elena Savva Phenotypes for gene: JAKMIP1 were changed from Intellectual disability; Seizures to Neurodevelopmental disorder (MONDO#0700092), JAKMIP1-related
Genetic Epilepsy v0.2149 ECM1 Andrew Fennell changed review comment from: PMID: 28434238 - 4 individuals with seizures from a cohort of 16. Note, that the authors focused on long-term progress of patients with seizures and/or brain calcification and excluded from the description those without those features. This means the quoted 57% prevalence of seizures was actually 25%. Seizure types included focal & absence.

PMID: 11929856 - references to previous studies predating the molecular understanding of the disorder with seizures being a common feature.
Sources: Literature; to: PMID: 28434238 - 4 individuals with seizures from a cohort of 16. Note, that the authors focused on long-term progress of patients with seizures and/or brain calcification and excluded from the description those without those features. This means the quoted 57% prevalence of seizures was actually 25%. Seizure types included focal & absence.

PMID: 11929856 - references to previous studies predating the molecular understanding of the disorder with seizures being a common feature.
Sources: Literature
Genetic Epilepsy v0.2149 EIF2AK2 Andrew Fennell gene: EIF2AK2 was added
gene: EIF2AK2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: EIF2AK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF2AK2 were set to PMID: 32197074
Phenotypes for gene: EIF2AK2 were set to Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, MIM# 618877
Review for gene: EIF2AK2 was set to GREEN
Added comment: PMID: 32197074 - Four individuals (50%) with seizures including GTCS, focal tonic, and focal complex types.

PMID: 33236446 - a single individual with neonatal generalised tonic seizures, dystonia, significant ID and later spasticity.
Sources: Literature
Genetic Epilepsy v0.2149 EED Andrew Fennell gene: EED was added
gene: EED was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: EED was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EED were set to PMID: 34533271
Phenotypes for gene: EED were set to Cohen-Gibson syndrome, MIM# 617561
Review for gene: EED was set to RED
Added comment: PMID: 34533271 - single case report of child with absence epilepsy aged 5yrs and subsequent GTC seizures throughout childhood.

Note, Griffiths et al (2019) reported 1 patient with seizures but later attributed this to hyperinsulinaemic hypoglycaemia.
Sources: Literature
Genetic Epilepsy v0.2149 ECM1 Andrew Fennell gene: ECM1 was added
gene: ECM1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ECM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ECM1 were set to PMID: 11929856; 28434238
Review for gene: ECM1 was set to GREEN
Added comment: PMID: 28434238 - 4 individuals with seizures from a cohort of 16. Note, that the authors focused on long-term progress of patients with seizures and/or brain calcification and excluded from the description those without those features. This means the quoted 57% prevalence of seizures was actually 25%. Seizure types included focal & absence.

PMID: 11929856 - references to previous studies predating the molecular understanding of the disorder with seizures being a common feature.
Sources: Literature
Genetic Epilepsy v0.2149 ECHS1 Andrew Fennell gene: ECHS1 was added
gene: ECHS1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ECHS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ECHS1 were set to PMID: 29575569; 35098523
Phenotypes for gene: ECHS1 were set to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, MIM# 616277; Leigh syndrome MONDO:0009723; cerebral palsy MONDO:0006497; paroxysmal dystonia MONDO:0016058
Review for gene: ECHS1 was set to GREEN
Added comment: PMID: 29575569 - 4 of 4 patients with Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1) had seizures onset in infancy.

PMID: 35098523 - single case report of an infant with Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency with status epilepticus after propofol administration.
Sources: Literature
Genetic Epilepsy v0.2149 DOHH Andrew Fennell gene: DOHH was added
gene: DOHH was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to PMID: 30661771; 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder, DOHH-related (MONDO#0700092)
Review for gene: DOHH was set to GREEN
Added comment: PMID: 35858628 - three of the five reported individuals with this neurodevelopmental disorder identified to have seizures. Two individuals had febrile seizures in mid-childhood with one going on to have generalised epilepsy. A third individual had generalised epilepsy.

PMID: 30661771 - Of note, DOHH is a key part of the same two-step enzymatic pathway as DHPS which is also associated with a neurodevelopmental disorder that prominently features seizures.
Sources: Literature
Genetic Epilepsy v0.2149 DHX16 Andrew Fennell gene: DHX16 was added
gene: DHX16 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: DHX16 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX16 were set to PMID: 31256877; 36211162
Phenotypes for gene: DHX16 were set to Neuromuscular disease and ocular or auditory anomalies with or without seizures, MIM# 618733
Review for gene: DHX16 was set to GREEN
Added comment: PMID: 31256877 - two of the four reported individuals had seizures (infantile spasms in one & GTC in one)

PMID: 36211162 - single case report of an 18-month old child with infantile spasms, likely for several months prior to presentation.
Sources: Literature
Motor Neurone Disease v1.8 DNAJC7 Sarah Leigh reviewed gene: DNAJC7: Rating: GREEN; Mode of pathogenicity: None; Publications: 31768050, 35039179, 34233860, 32897108, 37870677, 35456894; Phenotypes: amyotrophic lateral sclerosis; Mode of inheritance: None
Ciliary Dyskinesia v1.38 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Congenital nystagmus v1.19 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Overgrowth v1.11 SPIN4 Zornitza Stark Marked gene: SPIN4 as ready
Overgrowth v1.11 SPIN4 Zornitza Stark Gene: spin4 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2149 PRIMA1 Chris Ciotta gene: PRIMA1 was added
gene: PRIMA1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PRIMA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRIMA1 were set to PMID: 26339676
Phenotypes for gene: PRIMA1 were set to Frontal Lobe Epilepsy MONDO:0002612
Review for gene: PRIMA1 was set to RED
Added comment: - 2/3 siblings from unaffected parents in PMID: 26339676 were diagnosed with nocturnal frontal lobe epilepsy, which was confirmed by EEG. The affected siblings were homozygous for the c.93+2T>C variant canonical splice site variant. This variant was demonstrated by mini-gene assay to skip exon 2 of PRIMA1.

Overall 1 family, 2 individuals with epilepsy and high impact variants in PRIMA1.
Sources: Literature
Genetic Epilepsy v0.2149 POMGNT2 Chris Ciotta gene: POMGNT2 was added
gene: POMGNT2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: POMGNT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMGNT2 were set to PMID: 36808730
Phenotypes for gene: POMGNT2 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8 MIM#614830
Review for gene: POMGNT2 was set to RED
Added comment: This gene was included in the Genes4Epilepsy (PMID: 36808730) Gene resource and was said to be associated with developmental and epileptic encephalopathies and malformations of cortical development. In a review of the literature an association with individuals presenting with epilepsy was not found.
Sources: Literature
Genetic Epilepsy v0.2149 PLXNC1 Chris Ciotta gene: PLXNC1 was added
gene: PLXNC1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PLXNC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLXNC1 were set to PMID: 36808730
Phenotypes for gene: PLXNC1 were set to Malformations of cortical development
Review for gene: PLXNC1 was set to RED
Added comment: This gene was included in the genes4epilepsy resource (PMID:36808730) and was reported as being associated with the clinical phenotype "malformations of cortical development".

There are no current PubMed articles linking this gene with epilepsy however
Sources: Literature
Genetic Epilepsy v0.2149 PRDM8 Chris Ciotta gene: PRDM8 was added
gene: PRDM8 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PRDM8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDM8 were set to PMID: 2296154; 35034233
Phenotypes for gene: PRDM8 were set to ?Epilepsy, progressive myoclonic, 10 MIM#616640
Review for gene: PRDM8 was set to RED
Added comment: - PMID:22961547, 3 individuals from one family, all with myoclonic epilepsy, all had the Phe261Leu variant. This variant is absent from gnomAD V4.

- PMID: 35034233, Two individuals from one family, no clinical seizures but presented with myoclonus and abnormal EEG (generalised epileptiform charges), these individuals had the Ala230Gly missense change, which has currently been reported as a VUS.
Sources: Literature
Genetic Epilepsy v0.2149 PPP2R5D Chris Ciotta reviewed gene: PPP2R5D: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26168268, 29296277, 26576547; Phenotypes: Houge-Janssens syndrome 1 MIM#616355; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2149 PPP2R5D Chris Ciotta Deleted their review
Genetic Epilepsy v0.2149 PPP2R5D Chris Ciotta gene: PPP2R5D was added
gene: PPP2R5D was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PPP2R5D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PPP2R5D were set to Houge-Janssens syndrome 1 MIM#616355
Review for gene: PPP2R5D was set to GREEN
Added comment: - PMID:26168268, 3/11 individuals with intellectual disability also presented with epilepsy, In these three individuals two had the commonly reported pathogenic Glu198Lys variant while the third had another very well reported Glu200Lys variant.

- PMID:29296277, 2/2 individuals in this study with variants in PPP2R5D with epilepsy. Both individuals had the Glu198Lys variant.

- PMID: 26576547, 1/7 individuals with variants in this gene presented with complex partial seizures, this individual also had the Glu198Lys well reported variant.
Sources: Literature
Genetic Epilepsy v0.2149 POMK Chris Ciotta gene: POMK was added
gene: POMK was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: POMK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMK were set to PMID: 24925318
Phenotypes for gene: POMK were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 MIM#615249
Review for gene: POMK was set to RED
Added comment: - PMID:24925318, 1/3 unrelated individuals with bi-allelic POMK variants presented with seizures along with Cobblestone lissencephaly and hydrocephalus. This individual was compound heterozgyous for a high impact frameshift variant (c.286delT, p.F96fs) and a missense variant (c.905T>A , p.V302D).
Sources: Literature
Genetic Epilepsy v0.2149 POGZ Chris Ciotta gene: POGZ was added
gene: POGZ was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: POGZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POGZ were set to PMIS: 34645992; 31136090; 28490548; 26739615; 27824329
Phenotypes for gene: POGZ were set to White-Sutton syndrome MIM#616364
Review for gene: POGZ was set to GREEN
Added comment: - 2/12 Individuals in this in PMID:34645992 with POGZ PTVs were reported as having a history of at least 1 seizure. This information is mentioned in the article but seems to be left out in the clinical characteristics table on page 97 so we are unsure which individuals had a history of seizures.

- PMID:31136090, a de novo POGZ truncating variant (c.2711T>G; p.Leu904*) in an individual with dysmorphic features and poor tolerance to oral feeding. No family history of seizures or ID. First epileptic seizure occurred at age 2 and persisted despite clobazam. MRI at age 3 showed cortical and sub cortical atrophy and individual presented with dev delay and epileptic encephalopathy.

- PMID: 28480548, 15 year old female with healthy parents, MRI revealed global cerebellar atrophy, individual presented with dev delay and no verbal capacity, was being treated for epilepsy with medication. p.Asn941fs*3 variant was identified in this individual.

- PMID:26739615, 5 individuals with POGZ p.Ser278* variant, only 1/5 with complex, partial seizures.

- PMID:27824329, One chinese individual with autism, POGZ variant p.Gln127* who presented with seizures.

All the above variants are high impact and absent from gnomAD V4. 6 unique cases of individuals with high impact POGZ variants presenting with seizures/epilepsy.
Sources: Literature
Genetic Epilepsy v0.2149 POLG2 Zornitza Stark Marked gene: POLG2 as ready
Genetic Epilepsy v0.2149 POLG2 Zornitza Stark Gene: polg2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2149 POLG2 Zornitza Stark Classified gene: POLG2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2149 POLG2 Zornitza Stark Gene: polg2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2148 POLG2 Zornitza Stark reviewed gene: POLG2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4 MIM#610131; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2148 PLP1 Zornitza Stark Marked gene: PLP1 as ready
Genetic Epilepsy v0.2148 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2148 PLP1 Zornitza Stark Classified gene: PLP1 as Green List (high evidence)
Genetic Epilepsy v0.2148 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2147 PLP1 Zornitza Stark Classified gene: PLP1 as Green List (high evidence)
Genetic Epilepsy v0.2147 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2146 POLG2 Chris Ciotta gene: POLG2 was added
gene: POLG2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: POLG2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLG2 were set to PMID: 21555342
Phenotypes for gene: POLG2 were set to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4 MIM#610131
Review for gene: POLG2 was set to AMBER
Added comment: PMID:21555342 reports 4/11 unrelated individuals with mitochondrial disease as presenting with seizures and heterozygous variants in POLG2, 3/4 of these individuals had missense variants. Of these variants, 2 have been reported in Clinvar as benign and have high homozygote counts in gnomAD V4. The p.P205R variant was seen in an individual with seizures and is absent from gnomAD V4 and has been reported as pathogenic once in ClinVar for MIM#610131.

The last individual with seizures had a high impact variant (p.L475DfsX2) with 3 heterozygotes in the population (V4) which has been classified as pathogenic in ClinVar.

Overall, 2/11 unrelated individuals with plausible pathogenic variants presenting with seizures.
Sources: Literature
Genetic Epilepsy v0.2146 PPFIA3 Zornitza Stark Marked gene: PPFIA3 as ready
Genetic Epilepsy v0.2146 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2146 PPFIA3 Zornitza Stark Classified gene: PPFIA3 as Green List (high evidence)
Genetic Epilepsy v0.2146 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2145 PPFIA3 Zornitza Stark gene: PPFIA3 was added
gene: PPFIA3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PPFIA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPFIA3 were set to 37034625
Phenotypes for gene: PPFIA3 were set to Neurodevelopmental disorder, MONDO:0700092, PPFIA3-related
Review for gene: PPFIA3 was set to GREEN
Added comment: 19 individuals with mono-allelic variants presenting with features including developmental delay, intellectual disability, hypotonia, micro/macrocephaly, autism, and epilepsy. One individual with compound het variants: insufficient evidence for bi-allelic variants causing disease.
Sources: Literature
Mendeliome v1.1469 PPFIA3 Zornitza Stark Marked gene: PPFIA3 as ready
Mendeliome v1.1469 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Mendeliome v1.1469 PPFIA3 Zornitza Stark Classified gene: PPFIA3 as Green List (high evidence)
Mendeliome v1.1469 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5667 PPFIA3 Zornitza Stark Marked gene: PPFIA3 as ready
Intellectual disability syndromic and non-syndromic v0.5667 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5667 PPFIA3 Zornitza Stark Classified gene: PPFIA3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5667 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Mendeliome v1.1468 PPFIA3 Zornitza Stark gene: PPFIA3 was added
gene: PPFIA3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPFIA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPFIA3 were set to 37034625
Phenotypes for gene: PPFIA3 were set to Neurodevelopmental disorder, MONDO:0700092, PPFIA3-related
Review for gene: PPFIA3 was set to GREEN
Added comment: 19 individuals with mono-allelic variants presenting with features including developmental delay, intellectual disability, hypotonia, micro/macrocephaly, autism, and epilepsy.

One individual with compound het variants: insufficient evidence for bi-allelic variants causing disease.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5666 PPFIA3 Zornitza Stark gene: PPFIA3 was added
gene: PPFIA3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PPFIA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPFIA3 were set to 37034625
Phenotypes for gene: PPFIA3 were set to Neurodevelopmental disorder, MONDO:0700092, PPFIA3-related
Review for gene: PPFIA3 was set to GREEN
Added comment: 19 individuals with mono-allelic variants presenting with features including developmental delay, intellectual disability, hypotonia, micro/macrocephaly, autism, and epilepsy.

One individual with compound het variants: insufficient evidence for bi-allelic variants causing disease.
Sources: Literature
Genetic Epilepsy v0.2144 PLP1 Lisa Norbart gene: PLP1 was added
gene: PLP1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PLP1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: PLP1 were set to 7512350; 11071483; 21679407; 28133555; 29486744; 35346287; 37637647
Phenotypes for gene: PLP1 were set to Pelizaeus-Merzbacher Disease, MIM#312080
Review for gene: PLP1 was set to GREEN
Added comment: PMID: 7512350 (1994) - Mouse study demonstrating that seizures and convulsions are a result of a 2-fold increased PLP gene dosage. (Cited in OMIM)

PMID: 11071483 (2000) - One family with 2x brothers affected with PMD, both developing seizures in late teens. Other symptoms in both brothers include hypotonia at birth, nystagmus, and slowly progressive spastic paraplegia. (Cited in OMIM)

PMID: 21679407 (2011) - Male cohort, 43 individuals from 38 unrelated families with a PLP1-related disorder diagnosis. Seizures present in 2/43 males (both PLP1 duplication mutations). Additional symptoms include 3/43 stridor, 4/43 developmental delay, and 18/43 muscular hypotonia.

PMID: 28133555 (2017) - Case report on 9 year old male affected with classic PMD. Presented with a history of seizures since age 4. Also presents with developmental delay, nystagmus, microcephaly, spastic quadriplegia. Maternally inherited gain of 436Kb on Xq22.2 encompassing TCEAL1,MORF4L2, PLP1, and RAB9B, of which only PLP1 is associated with a disease.

PMID: 29486744 (2018) - Case report on family diagnosed with connatal PMD (previously diagnosed as X-linked epileptic seizures). The PLP1 missense mutation p.Ala84Asp was found to segregate in the family. 1x proband presenting with daily generalised seizures, onset at 8 months and no treatment response. 2x cousins and 2x maternal uncles also presented with epilepsy, all onset around 6 months and all died in childhood. Additional symptoms include 5/5 hypotonia and 5/5 psycho-motor delay. Consanguinity reported in the family.

PMID: 35346287 (2022) - Chinese cohort of 141 patients, 111 whom were followed up with. Seizures present in 4/28 individuals with connatal PMD, including 1 patient who died due to epileptic seizures at age 7, and 4/56 individuals with transitional PMD. Additional symptoms include 111/111 development delay, 110/111 nystagmus, 93/111 hypotonia, 35/111 stridor, and 4/111 respiratory difficulty.

PMID: 37637647 (2023) - Case report on 1x newborn individual diagnosed with failure to thrive and later PMD. Presented with episodes of rapid eye and side-to-side head movement episodes of 5-10 seconds, onset one month after birth. Diagnosis of seizure disorder considered before further testing. Individual hemizygous for PLP1: c.67G>A (p.Gly23Arg), maternally inherited.

GeneReviews: Seizures may develop in infants affected by 'severe connatal PMD'.
Sources: Literature
Leukodystrophy v0.301 SLC13A3 Zornitza Stark Marked gene: SLC13A3 as ready
Leukodystrophy v0.301 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Leukodystrophy v0.301 SLC13A3 Zornitza Stark Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Leukodystrophy v0.300 SLC13A3 Zornitza Stark Classified gene: SLC13A3 as Green List (high evidence)
Leukodystrophy v0.300 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2144 SLC13A3 Zornitza Stark Marked gene: SLC13A3 as ready
Genetic Epilepsy v0.2144 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2144 SLC13A3 Zornitza Stark Publications for gene: SLC13A3 were set to 30635937 35527102; https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Genetic Epilepsy v0.2143 SLC13A3 Zornitza Stark Publications for gene: SLC13A3 were set to 30635937 35527102; https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Genetic Epilepsy v0.2142 SLC13A3 Zornitza Stark Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Genetic Epilepsy v0.2141 SLC13A3 Zornitza Stark Classified gene: SLC13A3 as Green List (high evidence)
Genetic Epilepsy v0.2141 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Mendeliome v1.1467 SLC13A3 Zornitza Stark Marked gene: SLC13A3 as ready
Mendeliome v1.1467 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Mendeliome v1.1467 SLC13A3 Zornitza Stark Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Mendeliome v1.1466 SLC13A3 Zornitza Stark Classified gene: SLC13A3 as Green List (high evidence)
Mendeliome v1.1466 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Ataxia v1.17 SLC13A3 Zornitza Stark Marked gene: SLC13A3 as ready
Ataxia v1.17 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Ataxia v1.17 SLC13A3 Zornitza Stark Classified gene: SLC13A3 as Green List (high evidence)
Ataxia v1.17 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Fetal anomalies v1.182 MAX Zornitza Stark Marked gene: MAX as ready
Fetal anomalies v1.182 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Fetal anomalies v1.182 MAX Zornitza Stark Classified gene: MAX as Green List (high evidence)
Fetal anomalies v1.182 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5665 MAX Zornitza Stark Marked gene: MAX as ready
Intellectual disability syndromic and non-syndromic v0.5665 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5665 MAX Zornitza Stark Classified gene: MAX as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5665 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Polydactyly v0.270 MAX Zornitza Stark Marked gene: MAX as ready
Polydactyly v0.270 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Polydactyly v0.270 MAX Zornitza Stark Classified gene: MAX as Green List (high evidence)
Polydactyly v0.270 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Mendeliome v1.1465 MAX Zornitza Stark Phenotypes for gene: MAX were changed from {Pheochromocytoma, susceptibility to}, MIM# 171300 to {Pheochromocytoma, susceptibility to}, MIM# 171300; Syndromic disease (MONDO:0002254), MAX-related
Mendeliome v1.1464 MAX Zornitza Stark Publications for gene: MAX were set to 21685915
Macrocephaly_Megalencephaly v0.138 MAX Zornitza Stark Marked gene: MAX as ready
Macrocephaly_Megalencephaly v0.138 MAX Zornitza Stark Gene: max has been classified as Amber List (Moderate Evidence).
Macrocephaly_Megalencephaly v0.138 MAX Zornitza Stark Classified gene: MAX as Amber List (moderate evidence)
Macrocephaly_Megalencephaly v0.138 MAX Zornitza Stark Gene: max has been classified as Amber List (Moderate Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.55 SCN2A Zornitza Stark Marked gene: SCN2A as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.55 SCN2A Zornitza Stark Gene: scn2a has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.55 SCN2A Zornitza Stark Classified gene: SCN2A as Green List (high evidence)
Alternating Hemiplegia and Hemiplegic Migraine v0.55 SCN2A Zornitza Stark Gene: scn2a has been classified as Green List (High Evidence).
Fetal anomalies v1.181 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Fetal anomalies v1.181 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Fetal anomalies v1.181 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Fetal anomalies v1.181 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Clefting disorders v0.246 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Clefting disorders v0.246 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Clefting disorders v0.246 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Clefting disorders v0.246 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.34 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Pituitary hormone deficiency v0.34 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.34 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Pituitary hormone deficiency v0.34 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5664 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Intellectual disability syndromic and non-syndromic v0.5664 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5664 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5664 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v1.10 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Holoprosencephaly and septo-optic dysplasia v1.10 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v1.10 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Holoprosencephaly and septo-optic dysplasia v1.10 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.38 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Anophthalmia_Microphthalmia_Coloboma v1.38 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Amber List (Moderate Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.38 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Amber List (moderate evidence)
Anophthalmia_Microphthalmia_Coloboma v1.38 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Amber List (Moderate Evidence).
Polydactyly v0.269 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Polydactyly v0.269 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Polydactyly v0.269 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Polydactyly v0.269 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2140 TSPYL1 Zornitza Stark Publications for gene: TSPYL1 were set to 32885560; 15273283; 33075815
Overgrowth v1.11 SPIN4 Zornitza Stark Mode of inheritance for gene: SPIN4 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.1463 SPIN4 Zornitza Stark Marked gene: SPIN4 as ready
Mendeliome v1.1463 SPIN4 Zornitza Stark Gene: spin4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1463 SPIN4 Zornitza Stark Mode of inheritance for gene: SPIN4 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.1462 SPIN4 Zornitza Stark Classified gene: SPIN4 as Amber List (moderate evidence)
Mendeliome v1.1462 SPIN4 Zornitza Stark Gene: spin4 has been classified as Amber List (Moderate Evidence).
Overgrowth v1.10 SPIN4 Zornitza Stark Marked gene: SPIN4 as ready
Overgrowth v1.10 SPIN4 Zornitza Stark Gene: spin4 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.260 SOX8 Zornitza Stark Marked gene: SOX8 as ready
Skeletal dysplasia v0.260 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.260 SOX8 Zornitza Stark Classified gene: SOX8 as Red List (low evidence)
Skeletal dysplasia v0.260 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.8 SOX8 Zornitza Stark Marked gene: SOX8 as ready
Muscular dystrophy and myopathy_Paediatric v1.8 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.8 SOX8 Zornitza Stark Classified gene: SOX8 as Red List (low evidence)
Muscular dystrophy and myopathy_Paediatric v1.8 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2139 CP Zornitza Stark Marked gene: CP as ready
Genetic Epilepsy v0.2139 CP Zornitza Stark Gene: cp has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2139 CP Zornitza Stark Classified gene: CP as Amber List (moderate evidence)
Genetic Epilepsy v0.2139 CP Zornitza Stark Gene: cp has been classified as Amber List (Moderate Evidence).
Leukodystrophy v0.299 BORCS8 Zornitza Stark Marked gene: BORCS8 as ready
Leukodystrophy v0.299 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Leukodystrophy v0.299 BORCS8 Zornitza Stark Classified gene: BORCS8 as Green List (high evidence)
Leukodystrophy v0.299 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5663 BORCS8 Zornitza Stark Marked gene: BORCS8 as ready
Intellectual disability syndromic and non-syndromic v0.5663 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5663 BORCS8 Zornitza Stark Classified gene: BORCS8 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5663 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Microcephaly v1.248 GTPBP1 Zornitza Stark Marked gene: GTPBP1 as ready
Microcephaly v1.248 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Microcephaly v1.248 GTPBP1 Zornitza Stark Classified gene: GTPBP1 as Green List (high evidence)
Microcephaly v1.248 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Mendeliome v1.1461 GTPBP1 Zornitza Stark Marked gene: GTPBP1 as ready
Mendeliome v1.1461 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Mendeliome v1.1461 GTPBP1 Zornitza Stark Classified gene: GTPBP1 as Green List (high evidence)
Mendeliome v1.1461 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Fetal anomalies v1.180 CACHD1 Zornitza Stark Marked gene: CACHD1 as ready
Fetal anomalies v1.180 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Fetal anomalies v1.180 CACHD1 Zornitza Stark Classified gene: CACHD1 as Green List (high evidence)
Fetal anomalies v1.180 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5662 CACHD1 Zornitza Stark Marked gene: CACHD1 as ready
Intellectual disability syndromic and non-syndromic v0.5662 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5662 CACHD1 Zornitza Stark Classified gene: CACHD1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5662 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Mendeliome v1.1460 CACHD1 Zornitza Stark Marked gene: CACHD1 as ready
Mendeliome v1.1460 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Mendeliome v1.1460 CACHD1 Zornitza Stark Classified gene: CACHD1 as Green List (high evidence)
Mendeliome v1.1460 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Mendeliome v1.1459 CACHD1 Zornitza Stark reviewed gene: CACHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: syndromic complex neurodevelopmental disorder MONDO:0800439; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1459 SLC13A3 Daniel Flanagan gene: SLC13A3 was added
gene: SLC13A3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SLC13A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Phenotypes for gene: SLC13A3 were set to Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate (MIM# 618384)
Review for gene: SLC13A3 was set to GREEN
Added comment: Seven patients reported with biallelic SLC13A3 variants, causing acute reversible leukoencephalopathy and Ī±-ketoglutarate accumulation. Patients presented with acute neurological deterioration after a febrile illness. 5/7 with ataxia, 4/7 had seizures, 1/7 developmental delay.
Sources: Expert list
Leukodystrophy v0.298 SLC13A3 Daniel Flanagan gene: SLC13A3 was added
gene: SLC13A3 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: SLC13A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Phenotypes for gene: SLC13A3 were set to Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate (MIM# 618384)
Review for gene: SLC13A3 was set to GREEN
Added comment: Seven patients reported with biallelic SLC13A3 variants, causing acute reversible leukoencephalopathy and Ī±-ketoglutarate accumulation. Patients presented with acute neurological deterioration after a febrile illness. 5/7 with ataxia, 4/7 had seizures, 1/7 developmental delay.
Sources: Expert list
Genetic Epilepsy v0.2138 SLC13A3 Daniel Flanagan gene: SLC13A3 was added
gene: SLC13A3 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: SLC13A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Phenotypes for gene: SLC13A3 were set to Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate (MIM# 618384)
Review for gene: SLC13A3 was set to GREEN
Added comment: Seven patients reported with biallelic SLC13A3 variants, causing acute reversible leukoencephalopathy and Ī±-ketoglutarate accumulation. Patients presented with acute neurological deterioration after a febrile illness. 5/7 with ataxia, 4/7 had seizures, 1/7 developmental delay.
Sources: Expert list
Ataxia v1.16 SLC13A3 Daniel Flanagan gene: SLC13A3 was added
gene: SLC13A3 was added to Ataxia - paediatric. Sources: Expert list
Mode of inheritance for gene: SLC13A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Phenotypes for gene: SLC13A3 were set to Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate (MIM# 618384)
Review for gene: SLC13A3 was set to GREEN
Added comment: Seven patients reported with biallelic SLC13A3 variants, causing acute reversible leukoencephalopathy and Ī±-ketoglutarate accumulation. Patients presented with acute neurological deterioration after a febrile illness. 5/7 with ataxia, 4/7 had seizures, 1/7 developmental delay.
Sources: Expert list
Fetal anomalies v1.179 MAX Rylee Peters gene: MAX was added
gene: MAX was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAX were set to 38141607
Phenotypes for gene: MAX were set to Syndromic disease (MONDO:0002254), MAX-related
Review for gene: MAX was set to GREEN
Added comment: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5661 MAX Rylee Peters gene: MAX was added
gene: MAX was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAX were set to 38141607
Phenotypes for gene: MAX were set to Syndromic disease (MONDO:0002254), MAX-related
Review for gene: MAX was set to GREEN
Added comment: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Sources: Literature
Polydactyly v0.268 MAX Rylee Peters gene: MAX was added
gene: MAX was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAX were set to 38141607
Phenotypes for gene: MAX were set to Syndromic disease (MONDO:0002254), MAX-related
Review for gene: MAX was set to GREEN
Added comment: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Sources: Literature
Macrocephaly_Megalencephaly v0.137 MAX Rylee Peters gene: MAX was added
gene: MAX was added to Macrocephaly_Megalencephaly. Sources: Literature
Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAX were set to 38141607
Phenotypes for gene: MAX were set to Syndromic disease (MONDO:0002254), MAX-related
Review for gene: MAX was set to AMBER
Added comment: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Sources: Literature
Mendeliome v1.1459 MAX Rylee Peters reviewed gene: MAX: Rating: GREEN; Mode of pathogenicity: None; Publications: 38141607; Phenotypes: Syndromic disease (MONDO:0002254), MAX-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v1.10 SPIN4 Zornitza Stark Classified gene: SPIN4 as Amber List (moderate evidence)
Overgrowth v1.10 SPIN4 Zornitza Stark Gene: spin4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1459 SOX8 Zornitza Stark Marked gene: SOX8 as ready
Mendeliome v1.1459 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Mendeliome v1.1459 SOX8 Zornitza Stark Classified gene: SOX8 as Red List (low evidence)
Mendeliome v1.1459 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.37 ZRSR2 Michelle Torres gene: ZRSR2 was added
gene: ZRSR2 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to AMBER
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.

Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited

Only 2x probands with microphthalmia and/or optic disc coloboma.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5661 SOX8 Zornitza Stark Marked gene: SOX8 as ready
Intellectual disability syndromic and non-syndromic v0.5661 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Optic Atrophy v1.27 BORCS8 Zornitza Stark Marked gene: BORCS8 as ready
Optic Atrophy v1.27 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5661 SOX8 Zornitza Stark Classified gene: SOX8 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5661 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Optic Atrophy v1.27 BORCS8 Zornitza Stark Classified gene: BORCS8 as Green List (high evidence)
Optic Atrophy v1.27 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.259 SOX8 Paul De Fazio gene: SOX8 was added
gene: SOX8 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: SOX8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SOX8 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200088
Phenotypes for gene: SOX8 were set to Neurodevelopmental disorder (MONDO:0700092), SOX8-related
Review for gene: SOX8 was set to RED
gene: SOX8 was marked as current diagnostic
Added comment: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted). Functional studies on patient fibroblasts showed misregulation of downstream SOX8 targets.
Sources: Literature
Mendeliome v1.1458 BORCS8 Zornitza Stark Marked gene: BORCS8 as ready
Mendeliome v1.1458 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Clefting disorders v0.245 ZRSR2 Chris Ciotta gene: ZRSR2 was added
gene: ZRSR2 was added to Clefting disorders. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to PMID: 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.
Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Pituitary hormone deficiency v0.33 ZRSR2 Michelle Torres gene: ZRSR2 was added
gene: ZRSR2 was added to Pituitary hormone deficiency. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
gene: ZRSR2 was marked as current diagnostic
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.

Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Mendeliome v1.1458 BORCS8 Zornitza Stark Classified gene: BORCS8 as Green List (high evidence)
Mendeliome v1.1458 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.7 SOX8 Paul De Fazio gene: SOX8 was added
gene: SOX8 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: SOX8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SOX8 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200088
Phenotypes for gene: SOX8 were set to Neurodevelopmental disorder (MONDO:0700092), SOX8-related
Review for gene: SOX8 was set to RED
gene: SOX8 was marked as current diagnostic
Added comment: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Muscle biopsy of the right medial gastrocnemius at age 1 demonstrated mild variation in fiber size with scattered, moderately small, rounded polyhedral fibers of both types. There were no significant dystrophic features.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted). Functional studies on patient fibroblasts showed misregulation of downstream SOX8 targets.
Sources: Literature
Regression v0.541 BORCS8 Zornitza Stark Marked gene: BORCS8 as ready
Regression v0.541 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Fetal anomalies v1.179 ZRSR2 Chris Ciotta gene: ZRSR2 was added
gene: ZRSR2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to PMID: 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.
Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Mendeliome v1.1457 CACHD1 Suliman Khan gene: CACHD1 was added
gene: CACHD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CACHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACHD1 were set to PMID: 38158856
Phenotypes for gene: CACHD1 were set to syndromic complex neurodevelopmental disorder MONDO:0800439
Penetrance for gene: CACHD1 were set to unknown
Review for gene: CACHD1 was set to GREEN
Added comment: Sources: Literature
Alternating Hemiplegia and Hemiplegic Migraine v0.54 SCN2A Ee Ming Wong gene: SCN2A was added
gene: SCN2A was added to Alternating Hemiplegia and Hemiplegic Migraine. Sources: Literature
Mode of inheritance for gene: SCN2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN2A were set to 38097767
Phenotypes for gene: SCN2A were set to Alternating hemiplegia of childhood MONDO:0016241, SCN2A-related
Review for gene: SCN2A was set to GREEN
gene: SCN2A was marked as current diagnostic
Added comment: - 1x in-frame del and 2x missense variants identified in three individuals with typical alternating
hemiplegia of childhood (2x confirmed de novo, 1x unknown inheritance)
- Loss of function demonstrated by functional studies of all three variants (mutant transcripts transfected into HEK293T cells showed either complete loss of function or altered electrophysiological properties)
Sources: Literature
Holoprosencephaly and septo-optic dysplasia v1.9 ZRSR2 Michelle Torres gene: ZRSR2 was added
gene: ZRSR2 was added to Holoprosencephaly and septo-optic dysplasia. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
gene: ZRSR2 was marked as current diagnostic
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.

Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Regression v0.541 BORCS8 Zornitza Stark Classified gene: BORCS8 as Green List (high evidence)
Regression v0.541 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5660 ZRSR2 Chris Ciotta gene: ZRSR2 was added
gene: ZRSR2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to PMID: 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.
Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Fetal anomalies v1.179 CACHD1 Suliman Khan gene: CACHD1 was added
gene: CACHD1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CACHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACHD1 were set to PMID: 38158856
Phenotypes for gene: CACHD1 were set to syndromic complex neurodevelopmental disorder MONDO:0800439
Penetrance for gene: CACHD1 were set to unknown
Review for gene: CACHD1 was set to GREEN
Added comment: PMID: 38158856 - Six affected individuals from four unrelated families with homozygous CACHD1 variants (3 splice, 2 frameshift and 1 nonsense variant). Excluding the two fatal cases, all other were affected by syndromic neurodevelopmental abnormalities, multiple organ systems featuring global impairment of psychomotor development, dysmorphic facial features, genitourinary abnormalities, oculo-auricular and congenital malformation. Seizure was reported in one case. Whole exome sequencing identified bi-allelic loss of function variants in the CACHD1 gene. In vitro human neural models of CACHD1 depletion displayed dysregulated of Wnt signaling in the developing brain.
Sources: Literature
Polydactyly v0.268 ZRSR2 Michelle Torres gene: ZRSR2 was added
gene: ZRSR2 was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
gene: ZRSR2 was marked as current diagnostic
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.

Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Leukodystrophy v0.298 BORCS8 Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Mendeliome v1.1457 SPIN4 Belinda Chong gene: SPIN4 was added
gene: SPIN4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPIN4 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: SPIN4 were set to 36927955
Phenotypes for gene: SPIN4 were set to Lui-Jee-Baron syndrome MIM#301114
Review for gene: SPIN4 was set to AMBER
Added comment: PMID 36927955
* Single family, hemizygous frameshift variant (NM_001012968.3, c.312_313AGdel) identified in a male individual with generalized overgrowth of prenatal onset, variant also present in the mother and grandmother (both had adult heights 2 SDS greater than their midparental heights).
* In vitro shows loss of function and mice studies recapitulated the human phenotype with
generalized overgrowth, including increased longitudinal bone growth.
Sources: Literature
Sources: Literature
Leukodystrophy v0.298 BORCS8 Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5660 BORCS8 Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Regression v0.540 BORCS8 Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Genetic Epilepsy v0.2138 TSPYL1 Lilian Downie reviewed gene: TSPYL1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36082874; Phenotypes: Sudden infant death with dysgenesis of the testes syndrome MIM#608800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5660 SOX8 Paul De Fazio changed review comment from: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted).
Sources: Literature; to: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted). Functional studies on patient fibroblasts showed misregulation of downstream SOX8 targets.
Sources: Literature
Optic Atrophy v1.26 BORCS8 Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Mendeliome v1.1457 SOX8 Paul De Fazio gene: SOX8 was added
gene: SOX8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SOX8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SOX8 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200088
Phenotypes for gene: SOX8 were set to Neurodevelopmental disorder (MONDO:0700092), SOX8-related
Review for gene: SOX8 was set to RED
gene: SOX8 was marked as current diagnostic
Added comment: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted). Functional studies on patient fibroblasts showed misregulation of downstream SOX8 targets.
Sources: Literature
Mendeliome v1.1457 BORCS8 Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5660 CACHD1 Suliman Khan gene: CACHD1 was added
gene: CACHD1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CACHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACHD1 were set to PMID: 38158856
Phenotypes for gene: CACHD1 were set to syndromic complex neurodevelopmental disorder MONDO:0800439
Penetrance for gene: CACHD1 were set to unknown
Review for gene: CACHD1 was set to GREEN
Added comment: PMID: 38158856 - Six affected individuals from four unrelated families with homozygous CACHD1 variants (3 splice, 2 frameshift and 1 nonsense variant). Excluding the two fatal cases, all other were affected by syndromic neurodevelopmental abnormalities, multiple organ systems featuring global impairment of psychomotor development, dysmorphic facial features, genitourinary abnormalities, oculo-auricular and congenital malformation. Seizure was reported in one case. Whole exome sequencing identified bi-allelic loss of function variants in the CACHD1 gene. In vitro human neural models of CACHD1 depletion displayed dysregulated of Wnt signaling in the developing brain.
Sources: Literature
Overgrowth v1.9 SPIN4 Belinda Chong gene: SPIN4 was added
gene: SPIN4 was added to Overgrowth. Sources: Literature
Mode of inheritance for gene: SPIN4 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: SPIN4 were set to 36927955
Phenotypes for gene: SPIN4 were set to Lui-Jee-Baron syndrome MIM#301114
Review for gene: SPIN4 was set to AMBER
gene: SPIN4 was marked as current diagnostic
Added comment: PMID 36927955
* Single family, hemizygous frameshift variant (NM_001012968.3, c.312_313AGdel) identified in a male individual with generalized overgrowth of prenatal onset, variant also present in the mother and grandmother (both had adult heights 2 SDS greater than their midparental heights).
* In vitro shows loss of function and mice studies recapitulated the human phenotype with
generalized overgrowth, including increased longitudinal bone growth.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5660 SOX8 Paul De Fazio gene: SOX8 was added
gene: SOX8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SOX8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SOX8 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200088
Phenotypes for gene: SOX8 were set to Neurodevelopmental disorder (MONDO:0700092), SOX8-related
Review for gene: SOX8 was set to RED
gene: SOX8 was marked as current diagnostic
Added comment: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted).
Sources: Literature
Mendeliome v1.1457 BORCS8 Lauren Rogers gene: BORCS8 was added
gene: BORCS8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BORCS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BORCS8 were set to 38128568
Phenotypes for gene: BORCS8 were set to Neurodevelopmental disorder (MONDO#0700092), BORCS8-related
Review for gene: BORCS8 was set to GREEN
Added comment: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Optic Atrophy v1.26 BORCS8 Lauren Rogers gene: BORCS8 was added
gene: BORCS8 was added to Optic Atrophy. Sources: Literature
Mode of inheritance for gene: BORCS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BORCS8 were set to 38128568
Phenotypes for gene: BORCS8 were set to Neurodevelopmental disorder (MONDO#0700092), BORCS8-related
Review for gene: BORCS8 was set to GREEN
Added comment: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Leukodystrophy v0.298 BORCS8 Lauren Rogers gene: BORCS8 was added
gene: BORCS8 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: BORCS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BORCS8 were set to 38128568
Phenotypes for gene: BORCS8 were set to Neurodevelopmental disorder (MONDO#0700092), BORCS8-related
Review for gene: BORCS8 was set to GREEN
Added comment: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Genetic Epilepsy v0.2138 CP Lilian Downie gene: CP was added
gene: CP was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CP were set to PMID: 32741407, PMID: 18200628
Phenotypes for gene: CP were set to Hemosiderosis, systemic, due to aceruloplasminemia MIM#604290
Review for gene: CP was set to AMBER
Added comment: Reports of patients x3 with seizures as part of this phenotype.
***This is an adult onset brain iron accumulation neurodegenerative disorder***
Sources: Expert list
Regression v0.540 BORCS8 Lauren Rogers gene: BORCS8 was added
gene: BORCS8 was added to Regression. Sources: Literature
Mode of inheritance for gene: BORCS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BORCS8 were set to 38128568
Phenotypes for gene: BORCS8 were set to Neurodevelopmental disorder (MONDO#0700092), BORCS8-related
Review for gene: BORCS8 was set to GREEN
Added comment: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Genetic Epilepsy v0.2138 COQ8A Zornitza Stark Marked gene: COQ8A as ready
Genetic Epilepsy v0.2138 COQ8A Zornitza Stark Gene: coq8a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5660 BORCS8 Lauren Rogers gene: BORCS8 was added
gene: BORCS8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: BORCS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BORCS8 were set to 38128568
Phenotypes for gene: BORCS8 were set to Neurodevelopmental disorder (MONDO#0700092), BORCS8-related
Review for gene: BORCS8 was set to GREEN
Added comment: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Genetic Epilepsy v0.2138 COQ8A Zornitza Stark Classified gene: COQ8A as Green List (high evidence)
Genetic Epilepsy v0.2138 COQ8A Zornitza Stark Gene: coq8a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2137 COQ8A Zornitza Stark Classified gene: COQ8A as Green List (high evidence)
Genetic Epilepsy v0.2137 COQ8A Zornitza Stark Gene: coq8a has been classified as Green List (High Evidence).
Mendeliome v1.1457 GTPBP1 Lucy Spencer gene: GTPBP1 was added
gene: GTPBP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTPBP1 were set to 38118446
Phenotypes for gene: GTPBP1 were set to Neurodevelopmental disorder (MONDO#0700092), GTPBP1-related
Review for gene: GTPBP1 was set to GREEN
Added comment: PMID: 38118446- Cohort of individuals with variants in GTPBP2 (which has been previously described) and GTPBP1 (new) who have an identical neurodevelopmental syndrome. 4 homozygous individuals from 3 consanguineous families. 2 families have different NMD-predicted nonsense variants and the third has a missense, all are absent from gnomad v4.

The shared cardinal features of GTPBP1 and 2 related disease are microcephaly, profound neurodevelopmental impairment, and distinctive craniofacial features. Epilepsy was present in 10 of 20 individuals but its not clear if those individuals had GTPBP1 or 2 variants.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5660 GTPBP1 Zornitza Stark Marked gene: GTPBP1 as ready
Intellectual disability syndromic and non-syndromic v0.5660 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5660 GTPBP1 Zornitza Stark Marked gene: GTPBP1 as ready
Intellectual disability syndromic and non-syndromic v0.5660 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Microcephaly v1.247 GTPBP1 Lucy Spencer gene: GTPBP1 was added
gene: GTPBP1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: GTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTPBP1 were set to 38118446
Phenotypes for gene: GTPBP1 were set to Neurodevelopmental disorder (MONDO#0700092), GTPBP1-related
Review for gene: GTPBP1 was set to GREEN
Added comment: PMID: 38118446- Cohort of individuals with variants in GTPBP2 (which has been previously described) and GTPBP1 (new) who have an identical neurodevelopmental syndrome. 4 homozygous individuals from 3 consanguineous families. 2 families have different NMD-predicted nonsense variants and the third has a missense, all are absent from gnomad v4.

The shared cardinal features of GTPBP1 and 2 related disease are microcephaly, profound neurodevelopmental impairment, and distinctive craniofacial features. Epilepsy was present in 10 of 20 individuals but its not clear if those individuals had GTPBP1 or 2 variants.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5660 GTPBP1 Zornitza Stark Classified gene: GTPBP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5660 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5659 GTPBP1 Lucy Spencer gene: GTPBP1 was added
gene: GTPBP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTPBP1 were set to 38118446
Phenotypes for gene: GTPBP1 were set to Neurodevelopmental disorder (MONDO#0700092), GTPBP1-related
Review for gene: GTPBP1 was set to GREEN
Added comment: PMID: 38118446- Cohort of individuals with variants in GTPBP2 (which has been previously described) and GTPBP1 (new) who have an identical neurodevelopmental syndrome. 4 homozygous individuals from 3 consanguineous families. 2 families have different NMD-predicted nonsense variants and the third has a missense, all are absent from gnomad v4.

The shared cardinal features of GTPBP1 and 2 related disease are microcephaly, profound neurodevelopmental impairment, and distinctive craniofacial features. Epilepsy was present in 10 of 20 individuals but its not clear if those individuals had GTPBP1 or 2 variants.
Sources: Literature
Genetic Epilepsy v0.2136 COQ8A Lilian Downie gene: COQ8A was added
gene: COQ8A was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: COQ8A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ8A were set to PMID 32337771
Phenotypes for gene: COQ8A were set to Coenzyme Q10 deficiency, primary, 4 MIM#612016
Review for gene: COQ8A was set to GREEN
Added comment: PMID 32337771: cohort of 59 individuals. COQ8A-ataxia presented as variable multisystemic, early-onset cerebellar ataxia, with complicating features ranging from epilepsy (32%) and cognitive impairment (49%) to exercise intolerance (25%) and hyperkinetic movement disorders (41%), including dystonia and myoclonus as presenting symptoms.
Sources: Expert list
Fetal anomalies v1.179 NUDT2 Zornitza Stark Marked gene: NUDT2 as ready
Fetal anomalies v1.179 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Green List (High Evidence).
Fetal anomalies v1.179 NUDT2 Zornitza Stark Classified gene: NUDT2 as Green List (high evidence)
Fetal anomalies v1.179 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Green List (High Evidence).
Callosome v0.515 NUDT2 Zornitza Stark Marked gene: NUDT2 as ready
Callosome v0.515 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Green List (High Evidence).
Callosome v0.515 NUDT2 Zornitza Stark Classified gene: NUDT2 as Green List (high evidence)
Callosome v0.515 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2136 CENPF Zornitza Stark Marked gene: CENPF as ready
Genetic Epilepsy v0.2136 CENPF Zornitza Stark Gene: cenpf has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2136 CENPF Zornitza Stark Publications for gene: CENPF were set to
Fetal anomalies v1.178 NUDT2 Lilian Downie gene: NUDT2 was added
gene: NUDT2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NUDT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDT2 were set to PMID: 38141063
Phenotypes for gene: NUDT2 were set to Intellectual developmental disorder with or without peripheral neuropathy MIM#619844
Review for gene: NUDT2 was set to GREEN
Added comment: 9 individuals with partial agenesis or hypoplasia of the corpus callosum
Sources: Literature
Genetic Epilepsy v0.2135 CENPF Zornitza Stark Classified gene: CENPF as Red List (low evidence)
Genetic Epilepsy v0.2135 CENPF Zornitza Stark Gene: cenpf has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2134 CDK5 Zornitza Stark Marked gene: CDK5 as ready
Genetic Epilepsy v0.2134 CDK5 Zornitza Stark Gene: cdk5 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2134 CDK5 Zornitza Stark Classified gene: CDK5 as Amber List (moderate evidence)
Genetic Epilepsy v0.2134 CDK5 Zornitza Stark Gene: cdk5 has been classified as Amber List (Moderate Evidence).
Callosome v0.514 NUDT2 Lilian Downie edited their review of gene: NUDT2: Changed rating: GREEN
Callosome v0.514 NUDT2 Lilian Downie gene: NUDT2 was added
gene: NUDT2 was added to Callosome. Sources: Literature
Mode of inheritance for gene: NUDT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDT2 were set to PMID: 38141063
Phenotypes for gene: NUDT2 were set to Intellectual developmental disorder with or without peripheral neuropathy MIM#619844
Added comment: 9 individuals with partial agenesis or hypoplasia of the corpus callosum
Sources: Literature
Genetic Epilepsy v0.2133 CDK13 Zornitza Stark Marked gene: CDK13 as ready
Genetic Epilepsy v0.2133 CDK13 Zornitza Stark Gene: cdk13 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2133 CDK13 Zornitza Stark Classified gene: CDK13 as Green List (high evidence)
Genetic Epilepsy v0.2133 CDK13 Zornitza Stark Gene: cdk13 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2132 CCND2 Zornitza Stark Classified gene: CCND2 as Red List (low evidence)
Genetic Epilepsy v0.2132 CCND2 Zornitza Stark Gene: ccnd2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2131 CCND2 Zornitza Stark Marked gene: CCND2 as ready
Genetic Epilepsy v0.2131 CCND2 Zornitza Stark Gene: ccnd2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2131 CCND2 Zornitza Stark Classified gene: CCND2 as Red List (low evidence)
Genetic Epilepsy v0.2131 CCND2 Zornitza Stark Gene: ccnd2 has been classified as Red List (Low Evidence).
Fetal anomalies v1.178 CNOT2 Zornitza Stark Marked gene: CNOT2 as ready
Fetal anomalies v1.178 CNOT2 Zornitza Stark Gene: cnot2 has been classified as Green List (High Evidence).
Fetal anomalies v1.178 CNOT2 Zornitza Stark Classified gene: CNOT2 as Green List (high evidence)
Fetal anomalies v1.178 CNOT2 Zornitza Stark Gene: cnot2 has been classified as Green List (High Evidence).
Fetal anomalies v1.177 CNOT2 Zornitza Stark gene: CNOT2 was added
gene: CNOT2 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: CNOT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CNOT2 were set to 31512373; 31145527; 28135719
Phenotypes for gene: CNOT2 were set to Intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies 618608
Review for gene: CNOT2 was set to GREEN
Added comment: Congenital heart disease and poor growth may be detectable prenatally.
Sources: Expert Review
Genetic Epilepsy v0.2130 COL3A1 Lilian Downie gene: COL3A1 was added
gene: COL3A1 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: COL3A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL3A1 were set to PMID: 28258187, PMID: 37393059, PMID: 28742248, PMID: 22235340
Phenotypes for gene: COL3A1 were set to Polymicrogyria with or without vascular-type ehlers-danlos syndrome, MIM # 618343
Review for gene: COL3A1 was set to GREEN
Added comment: PMID: 37393059: 1 family with 2 sibs with epilepsy homozygous VUS variants in COL3A1
PMID: 28742248 1 family 2 sibs with seizures ID and biallelic variants in COL3A1
PMID: 22235340 mouse model with seizures
Sources: Expert list
Genetic Epilepsy v0.2130 CHD1 Lilian Downie gene: CHD1 was added
gene: CHD1 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CHD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD1 were set to 28866611
Phenotypes for gene: CHD1 were set to Pilarowski-Bjornsson syndrome, MIM#617682
Review for gene: CHD1 was set to GREEN
Added comment: 3/6 seizures
Sources: Expert list
Genetic Epilepsy v0.2130 CENPF Lilian Downie edited their review of gene: CENPF: Changed publications: PMID: 35488810; Changed phenotypes: Stromme syndrome MIM#243605
Genetic Epilepsy v0.2130 CENPF Lilian Downie changed review comment from: No reports of seizures in this phenotype
Sources: Expert list; to: No reports of seizures in this phenotype or in the microcephaly phenotype described
Sources: Expert list
Genetic Epilepsy v0.2130 CENPF Lilian Downie gene: CENPF was added
gene: CENPF was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CENPF was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CENPF were set to Stromme syndrome MIM#243605
Review for gene: CENPF was set to RED
Added comment: No reports of seizures in this phenotype
Sources: Expert list
Genetic Epilepsy v0.2130 CDK5 Lilian Downie gene: CDK5 was added
gene: CDK5 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CDK5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK5 were set to 25560765
Phenotypes for gene: CDK5 were set to Lissencephaly 7 with cerebellar hypoplasia MIM#616342
Review for gene: CDK5 was set to AMBER
Added comment: Single family multiple affected individuals, early onset seizures with burst supression pattern on EEG part of the phenotype
Sources: Expert list
Genetic Epilepsy v0.2130 CDK13 Lilian Downie gene: CDK13 was added
gene: CDK13 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CDK13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDK13 were set to PMID: 29021403, PMID: 35063350
Phenotypes for gene: CDK13 were set to Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder MIM#617360
Review for gene: CDK13 was set to GREEN
Added comment: PMID: 29021403 4/16 had seizures
PMID: 35063350 1 with seizures
Sources: Expert list
Genetic Epilepsy v0.2130 CCND2 Lilian Downie gene: CCND2 was added
gene: CCND2 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CCND2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCND2 were set to PMID: 24705253
Phenotypes for gene: CCND2 were set to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 MIM#615938
Review for gene: CCND2 was set to RED
Added comment: seizures not reported in MPPH due to this gene to date
Sources: Expert list
Genetic Epilepsy v0.2130 PIGF Zornitza Stark Marked gene: PIGF as ready
Genetic Epilepsy v0.2130 PIGF Zornitza Stark Gene: pigf has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2130 PIGF Zornitza Stark Classified gene: PIGF as Red List (low evidence)
Genetic Epilepsy v0.2130 PIGF Zornitza Stark Gene: pigf has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2129 PEX26 Zornitza Stark Marked gene: PEX26 as ready
Genetic Epilepsy v0.2129 PEX26 Zornitza Stark Gene: pex26 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2129 PEX26 Zornitza Stark Classified gene: PEX26 as Green List (high evidence)
Genetic Epilepsy v0.2129 PEX26 Zornitza Stark Gene: pex26 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2128 PEX26 Zornitza Stark reviewed gene: PEX26: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 7A (Zellweger), MIM#614872; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2128 PEX2 Zornitza Stark Marked gene: PEX2 as ready
Genetic Epilepsy v0.2128 PEX2 Zornitza Stark Gene: pex2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2128 PEX2 Zornitza Stark Classified gene: PEX2 as Green List (high evidence)
Genetic Epilepsy v0.2128 PEX2 Zornitza Stark Gene: pex2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2127 PEX2 Zornitza Stark Classified gene: PEX2 as Green List (high evidence)
Genetic Epilepsy v0.2127 PEX2 Zornitza Stark Gene: pex2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2126 PEX2 Zornitza Stark reviewed gene: PEX2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 5A (Zellweger), MIM#614866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2126 NAA10 Zornitza Stark Phenotypes for gene: NAA10 were changed from Microphthalmia, syndromic 1, MIM# 309800; NAA10-related syndrome; Seizures to NAA10-related syndrome MONDO:0100124
Genetic Epilepsy v0.2125 NAA10 Zornitza Stark Publications for gene: NAA10 were set to 11426460
Genetic Epilepsy v0.2124 NAA10 Zornitza Stark Classified gene: NAA10 as Green List (high evidence)
Genetic Epilepsy v0.2124 NAA10 Zornitza Stark Gene: naa10 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2123 LSS Zornitza Stark Marked gene: LSS as ready
Genetic Epilepsy v0.2123 LSS Zornitza Stark Gene: lss has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2123 LSS Zornitza Stark Classified gene: LSS as Green List (high evidence)
Genetic Epilepsy v0.2123 LSS Zornitza Stark Gene: lss has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2122 RPS6KA3 Zornitza Stark Marked gene: RPS6KA3 as ready
Genetic Epilepsy v0.2122 RPS6KA3 Zornitza Stark Gene: rps6ka3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2122 RPS6KA3 Zornitza Stark Classified gene: RPS6KA3 as Green List (high evidence)
Genetic Epilepsy v0.2122 RPS6KA3 Zornitza Stark Gene: rps6ka3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2121 RERE Zornitza Stark Marked gene: RERE as ready
Genetic Epilepsy v0.2121 RERE Zornitza Stark Gene: rere has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2121 RERE Zornitza Stark Classified gene: RERE as Green List (high evidence)
Genetic Epilepsy v0.2121 RERE Zornitza Stark Gene: rere has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2120 RAPGEF2 Zornitza Stark Tag STR tag was added to gene: RAPGEF2.
Mendeliome v1.1457 RAPGEF2 Zornitza Stark Tag STR tag was added to gene: RAPGEF2.
Genetic Epilepsy v0.2120 RANBP2 Zornitza Stark Marked gene: RANBP2 as ready
Genetic Epilepsy v0.2120 RANBP2 Zornitza Stark Gene: ranbp2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2120 RANBP2 Zornitza Stark Classified gene: RANBP2 as Green List (high evidence)
Genetic Epilepsy v0.2120 RANBP2 Zornitza Stark Gene: ranbp2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2119 PTBP1 Zornitza Stark Marked gene: PTBP1 as ready
Genetic Epilepsy v0.2119 PTBP1 Zornitza Stark Gene: ptbp1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2119 PTBP1 Zornitza Stark Classified gene: PTBP1 as Red List (low evidence)
Genetic Epilepsy v0.2119 PTBP1 Zornitza Stark Gene: ptbp1 has been classified as Red List (Low Evidence).
Mendeliome v1.1457 PTBP1 Zornitza Stark Marked gene: PTBP1 as ready
Mendeliome v1.1457 PTBP1 Zornitza Stark Gene: ptbp1 has been classified as Red List (Low Evidence).
Mendeliome v1.1457 PTBP1 Zornitza Stark Classified gene: PTBP1 as Red List (low evidence)
Mendeliome v1.1457 PTBP1 Zornitza Stark Gene: ptbp1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2118 RAI1 Zornitza Stark Marked gene: RAI1 as ready
Genetic Epilepsy v0.2118 RAI1 Zornitza Stark Gene: rai1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2118 RAI1 Zornitza Stark Classified gene: RAI1 as Green List (high evidence)
Genetic Epilepsy v0.2118 RAI1 Zornitza Stark Gene: rai1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2117 RAB39B Zornitza Stark Marked gene: RAB39B as ready
Genetic Epilepsy v0.2117 RAB39B Zornitza Stark Gene: rab39b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2117 RAB39B Zornitza Stark Classified gene: RAB39B as Green List (high evidence)
Genetic Epilepsy v0.2117 RAB39B Zornitza Stark Gene: rab39b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2116 CCDC88C Zornitza Stark Marked gene: CCDC88C as ready
Genetic Epilepsy v0.2116 CCDC88C Zornitza Stark Gene: ccdc88c has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2116 CCDC88C Zornitza Stark Classified gene: CCDC88C as Green List (high evidence)
Genetic Epilepsy v0.2116 CCDC88C Zornitza Stark Gene: ccdc88c has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2115 CCDC22 Zornitza Stark Marked gene: CCDC22 as ready
Genetic Epilepsy v0.2115 CCDC22 Zornitza Stark Gene: ccdc22 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2115 CCDC22 Zornitza Stark Classified gene: CCDC22 as Red List (low evidence)
Genetic Epilepsy v0.2115 CCDC22 Zornitza Stark Gene: ccdc22 has been classified as Red List (Low Evidence).
Microcephaly v1.247 COPB2 Zornitza Stark Publications for gene: COPB2 were set to 29036432
Genomic newborn screening: BabyScreen+ v1.110 TSHR Zornitza Stark Phenotypes for gene: TSHR were changed from Hypothyroidism, congenital, nongoitrous, 1 - MIM#275200; HYPERTHYROIDISM, FAMILIAL GESTATIONAL HYPERTHYROIDISM to Hypothyroidism, congenital, nongoitrous, 1 - MIM#275200
Genomic newborn screening: BabyScreen+ v1.109 TSHR Zornitza Stark Mode of inheritance for gene: TSHR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v1.108 TSHR Zornitza Stark edited their review of gene: TSHR: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2114 PIGF Lisa Norbart gene: PIGF was added
gene: PIGF was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PIGF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGF were set to 33386993
Phenotypes for gene: PIGF were set to Onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome, MIM#619356
Review for gene: PIGF was set to RED
Added comment: PMID: 33386993 (2021) - The same homozygous missense mutation (p.Pro172Arg) in 2x unrelated individuals affected with DOORS syndrome (without deafness). 1/2 presented with generalised tonic-clonic seizues and 1/2 with tonic posturing.
Sources: Literature
Genetic Epilepsy v0.2114 PEX26 Lisa Norbart gene: PEX26 was added
gene: PEX26 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PEX26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX26 were set to 34430430; 28823628
Phenotypes for gene: PEX26 were set to Peroxisome biogenesis disorder 7A (Zellweger), MIM#614872
Review for gene: PEX26 was set to AMBER
Added comment: PMID: 34430430 (2021) - Case report on 1 infant with a homozygous frameshift variant and Zellweger Syndrome diagnosis. Presented with an epileptic seizure at 8 months old and focal seizures during sleep, died at 9 months old. Also described a literature review resulting in 1/4 previously reported infants with Zellweger Syndrome presenting with seizures, described below.

PMID: 28823628 (2017) - Case report on 1 infant with a homozygous missense variant and Zellweger Syndrome diagnosis. Developed tonic-clonic jerking of extremities.

GeneReviews: Seizures can be a symptom of Zellweger Syndrome in newborns (caused by underlying neuronal migration defects).
Sources: Literature
Genetic Epilepsy v0.2114 PEX2 Lisa Norbart gene: PEX2 was added
gene: PEX2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PEX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX2 were set to 14630978; 23430938; 17041890
Phenotypes for gene: PEX2 were set to Peroxisome biogenesis disorder 5A (Zellweger), MIM#614866
Review for gene: PEX2 was set to AMBER
Added comment: PMID: 14630978 (2004) - 3 individuals with homozygous missense mutations and diagnosed with Zellweger syndrome. 1/3 presented with generalised seizures for which treatment was not effective. 2/3 had no seizures.

PMID: 23430938 (2012) - 1 individual with compound heterozygous nonsense mutations affected with mild Zellweger Syndrome, did not present with seizures.

PMID: 17041890 (2006) - 3/3 individuals with homozygous PEX2 nonsense/frameshift variants affected with Zellweger Syndrome. 2/3 presented with seizures, died at <6 months old.

GeneReviews: Seizures can be a symptom of Zellweger Syndrome in newborns (caused by underlying neuronal migration defects).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5659 PUS3 Zornitza Stark Phenotypes for gene: PUS3 were changed from Mental retardation, autosomal recessive 55, MIM# 617051 to Neurodevelopmental disorder with microcephaly and gray sclerae, MIM# 617051
Intellectual disability syndromic and non-syndromic v0.5658 PUS3 Zornitza Stark edited their review of gene: PUS3: Changed phenotypes: Neurodevelopmental disorder with microcephaly and gray sclerae, MIM# 617051
Mendeliome v1.1456 PUS3 Zornitza Stark Phenotypes for gene: PUS3 were changed from Mental retardation, autosomal recessive 55, MIM# 617051 to Neurodevelopmental disorder with microcephaly and gray sclerae, MIM# 617051
Mendeliome v1.1455 PUS3 Zornitza Stark edited their review of gene: PUS3: Changed phenotypes: Neurodevelopmental disorder with microcephaly and gray sclerae, MIM# 617051
Genetic Epilepsy v0.2114 PUS3 Zornitza Stark Marked gene: PUS3 as ready
Genetic Epilepsy v0.2114 PUS3 Zornitza Stark Gene: pus3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2114 PUS3 Zornitza Stark Phenotypes for gene: PUS3 were changed from Mental retardation, autosomal recessive 55, MIM# 617051 to Neurodevelopmental disorder with microcephaly and gray sclerae, MIM# 617051
Genetic Epilepsy v0.2113 PUS3 Zornitza Stark Classified gene: PUS3 as Green List (high evidence)
Genetic Epilepsy v0.2113 PUS3 Zornitza Stark Gene: pus3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2112 NAA10 Rylee Peters reviewed gene: NAA10: Rating: GREEN; Mode of pathogenicity: None; Publications: 37130971; Phenotypes: NAA10-related syndrome MONDO:0100124; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2112 LSS Rylee Peters changed review comment from: PMID: 30723320 - Cohort of 11 individuals from 7 unrelated families; all affected with alopecia, scaly skin, other ectodermal abnormalities, variable MRI abnormalities and neurological symptoms. All affected individuals (except 1x individual with a single missense variant and an allelic imbalance) were hom/compound het, whilst heterozygous carriers, for all the families, were asymptomatic. Epilepsy was reported in 7/11 individuals (Table 1).

PMID: 37157980 - Four-year-old male with global developmental delay, epilepsy and striking alopecia; identified novel compound heterozygous LSS splice site (c.14+2T>C) and missense (c.1357 G>A; p.V453L) variants. Presented with myoclonic epilepsy at 14 months.

Note: PanelApp UK has this gene rating as amber based on advice from Genomics England Clinical Team and West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group.
Sources: Literature; to: PMID: 30723320 - Cohort of 11 individuals from 7 unrelated families; all affected with alopecia, scaly skin, other ectodermal abnormalities, variable MRI abnormalities and neurological symptoms. All affected individuals (except 1x individual with a single missense variant and an allelic imbalance) were hom/compound het, whilst heterozygous carriers, for all the families, were asymptomatic. Epilepsy was reported in 7/11 individuals (Table 1).

PMID: 37157980 - Four-year-old male with global developmental delay, epilepsy and striking alopecia; identified novel compound heterozygous LSS splice site (c.14+2T>C) and missense (c.1357 G>A; p.V453L) variants. Presented with myoclonic epilepsy at 14 months.

Note: PanelApp UK has this gene rating as amber based on advice from Genomics England Clinical Team and West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group.
Sources: Literature
Genetic Epilepsy v0.2112 LSS Rylee Peters gene: LSS was added
gene: LSS was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: LSS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSS were set to PMID: 30723320; 37157980
Phenotypes for gene: LSS were set to Alopecia-intellectual disability syndrome 4, MIM#618840
Review for gene: LSS was set to GREEN
Added comment: PMID: 30723320 - Cohort of 11 individuals from 7 unrelated families; all affected with alopecia, scaly skin, other ectodermal abnormalities, variable MRI abnormalities and neurological symptoms. All affected individuals (except 1x individual with a single missense variant and an allelic imbalance) were hom/compound het, whilst heterozygous carriers, for all the families, were asymptomatic. Epilepsy was reported in 7/11 individuals (Table 1).

PMID: 37157980 - Four-year-old male with global developmental delay, epilepsy and striking alopecia; identified novel compound heterozygous LSS splice site (c.14+2T>C) and missense (c.1357 G>A; p.V453L) variants. Presented with myoclonic epilepsy at 14 months.

Note: PanelApp UK has this gene rating as amber based on advice from Genomics England Clinical Team and West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group.
Sources: Literature
Genetic Epilepsy v0.2112 RPS6KA3 Belinda Chong gene: RPS6KA3 was added
gene: RPS6KA3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RPS6KA3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RPS6KA3 were set to 12210291; 6879200
Phenotypes for gene: RPS6KA3 were set to Coffin-Lowry syndrome MIM# 303600; Intellectual disability; short stature; delayed bone age; hearing deficit; hypotonia; tapering fingers; abnormal facies (hypertelorism, anteverted nares, prominent frontal region)
Review for gene: RPS6KA3 was set to GREEN
gene: RPS6KA3 was marked as current diagnostic
Added comment: Seizures is a feature in Coffin-Lowry syndrome individuals.
Sources: Literature
Genetic Epilepsy v0.2112 RERE Belinda Chong gene: RERE was added
gene: RERE was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RERE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RERE were set to 30896913; 27087320; 23451234; 30558068
Phenotypes for gene: RERE were set to Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart, MIM# 616975
Review for gene: RERE was set to GREEN
gene: RERE was marked as current diagnostic
Added comment: Seizure is a feature
Sources: Literature
Genetic Epilepsy v0.2112 RAPGEF2 Belinda Chong gene: RAPGEF2 was added
gene: RAPGEF2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RAPGEF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAPGEF2 were set to 37021642; 30351492; 29507423
Phenotypes for gene: RAPGEF2 were set to ?Epilepsy, familial adult myoclonic, 7 MIM# 618075
Review for gene: RAPGEF2 was set to RED
Added comment: Heterozygous 5-bp repeat expansion (TTTCA(n)) in intron 14 of RAPGEF2 gene. Two individuals previously reported (PMID: 30351492 and 29507423) with seizures
Sources: Literature
Mendeliome v1.1455 RAPGEF2 Belinda Chong gene: RAPGEF2 was added
gene: RAPGEF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAPGEF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAPGEF2 were set to 37021642; 30351492; 29507423
Phenotypes for gene: RAPGEF2 were set to ?Epilepsy, familial adult myoclonic, 7 MIM# 618075
Review for gene: RAPGEF2 was set to RED
Added comment: Heterozygous 5-bp repeat expansion (TTTCA(n)) in intron 14 of RAPGEF2 gene. Two individuals previously reported (PMID: 30351492 and 29507423) with seizures
Sources: Literature
Genetic Epilepsy v0.2112 RANBP2 Belinda Chong gene: RANBP2 was added
gene: RANBP2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RANBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RANBP2 were set to 32426208; 35485383; 33777149; 19118815; 25128471; 25522933; 32048120
Phenotypes for gene: RANBP2 were set to {Encephalopathy, acute, infection-induced, 3, susceptibility to} MIM#608033
Review for gene: RANBP2 was set to GREEN
gene: RANBP2 was marked as current diagnostic
Added comment: Individuals have seizures
Sources: Literature
Genetic Epilepsy v0.2112 PTBP1 Belinda Chong gene: PTBP1 was added
gene: PTBP1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PTBP1 was set to Unknown
Review for gene: PTBP1 was set to RED
Added comment: No evidence for Mendelian disease association. In Oliver's Gene list.
Sources: Literature
Mendeliome v1.1455 PTBP1 Belinda Chong gene: PTBP1 was added
gene: PTBP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTBP1 was set to Unknown
Review for gene: PTBP1 was set to RED
Added comment: No evidence for Mendelian disease association.
Sources: Literature
Genetic Epilepsy v0.2112 RAI1 Belinda Chong gene: RAI1 was added
gene: RAI1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RAI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAI1 were set to 36256819; 11404004; 12652298; 15788730
Phenotypes for gene: RAI1 were set to Smith-Magenis syndrome MIM#182290
Review for gene: RAI1 was set to GREEN
gene: RAI1 was marked as current diagnostic
Added comment: PMID 36256819: Spontaneous seizures have been detected in 30% of Rai1āˆ’/āˆ’ mice and SMS patients

PMID: 16566870: Considering that close to one third of individuals with Smith-Magenis syndrome with epileptiform abnormalities also had a history of clinical seizures, cortical hyperexcitability and epilepsy should be considered an important component of the Smith-Magenis syndrome clinical phenotype.
Sources: Literature
Genetic Epilepsy v0.2112 RAB39B Belinda Chong gene: RAB39B was added
gene: RAB39B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RAB39B was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RAB39B were set to 4025396; 11050621; 20159109
Phenotypes for gene: RAB39B were set to Intellectual developmental disorder, X-linked 72 MIM#300271; Waisman syndrome MIM#311510
Review for gene: RAB39B was set to GREEN
Added comment: Seizures observed in most individuals.
Sources: Literature
Genetic Epilepsy v0.2112 CCDC88C Lilian Downie gene: CCDC88C was added
gene: CCDC88C was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CCDC88C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC88C were set to PMID: 29341397, PMID: 23042809, PMID: 21031079
Phenotypes for gene: CCDC88C were set to Hydrocephalus, congenital, 1 MIM#236600
Review for gene: CCDC88C was set to GREEN
Added comment: 3 independant families with seizures reported as a feature, onset between birth and 2 years. Focal and tonic clonic. Summary table in PMID: 29341397.
Sources: Expert list
Genetic Epilepsy v0.2112 CCDC22 Lilian Downie gene: CCDC22 was added
gene: CCDC22 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CCDC22 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CCDC22 were set to PMID: 34020006
Phenotypes for gene: CCDC22 were set to Ritscher-Schinzel syndrome 2 MIM#300963
Review for gene: CCDC22 was set to RED
Added comment: X-linked recessive syndromic form of intellectual disability associated with posterior fossa defects, cardiac malformations, and minor abnormalities of the face and distal extremities

Reviewed as on a research epilepsy gene list

PMID: 34020006 patient with epileptic encephalopathy but they had a missense variant VUS - segregated only in healthy mother and grandmother, no healthy males tested, maternal uncle deceased but wasn't tested. Didn't have the typical features of the condition (no posterior fossa anomalies or cardiac malformations).
Sources: Expert list
Microcephaly v1.246 COPB2 Rylee Peters changed review comment from: This paper reports an unrelated individual with the same homozygous variant (NM_004766.3:c.760C>T, p.Arg254Cys) identified in 2xsiblings in PMID: 29036432 (the same two siblings are also described in PMID: 34450031).

The proband is an 8.5yo Iranian female born to consanguineous parents. This individual has symptoms consistent with autosomal recessive microcephaly 19 (MIM#617800) including, global developmental delay, intellectual disability, microcephaly, seizures, spasticity, strabismus, and failure to thrive symptoms; she is unable to stand, walk, or speak.; to: PMID: 37734708 - This paper reports an unrelated individual with the same homozygous variant (NM_004766.3:c.760C>T, p.Arg254Cys) identified in 2xsiblings in PMID: 29036432 (the same two siblings are also described in PMID: 34450031).

The proband is an 8.5yo Iranian female born to consanguineous parents. This individual has symptoms consistent with autosomal recessive microcephaly 19 (MIM#617800) including, global developmental delay, intellectual disability, microcephaly, seizures, spasticity, strabismus, and failure to thrive symptoms; she is unable to stand, walk, or speak.
Microcephaly v1.246 COPB2 Rylee Peters reviewed gene: COPB2: Rating: AMBER; Mode of pathogenicity: None; Publications: 37734708, 29036432, 34450031; Phenotypes: Microcephaly 19, primary, autosomal recessive, MIM# 617800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2112 PUS3 Belinda Chong gene: PUS3 was added
gene: PUS3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PUS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PUS3 were set to 36125428; 30308082; 28454995; 27055666; 30697592; 31444731
Phenotypes for gene: PUS3 were set to Mental retardation, autosomal recessive 55, MIM# 617051
Review for gene: PUS3 was set to GREEN
gene: PUS3 was marked as current diagnostic
Added comment: Most affected individuals have seizures; some may have brain imaging abnormalities
Sources: Literature
Mendeliome v1.1455 ALG8 Zornitza Stark Publications for gene: ALG8 were set to 26066342; 28375157; 15235028
Intellectual disability syndromic and non-syndromic v0.5658 ALG8 Zornitza Stark Publications for gene: ALG8 were set to 26066342
Genetic Epilepsy v0.2112 ALG8 Zornitza Stark Publications for gene: ALG8 were set to 26066342
Genetic Epilepsy v0.2111 OCRL Zornitza Stark Marked gene: OCRL as ready
Genetic Epilepsy v0.2111 OCRL Zornitza Stark Gene: ocrl has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2111 OCRL Zornitza Stark Classified gene: OCRL as Red List (low evidence)
Genetic Epilepsy v0.2111 OCRL Zornitza Stark Gene: ocrl has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2110 CAMTA1 Zornitza Stark Marked gene: CAMTA1 as ready
Genetic Epilepsy v0.2110 CAMTA1 Zornitza Stark Gene: camta1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2110 CAMTA1 Zornitza Stark Classified gene: CAMTA1 as Red List (low evidence)
Genetic Epilepsy v0.2110 CAMTA1 Zornitza Stark Gene: camta1 has been classified as Red List (Low Evidence).
Microcephaly v1.246 SOX5 Zornitza Stark Marked gene: SOX5 as ready
Microcephaly v1.246 SOX5 Zornitza Stark Gene: sox5 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.246 SOX5 Zornitza Stark Classified gene: SOX5 as Amber List (moderate evidence)
Microcephaly v1.246 SOX5 Zornitza Stark Gene: sox5 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2109 C19orf12 Zornitza Stark Marked gene: C19orf12 as ready
Genetic Epilepsy v0.2109 C19orf12 Zornitza Stark Gene: c19orf12 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2109 C19orf12 Zornitza Stark Classified gene: C19orf12 as Red List (low evidence)
Genetic Epilepsy v0.2109 C19orf12 Zornitza Stark Gene: c19orf12 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2108 PDE2A Zornitza Stark Marked gene: PDE2A as ready
Genetic Epilepsy v0.2108 PDE2A Zornitza Stark Gene: pde2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2108 PDE2A Zornitza Stark Classified gene: PDE2A as Green List (high evidence)
Genetic Epilepsy v0.2108 PDE2A Zornitza Stark Gene: pde2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2107 PDE2A Zornitza Stark reviewed gene: PDE2A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder with paroxysmal dyskinesia or seizures MIM#619150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2107 PDCD10 Zornitza Stark Marked gene: PDCD10 as ready
Genetic Epilepsy v0.2107 PDCD10 Zornitza Stark Gene: pdcd10 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2107 PDCD10 Zornitza Stark Classified gene: PDCD10 as Green List (high evidence)
Genetic Epilepsy v0.2107 PDCD10 Zornitza Stark Gene: pdcd10 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2106 PDCD10 Zornitza Stark reviewed gene: PDCD10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral cavernous malformations-3 MIM#603285; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2106 OGT Zornitza Stark edited their review of gene: OGT: Changed rating: GREEN
Genetic Epilepsy v0.2106 OGT Zornitza Stark edited their review of gene: OGT: Changed rating: RED
Genetic Epilepsy v0.2106 ODC1 Zornitza Stark Publications for gene: ODC1 were set to PMID:30475435; 30239107
Genetic Epilepsy v0.2105 ODC1 Zornitza Stark edited their review of gene: ODC1: Changed rating: RED
Genetic Epilepsy v0.2105 PAK2 Zornitza Stark Marked gene: PAK2 as ready
Genetic Epilepsy v0.2105 PAK2 Zornitza Stark Gene: pak2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2105 PAK2 Zornitza Stark Classified gene: PAK2 as Red List (low evidence)
Genetic Epilepsy v0.2105 PAK2 Zornitza Stark Gene: pak2 has been classified as Red List (Low Evidence).
Mendeliome v1.1454 PRICKLE2 Zornitza Stark changed review comment from: LIMITED by ClinGen.; to: LIMITED by ClinGen; however, experimental evidence appears not to have been considered.
Intellectual disability syndromic and non-syndromic v0.5657 PRICKLE2 Zornitza Stark changed review comment from: LIMITED by ClinGen.; to: LIMITED by ClinGen; however, experimental evidence appears not to have been considered.
Genetic Epilepsy v0.2104 PRICKLE2 Zornitza Stark changed review comment from: LIMITED by ClinGen.; to: LIMITED by ClinGen, however experimental evidence appears not to have been considered.
Intellectual disability syndromic and non-syndromic v0.5657 PRICKLE2 Zornitza Stark Phenotypes for gene: PRICKLE2 were changed from Neurodevelopmental disorder; global developmental delay; behavioural difficultiesā€‰Ā±ā€‰epilepsy; autistic features; attention deficit hyperactive disorder; psychiatric symptoms to Neurodevelopmental disorder MONDO:0700092, PRICKLE2-related
Intellectual disability syndromic and non-syndromic v0.5656 PRICKLE2 Zornitza Stark Publications for gene: PRICKLE2 were set to PMID: 34092786
Intellectual disability syndromic and non-syndromic v0.5655 PRICKLE2 Zornitza Stark Classified gene: PRICKLE2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5655 PRICKLE2 Zornitza Stark Gene: prickle2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5654 PRICKLE2 Zornitza Stark reviewed gene: PRICKLE2: Rating: AMBER; Mode of pathogenicity: None; Publications: 34092786, 21276947, 26942291, 26942292; Phenotypes: Neurodevelopmental disorder MONDO:0700092, PRICKLE2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1454 PRICKLE2 Zornitza Stark Phenotypes for gene: PRICKLE2 were changed from Neurodevelopmental disorder, MONDO:0700092; global developmental delay, behavioural difficultiesā€‰Ā±ā€‰epilepsy, autistic features, and attention deficit hyperactive disorder. to Neurodevelopmental disorder MONDO:0700092, PRICKLE2-related
Mendeliome v1.1453 PRICKLE2 Zornitza Stark Publications for gene: PRICKLE2 were set to 34092786
Mendeliome v1.1452 PRICKLE2 Zornitza Stark Classified gene: PRICKLE2 as Amber List (moderate evidence)
Mendeliome v1.1452 PRICKLE2 Zornitza Stark Gene: prickle2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1451 PRICKLE2 Zornitza Stark reviewed gene: PRICKLE2: Rating: AMBER; Mode of pathogenicity: None; Publications: 34092786, 21276947, 26942291, 26942292; Phenotypes: Neurodevelopmental disorder MONDO:0700092, PRICKLE2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2104 PRICKLE2 Zornitza Stark Phenotypes for gene: PRICKLE2 were changed from Neurodevelopmental disorder; global developmental delay; behavioural difficultiesā€‰Ā±ā€‰epilepsy; autistic features; attention deficit hyperactive disorder; psychiatric symptoms to Neurodevelopmental disorder MONDO:0700092, PRICKLE2-related
Genetic Epilepsy v0.2103 PRICKLE2 Zornitza Stark Publications for gene: PRICKLE2 were set to 34092786
Genetic Epilepsy v0.2102 PRICKLE2 Zornitza Stark Classified gene: PRICKLE2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2102 PRICKLE2 Zornitza Stark Gene: prickle2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2101 PRICKLE2 Zornitza Stark edited their review of gene: PRICKLE2: Added comment: LIMITED by ClinGen.; Changed rating: AMBER
Prepair 1000+ v1.4 PRICKLE1 Zornitza Stark Tag for review tag was added to gene: PRICKLE1.
Prepair 1000+ v1.4 PRICKLE1 Zornitza Stark reviewed gene: PRICKLE1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy, progressive myoclonic 1B, MIM# 612437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v1.16 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Red List (low evidence)
Ataxia v1.16 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Red List (Low Evidence).
Ataxia v1.15 PRICKLE1 Zornitza Stark edited their review of gene: PRICKLE1: Added comment: LIMITED by ClinGen for AR PME.; Changed rating: RED
Regression v0.540 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Red List (low evidence)
Regression v0.540 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Red List (Low Evidence).
Regression v0.539 PRICKLE1 Zornitza Stark edited their review of gene: PRICKLE1: Added comment: LIMITED by ClinGen for AR PME, DISPUTED for AD epilepsy.; Changed rating: RED
Mendeliome v1.1451 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Red List (low evidence)
Mendeliome v1.1451 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Red List (Low Evidence).
Mendeliome v1.1450 PRICKLE1 Zornitza Stark edited their review of gene: PRICKLE1: Added comment: LIMITED by ClinGen for AR PME and DISPUTED for AD epilepsy.; Changed rating: RED
Progressive Myoclonic Epilepsy v0.19 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Red List (low evidence)
Progressive Myoclonic Epilepsy v0.19 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Red List (Low Evidence).
Progressive Myoclonic Epilepsy v0.18 PRICKLE1 Zornitza Stark changed review comment from: LIMITED by ClinGen.; to: LIMITED by ClinGen for AR PME, and DISPUTED for AD epilepsy.
Progressive Myoclonic Epilepsy v0.18 PRICKLE1 Zornitza Stark edited their review of gene: PRICKLE1: Added comment: LIMITED by ClinGen.; Changed rating: RED
Genetic Epilepsy v0.2101 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Red List (low evidence)
Genetic Epilepsy v0.2101 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2100 PRICKLE1 Zornitza Stark edited their review of gene: PRICKLE1: Changed rating: RED
Genetic Epilepsy v0.2100 PRICKLE1 Zornitza Stark changed review comment from: LIMITED by ClinGen for PME, and DISPUTED for epilepsy.; to: LIMITED by ClinGen for AR PME, and DISPUTED for AD epilepsy.
Genetic Epilepsy v0.2100 PRICKLE1 Zornitza Stark commented on gene: PRICKLE1: LIMITED by ClinGen for PME, and DISPUTED for epilepsy.
Progressive Myoclonic Epilepsy v0.18 PRICKLE1 Zornitza Stark Marked gene: PRICKLE1 as ready
Progressive Myoclonic Epilepsy v0.18 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Amber List (Moderate Evidence).
Progressive Myoclonic Epilepsy v0.18 PRICKLE1 Zornitza Stark Publications for gene: PRICKLE1 were set to
Progressive Myoclonic Epilepsy v0.17 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Amber List (moderate evidence)
Progressive Myoclonic Epilepsy v0.17 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Amber List (Moderate Evidence).
Progressive Myoclonic Epilepsy v0.16 PRICKLE1 Zornitza Stark reviewed gene: PRICKLE1: Rating: AMBER; Mode of pathogenicity: None; Publications: 18976727, 30564977; Phenotypes: Epilepsy, progressive myoclonic 1B, MIM# 612437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v1.15 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Amber List (moderate evidence)
Ataxia v1.15 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Amber List (Moderate Evidence).
Ataxia v1.14 PRICKLE1 Zornitza Stark edited their review of gene: PRICKLE1: Added comment: Note most reported variants are missense with little further supportive evidence and ClinVar variants in this gene are all VOUS/LB/B.; Changed rating: AMBER
Regression v0.539 PRICKLE1 Zornitza Stark Marked gene: PRICKLE1 as ready
Regression v0.539 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Amber List (Moderate Evidence).
Regression v0.539 PRICKLE1 Zornitza Stark Phenotypes for gene: PRICKLE1 were changed from to Epilepsy, progressive myoclonic 1B, MIM# 612437
Regression v0.538 PRICKLE1 Zornitza Stark Publications for gene: PRICKLE1 were set to
Regression v0.537 PRICKLE1 Zornitza Stark Mode of inheritance for gene: PRICKLE1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Regression v0.536 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Amber List (moderate evidence)
Regression v0.536 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Amber List (Moderate Evidence).
Regression v0.535 PRICKLE1 Zornitza Stark reviewed gene: PRICKLE1: Rating: AMBER; Mode of pathogenicity: None; Publications: 34597683, 30564977, 30345727, 29790814, 26727662, 31035234; Phenotypes: Epilepsy, progressive myoclonic 1B, MIM# 612437; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Callosome v0.514 PRICKLE1 Zornitza Stark Marked gene: PRICKLE1 as ready
Callosome v0.514 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Red List (Low Evidence).
Callosome v0.514 PRICKLE1 Zornitza Stark Phenotypes for gene: PRICKLE1 were changed from to Neurodevelopmental disorder, MONDO:0700092, PRICKLE1-related
Callosome v0.513 PRICKLE1 Zornitza Stark Publications for gene: PRICKLE1 were set to
Callosome v0.512 PRICKLE1 Zornitza Stark Mode of inheritance for gene: PRICKLE1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.511 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Red List (low evidence)
Callosome v0.511 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Red List (Low Evidence).
Callosome v0.510 PRICKLE1 Zornitza Stark reviewed gene: PRICKLE1: Rating: RED; Mode of pathogenicity: None; Publications: 26727662; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, PRICKLE1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1450 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Amber List (moderate evidence)
Mendeliome v1.1450 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1449 PRICKLE1 Zornitza Stark edited their review of gene: PRICKLE1: Added comment: Note all ClinVar entries for this gene are VOUS/LB/B. The variants reported in bi-allelic cases are almost all missense without further supportive data.; Changed rating: AMBER
Genetic Epilepsy v0.2100 PRICKLE1 Zornitza Stark edited their review of gene: PRICKLE1: Added comment: Note ClinVar submissions for this gene are all VOUS/LB/B.; Changed rating: AMBER
Genetic Epilepsy v0.2100 PGM3 Zornitza Stark Phenotypes for gene: PGM3 were changed from Idiopathic focal epilepsy to Idiopathic focal epilepsy; Immunodeficiency 23, MIM# 615816
Genetic Epilepsy v0.2099 PGM3 Zornitza Stark Mode of inheritance for gene: PGM3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.176 ERI1 Zornitza Stark Phenotypes for gene: ERI1 were changed from Spondyloepimetaphyseal dysplasia (MONDO#0100510) to Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663
Fetal anomalies v1.175 ERI1 Zornitza Stark Mode of inheritance for gene: ERI1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.174 ERI1 Zornitza Stark edited their review of gene: ERI1: Changed phenotypes: Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.259 ERI1 Zornitza Stark Phenotypes for gene: ERI1 were changed from Spondyloepimetaphyseal dysplasia (MONDO#0100510), ERI1-related to Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663
Skeletal dysplasia v0.258 ERI1 Zornitza Stark reviewed gene: ERI1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.211 ERI1 Zornitza Stark Phenotypes for gene: ERI1 were changed from Spondyloepimetaphyseal dysplasia (MONDO#0100510), ERI1-related to Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663
Skeletal Dysplasia_Fetal v0.210 ERI1 Zornitza Stark reviewed gene: ERI1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1449 ERI1 Zornitza Stark Phenotypes for gene: ERI1 were changed from Spondyloepimetaphyseal dysplasia (MONDO#0100510), ERI1-related, Intellectual disability (MONDO#0001071), ERI1-related to Hoxha-Aliu syndrome, MIM# 620662; Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663
Mendeliome v1.1448 ERI1 Zornitza Stark reviewed gene: ERI1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hoxha-Aliu syndrome, MIM# 620662, Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5654 ERI1 Zornitza Stark Phenotypes for gene: ERI1 were changed from Intellectual disability (MONDO#0001071), ERI1-related to Hoxha-Aliu syndrome, MIM# 620662
Intellectual disability syndromic and non-syndromic v0.5653 ERI1 Zornitza Stark reviewed gene: ERI1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hoxha-Aliu syndrome, MIM# 620662; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1448 ALG8 Rylee Peters reviewed gene: ALG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 35716054; Phenotypes: Congenital disorder of glycosylation, type Ih, MIM# 608104; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5653 ALG8 Rylee Peters reviewed gene: ALG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 35716054; Phenotypes: Congenital disorder of glycosylation, type Ih, MIM# 608104; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2098 ALG8 Rylee Peters reviewed gene: ALG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 35716054; Phenotypes: Congenital disorder of glycosylation, type Ih, MIM# 608104; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2098 OCRL Lauren Rogers gene: OCRL was added
gene: OCRL was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: OCRL was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: OCRL were set to 35919034
Phenotypes for gene: OCRL were set to Lowe syndrome MIM#309000
Review for gene: OCRL was set to RED
Added comment: PMID: 35919034: In a cohort of 83 Chinese individuals with Lowes syndrome or Dent-2 disease, 1/48 individuals with Lowes syndrome had epilepsy, developmental delay and intellectual disability with a maternally inherited p.R678X variant.
Sources: Literature
Genetic Epilepsy v0.2098 PANK2 Elena Savva Classified gene: PANK2 as Red List (low evidence)
Genetic Epilepsy v0.2098 PANK2 Elena Savva Gene: pank2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2098 PANK2 Elena Savva Classified gene: PANK2 as Red List (low evidence)
Genetic Epilepsy v0.2098 PANK2 Elena Savva Gene: pank2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2097 PANK2 Elena Savva Classified gene: PANK2 as Red List (low evidence)
Genetic Epilepsy v0.2097 PANK2 Elena Savva Gene: pank2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2097 PANK2 Elena Savva Marked gene: PANK2 as ready
Genetic Epilepsy v0.2097 PANK2 Elena Savva Gene: pank2 has been removed from the panel.
Genetic Epilepsy v0.2097 OGT Elena Savva Publications for gene: OGT were set to PMID: 28302723; 28584052; 31296563; 31627256; 29769320; 29606577
Genetic Epilepsy v0.2096 CAMTA1 Lilian Downie gene: CAMTA1 was added
gene: CAMTA1 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CAMTA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMTA1 were set to PMID: 31957018
Phenotypes for gene: CAMTA1 were set to Cerebellar dysfunction with variable cognitive and behavioral abnormalities MIM#614756
Review for gene: CAMTA1 was set to RED
Added comment: PMID: 31957018 sequencing in an epilepsy cohort - if negative looked at 'candidate epilepy genes', variant identified in CAMTA1 in patient with infantile spasms, refractory epilepsy, dev delay and corticovisual impairment.
Sources: Expert list
Microcephaly v1.245 SOX5 Rylee Peters gene: SOX5 was added
gene: SOX5 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SOX5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX5 were set to PMID: 36861937
Phenotypes for gene: SOX5 were set to Lamb-Shaffer syndrome, MIM#616803
Review for gene: SOX5 was set to AMBER
Added comment: Cohort of 16 patients with heterozygous variants in SOX5. Paper also describes 71 previously reported cases of individuals with variants in SOX5 associated with Lambā€“Shaffer Syndrome.

Microcephaly is reported in 14% of individuals with variants in SOX5 (calculated from both the current and previously reported cohorts).
Sources: Literature
Genetic Epilepsy v0.2096 C19orf12 Lilian Downie gene: C19orf12 was added
gene: C19orf12 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: C19orf12 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: C19orf12 were set to Neurodegeneration with brain iron accumulation 4 MIM#614298
Review for gene: C19orf12 was set to RED
Added comment: Review of literature, no evidence of seizures as part of the phenotype with this gene
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5653 PDE2A Lauren Rogers reviewed gene: PDE2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32467598, 29392776, 37317634; Phenotypes: Intellectual developmental disorder with paroxysmal dyskinesia or seizures MIM#619150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2096 PDE2A Lauren Rogers gene: PDE2A was added
gene: PDE2A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PDE2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE2A were set to 32467598; 32196122; 37317634
Phenotypes for gene: PDE2A were set to Intellectual developmental disorder with paroxysmal dyskinesia or seizures MIM#619150
Review for gene: PDE2A was set to AMBER
Added comment: PMID: 32467598: In a case report of 2 unrelated families with childhood-onset refractory paroxysmal dyskinesia with cognitive impairment, one family had two affected siblings who had a homozygous p.(Gln394*) variant. The younger sibling having epilepsy (unclear in the other sibling).

PMID: 32196122: A case report of 2 affected individuals from a consanguineous Iraqi family presenting with the atypical Rett phenotype with a homozygous c.323 + 1G > A variant. Both had epilepsy.

PMID: 37317634: 6 Pakistani individuals from 3 families with paroxysmal dyskinesia, developmental delay, cognitive abnormalities, speech impairment, and seizures with variable disease onset. Seizures included tonic clonic/generalised, upper limb only or myoclonic pattern/focal seizures. All individuals had the same homozygous missense variant p.(Phe505Ser), called a founder variant.
Sources: Literature
Genetic Epilepsy v0.2096 PDCD10 Lauren Rogers gene: PDCD10 was added
gene: PDCD10 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PDCD10 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PDCD10 were set to 25354366; 26246098
Phenotypes for gene: PDCD10 were set to Cerebral cavernous malformations-3 MIM#603285
Review for gene: PDCD10 was set to AMBER
Added comment: PMID: 25354366: in a cohort of 11 Italian individuals with multiple/familial cerebral cavernous malformations, and PDCD10 variants, 4 individuals had seizures, including left-sided focal sensory-motor seizures. The associated variants were a de novo p.(R35X) variant, c.376_380del; 392_393ins, p.(E54X) and a whole gene deletion. The father with the whole gene deletion had a child with the variant who does not have seizures.

PMID: 26246098: A case report of an Italian family with three individuals (2x sisters and daughter) with cerebral cavernous malformations associated with meningioma. They had a a p.(Gln112PhefsX13) variant. The daughter had a severe form of epilepsy and both sisters had seizures.
Sources: Literature
Genetic Epilepsy v0.2096 PANK2 Lauren Rogers gene: PANK2 was added
gene: PANK2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PANK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PANK2 were set to 27303611; 18462962
Phenotypes for gene: PANK2 were set to Neurodegeneration with brain iron accumulation 1 MIM#234200
Review for gene: PANK2 was set to RED
Added comment: PMID: 27303611: A case report of 1x child with neurodegeneration with brain iron accumulation 1, with seizure onset age 4 with frequent falls, not gaining milestones, progressive muscle dystonia, neuro-regression, and multiple injury marks of different stages. They had 2nd degree consanguineous parents. They were compound heterozygous for p.(Leu385CysfsX13) and p.(Arg440Pro).

PMID: 18462962: A case report of 1x child neurodegeneration with brain iron accumulation 1, with refractory severe dystonia resulting in essentially complete loss of motor control, and an episode of a reported single generalized tonic clonic seizure. They were homozygous for a p.(Ala382Val)
Sources: Literature
Fetal anomalies v1.174 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from Syndromic disease, MONDO:0002254, RAP1B-related to Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Fetal anomalies v1.173 RAP1B Zornitza Stark reviewed gene: RAP1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Growth failure v1.73 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from Syndromic disease, MONDO:0002254, RAP1B-related to Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Growth failure v1.72 RAP1B Zornitza Stark edited their review of gene: RAP1B: Changed phenotypes: Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Kabuki syndrome v0.15 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from Syndromic disease, MONDO:0002254, RAP1B-related; Kabuki-like syndrome to Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654; Kabuki-like syndrome
Kabuki syndrome v0.14 RAP1B Zornitza Stark edited their review of gene: RAP1B: Changed phenotypes: Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654, Kabuki-like syndrome
Bone Marrow Failure v1.80 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from Syndromic disease, MONDO:0002254, RAP1B-related to Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Bone Marrow Failure v1.79 RAP1B Zornitza Stark edited their review of gene: RAP1B: Changed phenotypes: Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Intellectual disability syndromic and non-syndromic v0.5653 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from Syndromic disease, MONDO:0002254, RAP1B-related to Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Intellectual disability syndromic and non-syndromic v0.5652 RAP1B Zornitza Stark edited their review of gene: RAP1B: Changed phenotypes: Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Mendeliome v1.1448 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from Syndromic disease, MONDO:0002254, RAP1B-related; intellectual disability; microcephaly; thrombocytopaenia to Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Mendeliome v1.1447 RAP1B Zornitza Stark edited their review of gene: RAP1B: Changed phenotypes: Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Genetic Epilepsy v0.2096 OGT Lauren Rogers reviewed gene: OGT: Rating: RED; Mode of pathogenicity: None; Publications: 29769320, 37334838; Phenotypes: Intellectual developmental disorder, X-linked 106 MIM#300997; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.2096 PRICKLE1 Elena Savva Publications for gene: PRICKLE1 were set to 34597683; 30564977; 30345727; 29790814; 26727662; 31035234
Genetic Epilepsy v0.2096 PRICKLE1 Elena Savva Classified gene: PRICKLE1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2096 PRICKLE1 Elena Savva Gene: prickle1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2095 PGM3 Elena Savva Publications for gene: PGM3 were set to 33193641
Genetic Epilepsy v0.2094 ODC1 Lauren Rogers reviewed gene: ODC1: Rating: RED; Mode of pathogenicity: None; Publications: 34477286; Phenotypes: Bachmann-Bupp syndrome MIM#619075; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2094 PAK2 Lauren Rogers gene: PAK2 was added
gene: PAK2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PAK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAK2 were set to 33693784
Phenotypes for gene: PAK2 were set to Knobloch 2 syndrome MIM#618458
Review for gene: PAK2 was set to RED
Added comment: Antonarakis et al., 2021 (PMID: 33693784) reported two affected siblings from a non-consanguineous New Zealand family. Both had retinal detachment and interstitial parenchymal pulmonary changes on chest X-rays, but only one child had additional significant features such as cataract, posterior encephalocele, severe DD/ID with ASD, and epilepsy. WES revealed a heterozygous PAK2 variant (c.1303 G>A, p.Glu435Lys) in both individuals that apparently occurred de novo indicating parental germ-line mosaicism; however, mosaicism could not be detected by deep sequencing of blood parental DNA. Functional studies showed that the variant, located in the kinase domain, results in a partial loss of the kinase activity.
Sources: Literature
Genetic Epilepsy v0.2094 RALGAPB Lisa Norbart reviewed gene: RALGAPB: Rating: AMBER; Mode of pathogenicity: None; Publications: 32853829; Phenotypes: Epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2094 RBL2 Lisa Norbart reviewed gene: RBL2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2094 PRICKLE2 Lisa Norbart reviewed gene: PRICKLE2: Rating: AMBER; Mode of pathogenicity: None; Publications: 34092786, 21276947, 26942291, 26942292; Phenotypes: Epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2094 PRICKLE1 Lisa Norbart reviewed gene: PRICKLE1: Rating: AMBER; Mode of pathogenicity: None; Publications: 18976727, 30564977; Phenotypes: Epilepsy, progressive myoclonic 1B, MIM# 612437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2094 PPP1CB Lisa Norbart reviewed gene: PPP1CB: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome-like disorder with loose anagen hair 2 MIM#617506; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2094 PGM3 Lisa Norbart reviewed gene: PGM3: Rating: AMBER; Mode of pathogenicity: None; Publications: 24589341; Phenotypes: Epilepsy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2094 OTUD7A Lisa Norbart reviewed gene: OTUD7A: Rating: AMBER; Mode of pathogenicity: None; Publications: 31997314, 29395075, 29395074, 33381903; Phenotypes: Epilepsy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2094 PRRT2 Zornitza Stark Marked gene: PRRT2 as ready
Genetic Epilepsy v0.2094 PRRT2 Zornitza Stark Gene: prrt2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2094 PRRT2 Zornitza Stark Phenotypes for gene: PRRT2 were changed from to Convulsions, familial infantile, with paroxysmal choreoathetosis 602066; Episodic kinesigenic dyskinesia 1 128200; Seizures, benign familial infantile, 2 605751
Genetic Epilepsy v0.2093 PRRT2 Zornitza Stark Publications for gene: PRRT2 were set to
Genetic Epilepsy v0.2092 PRRT2 Zornitza Stark Mode of inheritance for gene: PRRT2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2091 PTS Zornitza Stark Marked gene: PTS as ready
Genetic Epilepsy v0.2091 PTS Zornitza Stark Gene: pts has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2091 PTS Zornitza Stark Phenotypes for gene: PTS were changed from to Hyperphenylalaninemia, BH4-deficient, A, MIM# 261640
Genetic Epilepsy v0.2090 PTS Zornitza Stark Mode of inheritance for gene: PTS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2089 PTS Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association. Seizures are part of the phenotype.
Genetic Epilepsy v0.2089 PTPN23 Zornitza Stark Marked gene: PTPN23 as ready
Genetic Epilepsy v0.2089 PTPN23 Zornitza Stark Gene: ptpn23 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2089 PTPN23 Zornitza Stark Phenotypes for gene: PTPN23 were changed from to Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity, MIM# 618890
Genetic Epilepsy v0.2088 PTPN23 Zornitza Stark Publications for gene: PTPN23 were set to
Genetic Epilepsy v0.2087 PTPN23 Zornitza Stark Mode of inheritance for gene: PTPN23 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2086 PSAP Zornitza Stark Marked gene: PSAP as ready
Genetic Epilepsy v0.2086 PSAP Zornitza Stark Gene: psap has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2086 PSAP Zornitza Stark Phenotypes for gene: PSAP were changed from to Combined SAP deficiency, MIM# 611721; Encephalopathy due to prosaposin deficiency, MONDO:0012719; Krabbe disease, atypical, MIM# 611722; MONDO:0012720; Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900; MONDO:0009590; Gaucher disease, atypical, MIM# 610539; MONDO:0012517
Genetic Epilepsy v0.2085 PSAP Zornitza Stark Publications for gene: PSAP were set to
Genetic Epilepsy v0.2084 PSAP Zornitza Stark Mode of inheritance for gene: PSAP was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2083 PRODH Zornitza Stark Marked gene: PRODH as ready
Genetic Epilepsy v0.2083 PRODH Zornitza Stark Gene: prodh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2083 PRODH Zornitza Stark Phenotypes for gene: PRODH were changed from to Hyperprolinemia, type I, MIM# 239500; Proline oxidase deficiency
Genetic Epilepsy v0.2082 PRODH Zornitza Stark Publications for gene: PRODH were set to
Genetic Epilepsy v0.2081 PRODH Zornitza Stark Mode of inheritance for gene: PRODH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2080 PRODH Zornitza Stark changed review comment from: At least 5 unrelated families reported.
Sources: Expert list; to: At least 5 unrelated families reported. Epilepsy is part of the phenotype.
Sources: Expert list
Genetic Epilepsy v0.2080 PRICKLE1 Zornitza Stark Marked gene: PRICKLE1 as ready
Genetic Epilepsy v0.2080 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2080 PRICKLE1 Zornitza Stark Phenotypes for gene: PRICKLE1 were changed from to Epilepsy, progressive myoclonic 1B, MIM# 612437
Genetic Epilepsy v0.2079 PRICKLE1 Zornitza Stark Publications for gene: PRICKLE1 were set to
Genetic Epilepsy v0.2078 PRICKLE1 Zornitza Stark Mode of inheritance for gene: PRICKLE1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2077 PPP3CA Zornitza Stark Marked gene: PPP3CA as ready
Genetic Epilepsy v0.2077 PPP3CA Zornitza Stark Gene: ppp3ca has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2077 PPP3CA Zornitza Stark Publications for gene: PPP3CA were set to
Genetic Epilepsy v0.2076 PPP3CA Zornitza Stark Phenotypes for gene: PPP3CA were changed from Developmental and epileptic encephalopathy 91, MIM#617711 to Developmental and epileptic encephalopathy 91, MIM#617711
Genetic Epilepsy v0.2075 PPP3CA Zornitza Stark Phenotypes for gene: PPP3CA were changed from to Developmental and epileptic encephalopathy 91, MIM#617711
Genetic Epilepsy v0.2075 PPP3CA Zornitza Stark Mode of inheritance for gene: PPP3CA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2074 PPT1 Zornitza Stark Marked gene: PPT1 as ready
Genetic Epilepsy v0.2074 PPT1 Zornitza Stark Gene: ppt1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2074 PPT1 Zornitza Stark Phenotypes for gene: PPT1 were changed from to Ceroid lipofuscinosis, neuronal, 1, MIM# 256730; MONDO:0009744
Genetic Epilepsy v0.2073 PPT1 Zornitza Stark Publications for gene: PPT1 were set to
Genetic Epilepsy v0.2072 PPT1 Zornitza Stark Mode of inheritance for gene: PPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2071 PPT1 Zornitza Stark changed review comment from: Well established gene-disease association. Variable age of onset and severity.; to: Well established gene-disease association. Variable age of onset and severity Seizures are part of the phenotype.
Genetic Epilepsy v0.2071 FAM50A Zornitza Stark changed review comment from: Lee et al (2020 - PMID: 32703943) provide evidence that Armfield X-Linked intellectual disability syndrome is caused by monoallelic FAM50A pathogenic variants. The current review is based only on this reference. The authors provide clinical details on 6 affected individuals from 5 families. Features included postnatal growth delay, DD and ID (6/6 - also evident for those without formal IQ assesment), seizures (3/6 from 2 families), prominent forehead with presence of other facial features and variable head circumference (5th to >97th %le), ocular anomalies (5/6 - strabismus/nystagmus/Axenfeld-Rieger), cardiac (3/6 - ASD/Fallot) and genitourinary anomalies (3/6). In the first of these families (Armfield et al 1999 - PMID: 10398235), linkage analysis followed by additional studies (Sanger, NGS of 718 genes on chrX, X-exome NGS - several refs provided) allowed the identification of a FAM50A variant. Variants in other families were identified by singleton (1 fam) or trio-ES (3 fam). In affected individuals from 3 families, the variant had occurred de novo. Carrier females in the other families were unaffected (based on pedigrees and/or the original publication). XCI was rather biased in most obligate carrier females from the 1st family (although this ranged from 95:5 to 60:40). Missense variants were reported in all affected subjects incl. Trp206Gly, Asp255Gly, Asp255Asn (dn), Glu254Gly (dn), Arg273Trp (dn) (NM_004699.3). Previous studies have demonstrated that FAM50A has ubiquitous expression in human fetal and adult tissues (incl. brain in fetal ones). Immunostaining suggests a nuclear localization for the protein (NIH/3T3 cells). Comparison of protein levels in LCLs from affected males and controls did not demonstrate significant differences. Protein localization for 3 variants (transfection of COS-7 cells) was shown to be similar to wt. Complementation studies in zebrafish provided evidence that the identified variants confer partial loss of function (rescue of the morpholino phenotype with co-injection of wt but not mt mRNA). The zebrafish ko model seemed to recapitulate the abnormal development of cephalic structures and was indicative of diminished/defective neurogenesis. Transcriptional dysregulation was demonstrated in zebrafish (altered levels and mis-splicing). Upregulation of spliceosome effectors was demonstrated in ko zebrafish. Similarly, mRNA expression and splicing defects were demonstrated in LCLs from affected individuals. FAM50A pulldown followed by mass spectrometry in transfected HEK293T cells demonstrated enrichment of binding proteins involved in RNA processing and co-immunoprecipitation assays (transfected U-87 cells) suggested that FAM50A interacts with spliceosome U5 and C-complex proteins. Overall aberrant spliceosome C-complex function is suggested as the underlying pathogenetic mechanism. Several other neurodevelopmental syndromes are caused by variants in genes encoding C-complex affiliated proteins (incl. EFTUD2, EIF4A3, THOC2, etc.).
Sources: Literature; to: Lee et al (2020 - PMID: 32703943) 6 affected individuals from 5 families.

Seizures in 3/6 from 2 families.
Genetic Epilepsy v0.2071 FAM50A Zornitza Stark edited their review of gene: FAM50A: Changed rating: AMBER
Genetic Epilepsy v0.2071 HNRNPK Zornitza Stark Marked gene: HNRNPK as ready
Genetic Epilepsy v0.2071 HNRNPK Zornitza Stark Gene: hnrnpk has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2071 HNRNPK Zornitza Stark Classified gene: HNRNPK as Amber List (moderate evidence)
Genetic Epilepsy v0.2071 HNRNPK Zornitza Stark Gene: hnrnpk has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2070 HNRNPK Zornitza Stark gene: HNRNPK was added
gene: HNRNPK was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: HNRNPK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPK were set to 30998304; 26173930; 29904177; 26954065; 28771707
Phenotypes for gene: HNRNPK were set to Au-Kline syndrome MIM#616580
Review for gene: HNRNPK was set to AMBER
Added comment: Seizures are reported in a minority of individuals affected by Au-Kline syndrome.
Sources: Expert list
Genetic Epilepsy v0.2069 HIVEP2 Zornitza Stark Marked gene: HIVEP2 as ready
Genetic Epilepsy v0.2069 HIVEP2 Zornitza Stark Gene: hivep2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2069 HIVEP2 Zornitza Stark Classified gene: HIVEP2 as Green List (high evidence)
Genetic Epilepsy v0.2069 HIVEP2 Zornitza Stark Gene: hivep2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2068 HIVEP2 Zornitza Stark gene: HIVEP2 was added
gene: HIVEP2 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: HIVEP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIVEP2 were set to 27003583
Phenotypes for gene: HIVEP2 were set to Intellectual developmental disorder, autosomal dominant 43, MIM# 616977
Review for gene: HIVEP2 was set to GREEN
Added comment: Seizures reported in at least 3 affected individuals.
Sources: Expert list
Genetic Epilepsy v0.2067 HDAC8 Zornitza Stark Marked gene: HDAC8 as ready
Genetic Epilepsy v0.2067 HDAC8 Zornitza Stark Gene: hdac8 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2067 HDAC8 Zornitza Stark Classified gene: HDAC8 as Amber List (moderate evidence)
Genetic Epilepsy v0.2067 HDAC8 Zornitza Stark Gene: hdac8 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2066 HDAC8 Zornitza Stark gene: HDAC8 was added
gene: HDAC8 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: HDAC8 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: HDAC8 were set to Cornelia de Lange syndrome 5, MIM# 300882
Review for gene: HDAC8 was set to AMBER
Added comment: Seizures reported in 25% of individuals with CdL though what proportion of individuals with HDAC8-related disease have seizures is uncertain.
Sources: Expert list
Mitochondrial disease v0.910 AFG3L2 Zornitza Stark Marked gene: AFG3L2 as ready
Mitochondrial disease v0.910 AFG3L2 Zornitza Stark Gene: afg3l2 has been classified as Green List (High Evidence).
Mitochondrial disease v0.910 AFG3L2 Zornitza Stark Phenotypes for gene: AFG3L2 were changed from Spastic ataxia 5, autosomal recessive (MIM#614487); Spinocerebellar ataxia 28 (MIM#610246); Optic atrophy 12, MIM# 618977 to Spastic ataxia 5, autosomal recessive (MIM#614487); Spinocerebellar ataxia 28 (MIM#610246); Optic atrophy 12, MIM# 618977
Mitochondrial disease v0.909 AFG3L2 Zornitza Stark Phenotypes for gene: AFG3L2 were changed from to Spastic ataxia 5, autosomal recessive (MIM#614487); Spinocerebellar ataxia 28 (MIM#610246); Optic atrophy 12, MIM# 618977
Mitochondrial disease v0.908 AFG3L2 Zornitza Stark Publications for gene: AFG3L2 were set to
Mitochondrial disease v0.907 AFG3L2 Zornitza Stark Mode of inheritance for gene: AFG3L2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2065 GRIA1 Zornitza Stark Marked gene: GRIA1 as ready
Genetic Epilepsy v0.2065 GRIA1 Zornitza Stark Gene: gria1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2065 GRIA1 Zornitza Stark gene: GRIA1 was added
gene: GRIA1 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: GRIA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GRIA1 were set to 35675825
Phenotypes for gene: GRIA1 were set to Intellectual developmental disorder, autosomal dominant 67, MIM# 619927; Intellectual developmental disorder, autosomal recessive 76, MIM# 619931
Review for gene: GRIA1 was set to RED
Added comment: RED/AMBER for the bi-allelic association: single family reported.

Recurrent missense for the mono-allelic association. However phenotype was predominantly ID. Seizures in one individual only.
Sources: Expert list
Prepair 1000+ v1.4 GPT2 Zornitza Stark Phenotypes for gene: GPT2 were changed from Mental retardation, autosomal recessive 49, 616281 (3) to Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281
Hereditary Spastic Paraplegia v1.72 GPT2 Zornitza Stark Phenotypes for gene: GPT2 were changed from Mental retardation, autosomal recessive 49 MIM#616281 to Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281
Intellectual disability syndromic and non-syndromic v0.5652 GPT2 Zornitza Stark Phenotypes for gene: GPT2 were changed from Mental retardation, autosomal recessive 49, MIM#616281 to Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281
Microcephaly v1.245 GPT2 Zornitza Stark Phenotypes for gene: GPT2 were changed from Mental retardation, autosomal recessive 49, MIM#616281 to Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281
Microcephaly v1.244 GPT2 Zornitza Stark edited their review of gene: GPT2: Changed phenotypes: Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281
Mendeliome v1.1447 GPT2 Zornitza Stark Phenotypes for gene: GPT2 were changed from Mental retardation, autosomal recessive 49, MIM#616281 to Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281
Genetic Epilepsy v0.2064 GPT2 Zornitza Stark Marked gene: GPT2 as ready
Genetic Epilepsy v0.2064 GPT2 Zornitza Stark Gene: gpt2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2064 GPT2 Zornitza Stark Classified gene: GPT2 as Green List (high evidence)
Genetic Epilepsy v0.2064 GPT2 Zornitza Stark Gene: gpt2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2063 GPT2 Zornitza Stark gene: GPT2 was added
gene: GPT2 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: GPT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPT2 were set to 27601654; 25758935; 31471722
Phenotypes for gene: GPT2 were set to Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281
Review for gene: GPT2 was set to GREEN
Added comment: 10 families reported. Typically presents with ID, HSP and microcephaly but seizures reported in some.
Sources: Expert list
Mendeliome v1.1446 GPT2 Zornitza Stark edited their review of gene: GPT2: Added comment: 10 families reported.; Changed publications: 27601654, 25758935, 31471722
Mendeliome v1.1446 GPT2 Zornitza Stark edited their review of gene: GPT2: Changed phenotypes: Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281
Genetic Epilepsy v0.2062 GPSM2 Zornitza Stark Marked gene: GPSM2 as ready
Genetic Epilepsy v0.2062 GPSM2 Zornitza Stark Gene: gpsm2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2062 GPSM2 Zornitza Stark Classified gene: GPSM2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2062 GPSM2 Zornitza Stark Gene: gpsm2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2061 GPSM2 Zornitza Stark gene: GPSM2 was added
gene: GPSM2 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: GPSM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPSM2 were set to 20602914; 22578326; 28387217; 27180139; 27064331
Phenotypes for gene: GPSM2 were set to Chudley-McCullough syndrome, MIM# 604213
Review for gene: GPSM2 was set to AMBER
Added comment: Chudley-McCullough syndrome is an autosomal recessive neurologic disorder characterized by early-onset sensorineural deafness and specific brain anomalies on MRI, including hypoplasia of the corpus callosum, enlarged cysterna magna with mild focal cerebellar dysplasia, and nodular heterotopia/PMG. Some individuals have hydrocephalus. Development is generally normal. Over 10 families reported, supportive functional data.

Seizures reported but rare.
Sources: Expert list
Genetic Epilepsy v0.2060 NAGA Rylee Peters reviewed gene: NAGA: Rating: RED; Mode of pathogenicity: None; Publications: 8782044, 31468281, 15619430, 31890708, 11313741; Phenotypes: Kanzaki disease, MIM# 609242, Schindler disease, type I and type II 609241; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2060 NR2F1 Rylee Peters gene: NR2F1 was added
gene: NR2F1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: NR2F1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NR2F1 were set to 32275123
Phenotypes for gene: NR2F1 were set to Bosch-Boonstra-Schaaf optic atrophy syndrome, MIM# 615722
Review for gene: NR2F1 was set to GREEN
Added comment: PMID: 32275123
- Cohort of 54 individuals with a deletion of or likely pathogenic variant in NR2F1, including previously published individuals with Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS).
-24/46 (52%) individuals described with seizures, some of which include infantile spasms.
- Rech et al. (2020) also described that mutations in the DBD were associated with a higher prevalence of motor delay, the inability to walk unassisted, the absence of speech, seizures, and sensitivity to touch compared to other types of mutations.
Sources: Literature
Genetic Epilepsy v0.2060 NF1 Rylee Peters changed review comment from: Seizures occur in about 5% of individuals with NF1, with a slightly higher prevalence in adults than in children (PMIDs: 32613422, 34944956).

PMID: 34944956 - Cohort of NF1 patients; Epilepsy was reported in 37/784 cases. 24/37 individuals with NF1 and epilepsy had an NF1 mutation, 1 individual was negative (NGS+MLPA), remaining 12 individuals were not tested.
Sources: Literature; to: Seizures occur in about 5% of individuals with NF1, with a slightly higher prevalence in adults than in children (PMIDs: 32613422, 34944956, GeneReviews).

PMID: 34944956 - Cohort of NF1 patients; Epilepsy was reported in 37/784 cases. 24/37 individuals with NF1 and epilepsy had an NF1 mutation, 1 individual was negative (NGS+MLPA), remaining 12 individuals were not tested.
Sources: Literature
Genetic Epilepsy v0.2060 NF1 Rylee Peters gene: NF1 was added
gene: NF1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: NF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NF1 were set to 34944956
Phenotypes for gene: NF1 were set to Neurofibromatosis, type 1 (MIM#162200)
Review for gene: NF1 was set to RED
Added comment: Seizures occur in about 5% of individuals with NF1, with a slightly higher prevalence in adults than in children (PMIDs: 32613422, 34944956).

PMID: 34944956 - Cohort of NF1 patients; Epilepsy was reported in 37/784 cases. 24/37 individuals with NF1 and epilepsy had an NF1 mutation, 1 individual was negative (NGS+MLPA), remaining 12 individuals were not tested.
Sources: Literature
Genetic Epilepsy v0.2060 NALCN Rylee Peters gene: NALCN was added
gene: NALCN was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: NALCN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NALCN were set to 30167850
Phenotypes for gene: NALCN were set to Hypotonia, infantile, with psychomotor retardation and characteristic facies 1 (MIM#615419)
Review for gene: NALCN was set to GREEN
Added comment: PMID: 30167850
ā€“ Cohort of individuals with novel NALCN or UNC80 variants; includes 16 individuals with biallelic NALCN variants and 1 individual with a de novo NALCN variant.
- All individuals (16/16) with biallelic NALCN variants presented with neonatal hypotonia, failure to thrive, ID, and muscular hypotonia. Other clinical features include severe ID (14/16), nonverbal (14/16), non-walking (13/16), chronic constipation (14/16), extrapyramidal/abnormal movements (12/16), strabismus (12/16), sleeping difficulties (10/16), increased tendency to infections (9/16), and some individuals presented with seizures (7/16).
- Table 1 describes clinical features of individuals with biallelic NALCN variants, showing 13/19 previously published individuals also had seizures.
Sources: Literature
Genetic Epilepsy v0.2060 MCM3AP Rylee Peters gene: MCM3AP was added
gene: MCM3AP was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: MCM3AP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM3AP were set to 32202298
Phenotypes for gene: MCM3AP were set to Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development (MIM#618124)
Review for gene: MCM3AP was set to RED
Added comment: - 2 families with probands compound heterozygous for variants in MCM3AP and a phenotype consistent with peripheral neuropathy with or without impaired intellectual development (MIM#618124).
- Two siblings from one family have severe generalised epilepsy and mild spastic diplegia.
- Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants.
Sources: Literature
Genetic Epilepsy v0.2060 LRPPRC Rylee Peters gene: LRPPRC was added
gene: LRPPRC was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: LRPPRC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRPPRC were set to 21266382; 26510951; 38046674; 29152527
Phenotypes for gene: LRPPRC were set to Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian) (MIM#220111)
Review for gene: LRPPRC was set to AMBER
Added comment: PMID: 21266382
- Cohort of patients with French-Canadian Leigh disease (MIM#220111). 55 of 56 patients were homozygous for the A354V mutation in LRPPRC.
- Condition is distinct for metabolic crises. 6/44 affected patients experienced seizures.
- During presentation of metabolic crises, 5 patients presented seizures. During neurological crises, 9 patients presented seizures.
- 10 patients were living at the time of the study and have had a stable clinical course (since puberty), with mild ID and seizures (3/6 patients).

PMID: 26510951
- 10 individuals (7 unrelated families) with recessive LRPPRC variants (identified via WES and candidate gene sequencing) with phenotypes resembling French-Canadian Leigh syndrome patients.
- 1/10 patients compound heterozygous for premature termination variants, experienced several brief generalised seizures and developed a severe encephalopathy and persistent metabolic acidosis.
- Functional characterisation of patients' fibroblasts and skeletal muscle homogenates (homozygous p.Arg1276_Lys1300del and compound heterozygous p.Glu497*; p.Gly1050Argfs*4 individuals) showed decreased levels of mutant LRPPRC protein and impaired Complex IV enzyme activity, associated with abnormal COX assembly and reduced steady-state levels of numerous oxidative phosphorylation subunits.

PMID: 38046674
- Case report; 1 individual with novel homozygous splice donor variant (c.469+2T>A) in LRPPRC causing Leigh syndrome with epilepsy. Parents are consanguineous and are unaffected carriers. The affected child had intrauterine developmental delays, absence of the corpus callosum and was suspected of exhibiting neurodevelopmental disorder, specifically experiencing seizures.

PMID: 29152527
- 1 individual with novel compound heterozygous missense variants with mild French-Canadian Type Leigh Syndrome. Developed refractory multifocal epilepsy at 3 years of age requiring multiple antiepileptics and ketogenic diet to control his seizures.
Sources: Literature
Genetic Epilepsy v0.2060 LMNB1 Rylee Peters reviewed gene: LMNB1: Rating: AMBER; Mode of pathogenicity: None; Publications: 32910914, 33033404; Phenotypes: Microcephaly 26, primary, autosomal dominant (MIM#619179); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2060 LETM1 Rylee Peters reviewed gene: LETM1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36055214; Phenotypes: Mitochondrial disease MONDO#0044970, LETM1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2060 PEX10 Lauren Rogers gene: PEX10 was added
gene: PEX10 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PEX10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX10 were set to 32069232
Phenotypes for gene: PEX10 were set to Peroxisome biogenesis disorder 6A (Zellweger), MIM#614870
Review for gene: PEX10 was set to RED
Added comment: PMID: 32069232: A case report of a 4 month old boy with Zellweger syndrome, with myoclonic seizures, hypotonia and hepatosplenomegaly, who was homozygous for a p.(C296F) variant.
Sources: Literature
Genetic Epilepsy v0.2060 PCLO Lauren Rogers gene: PCLO was added
gene: PCLO was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PCLO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCLO were set to 25832664; 32122952
Phenotypes for gene: PCLO were set to Pontocerebellar hypoplasia, type 3, MIM#608027
Review for gene: PCLO was set to RED
Added comment: PMID: 25832664: Seizures are part of the phenotype, but a single consanguineous family reported with bi-allelic variant in this gene.

PMID: 32122952: Knockout PCLO rats had a smaller cerebral cortex, a reduced volume of the cerebellum and pons, as well as impaired motor control and the presence of seizures BUT they donā€™t talk about seizures in the results, only introduction and discussion
Sources: Literature
Genetic Epilepsy v0.2060 PEX13 Lauren Rogers gene: PEX13 was added
gene: PEX13 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PEX13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX13 were set to 19449432; 37962062; 34055681; 37962062; 30919572; 33547378; 35854306
Phenotypes for gene: PEX13 were set to Peroxisome biogenesis disorder 11A (Zellweger)
Review for gene: PEX13 was set to GREEN
Added comment: PMID: 19449432: 2x unrelated Saudi children of consanguineous parents with Zellweger syndrome. Both children had seizures alongside other features of Zellweger and died young. One patient had a homozygous deletion (147,308 bp) encompassing the entire PEX3 gene and the other had a homozygous p.(G36DfsX61) variant.

PMID: 37962062: A consanguineous patient had severe hypotonia, seizures, hepatic dysfunction, failure to thrive, and dysmorphic features. They had a homozygous p.(Ala165Pro) variant and died at 14 months.

PMID: 34055681: An individual with global developmental delay, focal seizures, peritrigonal white matter disease and thinning corpus callosum with a homozygous p.(Met1Val) variant.

PMID: 37962062: 1x individual with hypotonia, seizures, developmental delay and suspicious abnormal signal in the bilateral basal ganglia with a homozygous p.(A165P) variant.

PMID: 30919572: 1x individual with developmental delay and seizures, cerebral atrophy and white matter volume loss. Homozygous for a p.(G23R) variant.

PMID: 33547378: 1x individual with a homozygous p.(K177del) variant with motor regression, seizure at 2 months, digestive problems, hypotonia, hypodontia, abnormal white matter and demyelination.

PMID: 35854306: 1x individual with a homozygous p.(W313*) variant with phycomotor delay, motor impairments, intellectual disability, language impairment and seizures, cortical malformations.
Sources: Literature
Genetic Epilepsy v0.2060 PAX6 Lauren Rogers gene: PAX6 was added
gene: PAX6 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PAX6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PAX6 were set to 34200146; 17417613; 12731001
Phenotypes for gene: PAX6 were set to Aniridia (MIM#106210)
Review for gene: PAX6 was set to AMBER
Added comment: PMID: 34200146: A case report of 1x male born with anophthalmia, who underwent hypoglycemic seizures starting at 5 months old, and showed a prediabetic condition at 60 months. They were heterozygous for a p.(S63C) variant.

PMID: 17417613: in a cohort of 78 individuals affected by aniridia; those with diverse ocular manifestations; and those with Peters' anomaly, and unaffected relatives. 1 large family with congenital ocular abnormalities, 14/36 had a PAX6 p.(S74G) variant. Most affected patients of this family had minor or major bilateral foveal hypoplasia. At least four individuals of this family had epilepsy, while others displayed variable neurological deficits along with severe cognitive deficiencies.

PMID: 12731001: In a cohort of 24 individuals with ocular abnormalities and defined PAX6 variants, 4x individuals with a single or recurrent unprovoked seizures. 1x individual had isolated unilateral polymicrogyria with a C-terminal extension, gave a history of frequent complex partial seizures compatible with temporal lobe epilepsy. Variant was inherited from mother who had a subtle gyral abnormality of the left temporal lobe, most probably polymicrogyria but she did not give a history of seizure. For the other patients it is not clear which are associated with the epilepsy patients.
Sources: Literature
Genetic Epilepsy v0.2060 PAK3 Lauren Rogers gene: PAK3 was added
gene: PAK3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PAK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PAK3 were set to 17853471; 12884430; 29246092; 25666757
Phenotypes for gene: PAK3 were set to Intellectual developmental disorder, X-linked 30 (MIM#300558)
Review for gene: PAK3 was set to AMBER
Added comment: PMID: 17853471: Report of 1 family with intellectual disability (5 affected males and 4 carrier females), EEG was reported for 4 affected males and 1 carrier female; only one had epilepsy, another individual had one seizure but no epileptic discharges on EEG. The familial variant in affected males and carrier females was p.(W446S).

PMID: 12884430: In an Australian multigenerational family with mild to borderline non-syndromic X-linked intellectual disability, 1/13 affected males had myoclonic epilepsy. The familial variant in affected males and carrier females was p.(A365E) determined via linkage analysis.

PMID: 29246092: A case report of one individual with intellectual disability, severe auto-mutilation and epilepsy had a p.(Ser527Gly) variant.

PMID: 25666757: In a cohort of 183 individuals with cerebral palsy, 1 male individual had hemiplegic cerebral palsy and epilepsy and showed cognitive abilities in the upper limit of the low average range. They had a PAK3 p.(R493C) variant.
Sources: Literature
Genetic Epilepsy v0.2060 OFD1 Lauren Rogers gene: OFD1 was added
gene: OFD1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: OFD1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: OFD1 were set to 23033313; 31373179
Phenotypes for gene: OFD1 were set to Orofaciodigital syndrome I (MIM#311200)
Review for gene: OFD1 was set to AMBER
Added comment: PMID: 23033313: Cohort of 25 with OFD1 variants with orofaciodigital syndrome I. 4/25 had epilepsy. One female individual had a p.(His50Alafs*2) variant, the other variants it is not clear which were associated with the epilepsy patients.

PMID: 31373179: In a cohort of 3 males with primary ciliary dyskinesia, 1 individual had seizures, dysmorphic features, intellectual disability, minimally verbal and minimally able to ambulate, chronic cerebral atrophy, hypotonia, and apnea. He had a de novo hemizygous p.(Glu995*) variant.
Sources: Literature
Mendeliome v1.1446 POLD1 Zornitza Stark Phenotypes for gene: POLD1 were changed from Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381; MONDO:0014157 to Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381; MONDO:0014157; Combined immunodeficiency, MONDO:0015131, POLD1-related
Combined Immunodeficiency v1.59 POLD1 Zornitza Stark Publications for gene: POLD1 were set to 31629014
Mendeliome v1.1445 POLD1 Zornitza Stark Publications for gene: POLD1 were set to 23770608; 33618333; 33369179; 32826474; 30023403; 29199204; 28791128
Mendeliome v1.1444 POLD1 Zornitza Stark Mode of inheritance for gene: POLD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1443 POLD1 Zornitza Stark edited their review of gene: POLD1: Added comment: Association with combined immunodeficiency: Three individuals from two generations of a consanguineous family reported, some functional data. Another unrelated individual reported in PMID 31449058, more functional data. Third family identified in Melbourne, two affected sibs, compound het variants and combined immunodeficiency.; Changed phenotypes: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381, MONDO:0014157, Combined immunodeficiency, MONDO:0015131, POLD1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Combined Immunodeficiency v1.58 POLD1 Zornitza Stark Phenotypes for gene: POLD1 were changed from Low CD4 T cells; Low B cells, normal maturation; recurrent respiratory tract infections, skin infections, warts and molluscum; short stature; intellectual disability to Combined immunodeficiency, MONDO:0015131, POLD1-related; Low CD4 T cells; Low B cells, normal maturation; recurrent respiratory tract infections, skin infections, warts and molluscum; short stature; intellectual disability
Combined Immunodeficiency v1.57 POLD1 Zornitza Stark Classified gene: POLD1 as Green List (high evidence)
Combined Immunodeficiency v1.57 POLD1 Zornitza Stark Gene: pold1 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.56 POLD1 Zornitza Stark edited their review of gene: POLD1: Added comment: Another family identified in Melbourne: two affected siblings with compound heterozygous variants and combined immunodeficiency.; Changed rating: GREEN
Genetic Epilepsy v0.2060 PTCH1 Elena Savva Marked gene: PTCH1 as ready
Genetic Epilepsy v0.2060 PTCH1 Elena Savva Gene: ptch1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2060 PTCH1 Elena Savva Classified gene: PTCH1 as Red List (low evidence)
Genetic Epilepsy v0.2060 PTCH1 Elena Savva Gene: ptch1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2059 PTCH1 Belinda Chong gene: PTCH1 was added
gene: PTCH1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTCH1 were set to 11941477; 17001668; 29575684; 36171624
Phenotypes for gene: PTCH1 were set to Holoprosencephaly 7, MIM# 610828
Review for gene: PTCH1 was set to RED
Added comment: Currently red for this panel.

PMID: 11941477 - In a female with holoprosencephaly, seizures, and bilateral cleft lip, a heterozygous c.2467A>G variant was identified in the PTCH gene. However, this variant is classified as benign in ClinVar.

PMID: 36171624 - A 10-month-old Chinese female patient with mobility disorders on the right limbs and recurrent seizures. Epidermal nevus syndrome was diagnosed, the patient also has a de novo mutation (c.109G > T) in PTCH1 gene and cerebral infarction.
Sources: Literature
Genetic Epilepsy v0.2059 CTU2 Zornitza Stark Marked gene: CTU2 as ready
Genetic Epilepsy v0.2059 CTU2 Zornitza Stark Gene: ctu2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2059 CTU2 Zornitza Stark Classified gene: CTU2 as Green List (high evidence)
Genetic Epilepsy v0.2059 CTU2 Zornitza Stark Gene: ctu2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2058 CYP27A1 Zornitza Stark Marked gene: CYP27A1 as ready
Genetic Epilepsy v0.2058 CYP27A1 Zornitza Stark Gene: cyp27a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2058 CYP27A1 Zornitza Stark Classified gene: CYP27A1 as Green List (high evidence)
Genetic Epilepsy v0.2058 CYP27A1 Zornitza Stark Gene: cyp27a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2057 DAG1 Zornitza Stark Marked gene: DAG1 as ready
Genetic Epilepsy v0.2057 DAG1 Zornitza Stark Gene: dag1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2057 DAG1 Zornitza Stark Classified gene: DAG1 as Red List (low evidence)
Genetic Epilepsy v0.2057 DAG1 Zornitza Stark Gene: dag1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2057 DAG1 Zornitza Stark Classified gene: DAG1 as Red List (low evidence)
Genetic Epilepsy v0.2057 DAG1 Zornitza Stark Gene: dag1 has been classified as Red List (Low Evidence).
Mendeliome v1.1443 LCK Zornitza Stark Classified gene: LCK as Green List (high evidence)
Mendeliome v1.1443 LCK Zornitza Stark Gene: lck has been classified as Green List (High Evidence).
Mendeliome v1.1442 LCK Zornitza Stark edited their review of gene: LCK: Added comment: Additional cases:
PMID 38100037: Description of a second unrelated patient with novel biallelic missense LCK c.1393T>C, p.C465R variant in a patient from a consanguineous Syrian family with profound T-cell immune deficiency characterized by complete LCK protein expression deficiency and ensuing proximal TCR signaling-and CD4 and CD8-co-receptor-mediated functional and phenotypical defects.

PMID: 27087313 reported 3 siblings of a consanguineous family presenting with recurrent pneumonia and severe viral skin disease leading to malignant transformation. The patients had an intronic LCK c.188-2A>G splice site variant resulting in skipping of exon 3 and mRNA decay. Clinical data alongside with CD4+ T-cell lymphocytopenia suggested a hypomorphic LCK deficiency.; Changed rating: GREEN; Changed publications: 22985903, 1579166, 11021796, 27087313, 38100037
Combined Immunodeficiency v1.56 LCK Zornitza Stark Publications for gene: LCK were set to 22985903; 1579166; 11021796
Combined Immunodeficiency v1.55 LCK Zornitza Stark Classified gene: LCK as Green List (high evidence)
Combined Immunodeficiency v1.55 LCK Zornitza Stark Gene: lck has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5651 RAP1GDS1 Zornitza Stark Phenotypes for gene: RAP1GDS1 were changed from Intellectual disability; dysmorphic features to Alfadhel syndrome, MIM# 620655
Intellectual disability syndromic and non-syndromic v0.5650 RAP1GDS1 Zornitza Stark edited their review of gene: RAP1GDS1: Changed phenotypes: Alfadhel syndrome, MIM# 620655
Mendeliome v1.1442 RAP1GDS1 Zornitza Stark Phenotypes for gene: RAP1GDS1 were changed from Intellectual disability; dysmorphic features to Alfadhel syndrome, MIM# 620655
Mendeliome v1.1441 RAP1GDS1 Zornitza Stark edited their review of gene: RAP1GDS1: Changed phenotypes: Alfadhel syndrome, MIM# 620655
Fetal anomalies v1.173 CASP2 Zornitza Stark Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder MONDO:0700092, CASP2-related to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653
Fetal anomalies v1.172 CASP2 Zornitza Stark edited their review of gene: CASP2: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653
Intellectual disability syndromic and non-syndromic v0.5650 CASP2 Zornitza Stark Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder MONDO:0700092, CASP2-related to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653
Intellectual disability syndromic and non-syndromic v0.5649 CASP2 Zornitza Stark reviewed gene: CASP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1441 CASP2 Zornitza Stark Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder MONDO:0700092, CASP2-related to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653
Mendeliome v1.1440 CASP2 Zornitza Stark reviewed gene: CASP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lissencephaly and Band Heterotopia v1.19 CASP2 Zornitza Stark Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder MONDO:0700092, CASP2-related to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653
Lissencephaly and Band Heterotopia v1.18 CASP2 Zornitza Stark reviewed gene: CASP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v1.54 LCK Peter McNaughton reviewed gene: LCK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38100037, PMID: 27087313; Phenotypes: Combined Immune deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1440 RBFOX1 Zornitza Stark Phenotypes for gene: RBFOX1 were changed from Intellectual disability; autism to Neurodevelopmental disorder (MONDO:0700092), RBFOX1-related
Mendeliome v1.1439 RBFOX1 Zornitza Stark Publications for gene: RBFOX1 were set to 24664471
Mendeliome v1.1438 RBFOX1 Zornitza Stark Classified gene: RBFOX1 as Green List (high evidence)
Mendeliome v1.1438 RBFOX1 Zornitza Stark Gene: rbfox1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2056 RBFOX1 Zornitza Stark Marked gene: RBFOX1 as ready
Genetic Epilepsy v0.2056 RBFOX1 Zornitza Stark Gene: rbfox1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2056 RBFOX1 Zornitza Stark Classified gene: RBFOX1 as Green List (high evidence)
Genetic Epilepsy v0.2056 RBFOX1 Zornitza Stark Gene: rbfox1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2055 DAG1 Andrew Fennell gene: DAG1 was added
gene: DAG1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: DAG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DAG1 were set to PMID: 24052401; 25934851; 30450679
Phenotypes for gene: DAG1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9, 613818; Walker-Warburg syndrome and tectocerebellar dysgraphia
Review for gene: DAG1 was set to RED
Added comment: Only 7 individuals reported with MDDGA9 and none had seizures. MDDGC9 phenotype is related to limb-girdle dystrophy and also has no association with seizures.
Sources: Literature
Genetic Epilepsy v0.2055 CYP27A1 Andrew Fennell gene: CYP27A1 was added
gene: CYP27A1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CYP27A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP27A1 were set to PMID: 16816916; 20301583; 22658436
Phenotypes for gene: CYP27A1 were set to Cerebrotendinous xanthomatosis MIM#213700; Disorders of bile acid biosynthesis
Review for gene: CYP27A1 was set to GREEN
Added comment: PMID: 16816916 - Approximately 50% of CTX patients reported to have seizures in older literature.

PMID: 20301583 - GeneReviews quotes seizures are present in 33% of cases.

PMID 22336472, 22658436, 33414089 - Multiple single case reports of individuals with seizures onset earlier in the disease process ranging from 2.5yo to 12yo.
Sources: Literature
Genetic Epilepsy v0.2055 CTU2 Andrew Fennell gene: CTU2 was added
gene: CTU2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CTU2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTU2 were set to PMID: 27480277; 33559988
Phenotypes for gene: CTU2 were set to Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, MIM#618142
Review for gene: CTU2 was set to GREEN
Added comment: PMID: 33559988 - 6 individuals from 5 different families (2 individuals previously reported in PMID 27480277) with DREAM-PL reported to have seizures. The age of onset ranges from birth to 9yo.
Sources: Literature
Genetic Epilepsy v0.2055 GMPPB Zornitza Stark Marked gene: GMPPB as ready
Genetic Epilepsy v0.2055 GMPPB Zornitza Stark Gene: gmppb has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2055 GMPPB Zornitza Stark Classified gene: GMPPB as Green List (high evidence)
Genetic Epilepsy v0.2055 GMPPB Zornitza Stark Gene: gmppb has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2054 GMPPB Zornitza Stark gene: GMPPB was added
gene: GMPPB was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: GMPPB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GMPPB were set to 30257713
Phenotypes for gene: GMPPB were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 615350
Review for gene: GMPPB was set to GREEN
Added comment: Established gene-disease association, spectrum of severity. Seizures reported as part of the severe end of the spectrum.
Sources: Expert list
Genetic Epilepsy v0.2053 GMPPA Zornitza Stark Marked gene: GMPPA as ready
Genetic Epilepsy v0.2053 GMPPA Zornitza Stark Gene: gmppa has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2053 GMPPA Zornitza Stark Classified gene: GMPPA as Amber List (moderate evidence)
Genetic Epilepsy v0.2053 GMPPA Zornitza Stark Gene: gmppa has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2053 GMPPA Zornitza Stark Classified gene: GMPPA as Amber List (moderate evidence)
Genetic Epilepsy v0.2053 GMPPA Zornitza Stark Gene: gmppa has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2052 GMPPA Zornitza Stark gene: GMPPA was added
gene: GMPPA was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: GMPPA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GMPPA were set to 24035193; 28574218
Phenotypes for gene: GMPPA were set to Alacrima, achalasia, and mental retardation syndrome (MIM# 615510)
Review for gene: GMPPA was set to AMBER
Added comment: 10 families reported, of which one had seizures.
Sources: Expert list
Genetic Epilepsy v0.2051 GABRA4 Zornitza Stark Publications for gene: GABRA4 were set to 35152403
Genetic Epilepsy v0.2050 GABRA4 Zornitza Stark edited their review of gene: GABRA4: Changed publications: 35152403, 35781801
Genetic Epilepsy v0.2050 DARS2 Zornitza Stark Publications for gene: DARS2 were set to 17384640; 15002045; 16788019; 30352563
Genetic Epilepsy v0.2049 DARS2 Zornitza Stark Classified gene: DARS2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2049 DARS2 Zornitza Stark Gene: dars2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2048 CRADD Zornitza Stark Classified gene: CRADD as Green List (high evidence)
Genetic Epilepsy v0.2048 CRADD Zornitza Stark Gene: cradd has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2047 CRADD Zornitza Stark reviewed gene: CRADD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 34, with variant lissencephaly, MIM# 614499; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2047 ISPD Zornitza Stark Publications for gene: ISPD were set to
Genetic Epilepsy v0.2046 ISPD Zornitza Stark Classified gene: ISPD as Green List (high evidence)
Genetic Epilepsy v0.2046 ISPD Zornitza Stark Gene: ispd has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2045 CTSF Zornitza Stark Marked gene: CTSF as ready
Genetic Epilepsy v0.2045 CTSF Zornitza Stark Gene: ctsf has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2045 CTSF Elena Savva Phenotypes for gene: CTSF were changed from Ceroid lipofuscinosis, neuronal, 13 (Kufs type) MIM#615362 to Ceroid lipofuscinosis, neuronal, 13 (Kufs type) MIM#615362
Genetic Epilepsy v0.2044 CTSF Elena Savva Phenotypes for gene: CTSF were changed from to Ceroid lipofuscinosis, neuronal, 13 (Kufs type) MIM#615362
Genetic Epilepsy v0.2044 CTSF Elena Savva Classified gene: CTSF as Green List (high evidence)
Genetic Epilepsy v0.2044 CTSF Elena Savva Gene: ctsf has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2043 CRADD Elena Savva Classified gene: CRADD as Amber List (moderate evidence)
Genetic Epilepsy v0.2043 CRADD Elena Savva Gene: cradd has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2043 CSNK2A1 Elena Savva Classified gene: CSNK2A1 as Green List (high evidence)
Genetic Epilepsy v0.2043 CSNK2A1 Elena Savva Gene: csnk2a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2042 CSNK2A1 Elena Savva Classified gene: CSNK2A1 as Green List (high evidence)
Genetic Epilepsy v0.2042 CSNK2A1 Elena Savva Gene: csnk2a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2041 CSNK2A1 Elena Savva Marked gene: CSNK2A1 as ready
Genetic Epilepsy v0.2041 CSNK2A1 Elena Savva Gene: csnk2a1 has been removed from the panel.
Genetic Epilepsy v0.2041 CRADD Elena Savva Classified gene: CRADD as Amber List (moderate evidence)
Genetic Epilepsy v0.2041 CRADD Elena Savva Gene: cradd has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2040 CRADD Elena Savva Marked gene: CRADD as ready
Genetic Epilepsy v0.2040 CRADD Elena Savva Gene: cradd has been removed from the panel.
Genetic Epilepsy v0.2040 CPT2 Elena Savva Marked gene: CPT2 as ready
Genetic Epilepsy v0.2040 CPT2 Elena Savva Gene: cpt2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2040 CPT2 Elena Savva Classified gene: CPT2 as Green List (high evidence)
Genetic Epilepsy v0.2040 CPT2 Elena Savva Gene: cpt2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2040 CSF1R Elena Savva Classified gene: CSF1R as Green List (high evidence)
Genetic Epilepsy v0.2040 CSF1R Elena Savva Gene: csf1r has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2039 CSF1R Elena Savva Mode of pathogenicity for gene: CSF1R was changed from None to None
Genetic Epilepsy v0.2039 CSF1R Elena Savva Classified gene: CSF1R as Green List (high evidence)
Genetic Epilepsy v0.2039 CSF1R Elena Savva Gene: csf1r has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2038 CSF1R Elena Savva Marked gene: CSF1R as ready
Genetic Epilepsy v0.2038 CSF1R Elena Savva Gene: csf1r has been removed from the panel.
Genetic Epilepsy v0.2038 CTSF Andrew Fennell gene: CTSF was added
gene: CTSF was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CTSF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTSF were set to PMID: 23297359; 25274848; 27668283; 27524508; 35139754
Review for gene: CTSF was set to GREEN
Added comment: PMID: 23297359 - Four affected individuals from three different families all with seizures of varying types and frequency (two in family Ku4, one in family Ku10, one in family Ku16).

PMID: 25274848 - 5/6 affected individuals from a single family presented with tonic-clonic seizures as a first manifestation of their disease aged 21-66 years. All progressed to dementia. All were homozygous for c.213+1G>C.

PMID: 27668283 - 1/4 affected siblings, presented with myoclonic seizures at 35yo.

PMID: 27524508 - single report of 39yo female with chronic psychosis and new seizures.
Sources: Literature
Genetic Epilepsy v0.2038 CSNK2A1 Andrew Fennell gene: CSNK2A1 was added
gene: CSNK2A1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CSNK2A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CSNK2A1 were set to PMID: 35679446; 36588763
Phenotypes for gene: CSNK2A1 were set to Okur-Chung neurodevelopmental syndrome, MIM# 617062
Review for gene: CSNK2A1 was set to GREEN
Added comment: PMID 36588763 - Review of previously reported cases noted 9/31 (29%) individuals with Okur-Chung neurodevelopmental syndrome reported to have seizures.

PMID: 35679446 - GeneReviews article includes seizures among the more common features of the disorder, present in 11/36 cases reported to date. No specific type of seizure has been noted. Intractable seizures are reported in some individuals while only one case status has been reported.
Sources: Literature
Anophthalmia_Microphthalmia_Coloboma v1.37 FZD5 Elena Savva Phenotypes for gene: FZD5 were changed from Coloboma to Coloboma (MONDO:0001476), FZD5-related
Genetic Epilepsy v0.2038 CSF1R Andrew Fennell gene: CSF1R was added
gene: CSF1R was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CSF1R was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: CSF1R were set to PMID: 22197934; 24336230; 30982608; 30982609
Phenotypes for gene: CSF1R were set to Brain abnormalities, neurodegeneration, and dysosteosclerosis, (MIM#618476)
Review for gene: CSF1R was set to GREEN
Added comment: Monoallelic disease is onset in 3rd or 4th decades whereas biallelic disease is associated with early-onset disease in infancy or childhood.

Monoallelic association:
PMID: 22197934 - 13/23 individuals from 9 different families reported to have seizures.
PMID: 24336230 - 2/7 individuals with seizures reported from a Japanese cohort.

Biallelic association:
PMID: 30982608 - Two individuals with a seizure history. First was an infant who presented with prenatal structural brain abnormalities, including ACC, ventriculomegaly, and pontocerebellar hypoplasia, and died at 10 months had intractable epilepsy. Second individuals presented with generalized tonic-clonic seizures aged 12 years old associated with regression and loss of all skills.

PMID: 30982609 - Two individuals with seizures were reported from a cohort of 7 individuals. A-III-1 was a male infant who developed seizures in early infancy (after 3 months of age). Individual C-III-4 was a male who developed focal seizures in early infancy.
Sources: Literature
Genetic Epilepsy v0.2038 ISPD Andrew Fennell reviewed gene: ISPD: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24120487, 35863218; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 614643, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7 616052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2038 CRADD Andrew Fennell gene: CRADD was added
gene: CRADD was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CRADD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRADD were set to PMID: 27773430; 30914828
Phenotypes for gene: CRADD were set to Intellectual developmental disorder, autosomal recessive 34, with variant lissencephaly, MIM# 614499
Review for gene: CRADD was set to AMBER
Added comment: PMID: 27773430 - 3/13 individuals with IDD34 were reported to have seizures.

PMID: 30914828 - 2/22 individuals with a Finnish founder mutation were reported to have seizures
Sources: Literature
Genetic Epilepsy v0.2038 CPT2 Andrew Fennell gene: CPT2 was added
gene: CPT2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CPT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPT2 were set to PMID: 20301431; 35028265; 36478999
Phenotypes for gene: CPT2 were set to CPT II deficiency, infantile 600649; CPT II deficiency, lethal neonatal 608836; CPT II deficiency, myopathic, stress-induced 255110
Review for gene: CPT2 was set to GREEN
Added comment: GeneReviews quotes seizures as a core component of the phenotype in lethal neonatal and severe infantile forms of the disorder.

PMID: 36478999 - single report of a 10yo male with CPT2 who developed focal seizures during an acute episode.

PMID: 35028265 - single report of a male who presented at 5 months of age with infantileā€onset carnitine palmitoyltransferase 2 (CPT2) deficiency. He also had Xā€linked nephrogenic diabetes insipidus. He developed focal seizures at 17yo.
Sources: Literature
Genetic Epilepsy v0.2038 DARS2 Andrew Fennell reviewed gene: DARS2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 34104671; Phenotypes: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, MIM# 611105; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.244 BRD4 Zornitza Stark Phenotypes for gene: BRD4 were changed from Cornelia de Lange-like syndrome, MONDO:0016033 to Cornelia de Lange syndrome 6, MIM# 620568
Microcephaly v1.243 BRD4 Zornitza Stark edited their review of gene: BRD4: Changed phenotypes: Cornelia de Lange syndrome 6, MIM# 620568
Mendeliome v1.1437 BRD4 Zornitza Stark Phenotypes for gene: BRD4 were changed from Cornelia de Lange syndrome, MONDO:0016033 to Cornelia de Lange syndrome 6, MIM# 620568
Mendeliome v1.1436 BRD4 Zornitza Stark edited their review of gene: BRD4: Changed phenotypes: Cornelia de Lange syndrome 6, MIM# 620568
Hypertrichosis syndromes v0.44 BRD4 Zornitza Stark Phenotypes for gene: BRD4 were changed from Cornelia de Lange syndrome, MONDO:0016033 to Cornelia de Lange syndrome 6, MIM# 620568
Hypertrichosis syndromes v0.43 BRD4 Zornitza Stark edited their review of gene: BRD4: Changed phenotypes: Cornelia de Lange syndrome 6, MIM# 620568
Genetic Epilepsy v0.2038 ALG12 Zornitza Stark Marked gene: ALG12 as ready
Genetic Epilepsy v0.2038 ALG12 Zornitza Stark Gene: alg12 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2038 ALG12 Zornitza Stark Classified gene: ALG12 as Red List (low evidence)
Genetic Epilepsy v0.2038 ALG12 Zornitza Stark Gene: alg12 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2037 ASXL3 Zornitza Stark Classified gene: ASXL3 as Green List (high evidence)
Genetic Epilepsy v0.2037 ASXL3 Zornitza Stark Gene: asxl3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2037 ASXL3 Zornitza Stark Marked gene: ASXL3 as ready
Genetic Epilepsy v0.2037 ASXL3 Zornitza Stark Gene: asxl3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2037 ASXL3 Zornitza Stark Classified gene: ASXL3 as Green List (high evidence)
Genetic Epilepsy v0.2037 ASXL3 Zornitza Stark Gene: asxl3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2036 ABCA2 John Coleman reviewed gene: ABCA2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37777370, 30237576, 29302074, 31047799; Phenotypes: Intellectual developmental disorder with poor growth and with or without seizures or ataxia, OMIM 618808; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2036 TRAPPC2L Zornitza Stark Publications for gene: TRAPPC2L were set to 30120216; 32843486
Genetic Epilepsy v0.2035 TMEM163 Zornitza Stark Publications for gene: TMEM163 were set to PMID: 35953447
Genetic Epilepsy v0.2034 BICD2 Zornitza Stark Marked gene: BICD2 as ready
Genetic Epilepsy v0.2034 BICD2 Zornitza Stark Gene: bicd2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2034 BICD2 Zornitza Stark Phenotypes for gene: BICD2 were changed from spinal muscular atrophy MONDO:0001516 to Neurodevelopmental disorder, BICD2-related (MONDO#0700092)
Genetic Epilepsy v0.2033 BICD2 Zornitza Stark Classified gene: BICD2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2033 BICD2 Zornitza Stark Gene: bicd2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2032 BCKDK Zornitza Stark Marked gene: BCKDK as ready
Genetic Epilepsy v0.2032 BCKDK Zornitza Stark Gene: bckdk has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2032 BCKDK Zornitza Stark Classified gene: BCKDK as Green List (high evidence)
Genetic Epilepsy v0.2032 BCKDK Zornitza Stark Gene: bckdk has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.112 DUOX2 Zornitza Stark Mode of inheritance for gene: DUOX2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Inflammatory bowel disease v0.111 DUOX2 Zornitza Stark Classified gene: DUOX2 as Green List (high evidence)
Inflammatory bowel disease v0.111 DUOX2 Zornitza Stark Gene: duox2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2031 B4GAT1 Zornitza Stark Marked gene: B4GAT1 as ready
Genetic Epilepsy v0.2031 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2031 B4GAT1 Zornitza Stark Classified gene: B4GAT1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2031 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2030 B3GALNT2 Zornitza Stark Marked gene: B3GALNT2 as ready
Genetic Epilepsy v0.2030 B3GALNT2 Zornitza Stark Gene: b3galnt2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2030 B3GALNT2 Zornitza Stark Classified gene: B3GALNT2 as Green List (high evidence)
Genetic Epilepsy v0.2030 B3GALNT2 Zornitza Stark Gene: b3galnt2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2029 PRUNE1 Zornitza Stark Marked gene: PRUNE1 as ready
Genetic Epilepsy v0.2029 PRUNE1 Zornitza Stark Gene: prune1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2029 PRUNE1 Zornitza Stark Classified gene: PRUNE1 as Green List (high evidence)
Genetic Epilepsy v0.2029 PRUNE1 Zornitza Stark Gene: prune1 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.79 RPS15A Zornitza Stark Marked gene: RPS15A as ready
Bone Marrow Failure v1.79 RPS15A Zornitza Stark Gene: rps15a has been classified as Red List (Low Evidence).
Bone Marrow Failure v1.79 RPL35 Zornitza Stark Marked gene: RPL35 as ready
Bone Marrow Failure v1.79 RPL35 Zornitza Stark Gene: rpl35 has been classified as Red List (Low Evidence).
Bone Marrow Failure v1.79 RPS28 Zornitza Stark Marked gene: RPS28 as ready
Bone Marrow Failure v1.79 RPS28 Zornitza Stark Gene: rps28 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.79 RPL8 Zornitza Stark Marked gene: RPL8 as ready
Bone Marrow Failure v1.79 RPL8 Zornitza Stark Gene: rpl8 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.79 RPL18 Zornitza Stark Marked gene: RPL18 as ready
Bone Marrow Failure v1.79 RPL18 Zornitza Stark Gene: rpl18 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1436 MAP1LC3B2 Zornitza Stark Marked gene: MAP1LC3B2 as ready
Mendeliome v1.1436 MAP1LC3B2 Zornitza Stark Gene: map1lc3b2 has been classified as Red List (Low Evidence).
Mendeliome v1.1436 MAP1LC3B2 Zornitza Stark gene: MAP1LC3B2 was added
gene: MAP1LC3B2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: MAP1LC3B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP1LC3B2 were set to 35748970; 33310865
Phenotypes for gene: MAP1LC3B2 were set to Hereditary susceptibility to infection, MONDO:0015979, MAP1LC3B2 -related; Mollaretā€™s meningitis (recurrent lymphocytic meningitis) due to HSV2
Review for gene: MAP1LC3B2 was set to RED
Added comment: PMID: 35748970 Affects CNS (resident cells and fibroblasts) Impaired autophagy induction after HSV2 infection - increased viral replication and apoptosis of patient fibroblasts.

PMID: 33310865 one affected individual with heterozygous variant in MAP1LC3B2 (p.L109M)
Sources: Expert Review
Defects of intrinsic and innate immunity v0.134 MAP1LC3B2 Zornitza Stark Marked gene: MAP1LC3B2 as ready
Defects of intrinsic and innate immunity v0.134 MAP1LC3B2 Zornitza Stark Gene: map1lc3b2 has been classified as Red List (Low Evidence).
Defects of intrinsic and innate immunity v0.134 MAP1LC3B2 Zornitza Stark Phenotypes for gene: MAP1LC3B2 were changed from Mollaretā€™s meningitis (recurrent lymphocytic meningitis) due to HSV2 to Hereditary susceptibility to infection, MONDO:0015979, MAP1LC3B2 -related; Mollaretā€™s meningitis (recurrent lymphocytic meningitis) due to HSV2
Defects of intrinsic and innate immunity v0.133 MAP1LC3B2 Zornitza Stark Classified gene: MAP1LC3B2 as Red List (low evidence)
Defects of intrinsic and innate immunity v0.133 MAP1LC3B2 Zornitza Stark Gene: map1lc3b2 has been classified as Red List (Low Evidence).
Bone Marrow Failure v1.79 TBXAS1 Zornitza Stark Marked gene: TBXAS1 as ready
Bone Marrow Failure v1.79 TBXAS1 Zornitza Stark Gene: tbxas1 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.79 DNASE2 Zornitza Stark Marked gene: DNASE2 as ready
Bone Marrow Failure v1.79 DNASE2 Zornitza Stark Gene: dnase2 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.79 MPIG6B Zornitza Stark Marked gene: MPIG6B as ready
Bone Marrow Failure v1.79 MPIG6B Zornitza Stark Gene: mpig6b has been classified as Green List (High Evidence).
Bone Marrow Failure v1.79 ACTB Zornitza Stark Marked gene: ACTB as ready
Bone Marrow Failure v1.79 ACTB Zornitza Stark Gene: actb has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.185 ELF4 Zornitza Stark Marked gene: ELF4 as ready
Disorders of immune dysregulation v0.185 ELF4 Zornitza Stark Gene: elf4 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.185 ELF4 Zornitza Stark Classified gene: ELF4 as Green List (high evidence)
Disorders of immune dysregulation v0.185 ELF4 Zornitza Stark Gene: elf4 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.79 TCN2 Zornitza Stark Marked gene: TCN2 as ready
Bone Marrow Failure v1.79 TCN2 Zornitza Stark Gene: tcn2 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.79 NBN Zornitza Stark Marked gene: NBN as ready
Bone Marrow Failure v1.79 NBN Zornitza Stark Gene: nbn has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.31 RNU7-1 Zornitza Stark Marked gene: RNU7-1 as ready
Autoinflammatory Disorders v1.31 RNU7-1 Zornitza Stark Gene: rnu7-1 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.31 RNU7-1 Zornitza Stark Classified gene: RNU7-1 as Green List (high evidence)
Autoinflammatory Disorders v1.31 RNU7-1 Zornitza Stark Gene: rnu7-1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2028 ALG12 John Coleman gene: ALG12 was added
gene: ALG12 was added to Genetic Epilepsy. Sources: NHS GMS,Literature
Mode of inheritance for gene: ALG12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALG12 were set to (PMID: 33618527)
Phenotypes for gene: ALG12 were set to CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ig; OMIM: 607144
Review for gene: ALG12 was set to RED
Added comment: Causes AR congenital disorder of gylcosolation type Ig. Listed as red list on panel app UK for Genetic Epilepsy. Epilepsy/ seizures not reported on OMIM phenotype. Seizure listed on Gene-reviews under CDG Ig however citations for this are linked to papers about CDG overall/ biochemical evidence rather than ALG12 variants. Pubmed search for "ALG12" and "epilepsy" shows no results. Search for "ALG12" and "seizure" linked to one paper only (PMID: 33618527), again only mention of seizure in this paper is related to CDGs in general and not a specific patient with ALG12/ CDG Type Ig. No established evidence of seizures or epilepsy in ALG12/ CDG type Ig phenotype.
Sources: NHS GMS, Literature
Genetic Epilepsy v0.2028 ASXL3 John Coleman gene: ASXL3 was added
gene: ASXL3 was added to Genetic Epilepsy. Sources: NHS GMS,ClinGen,Literature
Mode of inheritance for gene: ASXL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ASXL3 were set to PMID:33151654; 34436830; 29367179
Phenotypes for gene: ASXL3 were set to Bainbridge-Ropers syndrome, OMIM:615115
Review for gene: ASXL3 was set to GREEN
Added comment: Listed as Green entity on panel app uk. De novo loss of function variants and dominant negative variants reported. 1/3rd of patients with epilepsy according to Clingen and Genereviews. 11/39 phenotyped patients in a large cohort (PMID: 34436830) had seizures. Various types - absence, GTC, onset in pediatric age group or adult. Generally treatment responsive. Some adults with intractable difficult to treat seizures. Smaller cohort of 3 unrelated individuals (29367179) with seizures, 2 had PTC variants and 1 patient had a splice variant.
Sources: NHS GMS, ClinGen, Literature
Genetic Epilepsy v0.2028 TRAPPC2L Belinda Chong reviewed gene: TRAPPC2L: Rating: RED; Mode of pathogenicity: None; Publications: 36849228, 30120216, 32843486; Phenotypes: Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis, MIM#618331; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2028 TRA2B Belinda Chong reviewed gene: TRA2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 36549593; Phenotypes: Neurodevelopmental disorder, TRA2B-related (MONDO#0700092); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2028 TMEM163 Belinda Chong reviewed gene: TMEM163: Rating: GREEN; Mode of pathogenicity: None; Publications: 35455965, 35953447; Phenotypes: Leukodystrophy, hypomyelinating, 25 MIM#620243; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2028 BICD2 Lilian Downie gene: BICD2 was added
gene: BICD2 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: BICD2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: BICD2 were set to PMID: 35896821, PMID: 28635954, PMID: 32057122, PMID: 25497877, PMID: 35338243
Phenotypes for gene: BICD2 were set to spinal muscular atrophy MONDO:0001516
Review for gene: BICD2 was set to AMBER
Added comment: mostly AD cases reported, new more severe presentation reported x2 with biallelic variants: seizures part of the AR phenotype in both cases

From the literature of AD SMA cases:
PMID: PMID: 32057122 2x patients from same family with seizures as part of the phenotype
PMID: 28635954 patient suspected clinically as having seizures but not proven
PMID: 25497877 large cohort (N=32 patients from 9 families) no seizures
Sources: Expert list
Genetic Epilepsy v0.2028 BCKDK Lilian Downie gene: BCKDK was added
gene: BCKDK was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: BCKDK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BCKDK were set to PMID: 22956686, PMID: 35216372, PMID: 36729635
Phenotypes for gene: BCKDK were set to Branched-chain keto acid dehydrogenase kinase deficiency MIM#614923
Review for gene: BCKDK was set to GREEN
Added comment: Epilepsy well reported part of this phenotype
Sources: Expert list
Inflammatory bowel disease v0.110 DUOX2 Peter McNaughton edited their review of gene: DUOX2: Added comment: 1mo girl with IBD and colonic polyps with compound het variants c.2524C>T and c.3175C>T with functional studies showing decreased H2O2 generation.
This case along with previous case reports - PMID: 28683258 & PMID: 35429653 suggest that biallelic DUOX2 variants should be part of evaluation for VEO-IBD.; Changed rating: GREEN; Changed publications: PMID: 38075699; Changed phenotypes: neonatal onset IBD
Genetic Epilepsy v0.2028 B4GAT1 Lilian Downie gene: B4GAT1 was added
gene: B4GAT1 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: B4GAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B4GAT1 were set to PMID 23877401, PMID: 23359570
Phenotypes for gene: B4GAT1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 MIM#615287
Review for gene: B4GAT1 was set to AMBER
Added comment: PMID 23877401 multiple family members affected, 1 with seizures
PMID: 23359570 affected 2yo with seizures
Sources: Expert list
Genetic Epilepsy v0.2028 B3GALNT2 Lilian Downie gene: B3GALNT2 was added
gene: B3GALNT2 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: B3GALNT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B3GALNT2 were set to PMID: 29791932, PMID: 29273094, PMID: 35127920
Phenotypes for gene: B3GALNT2 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 11 MIM#615181
Review for gene: B3GALNT2 was set to GREEN
Added comment: Severe congenital muscular dystrophy and ID phenotype. Seizures not consistent feature with early phenotypic reports
PMID: 29791932 epileptic encephalopathy
PMID: 29273094 5 individuals with ID and seizures from single large consanguineous family but they had no or mild muscle symptoms so quite different from previously reported phenotype
PMID: 35127920 not a great article but does have a table summarising the previous cases and 9/21 had seizures.
Sources: Expert list
Genetic Epilepsy v0.2028 PRUNE1 Chris Ciotta gene: PRUNE1 was added
gene: PRUNE1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PRUNE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRUNE1 were set to PMID: 28334956; 26539891; 30556349; 29940663; 29797509
Phenotypes for gene: PRUNE1 were set to Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies MIM#617481
Review for gene: PRUNE1 was set to GREEN
Added comment: PRUNE1 is associated with neurodevelopmental disorder with microcephaly, hypotonia and variable brain anomalies (MIM#617481). Seizures are a listed phenotype in OMIM in some patients.
- Seizures were seen in 6/13 individuals (PMID:28334956) from Oman, Iran, India and Italy, the variants identified in individuals with seizures were absent from gnomAD besides the commonly reported Asp109Asn variant (41 hets, 0 Homs in V4) which has also been extensively reported in ClinVar (10x pathogenic reports).
- Seizures were also reported in 7/9 Cree children from the Canadian province of Manitoba (PMID:30556349), they all shared a likely founder homozygous c.521-2A>G splicing variant. The normally spliced product was absent in RNA prepared from two individuals with exon 5 skipping or multiple exon skipping leading to a frameshift and premature termination observed as outcomes of this variant.
- Epilepsy was reported in 11/12 unrelated individuals (paediatric patients with neurological symptoms from Munich) with bi-allelic variants in PRUNE1 (PMID:29940663).
Sources: Literature
Bone Marrow Failure v1.79 RPS15A Chirag Patel gene: RPS15A was added
gene: RPS15A was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: RPS15A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPS15A were set to PMID: 27909223
Phenotypes for gene: RPS15A were set to Diamond-Blackfan anemia 20, MIM# 618313
Review for gene: RPS15A was set to RED
Added comment: Single family reported.
Sources: Expert list
Bone Marrow Failure v1.78 RPL35 Chirag Patel gene: RPL35 was added
gene: RPL35 was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: RPL35 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL35 were set to PMID: 28280134
Phenotypes for gene: RPL35 were set to Diamond-Blackfan anemia 19, MIM# 618312
Review for gene: RPL35 was set to RED
Added comment: Single family reported.
Sources: Expert list
Bone Marrow Failure v1.77 RPS28 Chirag Patel Classified gene: RPS28 as Amber List (moderate evidence)
Bone Marrow Failure v1.77 RPS28 Chirag Patel Gene: rps28 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.76 RPS28 Chirag Patel gene: RPS28 was added
gene: RPS28 was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: RPS28 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPS28 were set to PMID: 24942156
Phenotypes for gene: RPS28 were set to Diamond Blackfan anemia 15 with mandibulofacial dysostosis, MIM# 606164
Review for gene: RPS28 was set to AMBER
Added comment: Two individuals reported in 2014, none since.
Sources: Expert list
Bone Marrow Failure v1.75 RPL8 Chirag Patel Classified gene: RPL8 as Amber List (moderate evidence)
Bone Marrow Failure v1.75 RPL8 Chirag Patel Gene: rpl8 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.74 RPL8 Chirag Patel gene: RPL8 was added
gene: RPL8 was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: RPL8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL8 were set to PMID: 25424902, 34961992
Phenotypes for gene: RPL8 were set to Diamond-Blackfan anemia MONDO:0015253
Review for gene: RPL8 was set to AMBER
Added comment: 2 unrelated DBA cases with de novo missense variants, and functional studies in lymphoblastoid cells and yeast models demonstrate the 2 missense variants are functionally deficient proteins that affect ribosome production.
Sources: Literature
Bone Marrow Failure v1.73 RPL18 Chirag Patel Classified gene: RPL18 as Amber List (moderate evidence)
Bone Marrow Failure v1.73 RPL18 Chirag Patel Gene: rpl18 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.72 RPL18 Chirag Patel gene: RPL18 was added
gene: RPL18 was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: RPL18 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL18 were set to PMID: 28280134, 32075953
Phenotypes for gene: RPL18 were set to Diamond-Blackfan anemia 18, MIM# 618310
Review for gene: RPL18 was set to AMBER
Added comment: One family and a zebrafish model.
Sources: Expert list
Defects of intrinsic and innate immunity v0.132 MAP1LC3B2 Sangavi Sivagnanasundram gene: MAP1LC3B2 was added
gene: MAP1LC3B2 was added to Defects of innate immunity. Sources: Other
Mode of inheritance for gene: MAP1LC3B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP1LC3B2 were set to 35748970; 33310865
Phenotypes for gene: MAP1LC3B2 were set to Mollaretā€™s meningitis (recurrent lymphocytic meningitis) due to HSV2
Review for gene: MAP1LC3B2 was set to RED
Added comment: Reviewed from PMID: 35748970

No published gene-disease association as of yet.

Affects CNS (resident cells and fibroblasts)
Impaired autophagy induction after HSV2 infection - increased viral replication and apoptosis of patient fibroblasts.

PMID: 33310865
one affected individual with heterozygous mutation in MAP1LC3B2 (p.L109M)
Sources: Other
Bone Marrow Failure v1.71 TBXAS1 Chirag Patel Classified gene: TBXAS1 as Green List (high evidence)
Bone Marrow Failure v1.71 TBXAS1 Chirag Patel Gene: tbxas1 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.70 TBXAS1 Chirag Patel gene: TBXAS1 was added
gene: TBXAS1 was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: TBXAS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBXAS1 were set to PMID: 18264100
Phenotypes for gene: TBXAS1 were set to Ghosal hematodiaphyseal syndrome, MIM#231095
Review for gene: TBXAS1 was set to GREEN
gene: TBXAS1 was marked as current diagnostic
Added comment: Ghosal hematodiaphyseal dysplasia (GHDD) is an autosomal recessive disorder characterized by increased bone density with predominant diaphyseal involvement and aregenerative corticosteroid-sensitive anemia. Cases with severe anemia, leukopenia, thrombocytopenia, and hypocellular bone marrow.
Sources: Expert list
Bone Marrow Failure v1.69 DNASE2 Chirag Patel Classified gene: DNASE2 as Green List (high evidence)
Bone Marrow Failure v1.69 DNASE2 Chirag Patel Gene: dnase2 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.68 DNASE2 Chirag Patel gene: DNASE2 was added
gene: DNASE2 was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: DNASE2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNASE2 were set to PMID: 29259162, 31775019
Phenotypes for gene: DNASE2 were set to Autoinflammatory-pancytopenia syndrome, MIM#619858
Review for gene: DNASE2 was set to GREEN
gene: DNASE2 was marked as current diagnostic
Added comment: Autoinflammatory-pancytopenia syndrome (AIPCS) is an autosomal recessive disorder characterized by severe anemia and thrombocytopenia apparent from early infancy, hepatosplenomegaly, and recurrent fevers associated with a hyperinflammatory state. Additional systemic features may include chronic diarrhea, proteinuria with renal disease, liver fibrosis with elevated liver enzymes, deforming arthropathy, and vasculitic skin lesions. Some patients may have motor delay or learning difficulties associated with subcortical white matter lesions on brain imaging.
Sources: Expert list
Bone Marrow Failure v1.67 MPIG6B Chirag Patel Classified gene: MPIG6B as Green List (high evidence)
Bone Marrow Failure v1.67 MPIG6B Chirag Patel Gene: mpig6b has been classified as Green List (High Evidence).
Bone Marrow Failure v1.66 MPIG6B Chirag Patel gene: MPIG6B was added
gene: MPIG6B was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: MPIG6B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPIG6B were set to PMID: 31276734, 29898956, 27743390
Phenotypes for gene: MPIG6B were set to Thrombocytopenia, anemia, and myelofibrosis, MIM# 617441
Review for gene: MPIG6B was set to GREEN
gene: MPIG6B was marked as current diagnostic
Added comment: Six families reported.
Sources: Expert list
Bone Marrow Failure v1.65 ACTB Chirag Patel Classified gene: ACTB as Green List (high evidence)
Bone Marrow Failure v1.65 ACTB Chirag Patel Gene: actb has been classified as Green List (High Evidence).
Bone Marrow Failure v1.64 ACTB Chirag Patel gene: ACTB was added
gene: ACTB was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: ACTB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACTB were set to PMID: 30315159
Phenotypes for gene: ACTB were set to Thrombocytopenia 8, with dysmorphic features and developmental delay, MIM# 620475
Review for gene: ACTB was set to GREEN
gene: ACTB was marked as current diagnostic
Added comment: Six unrelated individuals reported with heterozygous variants clustered in the 3'-coding region of ACTB (exons 5 and 6) and clinical features distinct from BWCFF, including mild developmental disability, microcephaly, and thrombocytopenia with platelet anisotropy.
Sources: Expert list
Disorders of immune dysregulation v0.184 ELF4 Sangavi Sivagnanasundram gene: ELF4 was added
gene: ELF4 was added to Disorders of immune dysregulation. Sources: Other
Mode of inheritance for gene: ELF4 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ELF4 were set to 34326534, 35266071; 35748970
Phenotypes for gene: ELF4 were set to Autoinflammatory syndrome, familial, X-linked, Behcet-like 2 (MIM#301074)
Review for gene: ELF4 was set to GREEN
Added comment: Reviewed according to PMID: 35748970

AIFBL2 is characterised by the onset of inflammatory symptoms in the first decade of life in males. Typically present with oral mucosal ulceration and skin inflammation however can present with decreased NK cells and low memory B cells.
Individuals typical have normal levels of serum IgM, G, A but reduced responses to live viral vaccines

Hemizygous mutations reported in at least 3 unrelated affected males with an autoinflammatory condition
Sources: Other
Bone Marrow Failure v1.63 TCN2 Chirag Patel Classified gene: TCN2 as Green List (high evidence)
Bone Marrow Failure v1.63 TCN2 Chirag Patel Gene: tcn2 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.63 TCN2 Chirag Patel Classified gene: TCN2 as Green List (high evidence)
Bone Marrow Failure v1.63 TCN2 Chirag Patel Gene: tcn2 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.62 TCN2 Chirag Patel gene: TCN2 was added
gene: TCN2 was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: TCN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TCN2 were set to PMID: 24305960, 7980584, 7849710, 20352340, 18956254, 32841161, 33023511, 30124850
Phenotypes for gene: TCN2 were set to Transcobalamin II deficiency, MIM#275350
Review for gene: TCN2 was set to GREEN
gene: TCN2 was marked as current diagnostic
Added comment: 26 pathogenic TCN2 variants have been reported in over 40 individuals; Bi-allelic (deletions, insertions, nonsense, mutations) variants have been reported; multiple mouse models

Transcobalamin II deficiency is characterised by early onset (infancy) failure to thrive, megaloblastic anaemia, immunodeficiency and pancytopaenia. Other features include methylmalonic aciduria, recurrent infections, hypogammaglobulinaemia, pallor, hypotonia and vomiting and diarrhoea. Treatment with cobalamin (B12) may be of clinical benefit, but left untreated may result in intellectual disability and neurologic abnormalities.
Sources: Expert list
Bone Marrow Failure v1.61 NBN Chirag Patel Classified gene: NBN as Green List (high evidence)
Bone Marrow Failure v1.61 NBN Chirag Patel Gene: nbn has been classified as Green List (High Evidence).
Bone Marrow Failure v1.60 NBN Chirag Patel gene: NBN was added
gene: NBN was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: NBN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NBN were set to PMID: 11325820, 15338273, 33488600, 33082212
Phenotypes for gene: NBN were set to Nijmegen breakage syndrome, MIM#251260; Aplastic anemia, MIM#609135; Leukemia, acute lymphoblastic, MIM#613065
Review for gene: NBN was set to GREEN
gene: NBN was marked as current diagnostic
Added comment: The Nijmegen breakage syndrome and the phenotypically indistinguishable Berlin breakage syndrome are autosomal recessive chromosomal instability syndromes characterized by microcephaly, growth retardation, immunodeficiency, and predisposition to cancer. >100 patients reported.
Sources: Expert list
Autoinflammatory Disorders v1.30 RNU7-1 Sangavi Sivagnanasundram gene: RNU7-1 was added
gene: RNU7-1 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Other
Mode of inheritance for gene: RNU7-1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU7-1 were set to 33230297; 35748970
Phenotypes for gene: RNU7-1 were set to Aicardi-Goutieres syndrome 9 (MIM#619487)
Review for gene: RNU7-1 was set to GREEN
Added comment: Reviewed from PMID: 35748970

Aicardi-Goutieres syndrome 9 (AGS9) is a type I interferonopathy typically caused by compound heterozygous mutations in RNU7-1

PubMed: 33230297
16 individuals from 11 families with AGS - all affected individuals had typical clinical features of AGS (elevated interferon score).
RT-PCR functional assay on patient and control fibroblasts were conducted that showed a loss of function mechanism of disease.
Sources: Other
Genetic Epilepsy v0.2028 NDUFV2 Lauren Rogers reviewed gene: NDUFV2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 7 - MIM#618229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2028 NDUFA8 Lauren Rogers reviewed gene: NDUFA8: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 37 - 619272, Epilepsy, Microcephaly, Developmental Delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2028 NAT8L Lauren Rogers reviewed gene: NAT8L: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: N-acetylaspartate deficiency - MIM#614063; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2028 OSTC Lauren Rogers reviewed gene: OSTC: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Oligosaccharyltransferase complex-congenital disorders of glycosylation; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2028 STX1A Zornitza Stark Publications for gene: STX1A were set to
Genetic Epilepsy v0.2027 ATP5E Zornitza Stark Marked gene: ATP5E as ready
Genetic Epilepsy v0.2027 ATP5E Zornitza Stark Gene: atp5e has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2027 ATP5E Zornitza Stark Classified gene: ATP5E as Amber List (moderate evidence)
Genetic Epilepsy v0.2027 ATP5E Zornitza Stark Gene: atp5e has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2026 ATP5G3 Zornitza Stark Marked gene: ATP5G3 as ready
Genetic Epilepsy v0.2026 ATP5G3 Zornitza Stark Gene: atp5g3 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2026 ATP5G3 Zornitza Stark Classified gene: ATP5G3 as Red List (low evidence)
Genetic Epilepsy v0.2026 ATP5G3 Zornitza Stark Gene: atp5g3 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2025 ATP5G3 Zornitza Stark edited their review of gene: ATP5G3: Changed publications: 34954817
Genetic Epilepsy v0.2025 ATP5G3 Zornitza Stark reviewed gene: ATP5G3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia, early-onset, and/or spastic paraplegia MIM#619681; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2025 ATP5O Zornitza Stark Tag new gene name tag was added to gene: ATP5O.
Genetic Epilepsy v0.2025 AUTS2 Zornitza Stark Marked gene: AUTS2 as ready
Genetic Epilepsy v0.2025 AUTS2 Zornitza Stark Gene: auts2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2025 AUTS2 Zornitza Stark Classified gene: AUTS2 as Red List (low evidence)
Genetic Epilepsy v0.2025 AUTS2 Zornitza Stark Gene: auts2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2024 SYNCRIP Zornitza Stark Phenotypes for gene: SYNCRIP were changed from Global developmental delay; Intellectual disability; Autism; Myoclonic atonic seizures; Abnormality of nervous system morphology to Neurodevelopmental disorder, MONDO:0700092, SYNCRIP-related; Global developmental delay; Intellectual disability; Autism; Myoclonic atonic seizures; Abnormality of nervous system morphology
Genetic Epilepsy v0.2023 CPT1A Zornitza Stark Publications for gene: CPT1A were set to 12189492; 33565078
Genetic Epilepsy v0.2022 CPT1A Zornitza Stark Classified gene: CPT1A as Green List (high evidence)
Genetic Epilepsy v0.2022 CPT1A Zornitza Stark Gene: cpt1a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2021 CWF19L1 Zornitza Stark Publications for gene: CWF19L1 were set to 33012273
Genetic Epilepsy v0.2020 CWF19L1 Zornitza Stark Classified gene: CWF19L1 as Green List (high evidence)
Genetic Epilepsy v0.2020 CWF19L1 Zornitza Stark Gene: cwf19l1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2019 CWF19L1 Andrew Fennell reviewed gene: CWF19L1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36453471, 37752213; Phenotypes: Spinocerebellar ataxia, autosomal recessive 17, MIM# 616127; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2019 CPT1A Andrew Fennell reviewed gene: CPT1A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34869124, 20696606; Phenotypes: CPT deficiency, hepatic, type IA, MIM# 255120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2019 TCEAL1 Belinda Chong reviewed gene: TCEAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 36368327; Phenotypes: Neurodevelopmental disorder with gait disturbance, dysmorphic facies and behavioral abnormalities, X-linked, MIM# 301094; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2019 SYNCRIP Belinda Chong reviewed gene: SYNCRIP: Rating: AMBER; Mode of pathogenicity: None; Publications: 34157790, 30504930, 27479843, 23020937; Phenotypes: Global developmental delay, Intellectual disability, Autism, Myoclonic atonic seizures, Abnormality of nervous system morphology; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2019 SV2B Belinda Chong reviewed gene: SV2B: Rating: RED; Mode of pathogenicity: None; Publications: 23617838, 23937191; Phenotypes: seizures; Mode of inheritance: Unknown
Genetic Epilepsy v0.2019 AUTS2 Lilian Downie gene: AUTS2 was added
gene: AUTS2 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: AUTS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AUTS2 were set to PMID: 34573342, PMID: 33346930, PMID: 27075013, PMID: 23332918, PMID: 12160723
Phenotypes for gene: AUTS2 were set to Intellectual developmental disorder, autosomal dominant 26 MIM#615834
Review for gene: AUTS2 was set to RED
Added comment: PMID: 33346930 1 patient with epilepsy
PMID: 12160723 gene discovery paper with twins epilepsy was a feature as per description in PMID: 23332918 but the actual paper doesn't describe seizures.
Seizures are not part of the phenotype in the other reported cases.
Sources: Expert list
Genetic Epilepsy v0.2019 ATP5O Lilian Downie reviewed gene: ATP5O: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35621276, 34954817; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7, MIM# 620359; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2019 ATP5G3 Lilian Downie gene: ATP5G3 was added
gene: ATP5G3 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: ATP5G3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP5G3 were set to PMIDS: 34636445, 34954817
Phenotypes for gene: ATP5G3 were set to Dystonia, early-onset, and/or spastic paraplegia MIM#619681
Review for gene: ATP5G3 was set to RED
Added comment: Reviewed for epilepsy gene list review - no new evidence for seizures as part of this dystonia phenotype
Sources: Expert list
Genetic Epilepsy v0.2019 ATP5E Lilian Downie gene: ATP5E was added
gene: ATP5E was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: ATP5E was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP5E were set to PMID: 34954817, PMID: 22231385
Phenotypes for gene: ATP5E were set to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3 MIM#614053
Review for gene: ATP5E was set to AMBER
Added comment: Reviewed as included on the review list for genetic epilepsy
2/3 patients had seizures in the paper PMID 34954817
1 type not specified, the 2nd GTCS
1 patient in PMID: 22231385, no seizures
no new evidence
Sources: Expert list
Genetic Epilepsy v0.2019 ATP5A1 Lilian Downie reviewed gene: ATP5A1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 34954817; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4A MIM#620358; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2019 STX1A Belinda Chong reviewed gene: STX1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 37029317, 36564538; Phenotypes: Neurodevelopmental disorder MONDO#0700092, STX1A-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2019 SPEN Belinda Chong reviewed gene: SPEN: Rating: AMBER; Mode of pathogenicity: None; Publications: 33596411; Phenotypes: Radio-Tartaglia syndrome MIM#619312; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.5649 CAPRIN1 Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636 to Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Intellectual disability syndromic and non-syndromic v0.5648 CAPRIN1 Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092 to Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Intellectual disability syndromic and non-syndromic v0.5648 CAPRIN1 Zornitza Stark Publications for gene: CAPRIN1 were set to 35979925; 35977029; 28135719; 31398340
Intellectual disability syndromic and non-syndromic v0.5647 CAPRIN1 Zornitza Stark reviewed gene: CAPRIN1: Rating: AMBER; Mode of pathogenicity: None; Publications: 36136249; Phenotypes: Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1435 CAPRIN1 Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636 to Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Mendeliome v1.1434 CAPRIN1 Zornitza Stark Publications for gene: CAPRIN1 were set to 35979925
Mendeliome v1.1433 CAPRIN1 Zornitza Stark edited their review of gene: CAPRIN1: Added comment: Two individuals reported with the same de novo c.1535C > T (p.Pro512Leu) variant and a progressive course.; Changed rating: AMBER; Changed publications: 36136249
Regression v0.535 CAPRIN1 Zornitza Stark Marked gene: CAPRIN1 as ready
Regression v0.535 CAPRIN1 Zornitza Stark Gene: caprin1 has been classified as Amber List (Moderate Evidence).
Regression v0.535 CAPRIN1 Zornitza Stark Classified gene: CAPRIN1 as Amber List (moderate evidence)
Regression v0.535 CAPRIN1 Zornitza Stark Gene: caprin1 has been classified as Amber List (Moderate Evidence).
Regression v0.534 CAPRIN1 Zornitza Stark edited their review of gene: CAPRIN1: Changed rating: AMBER
Regression v0.534 CAPRIN1 Zornitza Stark gene: CAPRIN1 was added
gene: CAPRIN1 was added to Regression. Sources: Expert Review
Mode of inheritance for gene: CAPRIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAPRIN1 were set to 36136249
Phenotypes for gene: CAPRIN1 were set to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Review for gene: CAPRIN1 was set to GREEN
Added comment: Two individuals reported with the same de novo c.1535C > T (p.Pro512Leu) variant and a progressive course with onset in childhood.

Another 12 individuals reported in previous publications with ID/SZ.
Sources: Expert Review
Genetic Epilepsy v0.2019 CAPRIN1 Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636 to Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Genetic Epilepsy v0.2018 CAPRIN1 Zornitza Stark edited their review of gene: CAPRIN1: Added comment: Two individuals reported with the same de novo c.1535C > T (p.Pro512Leu) variant and a progressive course.; Changed publications: 36136249
Genetic Epilepsy v0.2018 CAPRIN1 Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636 to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Genetic Epilepsy v0.2018 CAPRIN1 Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092 to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Genetic Epilepsy v0.2017 CAPRIN1 Zornitza Stark reviewed gene: CAPRIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1433 CAPRIN1 Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092 to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Mendeliome v1.1432 CAPRIN1 Zornitza Stark reviewed gene: CAPRIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliary Dyskinesia v1.37 NME5 Achchuthan Shanmugasundram reviewed gene: NME5: Rating: GREEN; Mode of pathogenicity: None; Publications: 37957793; Phenotypes: Ciliary dyskinesia, primary, 48, without situs inversus, OMIM:620032; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5647 MANF Zornitza Stark Marked gene: MANF as ready
Intellectual disability syndromic and non-syndromic v0.5647 MANF Zornitza Stark Gene: manf has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5647 MANF Zornitza Stark Classified gene: MANF as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5647 MANF Zornitza Stark Gene: manf has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5646 MANF Zornitza Stark gene: MANF was added
gene: MANF was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: MANF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MANF were set to 26077850; 33500254; 34815294
Phenotypes for gene: MANF were set to Diabetes, deafness, developmental delay, and short stature syndrome, MIM# 620651
Review for gene: MANF was set to AMBER
Added comment: Two individuals reported with homozygous variants. Mouse model recapitulates deafness phenotype.
Sources: Expert Review
Monogenic Diabetes v0.43 MANF Zornitza Stark Marked gene: MANF as ready
Monogenic Diabetes v0.43 MANF Zornitza Stark Gene: manf has been classified as Amber List (Moderate Evidence).
Monogenic Diabetes v0.43 MANF Zornitza Stark Classified gene: MANF as Amber List (moderate evidence)
Monogenic Diabetes v0.43 MANF Zornitza Stark Gene: manf has been classified as Amber List (Moderate Evidence).
Monogenic Diabetes v0.42 MANF Zornitza Stark gene: MANF was added
gene: MANF was added to Monogenic Diabetes. Sources: Expert Review
Mode of inheritance for gene: MANF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MANF were set to 26077850; 33500254; 34815294
Phenotypes for gene: MANF were set to Diabetes, deafness, developmental delay, and short stature syndrome, MIM# 620651
Review for gene: MANF was set to AMBER
Added comment: Two individuals reported with homozygous variants. Mouse model recapitulates deafness phenotype.
Sources: Expert Review
Deafness_IsolatedAndComplex v1.168 MANF Zornitza Stark Marked gene: MANF as ready
Deafness_IsolatedAndComplex v1.168 MANF Zornitza Stark Gene: manf has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.168 MANF Zornitza Stark Classified gene: MANF as Amber List (moderate evidence)
Deafness_IsolatedAndComplex v1.168 MANF Zornitza Stark Gene: manf has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.167 MANF Zornitza Stark gene: MANF was added
gene: MANF was added to Deafness_IsolatedAndComplex. Sources: Expert Review
Mode of inheritance for gene: MANF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MANF were set to 26077850; 33500254; 34815294
Phenotypes for gene: MANF were set to Diabetes, deafness, developmental delay, and short stature syndrome, MIM# 620651
Review for gene: MANF was set to AMBER
Added comment: Two individuals reported with homozygous variants. Mouse model recapitulates deafness phenotype.
Sources: Expert Review
Mendeliome v1.1432 MANF Zornitza Stark Marked gene: MANF as ready
Mendeliome v1.1432 MANF Zornitza Stark Gene: manf has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1432 MANF Zornitza Stark Classified gene: MANF as Amber List (moderate evidence)
Mendeliome v1.1432 MANF Zornitza Stark Gene: manf has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1431 MANF Zornitza Stark gene: MANF was added
gene: MANF was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: MANF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MANF were set to 26077850; 33500254; 34815294
Phenotypes for gene: MANF were set to Diabetes, deafness, developmental delay, and short stature syndrome, MIM# 620651
Review for gene: MANF was set to AMBER
Added comment: Two individuals reported with homozygous variants. Mouse model recapitulates deafness phenotype.
Sources: Expert Review
Mendeliome v1.1430 RRM1 Zornitza Stark Phenotypes for gene: RRM1 were changed from Multiple mitochondrial DNA deletion syndrome (MONDO:0016797) to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 6, MIM# 620647
Mitochondrial disease v0.906 RRM1 Zornitza Stark Phenotypes for gene: RRM1 were changed from Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 6, MIM# 620647 to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 6, MIM# 620647
Mitochondrial disease v0.905 RRM1 Zornitza Stark Phenotypes for gene: RRM1 were changed from Multiple mitochondrial DNA deletion syndrome (MONDO:0016797) to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 6, MIM# 620647
Fetal anomalies v1.172 DRG1 Zornitza Stark Phenotypes for gene: DRG1 were changed from Neurodevelopmental disorder (MONDO:0700092), DRG1-related to Tan-Almurshedi syndrome, MIM# 620641
Growth failure v1.72 DRG1 Zornitza Stark Phenotypes for gene: DRG1 were changed from Neurodevelopmental disorder (MONDO:0700092), DRG1-related to Tan-Almurshedi syndrome, MIM# 620641
Intellectual disability syndromic and non-syndromic v0.5645 DRG1 Zornitza Stark Phenotypes for gene: DRG1 were changed from Neurodevelopmental disorder (MONDO:0700092), DRG1-related to Tan-Almurshedi syndrome, MIM# 620641
Microcephaly v1.243 DRG1 Zornitza Stark Phenotypes for gene: DRG1 were changed from Neurodevelopmental disorder (MONDO:0700092), DRG1-related to Tan-Almurshedi syndrome, MIM# 620641
Mendeliome v1.1429 DRG1 Zornitza Stark Phenotypes for gene: DRG1 were changed from Neurodevelopmental disorder (MONDO:0700092), DRG1-related to Tan-Almurshedi syndrome, MIM# 620641
Mitochondrial disease v0.904 AMACR Zornitza Stark Marked gene: AMACR as ready
Mitochondrial disease v0.904 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
Mitochondrial disease v0.904 AMACR Zornitza Stark Classified gene: AMACR as Green List (high evidence)
Mitochondrial disease v0.904 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
Mitochondrial disease v0.903 AMACR Zornitza Stark Classified gene: AMACR as Green List (high evidence)
Mitochondrial disease v0.903 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
Mitochondrial disease v0.902 AMACR Zornitza Stark gene: AMACR was added
gene: AMACR was added to Mitochondrial disease. Sources: Expert Review
Mode of inheritance for gene: AMACR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMACR were set to 35641312; 35428665
Phenotypes for gene: AMACR were set to Bile acid synthesis defect, congenital, 4, MIM# 214950; Alpha-methylacyl-CoA racemase deficiency, MIM# 614307
Review for gene: AMACR was set to GREEN
Added comment: Mito disease mimic, repeatedly identified in cohorts of patients undergoing testing for suspected mitochondrial disease.
Sources: Expert Review
Fetal anomalies v1.171 MMP13 Zornitza Stark Classified gene: MMP13 as Red List (low evidence)
Fetal anomalies v1.171 MMP13 Zornitza Stark Gene: mmp13 has been classified as Red List (Low Evidence).
Fetal anomalies v1.170 MMP13 Zornitza Stark reviewed gene: MMP13: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Metaphyseal anadysplasia 1 (MIM#602111), Metaphyseal dysplasia, Spahr type (MIM#250400); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2017 GLI3 Zornitza Stark Marked gene: GLI3 as ready
Genetic Epilepsy v0.2017 GLI3 Zornitza Stark Gene: gli3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2017 GLI3 Zornitza Stark Classified gene: GLI3 as Green List (high evidence)
Genetic Epilepsy v0.2017 GLI3 Zornitza Stark Gene: gli3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2016 GLI3 Zornitza Stark gene: GLI3 was added
gene: GLI3 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: GLI3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GLI3 were set to Pallister-Hall syndrome, MIM# 146510
Review for gene: GLI3 was set to GREEN
Added comment: Seizures in the setting of hypothalamic hamartomas associated with the Pallister-Hall syndrome (PHS) phenotype which is caused by truncating mutations in the middle third of the gene that produce a truncated functional repressor protein.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5644 GCDH Zornitza Stark Marked gene: GCDH as ready
Intellectual disability syndromic and non-syndromic v0.5644 GCDH Zornitza Stark Gene: gcdh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2015 GCDH Zornitza Stark Marked gene: GCDH as ready
Genetic Epilepsy v0.2015 GCDH Zornitza Stark Gene: gcdh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5644 GCDH Zornitza Stark Phenotypes for gene: GCDH were changed from to Glutaric aciduria, type I MIM#231670
Intellectual disability syndromic and non-syndromic v0.5643 GCDH Zornitza Stark Mode of inheritance for gene: GCDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2015 GCDH Zornitza Stark Classified gene: GCDH as Green List (high evidence)
Genetic Epilepsy v0.2015 GCDH Zornitza Stark Gene: gcdh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2014 GCDH Zornitza Stark gene: GCDH was added
gene: GCDH was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: GCDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GCDH were set to 25875215
Phenotypes for gene: GCDH were set to Glutaric aciduria, type I MIM#231670
Review for gene: GCDH was set to GREEN
Added comment: Well established gene-disease association. Seizures present in around 7% of affected individuals.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5642 GCDH Zornitza Stark reviewed gene: GCDH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glutaric aciduria, type I MIM#231670; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2013 GATM Zornitza Stark Marked gene: GATM as ready
Genetic Epilepsy v0.2013 GATM Zornitza Stark Gene: gatm has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2013 GATM Zornitza Stark Classified gene: GATM as Amber List (moderate evidence)
Genetic Epilepsy v0.2013 GATM Zornitza Stark Gene: gatm has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2012 GATM Zornitza Stark gene: GATM was added
gene: GATM was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: GATM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GATM were set to 36856349; 12468279; 20682460; 22386973
Phenotypes for gene: GATM were set to Cerebral creatine deficiency syndrome 3, MIM# 612718
Review for gene: GATM was set to AMBER
Added comment: Seizures described in cerebral creatine disorders in general.
Sources: Expert Review
Mendeliome v1.1428 GABRA4 Zornitza Stark Marked gene: GABRA4 as ready
Mendeliome v1.1428 GABRA4 Zornitza Stark Gene: gabra4 has been classified as Red List (Low Evidence).
Mendeliome v1.1428 GABRA4 Zornitza Stark gene: GABRA4 was added
gene: GABRA4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GABRA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRA4 were set to 35152403
Phenotypes for gene: GABRA4 were set to Developmental and epileptic encephalopathy MONDO:0100062, GABRA4-related
Review for gene: GABRA4 was set to RED
Added comment: Single individual with de novo missense variant reported, supportive functional data.
Sources: Literature
Genetic Epilepsy v0.2011 GABRA4 Zornitza Stark Marked gene: GABRA4 as ready
Genetic Epilepsy v0.2011 GABRA4 Zornitza Stark Gene: gabra4 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2011 GABRA4 Zornitza Stark gene: GABRA4 was added
gene: GABRA4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: GABRA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRA4 were set to 35152403
Phenotypes for gene: GABRA4 were set to Developmental and epileptic encephalopathy MONDO:0100062, GABRA4-related
Review for gene: GABRA4 was set to RED
Added comment: Single individual with de novo missense variant reported, supportive functional data.
Sources: Literature
Genetic Epilepsy v0.2010 FRA10AC1 Zornitza Stark Classified gene: FRA10AC1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2010 FRA10AC1 Zornitza Stark Gene: fra10ac1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2009 FRA10AC1 Zornitza Stark Marked gene: FRA10AC1 as ready
Genetic Epilepsy v0.2009 FRA10AC1 Zornitza Stark Gene: fra10ac1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2009 FRA10AC1 Zornitza Stark Classified gene: FRA10AC1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2009 FRA10AC1 Zornitza Stark Gene: fra10ac1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2008 FRA10AC1 Zornitza Stark gene: FRA10AC1 was added
gene: FRA10AC1 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: FRA10AC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRA10AC1 were set to 34694367; 35871492; 35821753
Phenotypes for gene: FRA10AC1 were set to Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities, MIM# 620113
Review for gene: FRA10AC1 was set to AMBER
Added comment: 6 families reported, 10 individuals with neurodevelopmental phenotype. 2 had seizures.
Sources: Expert Review
Hereditary Neuropathy v1.7 PLA2G16 Zornitza Stark Marked gene: PLA2G16 as ready
Hereditary Neuropathy v1.7 PLA2G16 Zornitza Stark Added comment: Comment when marking as ready: HGNC name is PLAAT3
Hereditary Neuropathy v1.7 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Hereditary Neuropathy v1.7 PLA2G16 Zornitza Stark Tag new gene name tag was added to gene: PLA2G16.
Intellectual disability syndromic and non-syndromic v0.5642 PLA2G16 Zornitza Stark Marked gene: PLA2G16 as ready
Intellectual disability syndromic and non-syndromic v0.5642 PLA2G16 Zornitza Stark Added comment: Comment when marking as ready: HGNC name is PLAAT3
Intellectual disability syndromic and non-syndromic v0.5642 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5642 PLA2G16 Zornitza Stark Tag new gene name tag was added to gene: PLA2G16.
Mendeliome v1.1427 PLA2G16 Zornitza Stark Marked gene: PLA2G16 as ready
Mendeliome v1.1427 PLA2G16 Zornitza Stark Added comment: Comment when marking as ready: HGNC name is PLAAT3
Mendeliome v1.1427 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Mendeliome v1.1427 PLA2G16 Zornitza Stark Tag new gene name tag was added to gene: PLA2G16.
Lipodystrophy_Lipoatrophy v1.12 PLA2G16 Zornitza Stark Marked gene: PLA2G16 as ready
Lipodystrophy_Lipoatrophy v1.12 PLA2G16 Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name is PLAAT3
Lipodystrophy_Lipoatrophy v1.12 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Lipodystrophy_Lipoatrophy v1.12 PLA2G16 Zornitza Stark Tag new gene name tag was added to gene: PLA2G16.
Deafness_IsolatedAndComplex v1.166 FOXL1 Zornitza Stark Marked gene: FOXL1 as ready
Deafness_IsolatedAndComplex v1.166 FOXL1 Zornitza Stark Gene: foxl1 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.166 FOXL1 Zornitza Stark Classified gene: FOXL1 as Red List (low evidence)
Deafness_IsolatedAndComplex v1.166 FOXL1 Zornitza Stark Gene: foxl1 has been classified as Red List (Low Evidence).
Mendeliome v1.1427 FOXL1 Zornitza Stark Marked gene: FOXL1 as ready
Mendeliome v1.1427 FOXL1 Zornitza Stark Gene: foxl1 has been classified as Red List (Low Evidence).
Mendeliome v1.1427 FOXL1 Zornitza Stark Classified gene: FOXL1 as Red List (low evidence)
Mendeliome v1.1427 FOXL1 Zornitza Stark Gene: foxl1 has been classified as Red List (Low Evidence).
Mitochondrial disease v0.901 RANBP2 Zornitza Stark Marked gene: RANBP2 as ready
Mitochondrial disease v0.901 RANBP2 Zornitza Stark Gene: ranbp2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2007 RBFOX1 Dean Phelan gene: RBFOX1 was added
gene: RBFOX1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RBFOX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBFOX1 were set to PMID: 37962958
Phenotypes for gene: RBFOX1 were set to Neurodevelopmental disorder (MONDO:0700092), RBFOX1-related
Review for gene: RBFOX1 was set to GREEN
Added comment: PMID: 37962958
De novo missense variants identified in six unrelated patients with neurodevelopmental disorder and severe seizures.
Sources: Literature
Mendeliome v1.1426 RBFOX1 Dean Phelan reviewed gene: RBFOX1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37962958; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), RBFOX1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mitochondrial disease v0.901 RANBP2 Zornitza Stark Classified gene: RANBP2 as Green List (high evidence)
Mitochondrial disease v0.901 RANBP2 Zornitza Stark Gene: ranbp2 has been classified as Green List (High Evidence).
Mitochondrial disease v0.900 RANBP2 Zornitza Stark gene: RANBP2 was added
gene: RANBP2 was added to Mitochondrial disease. Sources: Expert Review
Mode of inheritance for gene: RANBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RANBP2 were set to {Encephalopathy, acute, infection-induced, 3, susceptibility to} MIM#608033
Review for gene: RANBP2 was set to GREEN
Added comment: Not a mitochondrial condition, but significant overlap in clinical presentation, described as Leigh-like previously.
Sources: Expert Review
Mendeliome v1.1426 MGP Zornitza Stark Phenotypes for gene: MGP were changed from Keutel syndrome, MIM #245150 to Keutel syndrome, MIM #245150; Skeletal dysplasia MONDO:0018230, MGP-related
Mendeliome v1.1425 MGP Zornitza Stark Publications for gene: MGP were set to 9916809; 15810001; 33996798
Mendeliome v1.1424 MGP Zornitza Stark Mode of inheritance for gene: MGP was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1423 KIF5B Zornitza Stark Phenotypes for gene: KIF5B were changed from Skeletal dysplasia, MONDO:0018230, KIF5B-related; Kyphomelic dysplasia to osteogenesis imperfecta, MONDO:0019019; Skeletal dysplasia, MONDO:0018230, KIF5B-related; Kyphomelic dysplasia
Mendeliome v1.1422 KIF5B Zornitza Stark Publications for gene: KIF5B were set to PMID: 35342932; 36018820
Mendeliome v1.1421 KIF5B Zornitza Stark edited their review of gene: KIF5B: Added comment: Four additional patients with three distinct de-novo missense variants and features consistent with osteogenesis imperfecta. All variants are in the Kinesin motor domain (~50% of the protein). Functional data in C. Elegans and cell lines shows impaired protein function. Not clear what distinguishes OI causing variants from other phenotypes for this gene at this stage. Dominant negative effect proposed but not conclusively proven.; Changed publications: 37934770; Changed phenotypes: Skeletal dysplasia, MONDO:0018230, osteogenesis imperfecta, MONDO:0019019
Intellectual disability syndromic and non-syndromic v0.5642 PRPF19 Zornitza Stark Marked gene: PRPF19 as ready
Intellectual disability syndromic and non-syndromic v0.5642 PRPF19 Zornitza Stark Gene: prpf19 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5642 PRPF19 Zornitza Stark Classified gene: PRPF19 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5642 PRPF19 Zornitza Stark Gene: prpf19 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5641 PRPF19 Zornitza Stark gene: PRPF19 was added
gene: PRPF19 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PRPF19 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRPF19 were set to 37962958
Phenotypes for gene: PRPF19 were set to Neurodevelopmental disorder (MONDO:0700092), PRPF19-related
Review for gene: PRPF19 was set to GREEN
Added comment: PMID: 37962958 Six unrelated individuals with de novo variants. Five had speech language motor delay, four had formal diagnosis of autism, three hypotonia and one fetus with multiple congenital abnormalities.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5641 PRPF19 Zornitza Stark gene: PRPF19 was added
gene: PRPF19 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PRPF19 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRPF19 were set to 37962958
Phenotypes for gene: PRPF19 were set to Neurodevelopmental disorder (MONDO:0700092), PRPF19-related
Review for gene: PRPF19 was set to GREEN
Added comment: PMID: 37962958 Six unrelated individuals with de novo variants. Five had speech language motor delay, four had formal diagnosis of autism, three hypotonia and one fetus with multiple congenital abnormalities.
Sources: Literature
Mendeliome v1.1421 PRPF19 Zornitza Stark Marked gene: PRPF19 as ready
Mendeliome v1.1421 PRPF19 Zornitza Stark Gene: prpf19 has been classified as Green List (High Evidence).
Mendeliome v1.1421 PRPF19 Zornitza Stark Classified gene: PRPF19 as Green List (high evidence)
Mendeliome v1.1421 PRPF19 Zornitza Stark Gene: prpf19 has been classified as Green List (High Evidence).
Fetal anomalies v1.170 WBP4 Zornitza Stark Marked gene: WBP4 as ready
Fetal anomalies v1.170 WBP4 Zornitza Stark Gene: wbp4 has been classified as Green List (High Evidence).
Fetal anomalies v1.170 WBP4 Zornitza Stark Classified gene: WBP4 as Green List (high evidence)
Fetal anomalies v1.170 WBP4 Zornitza Stark Gene: wbp4 has been classified as Green List (High Evidence).
Callosome v0.510 WBP4 Zornitza Stark Marked gene: WBP4 as ready
Callosome v0.510 WBP4 Zornitza Stark Gene: wbp4 has been classified as Green List (High Evidence).
Callosome v0.510 WBP4 Zornitza Stark Classified gene: WBP4 as Green List (high evidence)
Callosome v0.510 WBP4 Zornitza Stark Gene: wbp4 has been classified as Green List (High Evidence).
Growth failure v1.71 WBP4 Zornitza Stark Marked gene: WBP4 as ready
Growth failure v1.71 WBP4 Zornitza Stark Gene: wbp4 has been classified as Green List (High Evidence).
Growth failure v1.71 WBP4 Zornitza Stark Classified gene: WBP4 as Green List (high evidence)
Growth failure v1.71 WBP4 Zornitza Stark Gene: wbp4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5640 PLA2G16 Zornitza Stark Marked gene: PLA2G16 as ready
Intellectual disability syndromic and non-syndromic v0.5640 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5640 PLA2G16 Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573) to Lipodystrophy (MONDO:0006573), PLA2G16-related
Intellectual disability syndromic and non-syndromic v0.5639 PLA2G16 Zornitza Stark Mode of inheritance for gene: PLA2G16 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.176 PKP2 Suliman Khan edited their review of gene: PKP2: Changed phenotypes: Cardiomyopathy, MONDO:0004994, PKP2-related
Intellectual disability syndromic and non-syndromic v0.5638 PLA2G16 Zornitza Stark Classified gene: PLA2G16 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5638 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Mendeliome v1.1420 PLA2G16 Zornitza Stark Marked gene: PLA2G16 as ready
Mendeliome v1.1420 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Mendeliome v1.1420 PLA2G16 Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573) to Lipodystrophy (MONDO:0006573), PLA2G16-related
Hydrops fetalis v0.305 PKP2 Suliman Khan reviewed gene: PKP2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, MONDO:0004994, PKP2-related; Mode of inheritance: None
Mendeliome v1.1419 PLA2G16 Zornitza Stark Mode of inheritance for gene: PLA2G16 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1418 PLA2G16 Zornitza Stark Classified gene: PLA2G16 as Green List (high evidence)
Mendeliome v1.1418 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Lipodystrophy_Lipoatrophy v1.12 PLA2G16 Zornitza Stark Marked gene: PLA2G16 as ready
Lipodystrophy_Lipoatrophy v1.12 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.30 PKP2 Suliman Khan edited their review of gene: PKP2: Changed phenotypes: Cardiomyopathy, MONDO:0004994, PKP2-related
Lipodystrophy_Lipoatrophy v1.12 PLA2G16 Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573) to Lipodystrophy (MONDO:0006573), PLA2G16-related
Lipodystrophy_Lipoatrophy v1.11 PLA2G16 Zornitza Stark Mode of inheritance for gene: PLA2G16 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Lipodystrophy_Lipoatrophy v1.10 PLA2G16 Zornitza Stark Classified gene: PLA2G16 as Green List (high evidence)
Lipodystrophy_Lipoatrophy v1.10 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Hereditary Neuropathy v1.7 PLA2G16 Zornitza Stark Marked gene: PLA2G16 as ready
Hereditary Neuropathy v1.7 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Hereditary Neuropathy v1.7 PLA2G16 Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573) to Lipodystrophy (MONDO:0006573), PLA2G16-related
Hereditary Neuropathy v1.6 PLA2G16 Zornitza Stark Mode of inheritance for gene: PLA2G16 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy v1.5 PLA2G16 Zornitza Stark Classified gene: PLA2G16 as Green List (high evidence)
Hereditary Neuropathy v1.5 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Hydrops fetalis v0.305 PKP2 Zornitza Stark Marked gene: PKP2 as ready
Hydrops fetalis v0.305 PKP2 Zornitza Stark Gene: pkp2 has been classified as Green List (High Evidence).
Hydrops fetalis v0.305 PKP2 Zornitza Stark Classified gene: PKP2 as Green List (high evidence)
Hydrops fetalis v0.305 PKP2 Zornitza Stark Gene: pkp2 has been classified as Green List (High Evidence).
Hydrops fetalis v0.304 PKP2 Zornitza Stark gene: PKP2 was added
gene: PKP2 was added to Hydrops fetalis. Sources: Literature
Mode of inheritance for gene: PKP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PKP2 were set to 30562116; 35059364; 38050058
Phenotypes for gene: PKP2 were set to Dilated cardiomyopathy, MONDO:0005021, PKP2-related
Review for gene: PKP2 was set to GREEN
Added comment: Reports of severe perinatal onset DCM and of HLH, some presenting with hydrops.
Sources: Literature
Fetal anomalies v1.169 PKP2 Zornitza Stark Marked gene: PKP2 as ready
Fetal anomalies v1.169 PKP2 Zornitza Stark Gene: pkp2 has been classified as Green List (High Evidence).
Fetal anomalies v1.169 PKP2 Zornitza Stark Phenotypes for gene: PKP2 were changed from dilated cardiomyopathy; hypoplastic left heart syndrome; hydrops fetalis; ventricular septal defect; left ventricular non-compaction to Dilated cardiomyopathy, MONDO:0005021, PKP2-related; dilated cardiomyopathy; hypoplastic left heart syndrome; hydrops fetalis; ventricular septal defect; left ventricular non-compaction
Fetal anomalies v1.168 PKP2 Zornitza Stark reviewed gene: PKP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dilated cardiomyopathy, MONDO:0005021, PKP2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.176 PKP2 Zornitza Stark Phenotypes for gene: PKP2 were changed from Arrhythmogenic right ventricular dysplasia 9; Arrhythmogenic right ventricular cardiomyopathy to Dilated cardiomyopathy, MONDO:0005021, PKP2-related; Arrhythmogenic right ventricular dysplasia 9; Arrhythmogenic right ventricular cardiomyopathy
Cardiomyopathy_Paediatric v0.175 PKP2 Zornitza Stark reviewed gene: PKP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dilated cardiomyopathy, MONDO:0005021, PKP2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.165 OTOA Zornitza Stark Tag SV/CNV tag was added to gene: OTOA.
Mendeliome v1.1417 OTOA Zornitza Stark Tag SV/CNV tag was added to gene: OTOA.
Mendeliome v1.1417 STRC Zornitza Stark Tag SV/CNV tag was added to gene: STRC.
Incidentalome v0.299 PKP2 Zornitza Stark Phenotypes for gene: PKP2 were changed from Arrhythmogenic right ventricular dysplasia 9, MIM# 609040 to Arrhythmogenic right ventricular dysplasia 9, MIM# 609040; Dilated cardiomyopathy, MONDO:0005021, PKP2-related
Incidentalome v0.298 PKP2 Zornitza Stark Publications for gene: PKP2 were set to 33831308
Incidentalome v0.297 PKP2 Zornitza Stark Mode of inheritance for gene: PKP2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.296 PKP2 Zornitza Stark edited their review of gene: PKP2: Added comment: PMID: 30562116: reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.

PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).

PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome.; Changed publications: 30562116, 35059364, 38050058
Incidentalome v0.296 PKP2 Zornitza Stark edited their review of gene: PKP2: Changed phenotypes: Arrhythmogenic right ventricular dysplasia 9, MIM# 609040, Dilated cardiomyopathy, MONDO:0005021, PKP2-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Dilated Cardiomyopathy v1.30 PKP2 Zornitza Stark Phenotypes for gene: PKP2 were changed from Arrhythmogenic right ventricular dysplasia 9 (MIM#609040); Dilated cardiomyopathy; hypoplastic left heart syndrome; hydrops fetalis; ventricular septal defect; left ventricular non-compaction to Arrhythmogenic right ventricular dysplasia 9 (MIM#609040); Dilated cardiomyopathy, MONDO:0005021, PKP2-related; hypoplastic left heart syndrome; hydrops fetalis; ventricular septal defect; left ventricular non-compaction
Genetic Epilepsy v0.2007 CRELD1 Zornitza Stark Publications for gene: CRELD1 were set to
Mendeliome v1.1417 SLC19A1 Zornitza Stark Phenotypes for gene: SLC19A1 were changed from Megaloblastic anemia, folate-responsive, MIM# 601775 to Megaloblastic anemia, folate-responsive, MIM# 601775; Combined immunodeficiency, SLC19A1-related MONDO:0015131
Red cell disorders v1.23 SLC19A1 Zornitza Stark Publications for gene: SLC19A1 were set to 32276275
Red cell disorders v1.22 SLC19A1 Zornitza Stark edited their review of gene: SLC19A1: Added comment: PMID: 36745868 report two distantly related patients (last common ancestor 5 generations prior) with the same homozygous missense variant, G348R. The variant is absent from gnomAD, although the residue is not conserved in mammals. Both patients experienced severe recurrent infection, neurologic and hematologic disorders, and gastroenteropathy. Functional studies on patient lymphocytes were consistent with reduced transporter activity.

PMID: 36517554 report two cousins with immunodeficiency with the same G348R variant as above. Functional studies on patient cells supported loss of transporter function. The patientā€™s symptoms ameliorated, and hematological and immunological tests normalized in the 2nd month of folinic acid supplementation.

Phenotypes not entirely consistent, homozygous variants.; Changed rating: AMBER; Changed publications: 32276275, 36745868, 36517554; Changed phenotypes: Megaloblastic anemia, folate-responsive, MIM# 601775
Mendeliome v1.1416 RAB1A Zornitza Stark Marked gene: RAB1A as ready
Mendeliome v1.1416 RAB1A Zornitza Stark Gene: rab1a has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1416 RAB1A Zornitza Stark Classified gene: RAB1A as Amber List (moderate evidence)
Mendeliome v1.1416 RAB1A Zornitza Stark Gene: rab1a has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1415 RAB1A Zornitza Stark gene: RAB1A was added
gene: RAB1A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAB1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB1A were set to 37924809
Phenotypes for gene: RAB1A were set to neurodevelopmental disorder MONDO:0700092, RAB1A-related
Review for gene: RAB1A was set to AMBER
Added comment: Four families and 5 individuals, 2/5 have speech delay and 4/5 have motor delay. Anxiety in 3/5 and autism in 2/5. Microcephaly in only one individual, spastic paraplegia observed in 2 individuals from one family. In 2 families variants were inherited from an affected parent.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5637 RAB1A Zornitza Stark Phenotypes for gene: RAB1A were changed from neurodevelopmental disorder MONDO:0700092, CASP2-related to neurodevelopmental disorder MONDO:0700092, RAB1A-related
Intellectual disability syndromic and non-syndromic v0.5636 RAB1A Zornitza Stark Classified gene: RAB1A as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5636 RAB1A Zornitza Stark Gene: rab1a has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1414 CRELD1 Zornitza Stark Publications for gene: CRELD1 were set to 22740159
Genetic Epilepsy v0.2006 FUK Zornitza Stark Classified gene: FUK as Green List (high evidence)
Genetic Epilepsy v0.2006 FUK Zornitza Stark Gene: fuk has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2005 FUK Zornitza Stark edited their review of gene: FUK: Added comment: PMID: 35718084: Reporting on 3 unrelated patients from literature and 1 new patient. All reported to have mild-severe intellectual disability, developmental delay and brain abnormalities, and 3/4 present with seizures. Phenotypes are childhood onset. Homozygous and compound heterozygous variants have been reported.

PMID: 36426412: Reporting on new 1 patient (homozygous missense). Not affected by intellectual disability, developmental delay, or brain abnormalities. Presents with seizures. Loss of function suggested due to depletion of the FUK gene expression.; Changed rating: GREEN; Changed publications: 30503518, 35718084, 36426412
Mendeliome v1.1413 FUK Zornitza Stark Publications for gene: FUK were set to 30503518
Mendeliome v1.1412 FUK Zornitza Stark Classified gene: FUK as Green List (high evidence)
Mendeliome v1.1412 FUK Zornitza Stark Gene: fuk has been classified as Green List (High Evidence).
Mendeliome v1.1411 FUK Zornitza Stark edited their review of gene: FUK: Added comment: PMID: 35718084: Reporting on 3 unrelated patients from literature and 1 new patient. All reported to have mild-severe intellectual disability, developmental delay and brain abnormalities, and 3/4 present with seizures. Phenotypes are childhood onset. Homozygous and compound heterozygous variants have been reported.

PMID: 36426412: Reporting on new 1 patient (homozygous missense). Not affected by intellectual disability, developmental delay, or brain abnormalities. Presents with seizures. Loss of function suggested due to depletion of the FUK gene expression.; Changed rating: GREEN; Changed publications: 30503518, 35718084, 36426412
Congenital Disorders of Glycosylation v1.44 FUK Zornitza Stark Publications for gene: FUK were set to 30503518
Congenital Disorders of Glycosylation v1.43 FUK Zornitza Stark Classified gene: FUK as Green List (high evidence)
Congenital Disorders of Glycosylation v1.43 FUK Zornitza Stark Gene: fuk has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v1.42 FUK Zornitza Stark edited their review of gene: FUK: Added comment: PMID: 35718084: Reporting on 3 unrelated patients from literature and 1 new patient. All reported to have mild-severe intellectual disability, developmental delay and brain abnormalities, and 3/4 present with seizures. Phenotypes are childhood onset. Homozygous and compound heterozygous variants have been reported.

PMID: 36426412: Reporting on new 1 patient (homozygous missense). Not affected by intellectual disability, developmental delay, or brain abnormalities. Presents with seizures. Loss of function suggested due to depletion of the FUK gene expression.; Changed rating: GREEN; Changed publications: 30503518, 35718084, 36426412; Changed phenotypes: Congenital disorder of glycosylation with defective fucosylation 2, MIM# 618324
Intellectual disability syndromic and non-syndromic v0.5635 FUK Zornitza Stark Marked gene: FUK as ready
Intellectual disability syndromic and non-syndromic v0.5635 FUK Zornitza Stark Added comment: Comment when marking as ready: Promoted to Green with the additional cases.
Intellectual disability syndromic and non-syndromic v0.5635 FUK Zornitza Stark Gene: fuk has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5635 FUK Zornitza Stark Publications for gene: FUK were set to 30503518
Intellectual disability syndromic and non-syndromic v0.5634 FUK Zornitza Stark Classified gene: FUK as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5634 FUK Zornitza Stark Gene: fuk has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5633 SV2A Zornitza Stark Marked gene: SV2A as ready
Intellectual disability syndromic and non-syndromic v0.5633 SV2A Zornitza Stark Gene: sv2a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5633 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Epilepsy, MONDO:0005027; microcephaly MONDO:0001149; intellectual disability MONDO:0001071 to Neurodevelopmental disorder, MONDO:0700092, SV2A-related
Intellectual disability syndromic and non-syndromic v0.5632 SV2A Zornitza Stark Classified gene: SV2A as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5632 SV2A Zornitza Stark Gene: sv2a has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2005 SV2A Zornitza Stark Marked gene: SV2A as ready
Genetic Epilepsy v0.2005 SV2A Zornitza Stark Gene: sv2a has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2005 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Epilepsy, MONDO:0005027 to Neurodevelopmental disorder, MONDO:0700092, SV2A-related
Genetic Epilepsy v0.2004 SV2A Zornitza Stark Classified gene: SV2A as Amber List (moderate evidence)
Genetic Epilepsy v0.2004 SV2A Zornitza Stark Gene: sv2a has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1411 SV2A Zornitza Stark Marked gene: SV2A as ready
Mendeliome v1.1411 SV2A Zornitza Stark Gene: sv2a has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1411 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Epilepsy, MONDO:0005027 to Neurodevelopmental disorder, MONDO:0700092, SV2A-related
Mendeliome v1.1410 SV2A Zornitza Stark Classified gene: SV2A as Amber List (moderate evidence)
Mendeliome v1.1410 SV2A Zornitza Stark Gene: sv2a has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1409 SV2A Zornitza Stark changed review comment from: Insufficient evidence for either the mono- or bi-allelic association: two convincing families with each.; to: Insufficient evidence for either the mono- or bi-allelic association: two convincing families with each.
Mendeliome v1.1409 SV2A Zornitza Stark reviewed gene: SV2A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, SV2A-related; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Microcephaly v1.242 SV2A Zornitza Stark Marked gene: SV2A as ready
Microcephaly v1.242 SV2A Zornitza Stark Gene: sv2a has been classified as Amber List (Moderate Evidence).
Microcephaly v1.242 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Epilepsy, MONDO:0005027; microcephaly MONDO:0001149 to Neurodevelopmental disorder, MONDO:0700092, SV2A-related
Microcephaly v1.241 SV2A Zornitza Stark Mode of inheritance for gene: SV2A was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.240 SV2A Zornitza Stark Classified gene: SV2A as Amber List (moderate evidence)
Microcephaly v1.240 SV2A Zornitza Stark Gene: sv2a has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1409 CEP192 Zornitza Stark Marked gene: CEP192 as ready
Mendeliome v1.1409 CEP192 Zornitza Stark Gene: cep192 has been classified as Red List (Low Evidence).
Dilated Cardiomyopathy v1.29 PKP2 Seb Lunke Publications for gene: PKP2 were set to 15489853; 16567567; 30562116; 35059364; 38050058
Dilated Cardiomyopathy v1.29 PKP2 Seb Lunke Publications for gene: PKP2 were set to 15489853; 16567567; 38050058
Dilated Cardiomyopathy v1.28 PKP2 Seb Lunke Mode of inheritance for gene: PKP2 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1409 CEP192 Zornitza Stark Classified gene: CEP192 as Red List (low evidence)
Mendeliome v1.1409 CEP192 Zornitza Stark Gene: cep192 has been classified as Red List (Low Evidence).
Fetal anomalies v1.168 PKP2 Seb Lunke Marked gene: PKP2 as ready
Fetal anomalies v1.168 PKP2 Seb Lunke Gene: pkp2 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.27 PKP2 Seb Lunke Classified gene: PKP2 as Green List (high evidence)
Dilated Cardiomyopathy v1.27 PKP2 Seb Lunke Gene: pkp2 has been classified as Green List (High Evidence).
Microcephaly v1.239 SV2A Karina Sandoval edited their review of gene: SV2A: Added comment: Updated - Only Biallelic causes microcephaly
Monoallelic variants cause epilepsy. Biallelic variant in this 5yo with p.Arg289Ter and another 5yo from another paper with homozygous p.Arg383Gln, reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation.
This paper references 5 other families with both AR & AD
Family #1 ā€“ p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 ā€“ p.Arg570Cys, AD, 2 affected, inherited from affected mother (in gnomAD v2 1 het, absent from gnomAD v3)
Family #3 ā€“ p.Gly660Arg, AD, de novo
Family #4 ā€“ p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) ā€“ p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers; Changed phenotypes: Epilepsy, MONDO:0005027, microcephaly MONDO:0001149, intellectual disability MONDO:0001071; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.175 PKP2 Seb Lunke Marked gene: PKP2 as ready
Cardiomyopathy_Paediatric v0.175 PKP2 Seb Lunke Gene: pkp2 has been classified as Green List (High Evidence).
Mendeliome v1.1408 CEP192 Chern Lim gene: CEP192 was added
gene: CEP192 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CEP192 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CEP192 were set to 37981762
Phenotypes for gene: CEP192 were set to microcephaly, short stature, limb-extremity dysplasia, and reduced testicular size
Review for gene: CEP192 was set to RED
gene: CEP192 was marked as current diagnostic
Added comment: PMID: 37981762:
- In one family, chet missense p.His638Tyr and p.Asn1917Ser segregated with microcephaly, short stature, limb-extremity dysplasia, and reduced testicular size in two affected siblings. Both sibs also fulfilled dx for mosaic variegated aneuploidy (MVA) syndrome and have tetraploidy.
- A lower but substantial proportion of MVA/tetraploidy cells was observed in II-1, II-2, and II-4 (who are het for one of the variants).

- In the same family, each variants in heterozygous state segregated with infertility and/or reduced testicular size in the probandā€™s father and maternal uncle.
- Variant screening of CEP192 coding regions performed for 1264 unrelated males with idiopathic infertility.
- Asn1917Ser was also detected in three additional unrelated infertile males with reduced testicular volumes.
- Two other missense and two synonymous variants were repeatedly detected in infertile males.

- qPCR showed CEP192 expression was decreased in individuals with c.1912C>T His638Tyr, mini-gene assay showed that c.1912C>T His638Tyr led to the skipping of exon 14, predicted to result in NMD.
- Epithelial cells cultured in vitro from patients with biallelic variants showed the number of cells arrested during the prophase increased because of the failure of spindle formation.

- Embyronic mouse lethality in Cep192-/- (hom for His638Tyr), Cep192M/M (hom for Asn1917Ser) and Cep192-/M (chet).
- Embryos of Cep192M/M mice had significant increase of MVA and tetraploidy cells.
- Number of apoptotic cells increased in Cep192M/M embryos compared with that of Cep192+/+, similar result in Cep192-/- embryos.
- Male mice with Cep192 heterozygous variants replicated infertility

Conclusions:
- Association of this gene with autosomal recessive disease has not been established.
- Association of monoallelic variants in this gene with infertility is not well established:
- Two variants with some supportive evidence from mouse model.
Sources: Literature
Microcephaly v1.239 SV2A Karina Sandoval changed review comment from: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo with p.Arg289Ter and another 5yo from another paper with homozygous p.Arg383Gln, reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation.
This paper references 5 other families with both AR & AD
Family #1 ā€“ p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 ā€“ p.Arg570Cys, AD, 2 affected, inherited from affected mother (in gnomAD v2 1 het, absent from gnomAD v3)
Family #3 ā€“ p.Gly660Arg, AD, de novo
Family #4 ā€“ p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) ā€“ p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers
Sources: Literature; to: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo with p.Arg289Ter and another 5yo from another paper with homozygous p.Arg383Gln, reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation.
This paper references 5 other families with both AR & AD
Family #1 ā€“ p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 ā€“ p.Arg570Cys, AD, 2 affected, inherited from affected mother (in gnomAD v2 1 het, absent from gnomAD v3)
Family #3 ā€“ p.Gly660Arg, AD, de novo
Family #4 ā€“ p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) ā€“ p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5631 SV2A Karina Sandoval gene: SV2A was added
gene: SV2A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SV2A was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SV2A were set to PMID: 37985816
Phenotypes for gene: SV2A were set to Epilepsy, MONDO:0005027; microcephaly MONDO:0001149; intellectual disability MONDO:0001071
Review for gene: SV2A was set to AMBER
Added comment: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo with p.Arg289Ter and another 5yo from another paper with homozygous p.Arg383Gln, reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation.
This paper references 5 other families with both AR & AD
Family #1 ā€“ p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 ā€“ p.Arg570Cys, AD, 2 affected, inherited from affected mother (in gnomAD v2 1 het, absent from gnomAD v3)
Family #3 ā€“ p.Gly660Arg, AD, de novo
Family #4 ā€“ p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) ā€“ p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers
Sources: Literature
Mendeliome v1.1408 SV2A Karina Sandoval changed review comment from: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo (Hom p.Arg383Gln) reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation. Consanguineous.
This paper references 5 other families with both AR & AD
Family #1 ā€“ p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 ā€“ p.Arg570Cys, AD, 2 affected, inherited from affected mother (in gnomAD v2 1 het, absent from gnomAD v3)
Family #3 ā€“ p.Gly660Arg, AD, de novo
Family #4 ā€“ p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) ā€“ p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers
Sources: Literature; to: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo with p.Arg289Ter and another 5yo from another paper with homozygous p.Arg383Gln, reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation.
This paper references 5 other families with both AR & AD
Family #1 ā€“ p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 ā€“ p.Arg570Cys, AD, 2 affected, inherited from affected mother (in gnomAD v2 1 het, absent from gnomAD v3)
Family #3 ā€“ p.Gly660Arg, AD, de novo
Family #4 ā€“ p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) ā€“ p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers
Sources: Literature
Genetic Epilepsy v0.2003 SV2A Karina Sandoval changed review comment from: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo (Hom p.Arg383Gln) reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation. Consanguineous.
This paper references 5 other families with both AR & AD
Family #1 ā€“ p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 ā€“ p.Arg570Cys, AD, 2 affected, inherited from affected mother (in gnomAD v2 1 het, absent from gnomAD v3)
Family #3 ā€“ p.Gly660Arg, AD, de novo
Family #4 ā€“ p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) ā€“ p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers
Sources: Literature; to: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo with p.Arg289Ter and another 5yo from another paper with homozygous p.Arg383Gln, reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation.
This paper references 5 other families with both AR & AD
Family #1 ā€“ p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 ā€“ p.Arg570Cys, AD, 2 affected, inherited from affected mother (in gnomAD v2 1 het, absent from gnomAD v3)
Family #3 ā€“ p.Gly660Arg, AD, de novo
Family #4 ā€“ p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) ā€“ p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers
Sources: Literature
Microcephaly v1.239 SV2A Karina Sandoval gene: SV2A was added
gene: SV2A was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SV2A was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SV2A were set to PMID: 37985816
Phenotypes for gene: SV2A were set to Epilepsy, MONDO:0005027; microcephaly MONDO:0001149
Review for gene: SV2A was set to AMBER
Added comment: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo with p.Arg289Ter and another 5yo from another paper with homozygous p.Arg383Gln, reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation.
This paper references 5 other families with both AR & AD
Family #1 ā€“ p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 ā€“ p.Arg570Cys, AD, 2 affected, inherited from affected mother (in gnomAD v2 1 het, absent from gnomAD v3)
Family #3 ā€“ p.Gly660Arg, AD, de novo
Family #4 ā€“ p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) ā€“ p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers
Sources: Literature
Cardiomyopathy_Paediatric v0.175 PKP2 Elena Savva Mode of inheritance for gene: PKP2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Dilated Cardiomyopathy v1.26 PKP2 Elena Savva Classified gene: PKP2 as Green List (high evidence)
Dilated Cardiomyopathy v1.26 PKP2 Elena Savva Gene: pkp2 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.25 PKP2 Elena Savva Phenotypes for gene: PKP2 were changed from Arrhythmogenic right ventricular dysplasia 9 (MIM#609040) to Arrhythmogenic right ventricular dysplasia 9 (MIM#609040); Dilated cardiomyopathy; hypoplastic left heart syndrome; hydrops fetalis; ventricular septal defect; left ventricular non-compaction
Dilated Cardiomyopathy v1.24 PKP2 Elena Savva Publications for gene: PKP2 were set to 15489853; 16567567
Mendeliome v1.1408 SV2A Karina Sandoval changed review comment from: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo (Hom p.Arg383Gln) reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation. Consanguineous.
This paper references 5 other families with both AR & AD
Family #1 ā€“ p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 ā€“ p.Arg570Cys, AD, 2 affected, inherited from affected mother
Family #3 ā€“ p.Gly660Arg, AD, de novo
Family #4 ā€“ p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) ā€“ p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers
Sources: Literature; to: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo (Hom p.Arg383Gln) reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation. Consanguineous.
This paper references 5 other families with both AR & AD
Family #1 ā€“ p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 ā€“ p.Arg570Cys, AD, 2 affected, inherited from affected mother (in gnomAD v2 1 het, absent from gnomAD v3)
Family #3 ā€“ p.Gly660Arg, AD, de novo
Family #4 ā€“ p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) ā€“ p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers
Sources: Literature
Genetic Epilepsy v0.2003 SV2A Karina Sandoval changed review comment from: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo (Hom p.Arg383Gln) reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation. Consanguineous.
This paper references 5 other families with both AR & AD
Family #1 ā€“ p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 ā€“ p.Arg570Cys, AD, 2 affected, inherited from affected mother
Family #3 ā€“ p.Gly660Arg, AD, de novo
Family #4 ā€“ p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) ā€“ p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers
Sources: Literature; to: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo (Hom p.Arg383Gln) reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation. Consanguineous.
This paper references 5 other families with both AR & AD
Family #1 ā€“ p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 ā€“ p.Arg570Cys, AD, 2 affected, inherited from affected mother (in gnomAD v2 1 het, absent from gnomAD v3)
Family #3 ā€“ p.Gly660Arg, AD, de novo
Family #4 ā€“ p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) ā€“ p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers
Sources: Literature
Dilated Cardiomyopathy v1.24 PKP2 Elena Savva Mode of inheritance for gene: PKP2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5631 FUK Lisa Norbart reviewed gene: FUK: Rating: AMBER; Mode of pathogenicity: None; Publications: (PMID: 35718084, 36426412); Phenotypes: Congenital disorder of glycosylation with defective fucosylation 2 (MIM#618324); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v1.14 ACBD6 Elena Savva Classified gene: ACBD6 as Green List (high evidence)
Ataxia v1.14 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Mendeliome v1.1408 CRELD1 Naomi Baker reviewed gene: CRELD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37947183; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), CRELD1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia and Chorea v0.234 ACBD6 Elena Savva Classified gene: ACBD6 as Green List (high evidence)
Dystonia and Chorea v0.234 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Ataxia v1.13 ACBD6 Elena Savva Classified gene: ACBD6 as Green List (high evidence)
Ataxia v1.13 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Ataxia v1.12 ACBD6 Elena Savva Marked gene: ACBD6 as ready
Ataxia v1.12 ACBD6 Elena Savva Gene: acbd6 has been removed from the panel.
Dystonia and Chorea v0.233 ACBD6 Elena Savva Classified gene: ACBD6 as Green List (high evidence)
Dystonia and Chorea v0.233 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.232 ACBD6 Elena Savva Marked gene: ACBD6 as ready
Dystonia and Chorea v0.232 ACBD6 Elena Savva Gene: acbd6 has been removed from the panel.
Intellectual disability syndromic and non-syndromic v0.5631 CRELD1 Naomi Baker gene: CRELD1 was added
gene: CRELD1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CRELD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRELD1 were set to PMID: 37947183
Phenotypes for gene: CRELD1 were set to Neurodevelopmental disorder (MONDO:0700092), CRELD1-related
Review for gene: CRELD1 was set to GREEN
Added comment: Publication reports 18 individuals from 14 unrelated families affected by biallelic recessive variants in CRELD1, presenting with early-onset neurodevelopmental features, most notably hypotonia and epilepsy, with developmental plateauing and slowly progressive nonneurologic medical complexities in survivors, including cardiac rhythm disturbances and frequent infections. Most individuals have a missense variant in trans with a putative null allele. Four variants were re-current: p.(Cys192Tyr) in 10 families, p.(Gln320Argfs) in 5 families, p.(Ala377Thrfs) in 2 families, and p.(Met369Val) also in 2 families. Some functional studies also reported (Xenopus tropicalis).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5631 RAB1A Chris Ciotta gene: RAB1A was added
gene: RAB1A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RAB1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB1A were set to PMID: 37924809
Phenotypes for gene: RAB1A were set to neurodevelopmental disorder MONDO:0700092, CASP2-related
Review for gene: RAB1A was set to AMBER
Added comment: 4 families and 5 individuals, 2/5 have speech delay and 4/5 have motor delay.
Anxiety in 3/5 and autism in 2/5. Microcephaly in only one individual, spastic paraplegia observed in 2 individuals from one family.
In 2 families variants were inherited from an affected parent.
Sources: Literature
Genetic Epilepsy v0.2003 SV2A Karina Sandoval gene: SV2A was added
gene: SV2A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SV2A was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SV2A were set to PMID: 37985816
Phenotypes for gene: SV2A were set to Epilepsy, MONDO:0005027
Review for gene: SV2A was set to AMBER
Added comment: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo (Hom p.Arg383Gln) reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation. Consanguineous.
This paper references 5 other families with both AR & AD
Family #1 ā€“ p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 ā€“ p.Arg570Cys, AD, 2 affected, inherited from affected mother
Family #3 ā€“ p.Gly660Arg, AD, de novo
Family #4 ā€“ p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) ā€“ p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers
Sources: Literature
Red cell disorders v1.22 SLC19A1 Elena Savva Classified gene: SLC19A1 as Amber List (moderate evidence)
Red cell disorders v1.22 SLC19A1 Elena Savva Gene: slc19a1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2003 CRELD1 Naomi Baker reviewed gene: CRELD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37947183; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), CRELD1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1408 SLC19A1 Elena Savva Classified gene: SLC19A1 as Amber List (moderate evidence)
Mendeliome v1.1408 SLC19A1 Elena Savva Gene: slc19a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1407 DDX17 Elena Savva Classified gene: DDX17 as Green List (high evidence)
Mendeliome v1.1407 DDX17 Elena Savva Gene: ddx17 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.54 SLC19A1 Elena Savva Classified gene: SLC19A1 as Amber List (moderate evidence)
Combined Immunodeficiency v1.54 SLC19A1 Elena Savva Gene: slc19a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1406 DDX17 Elena Savva Classified gene: DDX17 as Green List (high evidence)
Mendeliome v1.1406 DDX17 Elena Savva Gene: ddx17 has been classified as Green List (High Evidence).
Mendeliome v1.1405 DDX17 Elena Savva Marked gene: DDX17 as ready
Mendeliome v1.1405 DDX17 Elena Savva Gene: ddx17 has been removed from the panel.
Fetal anomalies v1.168 PKP2 Seb Lunke Classified gene: PKP2 as Green List (high evidence)
Fetal anomalies v1.168 PKP2 Seb Lunke Gene: pkp2 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.53 SLC19A1 Elena Savva Classified gene: SLC19A1 as Amber List (moderate evidence)
Combined Immunodeficiency v1.53 SLC19A1 Elena Savva Gene: slc19a1 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.52 SLC19A1 Elena Savva Marked gene: SLC19A1 as ready
Combined Immunodeficiency v1.52 SLC19A1 Elena Savva Gene: slc19a1 has been removed from the panel.
Mendeliome v1.1405 DDX17 Melanie Marty gene: DDX17 was added
gene: DDX17 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DDX17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DDX17 were set to https://www.medrxiv.org/search/DDX17
Phenotypes for gene: DDX17 were set to Neurodevelopmental disorder (MONDO#0700092), DDX17-related
Review for gene: DDX17 was set to GREEN
Added comment: https://www.medrxiv.org/search/DDX17 (pre-print)
11 patients with het de novo variants in DDX17 (5 NMD, 6 missense). Patient's phenotype included mild-moderate intellectual disability, delayed speech and language development and global developmental delay. 64% had dysmorphic facial features. Some patients also have gross and fine motor delay, generalized hypotonia, stereotypy, and evidence of autism spectrum disorder.

Knockdown of Ddx17 in newborn mice showed impaired axon outgrowth and reduced axon outgrowth and branching was observed in primary cortical neurons in vitro. This result was replicated in Crispant Xenopus tadpoles, which had clear functional neural defects and showed an impaired neurobehavioral phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5631 DDX17 Elena Savva Classified gene: DDX17 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5631 DDX17 Elena Savva Gene: ddx17 has been classified as Green List (High Evidence).
Mendeliome v1.1405 SV2A Karina Sandoval gene: SV2A was added
gene: SV2A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SV2A was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SV2A were set to PMID: 37985816
Phenotypes for gene: SV2A were set to Epilepsy, MONDO:0005027
Review for gene: SV2A was set to GREEN
Added comment: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo (Hom p.Arg383Gln) reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation. Consanguineous.
This paper references 5 other families with both AR & AD
Family #1 ā€“ p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 ā€“ p.Arg570Cys, AD, 2 affected, inherited from affected mother
Family #3 ā€“ p.Gly660Arg, AD, de novo
Family #4 ā€“ p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) ā€“ p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5630 DDX17 Elena Savva Classified gene: DDX17 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5630 DDX17 Elena Savva Gene: ddx17 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5629 DDX17 Elena Savva Marked gene: DDX17 as ready
Intellectual disability syndromic and non-syndromic v0.5629 DDX17 Elena Savva Gene: ddx17 has been removed from the panel.
Mitochondrial disease v0.899 RNF213 Seb Lunke Marked gene: RNF213 as ready
Mitochondrial disease v0.899 RNF213 Seb Lunke Gene: rnf213 has been classified as Green List (High Evidence).
Mitochondrial disease v0.899 RNF213 Seb Lunke Classified gene: RNF213 as Green List (high evidence)
Mitochondrial disease v0.899 RNF213 Seb Lunke Gene: rnf213 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.174 PKP2 Suliman Khan reviewed gene: PKP2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disease v0.898 RNF213 Seb Lunke Classified gene: RNF213 as Green List (high evidence)
Mitochondrial disease v0.898 RNF213 Seb Lunke Gene: rnf213 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5629 MARK4 Elena Savva Marked gene: MARK4 as ready
Intellectual disability syndromic and non-syndromic v0.5629 MARK4 Elena Savva Gene: mark4 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5629 MARK4 Elena Savva Phenotypes for gene: MARK4 were changed from neurodevelopmental disorder (MONDO:0700092), MARK4-related to Neurodevelopmental disorder (MONDO:0700092), MARK4-related
Stroke v1.12 RNF213 Seb Lunke Marked gene: RNF213 as ready
Stroke v1.12 RNF213 Seb Lunke Gene: rnf213 has been classified as Green List (High Evidence).
Mendeliome v1.1405 MARK4 Elena Savva Classified gene: MARK4 as Red List (low evidence)
Mendeliome v1.1405 MARK4 Elena Savva Gene: mark4 has been classified as Red List (Low Evidence).
Stroke v1.12 RNF213 Seb Lunke Classified gene: RNF213 as Green List (high evidence)
Stroke v1.12 RNF213 Seb Lunke Gene: rnf213 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5629 MARK4 Elena Savva Classified gene: MARK4 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5629 MARK4 Elena Savva Gene: mark4 has been classified as Red List (Low Evidence).
Mitochondrial disease v0.897 RNF213 Seb Lunke gene: RNF213 was added
gene: RNF213 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: RNF213 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNF213 were set to 37924258
Phenotypes for gene: RNF213 were set to Moyamoya disease, MONDO:0016820; pediatric arterial ischemic stroke, MONDO:0018585
Review for gene: RNF213 was set to GREEN
Added comment: 14 individuals from 13 unrelated families with (de novo) missensevariants in RNF213 clustering within or around the RING domain. Individuals presented either with early-onset stroke (n=11) or with Leigh syndrome like symptoms (n=3). No genotype-phenotype correlation could be established. Common features included Global Developmental Delay and Seizures, increased serum lactate, ischemic stroke, and carotid/cerebral artery stenosis. Onset of symptoms generally in the first 6 months of life. Moyamoya phenomenon was present in 10/13 individuals.
Sources: Literature
Mendeliome v1.1404 MARK4 Elena Savva Classified gene: MARK4 as Red List (low evidence)
Mendeliome v1.1404 MARK4 Elena Savva Gene: mark4 has been classified as Red List (Low Evidence).
Mendeliome v1.1403 RNF213 Seb Lunke changed review comment from: 14 individuals from 13 unrelated families with (de novo) missensevariants in RNF213 clustering within or around the RING domain. Individuals presented either with early-onset stroke (n=11) or with Leigh syndrome (n=3). No genotype-phenotype correlation could be established. Common features included Global Developmental Delay and Seizures, increased serum lactate, ischemic stroke, Moyamoya phenomenon and carotid/cerebral artery stenosis. Onset of symptoms generally in the first 6 months of life.; to: 14 individuals from 13 unrelated families with (de novo) missensevariants in RNF213 clustering within or around the RING domain. Individuals presented either with early-onset stroke (n=11) or with Leigh syndrome like symptoms (n=3). No genotype-phenotype correlation could be established. Common features included Global Developmental Delay and Seizures, increased serum lactate, ischemic stroke, and carotid/cerebral artery stenosis. Onset of symptoms generally in the first 6 months of life. Moyamoya phenomenon was present in 10/13 individuals.
Mendeliome v1.1403 MARK4 Elena Savva Marked gene: MARK4 as ready
Mendeliome v1.1403 MARK4 Elena Savva Gene: mark4 has been removed from the panel.
Mendeliome v1.1403 SLC19A1 Paul De Fazio edited their review of gene: SLC19A1: Changed rating: AMBER
Stroke v1.11 RNF213 Seb Lunke gene: RNF213 was added
gene: RNF213 was added to Stroke. Sources: Literature
Mode of inheritance for gene: RNF213 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNF213 were set to 37924258
Phenotypes for gene: RNF213 were set to Moyamoya disease, MONDO:0016820; pediatric arterial ischemic stroke, MONDO:0018585
Review for gene: RNF213 was set to GREEN
Added comment: 14 individuals from 13 unrelated families with (de novo) missensevariants in RNF213 clustering within or around the RING domain. Individuals presented either with early-onset stroke (n=11) or with Leigh syndrome like symptoms (n=3). No genotype-phenotype correlation could be established. Common features included Global Developmental Delay and Seizures, increased serum lactate, ischemic stroke, and carotid/cerebral artery stenosis. Onset of symptoms generally in the first 6 months of life. Moyamoya phenomenon was present in 10/13 individuals.
Sources: Literature
Combined Immunodeficiency v1.52 SLC19A1 Paul De Fazio edited their review of gene: SLC19A1: Changed rating: AMBER
Dilated Cardiomyopathy v1.23 PKP2 Suliman Khan changed review comment from: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome.
Sources: Literature; to: PMID: 30562116: reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome.; to: PMID: 30562116: reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.

PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).

PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome.
Mendeliome v1.1403 ACBD6 Lucy Spencer edited their review of gene: ACBD6: Changed publications: 37951597, 36457943, 21937992, 35446914
Mendeliome v1.1403 KCNJ3 Zornitza Stark Marked gene: KCNJ3 as ready
Mendeliome v1.1403 KCNJ3 Zornitza Stark Gene: kcnj3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1403 KCNJ3 Zornitza Stark Classified gene: KCNJ3 as Amber List (moderate evidence)
Mendeliome v1.1403 KCNJ3 Zornitza Stark Gene: kcnj3 has been classified as Amber List (Moderate Evidence).
Dilated Cardiomyopathy v1.23 PKP2 Suliman Khan reviewed gene: PKP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30562116, PMID: 35059364, PMID: 38050058; Phenotypes: Dilated cardiomyopathy, hypoplastic left heart syndrome, hydrops fetalis, ventricular septal defect, left ventricular non-compaction; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1402 RNF213 Seb Lunke edited their review of gene: RNF213: Changed phenotypes: Moyamoya disease, MONDO:0016820, pediatric arterial ischemic stroke, MONDO:0018585
Hereditary Neuropathy v1.4 PLA2G16 Lauren Rogers edited their review of gene: PLA2G16: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1402 SLC19A1 Paul De Fazio reviewed gene: SLC19A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36517554, 36745868; Phenotypes: Combined immunodeficiency, SLC19A1-related MONDO:0015131; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Growth failure v1.70 WBP4 Lilian Downie gene: WBP4 was added
gene: WBP4 was added to Growth failure. Sources: Literature
Mode of inheritance for gene: WBP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WBP4 were set to PMID: 37425688
Phenotypes for gene: WBP4 were set to Neurodevelopmental disorder, MONDO:0700092, WBP4-related
Review for gene: WBP4 was set to GREEN
Added comment: 11 individuals from 8 families, IUGR and postnatal growth restriction reported
Sources: Literature
Mendeliome v1.1402 PLA2G16 Lauren Rogers edited their review of gene: PLA2G16: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2003 KCNJ3 Zornitza Stark Marked gene: KCNJ3 as ready
Genetic Epilepsy v0.2003 KCNJ3 Zornitza Stark Gene: kcnj3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.167 PKP2 Suliman Khan changed review comment from: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome.
Sources: Literature; to: PMID: 30562116: reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome.
Sources: Literature
Fetal anomalies v1.167 PKP2 Suliman Khan changed review comment from: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consist to Wolff Parkinson-White syndrome.
Sources: Literature; to: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome.
Sources: Literature
Lipodystrophy_Lipoatrophy v1.9 PLA2G16 Lauren Rogers edited their review of gene: PLA2G16: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.167 PKP2 Suliman Khan changed review comment from: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In cases, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consist to Wolff Parkinson-White syndrome.
Sources: Literature; to: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consist to Wolff Parkinson-White syndrome.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5628 PLA2G16 Lauren Rogers reviewed gene: PLA2G16: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37919452; Phenotypes: Lipodystrophy (MONDO:0006573); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2003 KCNJ3 Zornitza Stark Classified gene: KCNJ3 as Amber List (moderate evidence)
Genetic Epilepsy v0.2003 KCNJ3 Zornitza Stark Gene: kcnj3 has been classified as Amber List (Moderate Evidence).
Callosome v0.509 WBP4 Lilian Downie gene: WBP4 was added
gene: WBP4 was added to Callosome. Sources: Literature
Mode of inheritance for gene: WBP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WBP4 were set to PMID: 37425688
Phenotypes for gene: WBP4 were set to Neurodevelopmental disorder, MONDO:0700092, WBP4-related
Added comment: 8 individuals from 11 families, 3 had hypoplastic/thin corpus callosum
Sources: Literature
Fetal anomalies v1.167 PKP2 Suliman Khan gene: PKP2 was added
gene: PKP2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PKP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PKP2 were set to PMID: 30562116; PMID: 35059364; PMID: 38050058
Phenotypes for gene: PKP2 were set to dilated cardiomyopathy; hypoplastic left heart syndrome; hydrops fetalis; ventricular septal defect; left ventricular non-compaction
Penetrance for gene: PKP2 were set to unknown
Review for gene: PKP2 was set to GREEN
Added comment: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In cases, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consist to Wolff Parkinson-White syndrome.
Sources: Literature
Mendeliome v1.1402 KCNJ3 Daniel Flanagan gene: KCNJ3 was added
gene: KCNJ3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: KCNJ3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNJ3 were set to PMID: 37963718
Phenotypes for gene: KCNJ3 were set to Epilepsy (MONDO#0005027), KCNJ3-related
Review for gene: KCNJ3 was set to AMBER
Added comment: Two de novo missense variants, p.(Leu333Ser) and p.(Arg313Gln), were identified in two unrelated probands with epilepsy. 1/2 had developmental delay. Whole-cell patch-clamp functional studies showed a significantly reduction in current amplitude and density.

Kcnj3-knockout mice display hyperactivity and decreased anxiety, while a knock-in mouse line displays spontaneous seizure-like activity.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5628 PLA2G16 Lauren Rogers Deleted their review
Intellectual disability syndromic and non-syndromic v0.5628 PLA2G16 Lauren Rogers reviewed gene: PLA2G16: Rating: ; Mode of pathogenicity: None; Publications: PMID: 37919452; Phenotypes: Lipodystrophy (MONDO:0006573); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5628 PLA2G16 Lauren Rogers Deleted their review
Intellectual disability syndromic and non-syndromic v0.5628 PLA2G16 Lauren Rogers reviewed gene: PLA2G16: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37919452; Phenotypes: Lipodystrophy (MONDO:0006573); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2002 KCNJ3 Zornitza Stark Classified gene: KCNJ3 as Amber List (moderate evidence)
Genetic Epilepsy v0.2002 KCNJ3 Zornitza Stark Gene: kcnj3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.167 WBP4 Lilian Downie gene: WBP4 was added
gene: WBP4 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: WBP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WBP4 were set to PMID: 37425688
Phenotypes for gene: WBP4 were set to Neurodevelopmental disorder, MONDO:0700092, WBP4-related
Review for gene: WBP4 was set to GREEN
Added comment: 11 individuals, with dysmorphic ID
3 presented in utero 2x IUGR, 1x ventriculomegaly and polyhydramnios
5 with brain anomalies (corpus callosum and cortical)
Sources: Literature
Mendeliome v1.1402 RNF213 Seb Lunke reviewed gene: RNF213: Rating: GREEN; Mode of pathogenicity: None; Publications: 37924258; Phenotypes: Leigh syndrome, MONDO:0009723, pediatric arterial ischemic stroke, MONDO:0018585, Moyamoya disease, MONDO:0016820; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5628 PLA2G16 Lauren Rogers Deleted their review
Genetic Epilepsy v0.2001 KCNJ3 Daniel Flanagan changed review comment from: Two de novo missense variants, p.(Leu333Ser) and p.(Arg313Gln), were identified in two unrelated probands with epilepsy. 1/2 had developmental delay. Whole-cell patch-clamp functional studies showed a significantly reduction in current amplitude and density.
Sources: Expert list; to: Two de novo missense variants, p.(Leu333Ser) and p.(Arg313Gln), were identified in two unrelated probands with epilepsy. 1/2 had developmental delay. Whole-cell patch-clamp functional studies showed a significantly reduction in current amplitude and density.

Kcnj3-knockout mice display hyperactivity and decreased anxiety, while a knock-in mouse line displays spontaneous seizure-like activity.

Sources: Expert list
Hereditary Neuropathy v1.4 PLA2G16 Lauren Rogers gene: PLA2G16 was added
gene: PLA2G16 was added to Hereditary Neuropathy - complex. Sources: Literature
Mode of inheritance for gene: PLA2G16 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLA2G16 were set to PMID: 37919452
Phenotypes for gene: PLA2G16 were set to Lipodystrophy (MONDO:0006573)
Review for gene: PLA2G16 was set to GREEN
Added comment: 7 patients from 4 unrelated consanguineous families with homozygous loss of function PTC variants. Features: 4/7 metabolic features, 6/7 neurological/skeletal features, 3/7 Psychomotor retardation/intellectual disability, 5/7 demyelinating peripheral neuropathy.

Null mouse and patient derived white adipose tissue showed enrichment of arachidonic acid-containing membrane phospholipids and a strong decrease in PPARĪ³. CRISPRā€“Cas9-mediated PLAAT3 inactivation in human adipose stem cells induced insulin resistance, altered adipocyte differentiation with decreased lipid droplet formation and reduced the expression of adipogenic and mature adipocyte markers, including PPARĪ³.
Sources: Literature
Mendeliome v1.1402 SEL1L Zornitza Stark Marked gene: SEL1L as ready
Mendeliome v1.1402 SEL1L Zornitza Stark Gene: sel1l has been classified as Green List (High Evidence).
Mendeliome v1.1402 PPID Elena Savva Marked gene: PPID as ready
Mendeliome v1.1402 PPID Elena Savva Gene: ppid has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5628 PLA2G16 Lauren Rogers gene: PLA2G16 was added
gene: PLA2G16 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PLA2G16 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLA2G16 were set to PMID: 37919452
Phenotypes for gene: PLA2G16 were set to Lipodystrophy (MONDO:0006573)
Added comment: 7 patients from 4 unrelated consanguineous families with homozygous loss of function PTC variants. Features: 4/7 metabolic features, 6/7 neurological/skeletal features, 3/7 Psychomotor retardation/intellectual disability, 5/7 demyelinating peripheral neuropathy.

Null mouse and patient derived white adipose tissue showed enrichment of arachidonic acid-containing membrane phospholipids and a strong decrease in PPARĪ³. CRISPRā€“Cas9-mediated PLAAT3 inactivation in human adipose stem cells induced insulin resistance, altered adipocyte differentiation with decreased lipid droplet formation and reduced the expression of adipogenic and mature adipocyte markers, including PPARĪ³.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5628 PPID Elena Savva Marked gene: PPID as ready
Intellectual disability syndromic and non-syndromic v0.5628 PPID Elena Savva Gene: ppid has been classified as Red List (Low Evidence).
Mendeliome v1.1402 SEL1L Zornitza Stark Classified gene: SEL1L as Green List (high evidence)
Mendeliome v1.1402 SEL1L Zornitza Stark Gene: sel1l has been classified as Green List (High Evidence).
Mendeliome v1.1401 PLA2G16 Lauren Rogers changed review comment from: 7 patients from 4 unrelated consanguineous families with homozygous loss of function PTC variants. Features: 4/7 metabolic features, 6/7 neurological/skeletal features, 3/7 Psychomotor retardation/intellectual disability, 5/7 demyelinating peripheral neuropathy.

Null mouse and patient derived white adipose tissue showed enrichment of arachidonic acid-containing membrane phospholipids and a strong decrease in PPARĪ³. CRISPRā€“Cas9-mediated PLAAT3 inactivation in human adipose stem cells induced insulin resistance, altered adipocyte diferentiation with decreased lipid droplet formation and reduced the expression of adipogenic and mature adipocyte markers, including PPARĪ³.
Sources: Literature; to: 7 patients from 4 unrelated consanguineous families with homozygous loss of function PTC variants. Features: 4/7 metabolic features, 6/7 neurological/skeletal features, 3/7 Psychomotor retardation/intellectual disability, 5/7 demyelinating peripheral neuropathy.

Null mouse and patient derived white adipose tissue showed enrichment of arachidonic acid-containing membrane phospholipids and a strong decrease in PPARĪ³. CRISPRā€“Cas9-mediated PLAAT3 inactivation in human adipose stem cells induced insulin resistance, altered adipocyte differentiation with decreased lipid droplet formation and reduced the expression of adipogenic and mature adipocyte markers, including PPARĪ³.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5628 MARK4 Rylee Peters changed review comment from: Missense variant, c.604T>C; p.Phe202Leu, identified in two siblings with childhood-onset neurodevelopmental disorder characterised by global developmental delay, intellectual disability, behavioural abnormalities, and dysmorphic features. The variant is located in the catalytic domain of the kinase, and is inherited from unaffected mosaic mother.

Functional investigation revealed that the variant results in a gain-of-function in the ability of MARK4 to phosphorylate tau and leads to up-regulation of the mTORC1 pathway.
Sources: Literature; to: Heterozygous missense variant, c.604T>C; p.Phe202Leu, identified in two siblings with childhood-onset neurodevelopmental disorder characterised by global developmental delay, intellectual disability, behavioural abnormalities, and dysmorphic features. The variant is located in the catalytic domain of the kinase, and is inherited from unaffected mosaic mother.

Functional investigation revealed that the variant results in a gain-of-function in the ability of MARK4 to phosphorylate tau and leads to up-regulation of the mTORC1 pathway.
Sources: Literature
Lipodystrophy_Lipoatrophy v1.9 PLA2G16 Lauren Rogers gene: PLA2G16 was added
gene: PLA2G16 was added to Lipodystrophy_Lipoatrophy. Sources: Literature
Mode of inheritance for gene: PLA2G16 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLA2G16 were set to PMID: 37919452
Phenotypes for gene: PLA2G16 were set to Lipodystrophy (MONDO:0006573)
Review for gene: PLA2G16 was set to GREEN
Added comment: 7 patients from 4 unrelated consanguineous families with homozygous loss of function PTC variants. Features: 4/7 metabolic features, 6/7 neurological/skeletal features, 3/7 Psychomotor retardation/intellectual disability, 5/7 demyelinating peripheral neuropathy.

Null mouse and patient derived white adipose tissue showed enrichment of arachidonic acid-containing membrane phospholipids and a strong decrease in PPARĪ³. CRISPRā€“Cas9-mediated PLAAT3 inactivation in human adipose stem cells induced insulin resistance, altered adipocyte differentiation with decreased lipid droplet formation and reduced the expression of adipogenic and mature adipocyte markers, including PPARĪ³.
Sources: Literature
Mendeliome v1.1401 MARK4 Rylee Peters changed review comment from: Missense variant, c.604T>C; p.Phe202Leu, identified in two siblings with childhood-onset neurodevelopmental disorder characterised by global developmental delay, intellectual disability, behavioural abnormalities, and dysmorphic features. The variant is located in the catalytic domain of the kinase, and is inherited from unaffected mosaic mother.

Functional investigation revealed that the variant results in a gain-of-function in the ability of MARK4 to phosphorylate tau and leads to up-regulation of the mTORC1 pathway.
Sources: Literature; to: Heterozygous missense variant, c.604T>C; p.Phe202Leu, identified in two siblings with childhood-onset neurodevelopmental disorder characterised by global developmental delay, intellectual disability, behavioural abnormalities, and dysmorphic features. The variant is located in the catalytic domain of the kinase, and is inherited from unaffected mosaic mother.

Functional investigation revealed that the variant results in a gain-of-function in the ability of MARK4 to phosphorylate tau and leads to up-regulation of the mTORC1 pathway.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5628 SEL1L Zornitza Stark Marked gene: SEL1L as ready
Intellectual disability syndromic and non-syndromic v0.5628 SEL1L Zornitza Stark Gene: sel1l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5628 SEL1L Zornitza Stark Classified gene: SEL1L as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5628 SEL1L Zornitza Stark Gene: sel1l has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.52 SLC19A1 Paul De Fazio edited their review of gene: SLC19A1: Changed publications: 36517554, 36745868
Mendeliome v1.1401 PLA2G16 Lauren Rogers gene: PLA2G16 was added
gene: PLA2G16 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLA2G16 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLA2G16 were set to PMID: 37919452
Phenotypes for gene: PLA2G16 were set to Lipodystrophy (MONDO:0006573)
Review for gene: PLA2G16 was set to GREEN
Added comment: 7 patients from 4 unrelated consanguineous families with homozygous loss of function PTC variants. Features: 4/7 metabolic features, 6/7 neurological/skeletal features, 3/7 Psychomotor retardation/intellectual disability, 5/7 demyelinating peripheral neuropathy.

Null mouse and patient derived white adipose tissue showed enrichment of arachidonic acid-containing membrane phospholipids and a strong decrease in PPARĪ³. CRISPRā€“Cas9-mediated PLAAT3 inactivation in human adipose stem cells induced insulin resistance, altered adipocyte diferentiation with decreased lipid droplet formation and reduced the expression of adipogenic and mature adipocyte markers, including PPARĪ³.
Sources: Literature
Dystonia and Chorea v0.232 ACBD6 Lucy Spencer gene: ACBD6 was added
gene: ACBD6 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: ACBD6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACBD6 were set to 37951597
Phenotypes for gene: ACBD6 were set to Neurodevelopmental disorder (MONDO#0700092), ACBD6-related
Review for gene: ACBD6 was set to GREEN
Added comment: PMID: 37951597
45 individuals from 28 families with a neurodevelopmental syndrome with complex and progressive movement disorder phenotype. 18 PTCs and splice, 1 missense 1 in frame insertion.

Phenotypes: weight was >50th percentile in 20/34 patients, all mod-severe GDD, facial dysmorphism in 38/40, mild cerebellar ataxia 35/41, limb spasticity/hypertonia 31/41, gait abnormalities in 33/35, dystonia in 30/31.
Sources: Literature
Mendeliome v1.1401 MARK4 Rylee Peters gene: MARK4 was added
gene: MARK4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MARK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MARK4 were set to PMID: 38041405
Phenotypes for gene: MARK4 were set to neurodevelopmental disorder (MONDO:0700092), MARK4-related
Mode of pathogenicity for gene: MARK4 was set to Other
Review for gene: MARK4 was set to AMBER
gene: MARK4 was marked as current diagnostic
Added comment: Missense variant, c.604T>C; p.Phe202Leu, identified in two siblings with childhood-onset neurodevelopmental disorder characterised by global developmental delay, intellectual disability, behavioural abnormalities, and dysmorphic features. The variant is located in the catalytic domain of the kinase, and is inherited from unaffected mosaic mother.

Functional investigation revealed that the variant results in a gain-of-function in the ability of MARK4 to phosphorylate tau and leads to up-regulation of the mTORC1 pathway.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5627 DDX17 Melanie Marty gene: DDX17 was added
gene: DDX17 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DDX17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DDX17 were set to https://www.medrxiv.org/search/DDX17
Phenotypes for gene: DDX17 were set to Neurodevelopmental disorder (MONDO#0700092), DDX17-related
Review for gene: DDX17 was set to GREEN
Added comment: https://www.medrxiv.org/search/DDX17 (pre-print)
11 patients with het de novo variants in DDX17 (5 NMD, 6 missense). Patient's phenotype included mild-moderate intellectual disability, delayed speech and language development and global developmental delay. 64% had dysmorphic facial features. Some patients also have gross and fine motor delay, generalized hypotonia, stereotypy, and evidence of autism spectrum disorder.

Knockdown of Ddx17 in newborn mice showed impaired axon outgrowth and reduced axon outgrowth and branching was observed in primary cortical neurons in vitro. This result was replicated in Crispant Xenopus tadpoles, which had clear functional neural defects and showed an impaired neurobehavioral phenotype.
Sources: Literature
Ataxia v1.12 ACBD6 Lucy Spencer gene: ACBD6 was added
gene: ACBD6 was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: ACBD6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACBD6 were set to 37951597
Phenotypes for gene: ACBD6 were set to Neurodevelopmental disorder (MONDO#0700092), ACBD6-related
Review for gene: ACBD6 was set to GREEN
Added comment: PMID: 37951597
45 individuals from 28 families with a neurodevelopmental syndrome with complex and progressive movement disorder phenotype. 18 PTCs and splice, 1 missense 1 in frame insertion.

Phenotypes: weight was >50th percentile in 20/34 patients, all mod-severe GDD, facial dysmorphism in 38/40, mild cerebellar ataxia 35/41, limb spasticity/hypertonia 31/41, gait abnormalities in 33/35, dystonia in 30/31.
Sources: Literature
Combined Immunodeficiency v1.52 SLC19A1 Paul De Fazio gene: SLC19A1 was added
gene: SLC19A1 was added to Combined Immunodeficiency. Sources: Literature
Mode of inheritance for gene: SLC19A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC19A1 were set to 36517554,36745868
Phenotypes for gene: SLC19A1 were set to Combined immunodeficiency, SLC19A1-related MONDO:0015131
Review for gene: SLC19A1 was set to GREEN
gene: SLC19A1 was marked as current diagnostic
Added comment: PMID: 36745868 report two distantly related patients (last common ancestor 5 generations prior) with the same homozygous missense variant, G348R. The variant is absent from gnomAD, although the residue is not conserved in mammals. Both patients experienced severe recurrent infection, neurologic and hematologic disorders, and gastroenteropathy. Functional studies on patient lymphocytes were consistent with reduced transporter activity.

PMID: 36517554 report two cousins with immunodeficiency with the same G348R variant as above. Functional studies on patient cells supported loss of transporter function. The patientā€™s symptoms ameliorated, and hematological and immunological tests normalized in the 2nd month of folinic acid supplementation.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5627 MARK4 Rylee Peters gene: MARK4 was added
gene: MARK4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MARK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MARK4 were set to PMID: 38041405
Phenotypes for gene: MARK4 were set to neurodevelopmental disorder (MONDO:0700092), MARK4-related
Mode of pathogenicity for gene: MARK4 was set to Other
Review for gene: MARK4 was set to AMBER
gene: MARK4 was marked as current diagnostic
Added comment: Missense variant, c.604T>C; p.Phe202Leu, identified in two siblings with childhood-onset neurodevelopmental disorder characterised by global developmental delay, intellectual disability, behavioural abnormalities, and dysmorphic features. The variant is located in the catalytic domain of the kinase, and is inherited from unaffected mosaic mother.

Functional investigation revealed that the variant results in a gain-of-function in the ability of MARK4 to phosphorylate tau and leads to up-regulation of the mTORC1 pathway.
Sources: Literature
Mendeliome v1.1401 SEL1L Sarah Pantaleo gene: SEL1L was added
gene: SEL1L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEL1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEL1L were set to PMID:Ā 37943610; PMID:Ā 37943617
Phenotypes for gene: SEL1L were set to Neurodevelopmental disorder, MONDO:0700092, SEL1L-related
Penetrance for gene: SEL1L were set to Complete
Added comment: Wang paper PMID:Ā 37943610

SEL1L protein is involved in the SEL1L-HRD1 endoplasmic reticulum (ER)-associated degradation.

Report two biallelic missense variants in SEL1L in six children from three independent families presenting with developmental delay, intellectual disability, microcephaly, facial dysmorphisms, hypotonia and/or ataxia (termed ERAD-associated neurodevelopment disorder with onset in infancy (ENDI). The variants were hypomorphic and impaired ERAD function.

Identified by WES. Parents heterozygous and asymptomatic. P.(Gly585Asp) in Patient 1, p.(Met528Arg) in Patients 2 and 3 (siblings).

All variants cause substrate accumulation. The extent of substrate accumulation in knockin cells was modest compared to those in knockout cells, pointing to a hypomorphic nature.

They also had a variant in HRD1.



Weis paper PMID:Ā 37943617

Third variant p.(Cys141Tyr), biallelic, causing premature death in five patients from a consanguineous family with early-onset neurodevelopmental disorders and agammaglobulinaemia due to severe SEL1L-HRD1 ERAD dysfunction.

This variant appears to have a more severe outcome, exhibiting B cell depletion and agammaglobulinaemia, causing the most severe dysfunction among all of the variants described by this group so far. They postulate that functionality of SEL1L-HRD1 ERAD is inversely correlated with disease severity in humans.

Their symptoms were dev delay, neurological disorder and agammaglobulinaemia in childhood. Along with severe axial hypotonia, short stature and microcephaly.

ā€œNot a complete loss-of-function variantā€.
Sources: Literature
Genetic Epilepsy v0.2001 KCNJ3 Daniel Flanagan gene: KCNJ3 was added
gene: KCNJ3 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: KCNJ3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNJ3 were set to PMID: 37963718
Phenotypes for gene: KCNJ3 were set to Epilepsy (MONDO#0005027), KCNJ3-related
Review for gene: KCNJ3 was set to AMBER
Added comment: Two de novo missense variants, p.(Leu333Ser) and p.(Arg313Gln), were identified in two unrelated probands with epilepsy. 1/2 had developmental delay. Whole-cell patch-clamp functional studies showed a significantly reduction in current amplitude and density.
Sources: Expert list
Deafness_IsolatedAndComplex v1.165 FOXL1 Lilian Downie gene: FOXL1 was added
gene: FOXL1 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: FOXL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXL1 were set to PMID: 34633540
Phenotypes for gene: FOXL1 were set to Otosclerosis 11 #MIM620576
Review for gene: FOXL1 was set to RED
Added comment: Single paper with variant in large AD family from Newfoundland with otosclerosis, hearing loss onset varied from late teens onwards. Segregation not completely convincing, 1 person with the deletion without otosclerosis. Conductive HL, sometimes mixed, not isolated SNHL. Second family with common haplotype and same 15bp deletion with otosclerosis. Functional studies. High population frequency and 3x homozygotes.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5627 SEL1L Sarah Pantaleo gene: SEL1L was added
gene: SEL1L was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SEL1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEL1L were set to PMID:Ā 37943610; PMID:Ā 37943617
Phenotypes for gene: SEL1L were set to Neurodevelopmental disorder, MONDO:0700092, SEL1L-related
Penetrance for gene: SEL1L were set to Complete
Review for gene: SEL1L was set to GREEN
Added comment: Wang paper PMID:Ā 37943610

SEL1L protein is involved in the SEL1L-HRD1 endoplasmic reticulum (ER)-associated degradation.

Report two biallelic missense variants in SEL1L in six children from three independent families presenting with developmental delay, intellectual disability, microcephaly, facial dysmorphisms, hypotonia and/or ataxia (termed ERAD-associated neurodevelopment disorder with onset in infancy (ENDI). The variants were hypomorphic and impaired ERAD function.

Identified by WES. Parents heterozygous and asymptomatic. P.(Gly585Asp) in Patient 1, p.(Met528Arg) in Patients 2 and 3 (siblings).

All variants cause substrate accumulation. The extent of substrate accumulation in knockin cells was modest compared to those in knockout cells, pointing to a hypomorphic nature.

They also had a variant in HRD1.



Weis paper PMID:Ā 37943617

Third variant p.(Cys141Tyr), biallelic, causing premature death in five patients from a consanguineous family with early-onset neurodevelopmental disorders and agammaglobulinaemia due to severe SEL1L-HRD1 ERAD dysfunction.

This variant appears to have a more severe outcome, exhibiting B cell depletion and agammaglobulinaemia, causing the most severe dysfunction among all of the variants described by this group so far. They postulate that functionality of SEL1L-HRD1 ERAD is inversely correlated with disease severity in humans.

Their symptoms were dev delay, neurological disorder and agammaglobulinaemia in childhood. Along with severe axial hypotonia, short stature and microcephaly.

ā€œNot a complete loss-of-function variantā€.
Sources: Literature
Mendeliome v1.1401 FOXL1 Lilian Downie gene: FOXL1 was added
gene: FOXL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FOXL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXL1 were set to PMID: 34633540
Phenotypes for gene: FOXL1 were set to Otosclerosis 11 #MIM620576
Review for gene: FOXL1 was set to RED
Added comment: Single paper with variant in large AD family from Newfoundland with otosclerosis, hearing loss onset varied from late teens onwards. Segregation not completely convincing, 1 person with the deletion without otosclerosis. Conductive HL, sometimes mixed, not isolated SNHL. Second family with common haplotype and same 15bp deletion with otosclerosis. Functional studies. High population frequency and 3x homozygotes.
Sources: Literature
Mendeliome v1.1401 PPID Elena Savva gene: PPID was added
gene: PPID was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPID was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPID were set to 37977818
Phenotypes for gene: PPID were set to Stutter disorder, (MONDO:0000723), PPID-related
Review for gene: PPID was set to RED
Added comment: PMID: 37977818 - a large family (10 affected confirmed to have the variant) with stuttering/language disorder and a het missense (p.(Pro270Ser)). Mouse K/I model showed microstructural changes in the corticospinal tract
Sources: Literature
Mendeliome v1.1400 ACBD6 Lucy Spencer edited their review of gene: ACBD6: Added comment: PMID: 37951597
Much larger cohort with - 45 individuals from 28 families with a neurodevelopmental syndrome with complex and progressive movement disorder phenotype. 18 PTCs and splice, 1 missense 1 in frame insertion.

Phenotypes: weight was >50th percentile in 20/34 patients, all mod-severe GDD, facial dysmorphism in 38/40, mild cerebellar ataxia 35/41, limb spasticity/hypertonia 31/41, gait abnormalities in 33/35.; Changed publications: 37951597
Mendeliome v1.1400 PRPF19 Dean Phelan gene: PRPF19 was added
gene: PRPF19 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRPF19 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRPF19 were set to PMID: 37962958
Phenotypes for gene: PRPF19 were set to Neurodevelopmental disorder (MONDO:0700092), PRPF19-related
Review for gene: PRPF19 was set to GREEN
Added comment: PMID: 37962958
Six unrelated individuals with de novo variants. Five had speech language motor delay, four had formal diagnosis of autism, three hypotonia and one fetus with multiple congenital abnormalities.
Sources: Literature
Osteogenesis Imperfecta and Osteoporosis v0.110 KIF5B Seb Lunke Marked gene: KIF5B as ready
Osteogenesis Imperfecta and Osteoporosis v0.110 KIF5B Seb Lunke Gene: kif5b has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.110 KIF5B Seb Lunke Classified gene: KIF5B as Green List (high evidence)
Osteogenesis Imperfecta and Osteoporosis v0.110 KIF5B Seb Lunke Gene: kif5b has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.110 KIF5B Seb Lunke Classified gene: KIF5B as Green List (high evidence)
Osteogenesis Imperfecta and Osteoporosis v0.110 KIF5B Seb Lunke Gene: kif5b has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.109 KIF5B Seb Lunke gene: KIF5B was added
gene: KIF5B was added to Osteogenesis Imperfecta and Osteoporosis. Sources: Literature
Mode of inheritance for gene: KIF5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF5B were set to 37934770
Phenotypes for gene: KIF5B were set to osteogenesis imperfecta, MONDO:0019019
Review for gene: KIF5B was set to GREEN
gene: KIF5B was marked as current diagnostic
Added comment: Four additional patients with three distinct de-novo missense variants and features consistent with osteogenesis imperfecta. All variants are in the Kinesin motor domain (~50% of the protein). Functional data in C. Elegans and cell lines shows impaired protein function. Not clear what distinguishes OI causing variants from other phenotypes for this gene at this stage. Dominant negative effect proposed but not conclusively proven.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5627 RBFOX1 Zornitza Stark Phenotypes for gene: RBFOX1 were changed from Intellectual disability; autism to Neurodevelopmental disorder (MONDO:0700092), RBFOX1-related
Intellectual disability syndromic and non-syndromic v0.5626 RBFOX1 Zornitza Stark Publications for gene: RBFOX1 were set to 24664471
Intellectual disability syndromic and non-syndromic v0.5625 RBFOX1 Zornitza Stark Classified gene: RBFOX1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5625 RBFOX1 Zornitza Stark Gene: rbfox1 has been classified as Green List (High Evidence).
Photosensitivity Syndromes v1.8 DNA2 Zornitza Stark Publications for gene: DNA2 were set to 37133451
Intellectual disability syndromic and non-syndromic v0.5624 RBFOX1 Dean Phelan reviewed gene: RBFOX1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37962958; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), RBFOX1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.258 MGP Zornitza Stark Marked gene: MGP as ready
Skeletal dysplasia v0.258 MGP Zornitza Stark Gene: mgp has been classified as Green List (High Evidence).
Skeletal dysplasia v0.258 MGP Zornitza Stark Phenotypes for gene: MGP were changed from Keutel syndrome 245150; Keutel syndrome 245150 to Keutel syndrome 245150; skeletal dysplasia MONDO:0018230, MGP-related
Skeletal dysplasia v0.257 MGP Zornitza Stark Mode of inheritance for gene: MGP was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hand and foot malformations v0.72 MGP Andrew Fennell reviewed gene: MGP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37675773; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Photosensitivity Syndromes v1.7 DNA2 Lucy Spencer reviewed gene: DNA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 37055165; Phenotypes: Rothmund-Thomson syndrome, MONDO:0010002, DNA2 associated; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1400 MGP Andrew Fennell reviewed gene: MGP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37675773; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.256 MGP Andrew Fennell reviewed gene: MGP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37923733; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1400 COL17A1 Zornitza Stark Phenotypes for gene: COL17A1 were changed from Epidermolysis bullosa, junctional 4, intermediate MIM#619787; Epithelial recurrent erosion dystrophy MIM#122400 to Epidermolysis bullosa, junctional 4, intermediate MIM#619787; Epithelial recurrent erosion dystrophy MIM#122400; Amelogenesis imperfecta MONDO:0019507, COL17A1-related
Intellectual disability syndromic and non-syndromic v0.5624 PPID Elena Savva gene: PPID was added
gene: PPID was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PPID was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPID were set to 37977818
Phenotypes for gene: PPID were set to Stutter disorder, (MONDO:0000723), PPID-related
Review for gene: PPID was set to RED
Added comment: PMID: 37977818 - a large family (10 affected confirmed to have the variant) with stuttering/language disorder and a het missense (p.(Pro270Ser)). Mouse K/I model showed microstructural changes in the corticospinal tract
Sources: Literature
Mendeliome v1.1399 COL17A1 Zornitza Stark Publications for gene: COL17A1 were set to 27309958; 29708937; 25676728; 20301304
Mendeliome v1.1398 COL17A1 Zornitza Stark reviewed gene: COL17A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37979963; Phenotypes: Amelogenesis imperfecta MONDO:0019507, COL17A1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Amelogenesis imperfecta v1.7 COL17A1 Zornitza Stark Phenotypes for gene: COL17A1 were changed from Epidermolysis bullosa, junctional, non-Herlitz type, MIM#226650 (includes enamel pitting); hypoplastic amelogenesis imperfecta to Epidermolysis bullosa, junctional, non-Herlitz type, MIM#226650 (includes enamel pitting); Amelogenesis imperfecta MONDO:0019507, COL17A1-related
Amelogenesis imperfecta v1.6 COL17A1 Zornitza Stark Mode of inheritance for gene: COL17A1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Amelogenesis imperfecta v1.5 COL17A1 Zornitza Stark edited their review of gene: COL17A1: Added comment: 19 unrelated individuals reported with het variants in this gene (several LoF) and isolated amelogenesis imperfecta.; Changed publications: 37979963; Changed phenotypes: Epidermolysis bullosa, junctional, non-Herlitz type, MIM# 226650, Amelogenesis imperfecta MONDO:0019507, COL17A1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5623 GRIA3 Zornitza Stark Publications for gene: GRIA3 were set to 32977175; 17989220
Intellectual disability syndromic and non-syndromic v0.5622 GRIA3 Zornitza Stark Mode of inheritance for gene: GRIA3 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5621 GRIA3 Zornitza Stark reviewed gene: GRIA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38038360; Phenotypes: Intellectual developmental disorder, X-linked, syndromic, Wu type (MIM#300699); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2001 GRIA3 Zornitza Stark Publications for gene: GRIA3 were set to 32977175; 17989220
Genetic Epilepsy v0.2000 GRIA3 Zornitza Stark Mode of inheritance for gene: GRIA3 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.1999 GRIA3 Zornitza Stark edited their review of gene: GRIA3: Added comment: New manuscript describing ~40 individuals with variants in GRIA3, including affected females. Some variants demonstrated to be LoF and others GoF. LoF variants generally caused a milder phenotype.; Changed publications: 32977175, 17989220, 38038360; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v1.1398 GRIA3 Zornitza Stark Publications for gene: GRIA3 were set to 32977175; 17989220
Mendeliome v1.1397 GRIA3 Zornitza Stark Mode of inheritance for gene: GRIA3 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v1.1396 GRIA3 Zornitza Stark edited their review of gene: GRIA3: Added comment: New manuscript describing ~40 individuals with variants in GRIA3, including affected females. Some variants demonstrated to be LoF and others GoF. LoF variants generally caused a milder phenotype.; Changed publications: 32977175, 17989220, 38038360; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.1999 FOXP1 Zornitza Stark Marked gene: FOXP1 as ready
Genetic Epilepsy v0.1999 FOXP1 Zornitza Stark Gene: foxp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1999 FOXP1 Zornitza Stark Classified gene: FOXP1 as Green List (high evidence)
Genetic Epilepsy v0.1999 FOXP1 Zornitza Stark Gene: foxp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1998 FOXP1 Zornitza Stark gene: FOXP1 was added
gene: FOXP1 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: FOXP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXP1 were set to 26633542; 28741757; 34109629
Phenotypes for gene: FOXP1 were set to Intellectual developmental disorder with language impairment with or without autistic features, MIM# 613670
Review for gene: FOXP1 was set to GREEN
Added comment: Well established gene-disease association. Seizures in ~12% according to Gene Reviews.
Sources: Expert Review
Microcephaly v1.239 VARS Zornitza Stark Marked gene: VARS as ready
Microcephaly v1.239 VARS Zornitza Stark Gene: vars has been classified as Green List (High Evidence).
Microcephaly v1.239 VARS Zornitza Stark Classified gene: VARS as Green List (high evidence)
Microcephaly v1.239 VARS Zornitza Stark Gene: vars has been classified as Green List (High Evidence).
Microcephaly v1.238 VARS Zornitza Stark gene: VARS was added
gene: VARS was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: VARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VARS were set to 30755616; 30755602; 26539891; 29691655; 30275004
Phenotypes for gene: VARS were set to Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy; OMIM #617802
Review for gene: VARS was set to GREEN
Added comment: 20 individuals from 14 families. Microcephaly is part of the phenotype.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5621 TRAPPC4 Zornitza Stark Phenotypes for gene: TRAPPC4 were changed from intellectual disability; epilepsy; spasticity; microcephaly to Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy, MIM# 618741
Intellectual disability syndromic and non-syndromic v0.5620 TRAPPC4 Zornitza Stark edited their review of gene: TRAPPC4: Changed phenotypes: Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy, MIM# 618741
Genetic Epilepsy v0.1997 TRAPPC4 Zornitza Stark Phenotypes for gene: TRAPPC4 were changed from intellectual disability; epilepsy; spasticity; microcephaly to Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy, MIM# 618741
Genetic Epilepsy v0.1996 TRAPPC4 Zornitza Stark edited their review of gene: TRAPPC4: Changed phenotypes: Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy, MIM# 618741
Mendeliome v1.1396 TRAPPC4 Zornitza Stark Phenotypes for gene: TRAPPC4 were changed from intellectual disability; epilepsy; spasticity; microcephaly to Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy, MIM# 618741
Mendeliome v1.1395 TRAPPC4 Zornitza Stark edited their review of gene: TRAPPC4: Changed phenotypes: Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy, MIM# 618741
Genetic Epilepsy v0.1996 AMACR Zornitza Stark Phenotypes for gene: AMACR were changed from ALPHA-METHYLACYL-CoA RACEMASE DEFICIENCY MIM#614307 to Alpha-methylacyl-CoA racemase deficiency, MIM# 614307
Genetic Epilepsy v0.1995 KRAS Zornitza Stark Tag somatic tag was added to gene: KRAS.
Disorders of immune dysregulation v0.184 MADD Zornitza Stark Marked gene: MADD as ready
Disorders of immune dysregulation v0.184 MADD Zornitza Stark Gene: madd has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.184 MADD Zornitza Stark Classified gene: MADD as Amber List (moderate evidence)
Disorders of immune dysregulation v0.184 MADD Zornitza Stark Gene: madd has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5620 WBP4 Zornitza Stark Publications for gene: WBP4 were set to
Intellectual disability syndromic and non-syndromic v0.5619 WBP4 Zornitza Stark reviewed gene: WBP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 37963460; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, WBP4-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1395 WBP4 Zornitza Stark Publications for gene: WBP4 were set to
Mendeliome v1.1394 WBP4 Zornitza Stark reviewed gene: WBP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 37963460; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, WBP4-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.896 MRPL39 Zornitza Stark Phenotypes for gene: MRPL39 were changed from Mitochondrial disease MONDO:0044970 to Combined oxidative phosphorylation deficiency-59 (COXPD59), MIM#620646
Mitochondrial disease v0.895 MRPL39 Zornitza Stark reviewed gene: MRPL39: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency-59 (COXPD59), MIM#620646; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1394 MRPL39 Zornitza Stark Marked gene: MRPL39 as ready
Mendeliome v1.1394 MRPL39 Zornitza Stark Gene: mrpl39 has been classified as Green List (High Evidence).
Mendeliome v1.1394 MRPL39 Zornitza Stark Phenotypes for gene: MRPL39 were changed from Mitochondrial disease MONDO:0044970 to Combined oxidative phosphorylation deficiency-59 (COXPD59), MIM#620646
Mendeliome v1.1393 MRPL39 Zornitza Stark reviewed gene: MRPL39: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency-59 (COXPD59), MIM#620646; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1995 KRAS Elena Savva Marked gene: KRAS as ready
Genetic Epilepsy v0.1995 KRAS Elena Savva Gene: kras has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1995 KRAS Elena Savva Phenotypes for gene: KRAS were changed from to Oculoectodermal syndrome, somatic MIM#600268; Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic MIM#163200
Genetic Epilepsy v0.1995 KRAS Elena Savva Publications for gene: KRAS were set to
Genetic Epilepsy v0.1995 KRAS Elena Savva Mode of pathogenicity for gene: KRAS was changed from to Other
Genetic Epilepsy v0.1995 KRAS Elena Savva Mode of inheritance for gene: KRAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.1994 KRAS Elena Savva edited their review of gene: KRAS: Added comment: PMID: 37126322 - somatic variants Drug-Resistant mesial temporal lobe epilepsy, variants are all located in mutational hot spots for cancer and neurodevelopmental disorders. Probands x2 (p.G12D) had mesial temporal sclerosis and/or focal cortical dysplasia

PMID: 37722300 - 14-month-old boy with Schimmelpenning syndrome (KRAS p.G12D, postzygotic somatic mutation) with refractory epilepsy; Changed publications: PMID: 37126322, 37722300; Changed phenotypes: Oculoectodermal syndrome, somatic MIM#600268, Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic MIM#163200
Genetic Epilepsy v0.1994 AMACR Elena Savva Phenotypes for gene: AMACR were changed from Alpha-methylacyl-CoA racemase deficiency (MIM#614307) to ALPHA-METHYLACYL-CoA RACEMASE DEFICIENCY MIM#614307
Genetic Epilepsy v0.1993 AMACR Elena Savva Phenotypes for gene: AMACR were changed from ALPHA-METHYLACYL-CoA RACEMASE DEFICIENCY - 614307 to Alpha-methylacyl-CoA racemase deficiency (MIM#614307)
Genetic Epilepsy v0.1992 AMACR Elena Savva Publications for gene: AMACR were set to (PMID:35428665; 21576695; 11060344; 21686617
Genetic Epilepsy v0.1991 COL4A2 Zornitza Stark Phenotypes for gene: COL4A2 were changed from Cerebral Palsy MONDO#0006497, COL4A2-related; Brain small vessel disease 2 MIM# 614483 to Cerebral Palsy MONDO#0006497, COL4A2-related; Brain small vessel disease 2 MIM# 614483
Genetic Epilepsy v0.1990 COL4A2 Zornitza Stark Marked gene: COL4A2 as ready
Genetic Epilepsy v0.1990 COL4A2 Zornitza Stark Gene: col4a2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1990 COL4A2 Zornitza Stark Phenotypes for gene: COL4A2 were changed from Cerebral Palsy MONDO#0006497, COL4A2-related; Brain small vessel disease 2 MIM# 614483 to Cerebral Palsy MONDO#0006497, COL4A2-related; Brain small vessel disease 2 MIM# 614483
Genetic Epilepsy v0.1990 COL4A2 Zornitza Stark Phenotypes for gene: COL4A2 were changed from to Cerebral Palsy MONDO#0006497, COL4A2-related; Brain small vessel disease 2 MIM# 614483
Genetic Epilepsy v0.1989 COL4A2 Zornitza Stark Publications for gene: COL4A2 were set to
Genetic Epilepsy v0.1988 COL4A2 Zornitza Stark Mode of inheritance for gene: COL4A2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1987 COL4A2 Zornitza Stark reviewed gene: COL4A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral Palsy MONDO#0006497, COL4A2-related, Brain small vessel disease 2 MIM# 614483; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1987 COL4A1 Zornitza Stark Marked gene: COL4A1 as ready
Genetic Epilepsy v0.1987 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1987 COL4A1 Zornitza Stark Phenotypes for gene: COL4A1 were changed from to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps MIM#611773; Brain small vessel disease with or without ocular anomalies MIM#175780; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant MIM#618564
Genetic Epilepsy v0.1986 COL4A1 Zornitza Stark Publications for gene: COL4A1 were set to
Genetic Epilepsy v0.1985 COL4A1 Zornitza Stark Mode of inheritance for gene: COL4A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1984 COL4A1 Zornitza Stark changed review comment from: Seizures are secondary.; to: Seizures are secondary but described. Included for completeness.
Genetic Epilepsy v0.1984 COL4A1 Zornitza Stark reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps MIM#611773, Brain small vessel disease with or without ocular anomalies MIM#175780, Microangiopathy and leukoencephalopathy, pontine, autosomal dominant MIM#618564; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1984 ALG2 Zornitza Stark Marked gene: ALG2 as ready
Genetic Epilepsy v0.1984 ALG2 Zornitza Stark Gene: alg2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1984 ALG2 Zornitza Stark Phenotypes for gene: ALG2 were changed from CONGENITAL MYASTHENIC SYNDROME - MIM # 616228; CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ii - MIM ## 607906 to Myasthenic syndrome, congenital, 14, with tubular aggregates, MIM# 616228; Congenital disorder of glycosylation, type Ii, MIM# 607906
Genetic Epilepsy v0.1983 ALG2 Zornitza Stark Classified gene: ALG2 as Red List (low evidence)
Genetic Epilepsy v0.1983 ALG2 Zornitza Stark Gene: alg2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1982 ALG2 Zornitza Stark reviewed gene: ALG2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Myasthenic syndrome, congenital, 14, with tubular aggregates, MIM# 616228, Congenital disorder of glycosylation, type Ii, MIM# 607906; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1982 AMACR Zornitza Stark Marked gene: AMACR as ready
Genetic Epilepsy v0.1982 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1982 AMACR Zornitza Stark Classified gene: AMACR as Green List (high evidence)
Genetic Epilepsy v0.1982 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1981 ARID1A Zornitza Stark Marked gene: ARID1A as ready
Genetic Epilepsy v0.1981 ARID1A Zornitza Stark Gene: arid1a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1981 ARID1A Zornitza Stark Phenotypes for gene: ARID1A were changed from Coffin-Siris Syndrome 2 to Coffin-Siris syndrome 2 #614607
Genetic Epilepsy v0.1980 ARID1A Zornitza Stark Classified gene: ARID1A as Green List (high evidence)
Genetic Epilepsy v0.1980 ARID1A Zornitza Stark Gene: arid1a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1979 ARID1A Zornitza Stark reviewed gene: ARID1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coffin-Siris syndrome 2 #614607; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1979 AP3D1 Zornitza Stark Marked gene: AP3D1 as ready
Genetic Epilepsy v0.1979 AP3D1 Zornitza Stark Gene: ap3d1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1979 AP3D1 Zornitza Stark Phenotypes for gene: AP3D1 were changed from HERMANSKY-PUDLAK SYNDROME 10 to Hermansky-Pudlak syndrome 10, MIM# 617050
Genetic Epilepsy v0.1978 AP3D1 Zornitza Stark Classified gene: AP3D1 as Amber List (moderate evidence)
Genetic Epilepsy v0.1978 AP3D1 Zornitza Stark Gene: ap3d1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1977 AP3D1 Zornitza Stark reviewed gene: AP3D1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Hermansky-Pudlak syndrome 10, MIM# 617050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ocular and Oculocutaneous Albinism v1.11 AP3D1 Zornitza Stark Marked gene: AP3D1 as ready
Ocular and Oculocutaneous Albinism v1.11 AP3D1 Zornitza Stark Gene: ap3d1 has been classified as Amber List (Moderate Evidence).
Ocular and Oculocutaneous Albinism v1.11 AP3D1 Zornitza Stark Phenotypes for gene: AP3D1 were changed from Hermansky-Pudlak Syndrome 10 to Hermansky-Pudlak syndrome 10, MIM# 617050
Ocular and Oculocutaneous Albinism v1.10 AP3D1 Zornitza Stark Classified gene: AP3D1 as Amber List (moderate evidence)
Ocular and Oculocutaneous Albinism v1.10 AP3D1 Zornitza Stark Gene: ap3d1 has been classified as Amber List (Moderate Evidence).
Ocular and Oculocutaneous Albinism v1.9 AP3D1 Zornitza Stark reviewed gene: AP3D1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Hermansky-Pudlak syndrome 10, MIM# 617050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1977 ARSA Zornitza Stark Marked gene: ARSA as ready
Genetic Epilepsy v0.1977 ARSA Zornitza Stark Gene: arsa has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1977 ARSA Zornitza Stark Classified gene: ARSA as Green List (high evidence)
Genetic Epilepsy v0.1977 ARSA Zornitza Stark Gene: arsa has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1976 ARSA Zornitza Stark reviewed gene: ARSA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Metachromatic leukodystrophy - # 250100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1976 ASPM Zornitza Stark Marked gene: ASPM as ready
Genetic Epilepsy v0.1976 ASPM Zornitza Stark Gene: aspm has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1976 ASPM Zornitza Stark Classified gene: ASPM as Green List (high evidence)
Genetic Epilepsy v0.1976 ASPM Zornitza Stark Gene: aspm has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1975 ASPM Zornitza Stark reviewed gene: ASPM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary autosomal recessive Microcephaly 5 - OMIM #608716; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1975 ASPM John Coleman gene: ASPM was added
gene: ASPM was added to Genetic Epilepsy. Sources: Expert Review,Literature,ClinGen
Mode of inheritance for gene: ASPM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASPM were set to (PMID:32239881; 19770472; 18452193; 16141009)
Phenotypes for gene: ASPM were set to Primary autosomal recessive Microcephaly 5 - OMIM #608716
Added comment: Known microcephaly gene (AR). Seizures reported in around 15% of cases (GENEREVIEWS). Seizures reported on OMIM. Clingen curated seizures is a feature of this gene. Primary feature microcephaly. Various seizure types focal or tonic and tonic-clonic generalized seizures have been reported. 3 of 18 patients in a neurology cohort with later onset seizures PMID 19770472, another case of a female age 5 with 2 seizures, not needing treatment PMID 18452193, and a third publication with 2 of 3 affected family members with seizure phenotype tonic clonic/ clonic PMID 16141009.
Sources: Expert Review, Literature, ClinGen
Genetic Epilepsy v0.1975 ARSA John Coleman gene: ARSA was added
gene: ARSA was added to Genetic Epilepsy. Sources: Expert Review,Literature
Mode of inheritance for gene: ARSA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARSA were set to (PMID: 33195324; 10987380; 37359369; 20301309; 36324388; 19021637)
Phenotypes for gene: ARSA were set to Metachromatic leukodystrophy - # 250100; Arylsulfatase A deficiency
Added comment: Arylsulfatase A deficiency (also known as metachromatic leukodystrophy or MLD) is characterized by three clinical subtypes: late-infantile MLD, juvenile MLD, and adult MLD. Typical features: lysosomal storage disorder, CNS abnormalities, dev delay and regression. Neuropsychiatric features. Seizures reported in all subtypes (GENEREVIEWS, OMIM, Review article 33195324). Later onset cases (2 in 10987380), 2 early onset cases (37359369) in consanguineous families. Also reported in a male with compunder heterozygous variants (36324388). 3 out of 6 patients in a Polish pediatric cohort with different mutations had seizures (clonic, tonic clonic) onset from as early as 7 months.
Sources: Expert Review, Literature
Ocular and Oculocutaneous Albinism v1.9 AP3D1 John Coleman gene: AP3D1 was added
gene: AP3D1 was added to Ocular and Oculocutaneous Albinism. Sources: Expert Review,Literature,NHS GMS
Mode of inheritance for gene: AP3D1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP3D1 were set to (PMID: 26744459; 30472485; 19032734; 36445457)
Phenotypes for gene: AP3D1 were set to Hermansky-Pudlak Syndrome 10
Penetrance for gene: AP3D1 were set to unknown
Review for gene: AP3D1 was set to AMBER
Added comment: First family Turkish consanguineous with with severe neurologic impairment, oculocutaneous albinism, and immunodeficiency. PTC variant. Progressive epilepsy with intractable seizures (myoclonic jerks/ tonic clonic) and passed away 3.5 years (PMID: 26744459). Features of this case included infantile onset of immunodeficiency, oculocutaneous albinism, and severe neurologic impairment, including severely delayed global development and intractable seizures. Another consanguineous family with Frameshift variants with 1 male and 2 females with seizures seizures (male 10 years, females shortly after birth), tonic clonic (PMID: 30472485) and other features of Hermansky-Pudlak Syndrome 10 (including platelet defects, oculocutaneous albinism, and immunodeficiency). Mouse model (19032734) shows knock out of AP3D1 shows albinism characteristics, difference in input resistance of the neurons, a difference in the synaptic short-term plasticity of glutamatergic autapses showing a larger synaptic depression than controls. 2023 paper (PMID 36445457) shows a family with missense homozygous variants - they present with hearing loss, 2 siblings with neurodevelopmental delay and 2 with abnormality of the brain structurally, no albinism in this family. 2 affected families with PTCs but albinism phenotype not clear in all cases. Imp: moderate evidence ?2 affected plus affected albinism mice knock out model = suspicious. Amber on Panel App UK.
Sources: Expert Review, Literature, NHS GMS
Genetic Epilepsy v0.1975 ARID1A John Coleman changed review comment from: Coffin siris type 2 - seizures present in some but not all patients. Known haploinsufficiency of ARID1A and association with seizures presentation & type (34942405). Seizure reported on OMIM. Multiple reports of affected and unaffected. Seizures in 2/9 patients in case series (25168959). 6 year old female with classic features of CS and fever provoked tonic clonic seizures (33303725). A female Chinese patient 24 days old with ARID1A and seizures with hypotonia (35571021- supplementary table 1). Paper from Zurich with 1 patient described in a CS cohort with ARID1A and seizures (23906836). Review article of 63 CS patients described another 1 of 4 patients with seizures (23929686)
Sources: Literature, Expert Review; to: Coffin Siris type 2 - seizures present in some but not all patients. Known haploinsufficiency of ARID1A and association with seizures presentation & type (34942405). Seizure reported on OMIM. Multiple reports of affected and unaffected. Seizures in 2/9 patients in case series (25168959). 6 year old female with classic features of CS and fever provoked tonic clonic seizures (33303725). A female Chinese patient 24 days old with ARID1A and seizures with hypotonia (35571021- supplementary table 1). Paper from Zurich with 1 patient described in a CS cohort with ARID1A and seizures (23906836). Review article of 63 CS patients described another 1 of 4 patients with seizures (23929686)
Sources: Literature, Expert Review
Genetic Epilepsy v0.1975 ARID1A John Coleman changed review comment from: Coffin siris type 2 - seizures present in some but not all patients. Known haploinsufficiency of ARID1A and association with seizures (34942405). Seizure reported on OMIM. Multiple reports of variable seizures. Seizures in 2/9 patients in case series (25168959). 6 year old female with classic features of CS and fever provoked tonic clonic seizures (33303725). A female Chinese patient 24 days old with ARID1A and seizures with hypotonia (35571021- supplementary table 1). Paper from Zurich with 1 patient described in a CS cohort with ARID1A and seizures (23906836). Review article of 63 CS patients described another 1 of 4 patients with seizures (23929686)
Sources: Literature, Expert Review; to: Coffin siris type 2 - seizures present in some but not all patients. Known haploinsufficiency of ARID1A and association with seizures presentation & type (34942405). Seizure reported on OMIM. Multiple reports of affected and unaffected. Seizures in 2/9 patients in case series (25168959). 6 year old female with classic features of CS and fever provoked tonic clonic seizures (33303725). A female Chinese patient 24 days old with ARID1A and seizures with hypotonia (35571021- supplementary table 1). Paper from Zurich with 1 patient described in a CS cohort with ARID1A and seizures (23906836). Review article of 63 CS patients described another 1 of 4 patients with seizures (23929686)
Sources: Literature, Expert Review
Genetic Epilepsy v0.1975 ARID1A John Coleman gene: ARID1A was added
gene: ARID1A was added to Genetic Epilepsy. Sources: Literature,Expert Review
Mode of inheritance for gene: ARID1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARID1A were set to (PMID:34942405; 25168959; 33303725; 35571021; 23906836; 23929686)
Phenotypes for gene: ARID1A were set to Coffin-Siris Syndrome 2
Review for gene: ARID1A was set to GREEN
Added comment: Coffin siris type 2 - seizures present in some but not all patients. Known haploinsufficiency of ARID1A and association with seizures (34942405). Seizure reported on OMIM. Multiple reports of variable seizures. Seizures in 2/9 patients in case series (25168959). 6 year old female with classic features of CS and fever provoked tonic clonic seizures (33303725). A female Chinese patient 24 days old with ARID1A and seizures with hypotonia (35571021- supplementary table 1). Paper from Zurich with 1 patient described in a CS cohort with ARID1A and seizures (23906836). Review article of 63 CS patients described another 1 of 4 patients with seizures (23929686)
Sources: Literature, Expert Review
Genetic Epilepsy v0.1975 AP3D1 John Coleman gene: AP3D1 was added
gene: AP3D1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: AP3D1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP3D1 were set to (PMID: 26744459; 30472485; 19032734; 36445457
Phenotypes for gene: AP3D1 were set to HERMANSKY-PUDLAK SYNDROME 10
Review for gene: AP3D1 was set to AMBER
Added comment: First family Turkish consanguineous with with severe neurologic impairment, albinism, and immunodeficiency. PTC variant. Progressive epilepsy with intractable seizures (myoclonic jerks/ tonic clonic) and passed away 3.5 years (PMID: 26744459). Features of this case included infantile onset of immunodeficiency, oculocutaneous albinism, and severe neurologic impairment, including severely delayed global development and intractable seizures. Another consanguineous family with Frameshift variants with 1 male and 2 females with seizures seizures (male 10 years, females shortly after birth), tonic clonic (PMID: 30472485) and other features of Hermansky-Pudlak Syndrome 10 (including platelet defects, oculocutaneous albinism, and immunodeficiency). Mouse model (19032734) shows knock out of AP3D1 shows albinism characteristics, difference in input resistance of the neurons, a difference in the synaptic short-term plasticity of glutamatergic autapses showing a larger synaptic depression than controls. 2023 paper (PMID 36445457) shows a family with missense homozygous variants - they present with hearing loss, 2 siblings with neurodevelopmental delay and 2 with abnormality of the brain structurally, no reported seizures in this family. 2 affected families with PTCs but seizure phenotype not clear in all cases. Imp: moderate evidence
Sources: Literature
Genetic Epilepsy v0.1975 AMACR John Coleman gene: AMACR was added
gene: AMACR was added to Genetic Epilepsy. Sources: Literature,Expert Review
Mode of inheritance for gene: AMACR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMACR were set to (PMID:35428665; 21576695; 11060344; 21686617
Phenotypes for gene: AMACR were set to ALPHA-METHYLACYL-CoA RACEMASE DEFICIENCY - 614307
Penetrance for gene: AMACR were set to unknown
Review for gene: AMACR was set to GREEN
Added comment: Autosomal recessive affecting AMACR enzyme which is active in the mitochondrial & peroxisome. AMACR deficiency and Congenital Bile Acid Synthesis Defect 4 are distinctive phenotypes. Epilepsy a feature of AMACR deficiency on OMIM. AMACR deficiency reported in adults with later onset tonic clonic seizures in a 58 year old male, also had cerebellar features. Second case of female in her 70s with lacosamide responsive seizures and other neurological manifestations. Case series (Thompson et al 2009) - 44 year old male seizures onset at age 18, 52 year old female seizure onset 50s, and 57 y/o female tonic clonic seizures onset at age 13. Variable condition.
Sources: Literature, Expert Review
Genetic Epilepsy v0.1975 ALG2 John Coleman gene: ALG2 was added
gene: ALG2 was added to Genetic Epilepsy. Sources: Literature,NHS GMS
Mode of inheritance for gene: ALG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALG2 were set to (PMID:12684507; 28733338; 28007376)
Phenotypes for gene: ALG2 were set to CONGENITAL MYASTHENIC SYNDROME - MIM # 616228; CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ii - MIM ## 607906
Review for gene: ALG2 was set to RED
Added comment: Red list on NHS panel app. Literature search shows one case with reported seizures although limited phenotype given at 1 year, patient was normal at birth apart from coloboma (Thiel 2003). no other cases on pubmed or literature wider search. Phenotype appears to present with varying onset of myasthenic syndrome with myopathic features. ALG2 not specifically linked with epilepsy phenotype in the literature the way other CDGS are. Developmental delay also a neurodevelopmental feature.
Sources: Literature, NHS GMS
Genetic Epilepsy v0.1975 TRMT10A Zornitza Stark Marked gene: TRMT10A as ready
Genetic Epilepsy v0.1975 TRMT10A Zornitza Stark Gene: trmt10a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1975 TRMT10A Zornitza Stark Phenotypes for gene: TRMT10A were changed from microcephaly; diabetes; intellectual disability; epilepsy to Microcephaly, short stature, and impaired glucose metabolism 1, MIM# 616033
Genetic Epilepsy v0.1974 TRMT10A Zornitza Stark Classified gene: TRMT10A as Green List (high evidence)
Genetic Epilepsy v0.1974 TRMT10A Zornitza Stark Gene: trmt10a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1973 SAMD12 Zornitza Stark Tag STR tag was added to gene: SAMD12.
Genetic Epilepsy v0.1973 ACTB Zornitza Stark Marked gene: ACTB as ready
Genetic Epilepsy v0.1973 ACTB Zornitza Stark Gene: actb has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1973 ACTB Zornitza Stark Phenotypes for gene: ACTB were changed from Seizures; Epilepsy to Baraitser-Winter syndrome 1 243310 Thrombocytopenia 8, with dysmorphic features and developmental delay, MIM# 620475
Genetic Epilepsy v0.1972 ACTB Zornitza Stark Classified gene: ACTB as Green List (high evidence)
Genetic Epilepsy v0.1972 ACTB Zornitza Stark Gene: actb has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1971 ACY1 Zornitza Stark Marked gene: ACY1 as ready
Genetic Epilepsy v0.1971 ACY1 Zornitza Stark Gene: acy1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1971 ACY1 Zornitza Stark Phenotypes for gene: ACY1 were changed from Seizures; Epilepsy; Febrile Seizures to Aminoacylase 1 deficiency, MIM# 609924
Genetic Epilepsy v0.1970 ACY1 Zornitza Stark Classified gene: ACY1 as Green List (high evidence)
Genetic Epilepsy v0.1970 ACY1 Zornitza Stark Gene: acy1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1969 ADCY5 Zornitza Stark Marked gene: ADCY5 as ready
Genetic Epilepsy v0.1969 ADCY5 Zornitza Stark Gene: adcy5 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1969 ADCY5 Zornitza Stark Phenotypes for gene: ADCY5 were changed from to Dyskinesia with orofacial involvement MIM#606703
Genetic Epilepsy v0.1968 ADCY5 Zornitza Stark Classified gene: ADCY5 as Red List (low evidence)
Genetic Epilepsy v0.1968 ADCY5 Zornitza Stark Gene: adcy5 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1967 ADCY5 Zornitza Stark reviewed gene: ADCY5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dyskinesia with orofacial involvement MIM#606703; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1967 ADNP Zornitza Stark Marked gene: ADNP as ready
Genetic Epilepsy v0.1967 ADNP Zornitza Stark Gene: adnp has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1967 ADNP Zornitza Stark Phenotypes for gene: ADNP were changed from Seizures; Epilpesy; Focal Seizures; Absence seizures to Helsmoortel-van der Aa syndrome MIM#615873
Genetic Epilepsy v0.1966 ADNP Zornitza Stark Classified gene: ADNP as Green List (high evidence)
Genetic Epilepsy v0.1966 ADNP Zornitza Stark Gene: adnp has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1965 BET1 Zornitza Stark Phenotypes for gene: BET1 were changed from Muscular dystrophy; Epilepsy to Muscular dystrophy MONDO:0020121
Genetic Epilepsy v0.1964 BET1 Zornitza Stark Classified gene: BET1 as Red List (low evidence)
Genetic Epilepsy v0.1964 BET1 Zornitza Stark Gene: bet1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1963 CLCN2 Zornitza Stark Publications for gene: CLCN2 were set to 23707145; 19191339; 20037607; 19710712
Genetic Epilepsy v0.1962 AFDN Zornitza Stark Phenotypes for gene: AFDN were changed from to Epilepsy, MONDO:0015653
Genetic Epilepsy v0.1961 AFDN Zornitza Stark Marked gene: AFDN as ready
Genetic Epilepsy v0.1961 AFDN Zornitza Stark Gene: afdn has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1961 AFDN Zornitza Stark Classified gene: AFDN as Red List (low evidence)
Genetic Epilepsy v0.1961 AFDN Zornitza Stark Gene: afdn has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1960 AFDN Zornitza Stark Tag SV/CNV tag was added to gene: AFDN.
Genetic Epilepsy v0.1960 CNTN2 Zornitza Stark Phenotypes for gene: CNTN2 were changed from Epilepsy, MONDO:0015653, CNTN2-related to Epilepsy, MONDO:0015653, CNTN2-related; Epilepsy, myoclonic, familial adult, 5 MIM#615400
Mendeliome v1.1393 CNTN2 Zornitza Stark Classified gene: CNTN2 as Green List (high evidence)
Mendeliome v1.1393 CNTN2 Zornitza Stark Gene: cntn2 has been classified as Green List (High Evidence).
Mendeliome v1.1392 CNTN2 Zornitza Stark Publications for gene: CNTN2 were set to 23518707; 34120799; 34691156
Mendeliome v1.1391 CNTN2 Zornitza Stark edited their review of gene: CNTN2: Added comment: Additional family, consanguineous, homozygous variants segregated in 3 affected sibs and was not homozygous in unaffected sib. Seizures later childhood onset and mild ID.; Changed rating: GREEN; Changed publications: 23518707, 37359369; Changed phenotypes: Epilepsy, MONDO:0015653, CNTN2-related
Genetic Epilepsy v0.1959 CNTN2 Zornitza Stark Classified gene: CNTN2 as Green List (high evidence)
Genetic Epilepsy v0.1959 CNTN2 Zornitza Stark Gene: cntn2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1958 AGA Zornitza Stark Marked gene: AGA as ready
Genetic Epilepsy v0.1958 AGA Zornitza Stark Gene: aga has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1958 AGA Zornitza Stark Phenotypes for gene: AGA were changed from to Aspartylglucosaminuria, MIM# 208400
Genetic Epilepsy v0.1957 AGA Zornitza Stark Classified gene: AGA as Green List (high evidence)
Genetic Epilepsy v0.1957 AGA Zornitza Stark Gene: aga has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1956 ALDH3A2 Zornitza Stark Marked gene: ALDH3A2 as ready
Genetic Epilepsy v0.1956 ALDH3A2 Zornitza Stark Gene: aldh3a2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1956 ALDH3A2 Zornitza Stark Phenotypes for gene: ALDH3A2 were changed from to Sjogren-Larsson syndrome, MIM# 270200
Genetic Epilepsy v0.1955 ALDH3A2 Zornitza Stark Classified gene: ALDH3A2 as Green List (high evidence)
Genetic Epilepsy v0.1955 ALDH3A2 Zornitza Stark Gene: aldh3a2 has been classified as Green List (High Evidence).
Mendeliome v1.1391 FA2H Zornitza Stark Publications for gene: FA2H were set to 29423566
Mendeliome v1.1390 FA2H Zornitza Stark edited their review of gene: FA2H: Changed publications: 29423566, 31135052, 18463364, 19068277, 20104589
Mendeliome v1.1390 FA2H Zornitza Stark changed review comment from: Well established gene-disease association, both peripheral and central features (dystonia, dysarthria, cognitive impairment, and epilepsy), childhood-onset, progressive.
Sources: Expert Review; to: Well established gene-disease association, both peripheral and central features (dystonia, dysarthria, cognitive impairment, and epilepsy), childhood-onset, progressive.

PubMed: 31135052 ā€“ 19 patients from 16 families consistent with a complicated form of SPG.
PubMed:18463364 ā€“ 7 individuals identified from a large consanguineous family with SPG.
PubMed: 19068277 ā€“ 7 patients from 2 unrelated consanguineous middle eastern families
PubMed: 20104589ā€“ Multiple affected individuals in an Omani family. Findings indicated that an abnormal hydroxylation of myelin galactocerebroside lipid components can lead to the progression of a severe phenotype.

Sources: Expert Review
Incidentalome v0.296 Zornitza Stark removed gene:FA2H from the panel
Mendeliome v1.1390 FA2H Zornitza Stark Marked gene: FA2H as ready
Mendeliome v1.1390 FA2H Zornitza Stark Gene: fa2h has been classified as Green List (High Evidence).
Mendeliome v1.1390 FA2H Zornitza Stark Classified gene: FA2H as Green List (high evidence)
Mendeliome v1.1390 FA2H Zornitza Stark Gene: fa2h has been classified as Green List (High Evidence).
Mendeliome v1.1389 FA2H Zornitza Stark gene: FA2H was added
gene: FA2H was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: FA2H was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FA2H were set to 29423566
Phenotypes for gene: FA2H were set to Spastic paraplegia 35, autosomal recessive, MIM#611026
Review for gene: FA2H was set to GREEN
Added comment: Well established gene-disease association, both peripheral and central features (dystonia, dysarthria, cognitive impairment, and epilepsy), childhood-onset, progressive.
Sources: Expert Review
Genetic Epilepsy v0.1954 FA2H Zornitza Stark Marked gene: FA2H as ready
Genetic Epilepsy v0.1954 FA2H Zornitza Stark Gene: fa2h has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1954 FA2H Zornitza Stark Classified gene: FA2H as Green List (high evidence)
Genetic Epilepsy v0.1954 FA2H Zornitza Stark Gene: fa2h has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1953 FA2H Zornitza Stark gene: FA2H was added
gene: FA2H was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: FA2H was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FA2H were set to 29423566
Phenotypes for gene: FA2H were set to Spastic paraplegia 35, autosomal recessive, MIM#611026
Review for gene: FA2H was set to GREEN
Added comment: Well established gene-disease association, both peripheral and central features, childhood-onset, progressive. Epilepsy reported in multiple individuals.
Sources: Expert Review
Genetic Epilepsy v0.1952 EMC1 Zornitza Stark Marked gene: EMC1 as ready
Genetic Epilepsy v0.1952 EMC1 Zornitza Stark Gene: emc1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1952 EMC1 Zornitza Stark Classified gene: EMC1 as Green List (high evidence)
Genetic Epilepsy v0.1952 EMC1 Zornitza Stark Gene: emc1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1951 EMC1 Zornitza Stark gene: EMC1 was added
gene: EMC1 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: EMC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EMC1 were set to 35234901; 26942288
Phenotypes for gene: EMC1 were set to Neurodevelopmental disorder, MONDO:0700092, EMC1-related
Review for gene: EMC1 was set to GREEN
Added comment: Chung et al 2022 (PMID: 35234901) report 3 unrelated children with severe to profound developmental delay, truncal hypotonia, seizures and cortical visual impairment. A c.1745Cā€‰>ā€‰A; p.Pro582His (de novo) variant in EMC1 was found in 2 of the individuals. The other child had EMC1 c.1745Cā€‰>ā€‰G; p.Pro582Arg (mosaic; not inherited from mother, father deceased). Variants were identified by WES and confirmed by Sanger sequencing. In a Drosophila model the identified variants didn't rescue the lethality of a null allele. They also found variations in dosage of the wild-type EMC1, specifically in glia, lead to pupal lethality.

Note variants in this gene are associated with an AR condition as well, but seizures not part of the phenotype.
Sources: Expert Review
Fetal anomalies v1.167 EFCAB1 Zornitza Stark Phenotypes for gene: EFCAB1 were changed from Primary ciliary dyskinesia, MONDO:0016575, EFCAB1-related to Ciliary dyskinesia, primary, 53, MIM# 620642
Fetal anomalies v1.166 EFCAB1 Zornitza Stark Tag new gene name tag was added to gene: EFCAB1.
Fetal anomalies v1.166 EFCAB1 Zornitza Stark edited their review of gene: EFCAB1: Added comment: HGNC approved name is CLXN; Changed phenotypes: Ciliary dyskinesia, primary, 53, MIM# 620642
Mendeliome v1.1388 EFCAB1 Zornitza Stark Tag new gene name tag was added to gene: EFCAB1.
Mendeliome v1.1388 EFCAB1 Zornitza Stark Phenotypes for gene: EFCAB1 were changed from Primary ciliary dyskinesia, MONDO:0016575, EFCAB1-related to Ciliary dyskinesia, primary, 53, MIM# 620642
Mendeliome v1.1387 EFCAB1 Zornitza Stark edited their review of gene: EFCAB1: Added comment: Ciliary dyskinesia, primary, 53, MIM# 620642; Changed phenotypes: Ciliary dyskinesia, primary, 53, MIM# 620642
Heterotaxy v1.32 EFCAB1 Zornitza Stark Phenotypes for gene: EFCAB1 were changed from Primary ciliary dyskinesia, MONDO:0016575, EFCAB1-related to Ciliary dyskinesia, primary, 53, MIM# 620642
Heterotaxy v1.31 EFCAB1 Zornitza Stark Tag new gene name tag was added to gene: EFCAB1.
Heterotaxy v1.31 EFCAB1 Zornitza Stark reviewed gene: EFCAB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 53, MIM# 620642; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v1.37 EFCAB1 Zornitza Stark Phenotypes for gene: EFCAB1 were changed from Primary ciliary dyskinesia, MONDO:0016575, EFCAB1-related to Ciliary dyskinesia, primary, 53, MIM# 620642
Ciliary Dyskinesia v1.36 EFCAB1 Zornitza Stark Tag new gene name tag was added to gene: EFCAB1.
Ciliary Dyskinesia v1.36 EFCAB1 Zornitza Stark reviewed gene: EFCAB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 53, MIM# 620642; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1950 ALDH3A2 John Coleman edited their review of gene: ALDH3A2: Changed rating: GREEN; Changed phenotypes: Epilepsy, Seizures, Generalized Tonic Clonic Seizures
Genetic Epilepsy v0.1950 ALDH3A2 John Coleman changed review comment from: Established gene with variable neurocutaneous phenotype. Causes an inborn error of lipid metabolism. Can present in seizures estimated 35-40% in review paper. Multiple published cases with GTC being the predominant seizure type. Seizures a common feature reported on OMIM. Multiple epilepsy cases reported across various differing cohorts (Northern Europe, Belgium, German, Egypt). Curated on the multiple other panels including intellectual delay, itchyiosis, Mendeliome, leukodystophy, and metabolic disoders.

Sources: Expert Review, Literature; to: Established gene with variable neurocutaneous phenotype. Causes an inborn error of lipid metabolism. Can present in seizures estimated 35-40% in review paper. Multiple published cases with GTC being the predominant seizure type. Seizures a common feature reported on OMIM. Multiple epilepsy cases reported across various differing cohorts (Northern Europe, Belgium, German, Egypt). Curated on the multiple other panels including intellectual delay, Ichthyosis, Mendeliome, leukodystrophy, and metabolic disorders.

Sources: Expert Review, Literature
Genetic Epilepsy v0.1950 ALDH3A2 John Coleman changed review comment from: Established gene with variable neurocutaneous phenotype. Can present in seizures estimaed 35-40% in review paper. Multiple published cases with GTC
Sources: Expert Review, Literature; to: Established gene with variable neurocutaneous phenotype. Causes an inborn error of lipid metabolism. Can present in seizures estimated 35-40% in review paper. Multiple published cases with GTC being the predominant seizure type. Seizures a common feature reported on OMIM. Multiple epilepsy cases reported across various differing cohorts (Northern Europe, Belgium, German, Egypt). Curated on the multiple other panels including intellectual delay, itchyiosis, Mendeliome, leukodystophy, and metabolic disoders.

Sources: Expert Review, Literature
Genetic Epilepsy v0.1950 ALDH3A2 John Coleman gene: ALDH3A2 was added
gene: ALDH3A2 was added to Genetic Epilepsy. Sources: Expert Review,Literature
Mode of inheritance for gene: ALDH3A2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ALDH3A2 were set to (PMID:32021380,30372562
Added comment: Established gene with variable neurocutaneous phenotype. Can present in seizures estimaed 35-40% in review paper. Multiple published cases with GTC
Sources: Expert Review, Literature
Genetic Epilepsy v0.1950 AGA John Coleman edited their review of gene: AGA: Changed phenotypes: Seizures, Epilepsy
Genetic Epilepsy v0.1950 AGA John Coleman gene: AGA was added
gene: AGA was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: AGA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGA were set to (PMID: 33439067; 8333236; 19175389; 15036433; 8064811; 8946839; 1756604)
Review for gene: AGA was set to GREEN
Added comment: ASPARTYLGLUCOSAMINURIA (amino acid disorder) a severe lysosomal recessive disorder presenting with CNS, skeletal and connective tissue manifestations. Seizures or epilpesy of various types recorded across the literature. A Finnish cohort reported 1 child and 22 adults with epilepsy. Likely a founder finish mutation common with some cases in Norway and Sweden reported. Case reports of startle epilepsy and Sleep-related hypermotor seizures in aspartylglucosaminuria are also present. Japanese family with 2 siblings with seizures reported outside of common Finnish variant.
Sources: Literature
Genetic Epilepsy v0.1950 CNTN2 Lilian Downie reviewed gene: CNTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37359369; Phenotypes: ?Epilepsy, myoclonic, familial adult, 5 MIM#615400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1950 AFDN John Coleman gene: AFDN was added
gene: AFDN was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: AFDN was set to Unknown
Publications for gene: AFDN were set to (PMID: 31690835; 9679199)
Review for gene: AFDN was set to RED
Added comment: Limited information regarding this gene. 1 published case with epilepsy reported on clinvar however this is part of a CNV deletion involving multiple other genes at the locus. No neurological phenotype reported apart from a gene as part of larger CNV changes at the locus (terminal 6q deletions) with multiple other genes implicated. Clinical phenotype not on ClinGen, No neurological phenotype reported on OMIM. Pubmed and other literature search returns no results for "AFDN" and "seizures", "seizure" or "AFDN" and "epilepsy". Not included on other testing panels (panelapp UK). Previous cytogenetic and animal models suggested implication in T6,11 with MLL.
Sources: Literature
Genetic Epilepsy v0.1950 CLCN2 Lilian Downie reviewed gene: CLCN2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 36374051; Phenotypes: Epilepsy susceptibility MIM#607628; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1950 BET1 Lilian Downie reviewed gene: BET1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34779586; Phenotypes: Muscular dystrophy MONDO:0020121; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1950 ADNP John Coleman gene: ADNP was added
gene: ADNP was added to Genetic Epilepsy. Sources: Literature,Expert Review
Mode of inheritance for gene: ADNP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADNP were set to (PMID: 27054228; 24531329)
Phenotypes for gene: ADNP were set to Seizures; Epilpesy; Focal Seizures; Absence seizures
Review for gene: ADNP was set to GREEN
Added comment: ADNP related disorders. Review paper showing 12 of 78 patient cohort with seizures of various types - focal, absence. Other features: hypotonia, developmental delay, mild-to-severe intellectual disability, facial dysmorphic features, behavioral problems, sleep disturbance, brain abnormalities, feeding issues, gastrointestinal problems, visual dysfunction, musculoskeletal anomalies, endocrine issues including short stature and hormonal deficiencies, cardiac and urinary tract anomalies & hearing loss. An older cohort showed 2 of 10 individuals with seizures. Seizures is not the predominant phenotype but a feature in some cases.
Sources: Literature, Expert Review
Genetic Epilepsy v0.1950 ADCY5 John Coleman gene: ADCY5 was added
gene: ADCY5 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ADCY5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ADCY5 were set to (PMID: 36003298; 33564903; 27061943)
Review for gene: ADCY5 was set to AMBER
Added comment: AD and AR dyskinesia phenotype. Only one confirmed case of epilepsy of 119 cases, 2 suspected but unconfirmed. Strong dyskinesia phenotype that may have similar overlapping features. Epilepsy/ seizures not a reported phenotype on OMIM. No other cases reported on literature search. Gene not curated on ClinGen. Dystonia, myoclonus and choreoathetosis the predominant phenotype (gene included in Mediliome, CP, channelopathies, dystonia and dyskinesia panels). Caution regarding overlap of epilepsy features and phenotyping but appears to have distinct dyskinesia phenotype. ?Moderate Vs limited evidence.
Sources: Literature
Genetic Epilepsy v0.1950 ACY1 John Coleman edited their review of gene: ACY1: Changed rating: GREEN
Genetic Epilepsy v0.1950 ACY1 John Coleman changed review comment from: Known ACY1 amino acid disorder with neurological phenotype. Seizures reported as a feature on OMIM. Phenotype includes seizures both febrile and afebrile. One paper with 3 families (1 German, 1 English and 1 Romani) with seizure phenotype. 2 other publications with seizure phenotype. Seizures reported strongly with intercurrent illness.
Sources: Literature; to: Known ACY1 amino acid disorder with neurological phenotype. Seizures reported as a feature on OMIM. Phenotype includes seizures both febrile and afebrile. One paper with 3 families (1 German, 1 English and 1 Romani) with seizure phenotype. 2 other publications with seizure phenotype. Seizures reported strongly with intercurrent illness.
Sources: Literature
Genetic Epilepsy v0.1950 ACY1 John Coleman gene: ACY1 was added
gene: ACY1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ACY1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACY1 were set to (PMID: 16465618,16274666, 24117009)
Phenotypes for gene: ACY1 were set to Seizures; Epilepsy; Febrile Seizures
Penetrance for gene: ACY1 were set to unknown
Added comment: Known ACY1 amino acid disorder with neurological phenotype. Seizures reported as a feature on OMIM. Phenotype includes seizures both febrile and afebrile. One paper with 3 families (1 German, 1 English and 1 Romani) with seizure phenotype. 2 other publications with seizure phenotype. Seizures reported strongly with intercurrent illness.
Sources: Literature
Genetic Epilepsy v0.1950 ACTB John Coleman gene: ACTB was added
gene: ACTB was added to Genetic Epilepsy. Sources: Literature,Expert Review
Mode of inheritance for gene: ACTB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACTB were set to (PMID:22366783,25052316,31970217)
Phenotypes for gene: ACTB were set to Seizures; Epilepsy
Review for gene: ACTB was set to GREEN
Added comment: Missense variants cause gain of function and are associated with Baraitser-Winter syndrome. PTC variants result in haploinsufficiency (loss of function) and cause a similar, but distinct phenotype to Baraitser-Winter syndrome. Seizures reported in 50% of cases with ACTB (GENEREVIEWS). 9 individuals with Baraitser-Winter with epilepsy in one paper and 13 with epilepsy in another review. Estimated 50% with Baraitser-Winter with seizures. Seizures also reported in one case of the LOF distinctive Dystonia-deafness syndrome (Brazilian woman).
Sources: Literature, Expert Review
Intellectual disability syndromic and non-syndromic v0.5619 WNK3 Zornitza Stark Phenotypes for gene: WNK3 were changed from Neurodevelopmental disorder, WNK3-related (MONDO#0700092) to Prieto syndrome, MIM# 309610
Intellectual disability syndromic and non-syndromic v0.5618 WNK3 Zornitza Stark reviewed gene: WNK3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Prieto syndrome, MIM# 309610; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.1950 WNK3 Zornitza Stark Phenotypes for gene: WNK3 were changed from Neurodevelopmental disorder, WNK3-related (MONDO#0700092) to Prieto syndrome, MIM# 309610
Genetic Epilepsy v0.1949 WNK3 Zornitza Stark edited their review of gene: WNK3: Changed phenotypes: Prieto syndrome, MIM# 309610
Microcephaly v1.237 WNK3 Zornitza Stark Phenotypes for gene: WNK3 were changed from Neurodevelopmental disorder, WNK3-related (MONDO#0700092) to Prieto syndrome, MIM# 309610
Microcephaly v1.236 WNK3 Zornitza Stark reviewed gene: WNK3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Prieto syndrome, MIM# 309610; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.1387 WNK3 Zornitza Stark Phenotypes for gene: WNK3 were changed from Neurodevelopmental disorder, WNK3-related (MONDO#0700092) to Prieto syndrome, MIM# 309610
Mendeliome v1.1386 WNK3 Zornitza Stark edited their review of gene: WNK3: Changed phenotypes: Prieto syndrome, MIM# 309610
Genetic Epilepsy v0.1949 ABHD16A Zornitza Stark Marked gene: ABHD16A as ready
Genetic Epilepsy v0.1949 ABHD16A Zornitza Stark Gene: abhd16a has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1949 ABHD16A Zornitza Stark Phenotypes for gene: ABHD16A were changed from seizures; myoclonic seizures; developmental delay to Spastic paraplegia 86, autosomal recessive, MIM# 619735; seizures; myoclonic seizures; developmental delay
Genetic Epilepsy v0.1948 ABHD16A Zornitza Stark Classified gene: ABHD16A as Amber List (moderate evidence)
Genetic Epilepsy v0.1948 ABHD16A Zornitza Stark Gene: abhd16a has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1947 ABHD16A Zornitza Stark reviewed gene: ABHD16A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 86, autosomal recessive, MIM# 619735; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.108 PHLDB1 Zornitza Stark Phenotypes for gene: PHLDB1 were changed from osteogenesis imperfecta, MONDO:0019019 to Osteogenesis imperfecta, type XXIII, MIM# 620639
Osteogenesis Imperfecta and Osteoporosis v0.107 PHLDB1 Zornitza Stark reviewed gene: PHLDB1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteogenesis imperfecta, type XXIII, MIM# 620639; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1386 PHLDB1 Zornitza Stark Phenotypes for gene: PHLDB1 were changed from osteogenesis imperfecta, MONDO:0019019 to Osteogenesis imperfecta, type XXIII, MIM# 620639
Mendeliome v1.1385 PHLDB1 Zornitza Stark reviewed gene: PHLDB1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteogenesis imperfecta, type XXIII, MIM# 620639; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1947 ABHD16A John Coleman changed review comment from: 11 individuals from 6 families with loss of function, bi-allelic variants in ABHD16A. 2 unrelated families (1 French-Canadian, 1 Armenian) with different homozygous variants have seizures reported. 1 patient with myoclonic seizure type reported. No direct phenotype for other patient. Immunoblot from the fibroblasts demonstrated recued ABHD16A for these families. Strong neurodevelopmental phenotype. Other paper with Homozygotes family 1 of 4 individuals presenting with febrile convulsions. ABHD16A is a phospholipase that converts PS to Lyso PS. It is present in all cell types but most abundant in neurological tissue and involved in a key process of neurophysiology. Present in callosome, intellectual disability and HSP panels.
Sources: Literature; to: 11 individuals from 6 families with loss of function, bi-allelic variants in ABHD16A. 2 unrelated families (1 French-Canadian, 1 Armenian) with different homozygous variants have seizures reported. 1 patient with myoclonic seizure type reported. No direct phenotype for other patient. Immunoblot from the fibroblasts demonstrated recued ABHD16A for these families. Strong neurodevelopmental phenotype. Other paper with Homozygotes family 1 of 4 individuals presenting with febrile convulsions. ABHD16A is a phospholipase that converts PS to Lyso PS. It is present in all cell types but most abundant in neurological tissue and involved in a key process of neurophysiology. Present in callosome, intellectual disability and HSP panels. ?Moderate
Sources: Literature
Genetic Epilepsy v0.1947 ABHD16A John Coleman changed review comment from: 11 individuals from 6 families with loss of function, bi-allelic variants in ABHD16A. 2 unrelated families (1 French-Canadian, 1 Armenian) with different homozygous variants have seizures reported. 1 patient with myoclonic seizure type reported. No direct phenotype for other patient. Immunoblot from the fibroblasts demonstrated recued ABHD16A for these families. Strong neurodevelopmental phenotype. Other paper with Homozygotes family 1 of 4 individuals presenting with febrile convulsions ABHD16A is a phospholipase that converts PS to Lyso PS. It is present in all cell types but most abundant in neurological tissue and involved in a key process of neurophysiology. Present in callosome, intellectual disability and HSP panels.
Sources: Literature; to: 11 individuals from 6 families with loss of function, bi-allelic variants in ABHD16A. 2 unrelated families (1 French-Canadian, 1 Armenian) with different homozygous variants have seizures reported. 1 patient with myoclonic seizure type reported. No direct phenotype for other patient. Immunoblot from the fibroblasts demonstrated recued ABHD16A for these families. Strong neurodevelopmental phenotype. Other paper with Homozygotes family 1 of 4 individuals presenting with febrile convulsions. ABHD16A is a phospholipase that converts PS to Lyso PS. It is present in all cell types but most abundant in neurological tissue and involved in a key process of neurophysiology. Present in callosome, intellectual disability and HSP panels.
Sources: Literature
Genetic Epilepsy v0.1947 ABHD16A John Coleman gene: ABHD16A was added
gene: ABHD16A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ABHD16A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABHD16A were set to (PMID: 34587489,34489854; 32462874)
Phenotypes for gene: ABHD16A were set to seizures; myoclonic seizures; developmental delay
Penetrance for gene: ABHD16A were set to Incomplete
Review for gene: ABHD16A was set to RED
Added comment: 11 individuals from 6 families with loss of function, bi-allelic variants in ABHD16A. 2 unrelated families (1 French-Canadian, 1 Armenian) with different homozygous variants have seizures reported. 1 patient with myoclonic seizure type reported. No direct phenotype for other patient. Immunoblot from the fibroblasts demonstrated recued ABHD16A for these families. Strong neurodevelopmental phenotype. Other paper with Homozygotes family 1 of 4 individuals presenting with febrile convulsions ABHD16A is a phospholipase that converts PS to Lyso PS. It is present in all cell types but most abundant in neurological tissue and involved in a key process of neurophysiology. Present in callosome, intellectual disability and HSP panels.
Sources: Literature
Mendeliome v1.1385 FLII Zornitza Stark Phenotypes for gene: FLII were changed from Dilated cardiomyopathy MONDO:0005021 to Cardiomyopathy, dilated, 2J, MIM# 620635
Mendeliome v1.1384 FLII Zornitza Stark edited their review of gene: FLII: Changed phenotypes: Cardiomyopathy, dilated, 2J, MIM# 620635
Cardiomyopathy_Paediatric v0.174 FLII Zornitza Stark Phenotypes for gene: FLII were changed from Dilated cardiomyopathy to Cardiomyopathy, dilated, 2J, MIM# 620635
Cardiomyopathy_Paediatric v0.173 FLII Zornitza Stark edited their review of gene: FLII: Changed phenotypes: Cardiomyopathy, dilated, 2J, MIM# 620635
Autoinflammatory Disorders v1.30 RNF31 Zornitza Stark Marked gene: RNF31 as ready
Autoinflammatory Disorders v1.30 RNF31 Zornitza Stark Gene: rnf31 has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v1.30 RNF31 Zornitza Stark Classified gene: RNF31 as Amber List (moderate evidence)
Autoinflammatory Disorders v1.30 RNF31 Zornitza Stark Gene: rnf31 has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v1.29 RNF31 Zornitza Stark gene: RNF31 was added
gene: RNF31 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Expert Review
Mode of inheritance for gene: RNF31 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNF31 were set to 26008899; 30936877
Phenotypes for gene: RNF31 were set to Immunodeficiency 115 with autoinflammation, MIM# 620632
Review for gene: RNF31 was set to AMBER
Added comment: Two unrelated individuals reported.
Sources: Expert Review
Combined Immunodeficiency v1.52 RNF31 Zornitza Stark Phenotypes for gene: RNF31 were changed from Immune deficiency; Autoinflammation to Immunodeficiency 115 with autoinflammation, MIM# 620632
Combined Immunodeficiency v1.51 RNF31 Zornitza Stark edited their review of gene: RNF31: Changed phenotypes: Immunodeficiency 115 with autoinflammation, MIM# 620632
Mendeliome v1.1384 RNF31 Zornitza Stark Phenotypes for gene: RNF31 were changed from Immune deficiency; Autoinflammation to Immunodeficiency 115 with autoinflammation, MIM# 620632
Mendeliome v1.1383 RNF31 Zornitza Stark edited their review of gene: RNF31: Changed phenotypes: Immunodeficiency 115 with autoinflammation, MIM# 620632
Mitochondrial disease v0.895 TANGO2 Zornitza Stark Marked gene: TANGO2 as ready
Mitochondrial disease v0.895 TANGO2 Zornitza Stark Gene: tango2 has been classified as Green List (High Evidence).
Mitochondrial disease v0.895 TANGO2 Zornitza Stark Classified gene: TANGO2 as Green List (high evidence)
Mitochondrial disease v0.895 TANGO2 Zornitza Stark Gene: tango2 has been classified as Green List (High Evidence).
Mitochondrial disease v0.894 TANGO2 Zornitza Stark gene: TANGO2 was added
gene: TANGO2 was added to Mitochondrial disease. Sources: Expert Review
Mode of inheritance for gene: TANGO2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TANGO2 were set to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM# 616878
Review for gene: TANGO2 was set to GREEN
Added comment: Large phenotypic overlap with mitochondrial disease.
Sources: Expert Review
Congenital Heart Defect v0.409 GATA4 Zornitza Stark Marked gene: GATA4 as ready
Congenital Heart Defect v0.409 GATA4 Zornitza Stark Gene: gata4 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.409 GATA4 Zornitza Stark Phenotypes for gene: GATA4 were changed from to Atrial septal defect 2 MIM#607941; Atrioventricular septal defect 4 MIM#614430; Ventricular septal defect 1 MIM#614429
Congenital Heart Defect v0.408 GATA4 Zornitza Stark Publications for gene: GATA4 were set to
Congenital Heart Defect v0.407 GATA4 Zornitza Stark Mode of inheritance for gene: GATA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.406 GATA4 Zornitza Stark reviewed gene: GATA4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Atrial septal defect 2 MIM#607941, Atrioventricular septal defect 4 MIM#614430, Ventricular septal defect 1 MIM#614429; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5618 WDR11 Elena Savva Mode of inheritance for gene: WDR11 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.406 GATA4 Sharyn Stockmyer reviewed gene: GATA4: Rating: GREEN; Mode of pathogenicity: None; Publications: 15810002, 12845333, 22101736, 18672102, 24000169, 29377543, 28991257; Phenotypes: Congenital heart disease - multiple types; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.406 EVC2 Zornitza Stark Marked gene: EVC2 as ready
Congenital Heart Defect v0.406 EVC2 Zornitza Stark Gene: evc2 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.406 EVC2 Zornitza Stark Phenotypes for gene: EVC2 were changed from to Ellis-van Creveld syndrome (MIM#225500)
Congenital Heart Defect v0.405 EVC2 Zornitza Stark Mode of inheritance for gene: EVC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.404 EVC2 Zornitza Stark reviewed gene: EVC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ellis-van Creveld syndrome (MIM#225500); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.404 EVC Zornitza Stark Marked gene: EVC as ready
Congenital Heart Defect v0.404 EVC Zornitza Stark Gene: evc has been classified as Green List (High Evidence).
Congenital Heart Defect v0.404 EVC Zornitza Stark Phenotypes for gene: EVC were changed from to Ellis-van Creveld syndrome, MIM# 225500
Congenital Heart Defect v0.403 EVC Zornitza Stark Mode of inheritance for gene: EVC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.402 EVC Zornitza Stark reviewed gene: EVC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ellis-van Creveld syndrome, MIM# 225500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.402 ELN Zornitza Stark Marked gene: ELN as ready
Congenital Heart Defect v0.402 ELN Zornitza Stark Gene: eln has been classified as Green List (High Evidence).
Congenital Heart Defect v0.402 ELN Zornitza Stark Phenotypes for gene: ELN were changed from to Supravalvar aortic stenosis, MIM# 185500
Congenital Heart Defect v0.401 ELN Zornitza Stark Mode of inheritance for gene: ELN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.400 ELN Zornitza Stark reviewed gene: ELN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Supravalvar aortic stenosis, MIM# 185500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.400 CREBBP Zornitza Stark Marked gene: CREBBP as ready
Congenital Heart Defect v0.400 CREBBP Zornitza Stark Gene: crebbp has been classified as Green List (High Evidence).
Congenital Heart Defect v0.400 CREBBP Zornitza Stark Phenotypes for gene: CREBBP were changed from to Rubinstein-Taybi syndrome 1 , MIM#180849
Congenital Heart Defect v0.399 CREBBP Zornitza Stark Mode of inheritance for gene: CREBBP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.398 CREBBP Zornitza Stark reviewed gene: CREBBP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Rubinstein-Taybi syndrome 1 , MIM#180849; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.398 BMPR2 Zornitza Stark Marked gene: BMPR2 as ready
Congenital Heart Defect v0.398 BMPR2 Zornitza Stark Gene: bmpr2 has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.398 BMPR2 Zornitza Stark Phenotypes for gene: BMPR2 were changed from to Pulmonary hypertension, familial primary, 1, with or without HHT MIM#178600 Pulmonary hypertension, primary, fenfluramine or dexfenfluramine-associated MIM#178600 Pulmonary venoocclusive disease 1 MIM#265450
Congenital Heart Defect v0.397 BMPR2 Zornitza Stark Mode of inheritance for gene: BMPR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.396 BMPR2 Zornitza Stark Classified gene: BMPR2 as Red List (low evidence)
Congenital Heart Defect v0.396 BMPR2 Zornitza Stark Gene: bmpr2 has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.395 BMPR2 Zornitza Stark reviewed gene: BMPR2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary hypertension, familial primary, 1, with or without HHT MIM#178600 Pulmonary hypertension, primary, fenfluramine or dexfenfluramine-associated MIM#178600 Pulmonary venoocclusive disease 1 MIM#265450; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.395 B3GAT3 Zornitza Stark Marked gene: B3GAT3 as ready
Congenital Heart Defect v0.395 B3GAT3 Zornitza Stark Gene: b3gat3 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.395 B3GAT3 Zornitza Stark Phenotypes for gene: B3GAT3 were changed from to Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects -MIM#245600
Congenital Heart Defect v0.394 B3GAT3 Zornitza Stark Publications for gene: B3GAT3 were set to
Congenital Heart Defect v0.393 B3GAT3 Zornitza Stark Mode of inheritance for gene: B3GAT3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.392 B3GAT3 Zornitza Stark reviewed gene: B3GAT3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26754439, 31988067, 26086840, 25893793, 21763480, 24668659; Phenotypes: Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects -MIM#245600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Eye Anterior Segment Abnormalities v1.12 ASPH Zornitza Stark Marked gene: ASPH as ready
Eye Anterior Segment Abnormalities v1.12 ASPH Zornitza Stark Gene: asph has been classified as Green List (High Evidence).
Eye Anterior Segment Abnormalities v1.12 ASPH Zornitza Stark reviewed gene: ASPH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Traboulsi syndrome , MIM#601552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Eye Anterior Segment Abnormalities v1.12 LTBP2 Zornitza Stark Marked gene: LTBP2 as ready
Eye Anterior Segment Abnormalities v1.12 LTBP2 Zornitza Stark Gene: ltbp2 has been classified as Green List (High Evidence).
Eye Anterior Segment Abnormalities v1.12 LTBP2 Zornitza Stark Classified gene: LTBP2 as Green List (high evidence)
Eye Anterior Segment Abnormalities v1.12 LTBP2 Zornitza Stark Gene: ltbp2 has been classified as Green List (High Evidence).
Eye Anterior Segment Abnormalities v1.11 LTBP2 Elena Savva gene: LTBP2 was added
gene: LTBP2 was added to Eye Anterior Segment Abnormalities. Sources: Literature
Mode of inheritance for gene: LTBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LTBP2 were set to Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma MIM#251750
Review for gene: LTBP2 was set to GREEN
Added comment: Established gene-disease association
Sources: Literature
Eye Anterior Segment Abnormalities v1.10 FBN1 Elena Savva Classified gene: FBN1 as Green List (high evidence)
Eye Anterior Segment Abnormalities v1.10 FBN1 Elena Savva Gene: fbn1 has been classified as Green List (High Evidence).
Eye Anterior Segment Abnormalities v1.9 FBN1 Elena Savva Classified gene: FBN1 as Green List (high evidence)
Eye Anterior Segment Abnormalities v1.9 FBN1 Elena Savva Gene: fbn1 has been classified as Green List (High Evidence).
Eye Anterior Segment Abnormalities v1.8 FBN1 Elena Savva Marked gene: FBN1 as ready
Eye Anterior Segment Abnormalities v1.8 FBN1 Elena Savva Gene: fbn1 has been classified as Red List (Low Evidence).
Eye Anterior Segment Abnormalities v1.8 ADAMTSL4 Elena Savva Classified gene: ADAMTSL4 as Green List (high evidence)
Eye Anterior Segment Abnormalities v1.8 ADAMTSL4 Elena Savva Gene: adamtsl4 has been classified as Green List (High Evidence).
Eye Anterior Segment Abnormalities v1.7 ADAMTSL4 Elena Savva Classified gene: ADAMTSL4 as Green List (high evidence)
Eye Anterior Segment Abnormalities v1.7 ADAMTSL4 Elena Savva Gene: adamtsl4 has been classified as Green List (High Evidence).
Eye Anterior Segment Abnormalities v1.7 FBN1 Elena Savva gene: FBN1 was added
gene: FBN1 was added to Eye Anterior Segment Abnormalities. Sources: Literature
Mode of inheritance for gene: FBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: FBN1 were set to Ectopia lentis, familial (MIM#129600)
Review for gene: FBN1 was set to GREEN
Added comment: Established gene-disease association
Sources: Literature
Eye Anterior Segment Abnormalities v1.6 ADAMTSL4 Elena Savva Marked gene: ADAMTSL4 as ready
Eye Anterior Segment Abnormalities v1.6 ADAMTSL4 Elena Savva Gene: adamtsl4 has been classified as Red List (Low Evidence).
Eye Anterior Segment Abnormalities v1.6 ADAMTSL4 Elena Savva gene: ADAMTSL4 was added
gene: ADAMTSL4 was added to Eye Anterior Segment Abnormalities. Sources: Literature
Mode of inheritance for gene: ADAMTSL4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ADAMTSL4 were set to Ectopia lentis et pupillae, AR (MIM#225200); Isolated ectopia lentis, autosomal recessive, AR (MIM#225100), Craniosynostosis with ectopia lentis, AR (MONDO#0011347)
Review for gene: ADAMTSL4 was set to GREEN
Added comment: Established phenotypic association to ectopia lentis
Sources: Literature
Congenital Heart Defect v0.392 SMC3 Zornitza Stark Marked gene: SMC3 as ready
Congenital Heart Defect v0.392 SMC3 Zornitza Stark Gene: smc3 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.392 SMC3 Zornitza Stark Phenotypes for gene: SMC3 were changed from to Cornelia de Lange syndrome 3, MIM# 610759
Congenital Heart Defect v0.391 SMC3 Zornitza Stark Mode of inheritance for gene: SMC3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.390 SMC3 Zornitza Stark reviewed gene: SMC3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cornelia de Lange syndrome 3, MIM# 610759; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.390 SOS1 Zornitza Stark Marked gene: SOS1 as ready
Congenital Heart Defect v0.390 SOS1 Zornitza Stark Gene: sos1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.390 SOS1 Zornitza Stark Phenotypes for gene: SOS1 were changed from to Noonan syndrome 4, MIM# 610733
Congenital Heart Defect v0.389 SOS1 Zornitza Stark Mode of inheritance for gene: SOS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.388 SOS1 Zornitza Stark reviewed gene: SOS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome 4, MIM# 610733; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.388 STRA6 Zornitza Stark Marked gene: STRA6 as ready
Congenital Heart Defect v0.388 STRA6 Zornitza Stark Gene: stra6 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.388 STRA6 Zornitza Stark Phenotypes for gene: STRA6 were changed from to Microphthalmia, syndromic 9, MIM# 601186
Congenital Heart Defect v0.387 STRA6 Zornitza Stark Mode of inheritance for gene: STRA6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.386 STRA6 Zornitza Stark reviewed gene: STRA6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Microphthalmia, syndromic 9, MIM# 601186; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.386 TBX20 Zornitza Stark Marked gene: TBX20 as ready
Congenital Heart Defect v0.386 TBX20 Zornitza Stark Gene: tbx20 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.386 TBX20 Zornitza Stark Phenotypes for gene: TBX20 were changed from to Atrial septal defect 4, MIM# 611363
Congenital Heart Defect v0.385 TBX20 Zornitza Stark Publications for gene: TBX20 were set to
Congenital Heart Defect v0.384 TBX20 Zornitza Stark Mode of inheritance for gene: TBX20 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.383 TBX20 Zornitza Stark reviewed gene: TBX20: Rating: GREEN; Mode of pathogenicity: None; Publications: 17668378, 19762328, 33585493, 29089047; Phenotypes: Atrial septal defect 4, MIM# 611363; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.383 TBX5 Zornitza Stark Marked gene: TBX5 as ready
Congenital Heart Defect v0.383 TBX5 Zornitza Stark Gene: tbx5 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.383 TBX5 Zornitza Stark Phenotypes for gene: TBX5 were changed from to Holt-Oram syndrome, MIM# 142900
Congenital Heart Defect v0.382 TBX5 Zornitza Stark Mode of inheritance for gene: TBX5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.381 TBX5 Zornitza Stark reviewed gene: TBX5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Holt-Oram syndrome, MIM# 142900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.381 TGFBR1 Zornitza Stark Marked gene: TGFBR1 as ready
Congenital Heart Defect v0.381 TGFBR1 Zornitza Stark Gene: tgfbr1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.381 TGFBR1 Zornitza Stark Phenotypes for gene: TGFBR1 were changed from to Loeys-Dietz syndrome 1, MIM# 609192
Congenital Heart Defect v0.380 TGFBR1 Zornitza Stark Mode of inheritance for gene: TGFBR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.379 TGFBR1 Zornitza Stark reviewed gene: TGFBR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Loeys-Dietz syndrome 1, MIM# 609192; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Combined Immunodeficiency v1.51 RELB Peter McNaughton reviewed gene: RELB: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 36402602; Phenotypes: Complex autoimmunity; Mode of inheritance: None
Congenital Heart Defect v0.379 TGFBR2 Zornitza Stark Marked gene: TGFBR2 as ready
Congenital Heart Defect v0.379 TGFBR2 Zornitza Stark Gene: tgfbr2 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.379 TGFBR2 Zornitza Stark Phenotypes for gene: TGFBR2 were changed from to Loeys-Dietz syndrome 2, MIM# 610168
Congenital Heart Defect v0.378 TGFBR2 Zornitza Stark Mode of inheritance for gene: TGFBR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.377 TGFBR2 Zornitza Stark reviewed gene: TGFBR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Loeys-Dietz syndrome 2, MIM# 610168; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.377 ZIC3 Zornitza Stark Marked gene: ZIC3 as ready
Congenital Heart Defect v0.377 ZIC3 Zornitza Stark Gene: zic3 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.377 ZIC3 Zornitza Stark Phenotypes for gene: ZIC3 were changed from to Heterotaxy, visceral, 1, X-linked (MIM#306955)
Congenital Heart Defect v0.376 ZIC3 Zornitza Stark Publications for gene: ZIC3 were set to
Congenital Heart Defect v0.375 ZIC3 Zornitza Stark Mode of inheritance for gene: ZIC3 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Congenital Heart Defect v0.374 ZIC3 Zornitza Stark reviewed gene: ZIC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 27406248, 30120289; Phenotypes: Heterotaxy, visceral, 1, X-linked (MIM#306955); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Congenital Heart Defect v0.374 MESP1 Zornitza Stark Phenotypes for gene: MESP1 were changed from Congenital heart disease, MONDO:0005453, MESP1-related to Congenital heart disease, MONDO:0005453, MESP1-related
Congenital Heart Defect v0.374 MESP1 Zornitza Stark Phenotypes for gene: MESP1 were changed from Congenital heart disease to Congenital heart disease, MONDO:0005453, MESP1-related
Congenital Heart Defect v0.373 FOXH1 Zornitza Stark Phenotypes for gene: FOXH1 were changed from Congenital heart disease to Congenital heart disease, MONDO:0005453, FOXH1-related
Congenital Heart Defect v0.372 ACVR2B Zornitza Stark Marked gene: ACVR2B as ready
Congenital Heart Defect v0.372 ACVR2B Zornitza Stark Gene: acvr2b has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.372 NR2F2 Zornitza Stark Marked gene: NR2F2 as ready
Congenital Heart Defect v0.372 NR2F2 Zornitza Stark Gene: nr2f2 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.372 NR2F2 Zornitza Stark Phenotypes for gene: NR2F2 were changed from to 46,XX sex reversal 5 - MIM#618901; Congenital heart defects, multiple types, 4 - MIM#615779
Congenital Heart Defect v0.371 NR2F2 Zornitza Stark Publications for gene: NR2F2 were set to
Congenital Heart Defect v0.370 NR2F2 Zornitza Stark Mode of inheritance for gene: NR2F2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1383 KDR Zornitza Stark Phenotypes for gene: KDR were changed from Pulmonary hypertension; Haemangioma, capillary infantile, somatic 602089 to Pulmonary hypertension; Haemangioma, capillary infantile, somatic 602089; Tetralogy of Fallot, MONDO:0008542
Mendeliome v1.1382 KDR Zornitza Stark Mode of inheritance for gene: KDR was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1381 KDR Zornitza Stark edited their review of gene: KDR: Added comment: PMID 34113005: Exome sequencing in a family with two siblings affected by ToF revealed biallelic missense variants in KDR. Studies in knock-in mice and in HEK 293T cells identified embryonic lethality for one variant when occurring in the homozygous state, and a significantly reduced VEGFR2 phosphorylation for both variants.

Rare variant burden analysis conducted in a set of 1,569 patients of European descent with ToF identified a 46-fold enrichment of protein-truncating variants (PTVs) in TOF cases compared to controls (P = 7 Ɨ 10-11). At this stage MOI unclear and insufficient evidence for either MOI.; Changed publications: 31980491, 29650961, 18931684, 34113005; Changed phenotypes: Pulmonary hypertension, Haemangioma, capillary infantile, somatic 602089, Tetralogy of Fallot, MONDO:0008542; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Heart Defect v0.369 KDR Zornitza Stark Mode of inheritance for gene: KDR was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Heart Defect v0.368 KDR Zornitza Stark Classified gene: KDR as Amber List (moderate evidence)
Congenital Heart Defect v0.368 KDR Zornitza Stark Gene: kdr has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.367 KDR Zornitza Stark edited their review of gene: KDR: Added comment: PMID 34113005: Exome sequencing in a family with two siblings affected by ToF revealed biallelic missense variants in KDR. Studies in knock-in mice and in HEK 293T cells identified embryonic lethality for one variant when occurring in the homozygous state, and a significantly reduced VEGFR2 phosphorylation for both variants.

Rare variant burden analysis conducted in a set of 1,569 patients of European descent with ToF identified a 46-fold enrichment of protein-truncating variants (PTVs) in TOF cases compared to controls (P = 7 Ɨ 10-11).

At this stage MOI unclear and insufficient evidence for either MOI.; Changed rating: AMBER; Changed publications: 34113005; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1381 DOT1L Zornitza Stark Marked gene: DOT1L as ready
Mendeliome v1.1381 DOT1L Zornitza Stark Gene: dot1l has been classified as Green List (High Evidence).
Mendeliome v1.1381 DOT1L Zornitza Stark Classified gene: DOT1L as Green List (high evidence)
Mendeliome v1.1381 DOT1L Zornitza Stark Gene: dot1l has been classified as Green List (High Evidence).
Mendeliome v1.1380 DOT1L Zornitza Stark gene: DOT1L was added
gene: DOT1L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DOT1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DOT1L were set to 37827158
Phenotypes for gene: DOT1L were set to Neurodevelopmental disorder, MONDO:0700092, DOT1L-related
Mode of pathogenicity for gene: DOT1L was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: DOT1L was set to GREEN
Added comment: Nine individuals reported with seven de novo missense variants.

All had DD/ID and variable patterns of associated congenital anomalies.

Variants demonstrated to be GoF and lead to increased H3K79 methylation levels in flies and human cells.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5617 DOT1L Zornitza Stark Marked gene: DOT1L as ready
Intellectual disability syndromic and non-syndromic v0.5617 DOT1L Zornitza Stark Gene: dot1l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5617 DOT1L Zornitza Stark Classified gene: DOT1L as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5617 DOT1L Zornitza Stark Gene: dot1l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5616 DOT1L Zornitza Stark gene: DOT1L was added
gene: DOT1L was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DOT1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DOT1L were set to 37827158
Phenotypes for gene: DOT1L were set to Neurodevelopmental disorder, MONDO:0700092, DOT1L-related
Mode of pathogenicity for gene: DOT1L was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: DOT1L was set to GREEN
Added comment: Nine individuals reported with seven de novo missense variants.

All had DD/ID and variable patterns of associated congenital anomalies.

Variants demonstrated to be GoF and lead to increased H3K79 methylation levels in flies and human cells.
Sources: Literature
Mendeliome v1.1379 UNC119 Zornitza Stark Classified gene: UNC119 as Amber List (moderate evidence)
Mendeliome v1.1379 UNC119 Zornitza Stark Gene: unc119 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1378 UNC119 Zornitza Stark changed review comment from: Immunodeficiency 13: Single case reported with the missense Gly22Val. The allele frequency of this variant is >2% in the African/African American subpopulation in gnomAD v2.1, including 6 homozygotes. RED for this association.

Borderline Green for association with cone-rod dystrophy.; to: Immunodeficiency 13: Single case reported with the missense Gly22Val. The allele frequency of this variant is >2% in the African/African American subpopulation in gnomAD v2.1, including 6 homozygotes. RED for this association.

Cone-rod dystrophy: one of the reported variants is missense with no other supporting evidence.
Mendeliome v1.1378 UNC119 Zornitza Stark edited their review of gene: UNC119: Changed rating: AMBER
Cone-rod Dystrophy v0.53 UNC119 Zornitza Stark Mode of inheritance for gene: UNC119 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cone-rod Dystrophy v0.52 UNC119 Zornitza Stark Classified gene: UNC119 as Amber List (moderate evidence)
Cone-rod Dystrophy v0.52 UNC119 Zornitza Stark Gene: unc119 has been classified as Amber List (Moderate Evidence).
Cone-rod Dystrophy v0.51 UNC119 Zornitza Stark edited their review of gene: UNC119: Added comment: One of the variants reported is missense with no other supporting information.; Changed rating: AMBER
Genetic Epilepsy v0.1947 TRMT10A Shekeeb Mohammad gene: TRMT10A was added
gene: TRMT10A was added to Genetic Epilepsy. Sources: Literature,Expert Review,Expert list
Mode of inheritance for gene: TRMT10A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRMT10A were set to 26535115; 4995728
Phenotypes for gene: TRMT10A were set to microcephaly; diabetes; intellectual disability; epilepsy
Penetrance for gene: TRMT10A were set to unknown
Review for gene: TRMT10A was set to GREEN
gene: TRMT10A was marked as current diagnostic
Added comment: Epilepsy is reported with cortical malformations, or due to glycaemic control issues but also at varying ages without malformations or low/high blood sugar.
Sources: Literature, Expert Review, Expert list
Mitochondrial disease v0.893 MECR Zornitza Stark edited their review of gene: MECR: Changed phenotypes: Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, MIM# 617282, MONDO:0015003, Optic atrophy 16, MIM# 620629
Mendeliome v1.1378 MECR Zornitza Stark Phenotypes for gene: MECR were changed from Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, MIM# 617282; MONDO:0015003 to Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, MIM# 617282; MONDO:0015003; Optic atrophy 16, MIM# 620629
Mendeliome v1.1377 MECR Zornitza Stark edited their review of gene: MECR: Changed phenotypes: Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, MIM# 617282, MONDO:0015003, Optic atrophy 16, MIM# 620629
Optic Atrophy v1.26 MECR Zornitza Stark Phenotypes for gene: MECR were changed from Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities to Optic atrophy 16, MIM# 620629
Optic Atrophy v1.25 MECR Zornitza Stark reviewed gene: MECR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Optic atrophy 16, MIM# 620629; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.367 KMT2B Violeta Velkoska-Ivanova changed review comment from: There is insufficient evidence in the published data to rate this gene as green in the context of congenital heart disease. The supporting evidence for rating this gene AMBER is as follows:
No heart abnormalities were noted in the two KMT2B-associated disease phenotypes listed in OMIM ( both reviewed in 2022).
The GenCC database( https://thegencc.org/) has summarised evidence from four reputable submitters: Genomic England Panel App, ClinGen, Ambry Genetics and Orphanet). Three classifications (two supportive, one strong) implicate KMT2B in two diseases: Dystonia,28, childhood-onset (MONDO:0015004; OMIM: 617284) and Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516) where the KMT2B variations are inherited in autosomal dominant mode.
The ClinGen evaluation (The Clinical Genome Resource), with ten variants (missense, nonsense, and frameshift) being reported in 10 probands in 2 publications (PMIDs: 29276005, 33150406) and also in a non-human animal model (PMID: 23426673) provides definitive evidence for the KMT2B gene relationship with autosomal dominant, Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516). Regarding dosage sensitivity, there is sufficient evidence that this gene exhibits haploinsufficiency and is intolerant to LoF variation.
The G2P database (https://www.ebi.ac.uk/gene2phenotype/) lists the KMT2B-associated complex early-onset dystonia in the Developmental Delay panel. Also, the KMT2B is absent from the Cardiac G2P, a publicly available resource designed for filtering and analysing genetic variants of inherited cardiac conditions (ICC)(PMID 37872640).
The largest cohort with KMT2B variants (133 patients: 53 as the initial study cohort in addition to 80 published cases)(PMID:33150406) provides a detailed delineation of their clinical phenotype and molecular genetic features. Although this study emphasised that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants, it reported on new disease features ( i.e. atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype). It also identified co-morbidities ( i.e. risk of status dystonicus, intrauterine growth retardation, and endocrinopathies); however, it failed to associate the KMT2B gene with congenital abnormalities of the heart.
; to: There is insufficient evidence in the published data to rate this gene as green in the context of congenital heart disease. The supporting evidence for rating this gene AMBER is as follows:
No heart abnormalities were noted in the two KMT2B-associated disease phenotypes listed in OMIM ( both reviewed in 2022).
The GenCC database( https://thegencc.org/) has summarised evidence from four reputable submitters: Genomic England Panel App, ClinGen, Ambry Genetics and Orphanet). Three classifications (two supportive, one strong) implicate KMT2B in two diseases: Dystonia,28, childhood-onset (MONDO:0015004; OMIM: 617284) and Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516) where the KMT2B variations are inherited in autosomal dominant mode.
The ClinGen evaluation (The Clinical Genome Resource), with ten variants (missense, nonsense, and frameshift) being reported in 10 probands in 2 publications (PMIDs: 29276005, 33150406) and also in a non-human animal model (PMID: 23426673) provides definitive evidence for the KMT2B gene relationship with autosomal dominant, Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516). Regarding dosage sensitivity, there is sufficient evidence that this gene exhibits haploinsufficiency and is intolerant to LoF variation.
The G2P database (https://www.ebi.ac.uk/gene2phenotype/) lists the KMT2B-associated complex early-onset dystonia in the Developmental Delay panel whose scope is" severe undiagnosed neurodevelopmental disorder and/or congenital anomalies, abnormal growth parameters, dysmorphic features and unusual behavioural phenotypes" and as such is part of the DD2P panel in Panel App England. Also, the KMT2B is absent from the Cardiac G2P, a publicly available resource designed for filtering and analysing genetic variants of inherited cardiac conditions (ICC)(PMID 37872640).
The largest cohort of 133 patients with KMT2B variants (PMID:33150406) delineates their clinical phenotype and molecular genetic features. Although this study emphasised that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants, it reported on new disease features ( i.e. atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype). It also identified co-morbidities ( i.e. risk of status dystonicus, intrauterine growth retardation, and endocrinopathies); however, it failed to associate the KMT2B gene with congenital abnormalities of the heart.
However, the following evidence may be considered when upgrading the KMT2B gene to Green:
KMT2B methyltransferase is a family of histone-modifying enzymes (KMTs) that catalyse the methylation of lysine 4 of the Histone 3 protein and regulate transcriptional activity at the chromatin level. As methylation is critical in transcriptional changes occurring during development, it is not unexpected that deregulated methylation marks are found in developmental disorders, human aging, and cancer. A range of neurodevelopmental disorders is caused by pathogenic variants in genes regulating chromatin function and structure that display abnormal DNA methylation patterns (episignatures) in peripheral blood. Similarly, deregulation of histone lysine methylation, essential during cardiac development, is associated with cardiac disease. ( 35506254)
A recent review states that the known KMT2B paralogs (Gene Cards), KMT2A, KMT2C and KMT2D exhibit regulatory roles during heart development or disease (as defined by supporting data from multiple model systems and /or by disease association. (37504561).
One such example is the KMT2D gene that confusingly shares the same alternate name as KMT2B- MLL2 despite the different genomic locations of both genes and other differences. Molecular rearrangements of KMT2D are associated with Kabuki Syndrome 1(KS) (OMIM: 147920) where, in addition to neurodevelopmental presentation, congenital heart defect, ventricular and atrial septal defect are also part of the phenotypic spectrum.
Comparison of the methylation patterns in peripheral blood from patients with KMT2-dystonia, KMT2-Kabuki Syndrome and controls showed that most DNA regions with altered methylation patterns differ between these two disorders and controls with KMT2B being hypermethylated. The KMT2B is unique among ā€™chromatin neurodevelopmental disordersā€™ genes as its most prominent clinical feature is childhood-onset dystonia rather than developmental delay or congenital anomalies. (PMID:35506254).
The KMT2B paralogs, KMT2A and KMT2D supported by patient phenotypic presentation and likely valid functional evidence in animal models have been investigated thus far as candidate genes in genomic sequencing studies of cardiac disease, including those for patients with congenital heart defect (PMID3378394;25972376;28884922). Thus far, the function of KMT2B in the context of congenital heart disease is yet to be phenotypically confirmed and recapitulated through further research.
Congenital Heart Defect v0.367 SMG9 Zornitza Stark Marked gene: SMG9 as ready
Congenital Heart Defect v0.367 SMG9 Zornitza Stark Gene: smg9 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.367 SMG9 Zornitza Stark Phenotypes for gene: SMG9 were changed from to Heart and brain malformation syndrome, MIM# 616920
Congenital Heart Defect v0.366 SMG9 Zornitza Stark Publications for gene: SMG9 were set to 27018474
Congenital Heart Defect v0.365 SMG9 Zornitza Stark Mode of inheritance for gene: SMG9 was changed from Other to BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.364 SMG9 Zornitza Stark Classified gene: SMG9 as Green List (high evidence)
Congenital Heart Defect v0.364 SMG9 Zornitza Stark Gene: smg9 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.363 SMG9 Zornitza Stark reviewed gene: SMG9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Heart and brain malformation syndrome, MIM# 616920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.363 TXNL4A Zornitza Stark Marked gene: TXNL4A as ready
Congenital Heart Defect v0.363 TXNL4A Zornitza Stark Gene: txnl4a has been classified as Green List (High Evidence).
Congenital Heart Defect v0.363 TXNL4A Zornitza Stark Classified gene: TXNL4A as Green List (high evidence)
Congenital Heart Defect v0.363 TXNL4A Zornitza Stark Gene: txnl4a has been classified as Green List (High Evidence).
Congenital Heart Defect v0.362 TXNL4A Zornitza Stark Tag SV/CNV tag was added to gene: TXNL4A.
Tag UTR tag was added to gene: TXNL4A.
Congenital Heart Defect v0.362 TXNL4A Zornitza Stark reviewed gene: TXNL4A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Burn-McKeown syndrome - MIM#608572; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.362 WASHC5 Zornitza Stark Marked gene: WASHC5 as ready
Congenital Heart Defect v0.362 WASHC5 Zornitza Stark Gene: washc5 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.362 WASHC5 Zornitza Stark Classified gene: WASHC5 as Green List (high evidence)
Congenital Heart Defect v0.362 WASHC5 Zornitza Stark Gene: washc5 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.361 WASHC5 Zornitza Stark reviewed gene: WASHC5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ritscher-Schinzel syndrome 1, MIM# 220210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.361 PIGL Zornitza Stark Marked gene: PIGL as ready
Congenital Heart Defect v0.361 PIGL Zornitza Stark Gene: pigl has been classified as Green List (High Evidence).
Congenital Heart Defect v0.361 PIGL Zornitza Stark Classified gene: PIGL as Green List (high evidence)
Congenital Heart Defect v0.361 PIGL Zornitza Stark Gene: pigl has been classified as Green List (High Evidence).
Congenital Heart Defect v0.360 PIGL Zornitza Stark Publications for gene: PIGL were set to
Congenital Heart Defect v0.359 PIGL Zornitza Stark Phenotypes for gene: PIGL were changed from to CHIME syndrome, MIIM# 280000
Congenital Heart Defect v0.358 PIGV Zornitza Stark Marked gene: PIGV as ready
Congenital Heart Defect v0.358 PIGV Zornitza Stark Gene: pigv has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.358 PIGV Zornitza Stark Phenotypes for gene: PIGV were changed from mental retardation; seizures and hypotonia; hyperphosphatasia; facial dysmorphism; variable degrees of brachytelephalangy to Hyperphosphatasia with impaired intellectual development syndrome 1, MIM# 239300
Congenital Heart Defect v0.357 PIGV Zornitza Stark Classified gene: PIGV as Amber List (moderate evidence)
Congenital Heart Defect v0.357 PIGV Zornitza Stark Gene: pigv has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.356 PIGV Zornitza Stark reviewed gene: PIGV: Rating: AMBER; Mode of pathogenicity: None; Publications: 24129430; Phenotypes: Hyperphosphatasia with impaired intellectual development syndrome 1, MIM# 239300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.356 CRELD1 Zornitza Stark Marked gene: CRELD1 as ready
Congenital Heart Defect v0.356 CRELD1 Zornitza Stark Gene: creld1 has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.356 CRELD1 Zornitza Stark Phenotypes for gene: CRELD1 were changed from to Atrioventricular septal defect, susceptibility to, 2; Atrioventricular septal defect, partial, with heterotaxy syndrome MIM#606217
Congenital Heart Defect v0.355 CRELD1 Zornitza Stark Publications for gene: CRELD1 were set to
Congenital Heart Defect v0.354 CRELD1 Zornitza Stark Mode of inheritance for gene: CRELD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.353 CRELD1 Zornitza Stark Classified gene: CRELD1 as Red List (low evidence)
Congenital Heart Defect v0.353 CRELD1 Zornitza Stark Gene: creld1 has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.352 CRELD1 Zornitza Stark reviewed gene: CRELD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Atrioventricular septal defect, susceptibility to, 2, Atrioventricular septal defect, partial, with heterotaxy syndrome MIM#606217; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.352 ARID1A Zornitza Stark Marked gene: ARID1A as ready
Congenital Heart Defect v0.352 ARID1A Zornitza Stark Gene: arid1a has been classified as Green List (High Evidence).
Congenital Heart Defect v0.352 ARID1A Zornitza Stark Phenotypes for gene: ARID1A were changed from to Coffin-Siris syndrome MONDO:0015452
Congenital Heart Defect v0.351 ARID1A Zornitza Stark Publications for gene: ARID1A were set to
Congenital Heart Defect v0.350 ARID1A Zornitza Stark Mode of inheritance for gene: ARID1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.349 MAP3K7 Zornitza Stark Marked gene: MAP3K7 as ready
Congenital Heart Defect v0.349 MAP3K7 Zornitza Stark Gene: map3k7 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.349 MAP3K7 Zornitza Stark Classified gene: MAP3K7 as Green List (high evidence)
Congenital Heart Defect v0.349 MAP3K7 Zornitza Stark Gene: map3k7 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.348 NUP188 Zornitza Stark Marked gene: NUP188 as ready
Congenital Heart Defect v0.348 NUP188 Zornitza Stark Gene: nup188 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.348 NUP188 Zornitza Stark Classified gene: NUP188 as Green List (high evidence)
Congenital Heart Defect v0.348 NUP188 Zornitza Stark Gene: nup188 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.347 JAG1 Zornitza Stark Marked gene: JAG1 as ready
Congenital Heart Defect v0.347 JAG1 Zornitza Stark Gene: jag1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.347 JAG1 Zornitza Stark Phenotypes for gene: JAG1 were changed from to Alagille syndrome 1 #118450
Congenital Heart Defect v0.346 JAG1 Zornitza Stark Publications for gene: JAG1 were set to
Congenital Heart Defect v0.345 JAG1 Zornitza Stark Mode of inheritance for gene: JAG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.344 GATA6 Zornitza Stark Marked gene: GATA6 as ready
Congenital Heart Defect v0.344 GATA6 Zornitza Stark Gene: gata6 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.344 GATA6 Zornitza Stark Mode of inheritance for gene: GATA6 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.343 GATA6 Zornitza Stark Publications for gene: GATA6 were set to 22158542; 23223019; 23635550
Congenital Heart Defect v0.342 GATA6 Zornitza Stark Phenotypes for gene: GATA6 were changed from to Pancreatic agenesis and congenital heart defects, MIM# 600001
Congenital Heart Defect v0.341 GATA6 Zornitza Stark Publications for gene: GATA6 were set to
Congenital Heart Defect v0.340 GATA6 Zornitza Stark Mode of inheritance for gene: GATA6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.339 BRAF Zornitza Stark Marked gene: BRAF as ready
Congenital Heart Defect v0.339 BRAF Zornitza Stark Gene: braf has been classified as Green List (High Evidence).
Congenital Heart Defect v0.339 BRAF Zornitza Stark Phenotypes for gene: BRAF were changed from to Cardiofaciocutaneous syndrome, 115150; Noonan syndrome 7, 613706
Congenital Heart Defect v0.338 BRAF Zornitza Stark Publications for gene: BRAF were set to
Congenital Heart Defect v0.337 BRAF Zornitza Stark Mode of pathogenicity for gene: BRAF was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Congenital Heart Defect v0.336 BRAF Zornitza Stark Mode of inheritance for gene: BRAF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.335 MED12 Zornitza Stark Marked gene: MED12 as ready
Congenital Heart Defect v0.335 MED12 Zornitza Stark Gene: med12 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.335 MED12 Zornitza Stark Phenotypes for gene: MED12 were changed from Dilated cardiomyopathy (DCM); left ventricular non-compaction (LVNC); dilated cardiomyopathy (DCM); arrhythmia; ventricular septal defect (VSD) to Hardikar syndrome, MIM# 301068; Lujan-Fryns syndrome, MIM# 309520; Ohdo syndrome, X-linked, MIM# 300895
Congenital Heart Defect v0.334 MED12 Zornitza Stark Classified gene: MED12 as Green List (high evidence)
Congenital Heart Defect v0.334 MED12 Zornitza Stark Gene: med12 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.333 MED12 Zornitza Stark reviewed gene: MED12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hardikar syndrome, MIM# 301068, Lujan-Fryns syndrome, MIM# 309520, Ohdo syndrome, X-linked, MIM# 300895; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Congenital Heart Defect v0.333 THOC6 Zornitza Stark Marked gene: THOC6 as ready
Congenital Heart Defect v0.333 THOC6 Zornitza Stark Gene: thoc6 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.333 THOC6 Zornitza Stark Phenotypes for gene: THOC6 were changed from VSD/ASD; severe aortic and left ventricular hypoplasia; Mild dilation of the right chambers and a mild myocardial hypertrophy secondary to a chronic hypertension; ventriculomegaly to Beaulieu-Boycott-Innes syndrome (OMIM#613680)
Congenital Heart Defect v0.332 THOC6 Zornitza Stark Classified gene: THOC6 as Green List (high evidence)
Congenital Heart Defect v0.332 THOC6 Zornitza Stark Gene: thoc6 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.331 THOC6 Zornitza Stark reviewed gene: THOC6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Beaulieu-Boycott-Innes syndrome (OMIM#613680); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.331 LTBP2 Zornitza Stark Marked gene: LTBP2 as ready
Congenital Heart Defect v0.331 LTBP2 Zornitza Stark Gene: ltbp2 has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.331 LTBP2 Zornitza Stark Publications for gene: LTBP2 were set to 33098376; 35245370; 31512380; 22539340
Congenital Heart Defect v0.330 LTBP2 Zornitza Stark Mode of inheritance for gene: LTBP2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Heart Defect v0.329 LTBP2 Zornitza Stark Classified gene: LTBP2 as Red List (low evidence)
Congenital Heart Defect v0.329 LTBP2 Zornitza Stark Gene: ltbp2 has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.328 LTBP2 Zornitza Stark reviewed gene: LTBP2: Rating: RED; Mode of pathogenicity: None; Publications: 30565850; Phenotypes: Marfan-like disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.328 MYBPC3 Zornitza Stark Marked gene: MYBPC3 as ready
Congenital Heart Defect v0.328 MYBPC3 Zornitza Stark Gene: mybpc3 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.328 MYBPC3 Zornitza Stark Publications for gene: MYBPC3 were set to 25335496; 16679492
Congenital Heart Defect v0.327 MYBPC3 Zornitza Stark Phenotypes for gene: MYBPC3 were changed from to Cardiomyopathy, hypertrophic, 4, MIM# 115197
Congenital Heart Defect v0.327 MYBPC3 Zornitza Stark Publications for gene: MYBPC3 were set to
Congenital Heart Defect v0.326 MYBPC3 Zornitza Stark Mode of inheritance for gene: MYBPC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.325 MYBPC3 Zornitza Stark Classified gene: MYBPC3 as Amber List (moderate evidence)
Congenital Heart Defect v0.325 MYBPC3 Zornitza Stark Gene: mybpc3 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.324 MYBPC3 Zornitza Stark reviewed gene: MYBPC3: Rating: AMBER; Mode of pathogenicity: None; Publications: 25335496, 16679492; Phenotypes: Cardiomyopathy, hypertrophic, 4, MIM# 115197; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.324 PKD1L1 Zornitza Stark Marked gene: PKD1L1 as ready
Congenital Heart Defect v0.324 PKD1L1 Zornitza Stark Gene: pkd1l1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.324 PKD1L1 Zornitza Stark Classified gene: PKD1L1 as Green List (high evidence)
Congenital Heart Defect v0.324 PKD1L1 Zornitza Stark Gene: pkd1l1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.323 ARID1B Zornitza Stark Marked gene: ARID1B as ready
Congenital Heart Defect v0.323 ARID1B Zornitza Stark Gene: arid1b has been classified as Green List (High Evidence).
Congenital Heart Defect v0.323 ARID1B Zornitza Stark Publications for gene: ARID1B were set to 35579625; 35445787; 29549119; 34324492
Congenital Heart Defect v0.322 ARID1B Zornitza Stark Phenotypes for gene: ARID1B were changed from to Coffin-Siris syndrome 1, MIM# 135900
Congenital Heart Defect v0.321 ARID1B Zornitza Stark Publications for gene: ARID1B were set to
Congenital Heart Defect v0.320 ARID1B Zornitza Stark Mode of inheritance for gene: ARID1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.319 KMT2B Zornitza Stark Marked gene: KMT2B as ready
Congenital Heart Defect v0.319 KMT2B Zornitza Stark Gene: kmt2b has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.319 KMT2B Zornitza Stark Phenotypes for gene: KMT2B were changed from to Dystonia 28,Childhood-onset; DYT28(617284); Intellectual Developmental disorder, Autosomal dominant; MRD68(619934)
Congenital Heart Defect v0.318 KMT2B Zornitza Stark Publications for gene: KMT2B were set to
Congenital Heart Defect v0.317 KMT2B Zornitza Stark Mode of inheritance for gene: KMT2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.316 KMT2B Zornitza Stark Classified gene: KMT2B as Red List (low evidence)
Congenital Heart Defect v0.316 KMT2B Zornitza Stark Gene: kmt2b has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.315 KMT2B Zornitza Stark reviewed gene: KMT2B: Rating: RED; Mode of pathogenicity: None; Publications: 33150406; Phenotypes: Dystonia 28,Childhood-onset, DYT28(617284), Intellectual Developmental disorder, Autosomal dominant, MRD68(619934); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.295 CCNF Zornitza Stark commented on gene: CCNF: LIMITED by ClinGen
Incidentalome v0.295 CCNF Zornitza Stark edited their review of gene: CCNF: Changed rating: AMBER
Motor Neurone Disease v1.8 CCNF Zornitza Stark edited their review of gene: CCNF: Changed rating: AMBER
Early-onset Dementia v1.5 CCNF Zornitza Stark edited their review of gene: CCNF: Changed rating: AMBER
Congenital Heart Defect v0.315 KMT2B Violeta Velkoska-Ivanova changed review comment from: There is insufficient evidence in the published data to rate this gene as green in the context of congenital heart disease. The supporting evidence for rating this gene AMBER is as follows:
No heart abnormalities were noted in the synopsis of the two KMT2B-associated disease phenotypes listed in OMIM ( both reviewed in 2022).
The GenCC database( https://thegencc.org/) has summarised evidence from four reputable submitters: Genomic England Panel App, ClinGen, Ambry Genetics and Orphanet). Three classifications (two supportive, one strong) implicate KMT2B in two diseases: Dystonia,28, childhood-onset (MONDO:0015004; OMIM: 617284) and Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516) where the KMT2B variations are inherited in autosomal dominant mode.
The ClinGen evaluation (The Clinical Genome Resource), with ten variants (missense, nonsense, and frameshift) being reported in 10 probands in 2 publications (PMIDs: 29276005, 33150406) and also in a non-human animal model (PMID: 23426673) provides definitive evidence for the KMT2B gene relationship with autosomal dominant, Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516). Regarding dosage sensitivity, there is sufficient evidence that this gene exhibits haploinsufficiency and is intolerant to LoF variation.
The G2P database (https://www.ebi.ac.uk/gene2phenotype/) lists the KMT2B-associated complex early-onset dystonia in the Developmental Delay panel. Also, the KMT2B is absent from the Cardiac G2P, a publicly available resource designed for filtering and analysing genetic variants of inherited cardiac conditions (ICC)(PMID 37872640).
The largest cohort with KMT2B variants (133 patients: 53 as the initial study cohort in addition to 80 published cases)(PMID:33150406) provides a detailed delineation of their clinical phenotype and molecular genetic features. Although this study emphasised that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants, it reported on new disease features ( i.e. atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype). It also identified co-morbidities ( i.e. risk of status dystonicus, intrauterine growth retardation, and endocrinopathies); however, it failed to associate the KMT2B gene with congenital abnormalities of the heart.; to: There is insufficient evidence in the published data to rate this gene as green in the context of congenital heart disease. The supporting evidence for rating this gene AMBER is as follows:
No heart abnormalities were noted in the two KMT2B-associated disease phenotypes listed in OMIM ( both reviewed in 2022).
The GenCC database( https://thegencc.org/) has summarised evidence from four reputable submitters: Genomic England Panel App, ClinGen, Ambry Genetics and Orphanet). Three classifications (two supportive, one strong) implicate KMT2B in two diseases: Dystonia,28, childhood-onset (MONDO:0015004; OMIM: 617284) and Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516) where the KMT2B variations are inherited in autosomal dominant mode.
The ClinGen evaluation (The Clinical Genome Resource), with ten variants (missense, nonsense, and frameshift) being reported in 10 probands in 2 publications (PMIDs: 29276005, 33150406) and also in a non-human animal model (PMID: 23426673) provides definitive evidence for the KMT2B gene relationship with autosomal dominant, Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516). Regarding dosage sensitivity, there is sufficient evidence that this gene exhibits haploinsufficiency and is intolerant to LoF variation.
The G2P database (https://www.ebi.ac.uk/gene2phenotype/) lists the KMT2B-associated complex early-onset dystonia in the Developmental Delay panel. Also, the KMT2B is absent from the Cardiac G2P, a publicly available resource designed for filtering and analysing genetic variants of inherited cardiac conditions (ICC)(PMID 37872640).
The largest cohort with KMT2B variants (133 patients: 53 as the initial study cohort in addition to 80 published cases)(PMID:33150406) provides a detailed delineation of their clinical phenotype and molecular genetic features. Although this study emphasised that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants, it reported on new disease features ( i.e. atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype). It also identified co-morbidities ( i.e. risk of status dystonicus, intrauterine growth retardation, and endocrinopathies); however, it failed to associate the KMT2B gene with congenital abnormalities of the heart.
Congenital Heart Defect v0.315 KMT2B Violeta Velkoska-Ivanova changed review comment from: There is insufficient evidence in the published data to rate this gene as green in the context of congenital heart disease. The supporting evidence for rating this gene AMBER is as follows:
No heart abnormalities were noted in the synopsis of the two KMT2B-associated disease phenotypes listed in OMIM ( both reviewed in 2022).
The GenCC database( https://thegencc.org/) has summarised evidence from four reputable submitters: Genomic England Panel App, ClinGen, Ambry Genetics and Orphanet). Three classifications (two supportive, one strong) implicate KMT2B in two diseases: Dystonia,28, childhood-onset (MONDO:0015004; OMIM: 617284) and Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516) where the KMT2B variations are inherited in autosomal dominant mode.
The ClinGen evaluation (The Clinical Genome Resource), with ten variants (missense, nonsense, and frameshift) being reported in 10 probands in 2 publications (PMIDs: 29276005, 33150406) and also in a non-human animal model (PMID: 23426673) provides definitive evidence for the KMT2B gene relationship with autosomal dominant, Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516). Regarding dosage sensitivity, there is sufficient evidence that this gene exhibits haploinsufficiency and is intolerant to LoF variation.
The G2P database (https://www.ebi.ac.uk/gene2phenotype/) only enlists the KMT2B gene in the Developmental Delay panel. The KMT2B is absent from the Cardiac G2P, a publicly available resource designed to aid in the filtering and analysing genetic variants of inherited cardiac conditions (ICC)(PMID 37872640).
The largest cohort with KMT2B variants (133 patients: 53 as the initial study cohort in addition to 80 published cases)(PMID:33150406) provides a detailed delineation of their clinical phenotype and molecular genetic features. Although this study emphasised that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants, it reported on new disease features ( i.e. atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype). It also identified co-morbidities ( i.e. risk of status dystonicus, intrauterine growth retardation, and endocrinopathies); however, it failed to associate the KMT2B gene with congenital abnormalities of the heart.; to: There is insufficient evidence in the published data to rate this gene as green in the context of congenital heart disease. The supporting evidence for rating this gene AMBER is as follows:
No heart abnormalities were noted in the synopsis of the two KMT2B-associated disease phenotypes listed in OMIM ( both reviewed in 2022).
The GenCC database( https://thegencc.org/) has summarised evidence from four reputable submitters: Genomic England Panel App, ClinGen, Ambry Genetics and Orphanet). Three classifications (two supportive, one strong) implicate KMT2B in two diseases: Dystonia,28, childhood-onset (MONDO:0015004; OMIM: 617284) and Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516) where the KMT2B variations are inherited in autosomal dominant mode.
The ClinGen evaluation (The Clinical Genome Resource), with ten variants (missense, nonsense, and frameshift) being reported in 10 probands in 2 publications (PMIDs: 29276005, 33150406) and also in a non-human animal model (PMID: 23426673) provides definitive evidence for the KMT2B gene relationship with autosomal dominant, Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516). Regarding dosage sensitivity, there is sufficient evidence that this gene exhibits haploinsufficiency and is intolerant to LoF variation.
The G2P database (https://www.ebi.ac.uk/gene2phenotype/) lists the KMT2B-associated complex early-onset dystonia in the Developmental Delay panel. Also, the KMT2B is absent from the Cardiac G2P, a publicly available resource designed for filtering and analysing genetic variants of inherited cardiac conditions (ICC)(PMID 37872640).
The largest cohort with KMT2B variants (133 patients: 53 as the initial study cohort in addition to 80 published cases)(PMID:33150406) provides a detailed delineation of their clinical phenotype and molecular genetic features. Although this study emphasised that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants, it reported on new disease features ( i.e. atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype). It also identified co-morbidities ( i.e. risk of status dystonicus, intrauterine growth retardation, and endocrinopathies); however, it failed to associate the KMT2B gene with congenital abnormalities of the heart.
Congenital Heart Defect v0.315 KMT2B Violeta Velkoska-Ivanova changed review comment from: There is insufficient evidence in the published data to rate this gene as green in the context of congenital heart disease.
The Gene Cards summary emphasises the
The supporting evidence for rating this gene AMBER is as follows:
No heart abnormalities have been noted in the synopsis of two phenotypes listed in OMIM ( both reviewed in the year 2022).
The GenCC database( https://thegencc.org/) has summarised evidence from four reputable submitters: Genomic England Panel App, ClinGen, Ambry Genetics and Orphanet). Three classifications (two supportive, one strong) implicate KMT2B in two diseases: Dystonia,28, childhood-onset (MONDO:0015004; OMIM: 617284) and Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516) where the KMT2B variations are inherited in autosomal dominant mode.
The KMT2B gene has been evaluated in ClinGen (The Clinical Genome Resource), with ten variants (missense, nonsense, and frameshift) being reported in 10 probands in 2 publications (PMIDs: 29276005, 33150406) and also in a non-human animal model (PMID: 23426673) providing definitive evidence for the KMT2B gene relationship with autosomal dominant, Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516).In terms of dosage sensitivity, there is sufficient evidence this gene exhibits haploinsufficiency and is intolerant to LoF variation.
The G2P database (https://www.ebi.ac.uk/gene2phenotype/) only enlists the KMT2B gene in the Developmental Delay panel. The KMT2B is absent from the Cardiac G2P, a publicly available resource designed to aid in the filtering and analysing genetic variants of inherited cardiac conditions (ICC)(PMID 37872640).
The largest cohort with KMT2B variants (133 patients: 53 as the initial study cohort in addition to 80 published cases)(PMID:33150406) provides a detailed delineation of their clinical phenotype and molecular genetic features. Although this study emphasised that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants, it reported on new disease features ( i.e. atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype). It also identified co-morbidities ( i.e. risk of status dystonicus, intrauterine growth retardation, and endocrinopathies); however, it failed to associate the KMT2B gene with congenital abnormalities of the heart.; to: There is insufficient evidence in the published data to rate this gene as green in the context of congenital heart disease. The supporting evidence for rating this gene AMBER is as follows:
No heart abnormalities were noted in the synopsis of the two KMT2B-associated disease phenotypes listed in OMIM ( both reviewed in 2022).
The GenCC database( https://thegencc.org/) has summarised evidence from four reputable submitters: Genomic England Panel App, ClinGen, Ambry Genetics and Orphanet). Three classifications (two supportive, one strong) implicate KMT2B in two diseases: Dystonia,28, childhood-onset (MONDO:0015004; OMIM: 617284) and Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516) where the KMT2B variations are inherited in autosomal dominant mode.
The ClinGen evaluation (The Clinical Genome Resource), with ten variants (missense, nonsense, and frameshift) being reported in 10 probands in 2 publications (PMIDs: 29276005, 33150406) and also in a non-human animal model (PMID: 23426673) provides definitive evidence for the KMT2B gene relationship with autosomal dominant, Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516). Regarding dosage sensitivity, there is sufficient evidence that this gene exhibits haploinsufficiency and is intolerant to LoF variation.
The G2P database (https://www.ebi.ac.uk/gene2phenotype/) only enlists the KMT2B gene in the Developmental Delay panel. The KMT2B is absent from the Cardiac G2P, a publicly available resource designed to aid in the filtering and analysing genetic variants of inherited cardiac conditions (ICC)(PMID 37872640).
The largest cohort with KMT2B variants (133 patients: 53 as the initial study cohort in addition to 80 published cases)(PMID:33150406) provides a detailed delineation of their clinical phenotype and molecular genetic features. Although this study emphasised that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants, it reported on new disease features ( i.e. atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype). It also identified co-morbidities ( i.e. risk of status dystonicus, intrauterine growth retardation, and endocrinopathies); however, it failed to associate the KMT2B gene with congenital abnormalities of the heart.
Congenital Heart Defect v0.315 KMT2B Violeta Velkoska-Ivanova edited their review of gene: KMT2B: Changed publications: PMID:29276005, 23426673, 33150406, 23665959, 37504561, 28902362, 21646717; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital Heart Defect v0.315 KMT2B Violeta Velkoska-Ivanova changed review comment from: There is insufficient evidence to rate this gene as green in the context of congenital heart disease. However, this gene is enlisted as Green in PanelApp England in the Fetal Anomalies Panel( v?????)
The supporting evidence for rating this gene AMBER is as follows:
No heart abnormalities have been noted in the synopsis of two phenotypes listed in OMIM ( both reviewed in the year 2022).
The GenCC database ( https://thegencc.org/) has summarised evidence from four reputable submitters: Genomic England Panel App, ClinGen, Ambry Genetics and Orphanet). Three classifications (two supportive, one strong) implicate KMT2B in two diseases: Dystonia,28, childhood-onset (MONDO:0015004; OMIM: 617284) and Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516) where the KMT2B variations are inherited in autosomal dominant mode.
The KMT2B gene has been evaluated in ClinGen (The Clinical Genome Resource), with ten variants (missense, nonsense, and frameshift) being reported in 10 probands in 2 publications (PMIDs: 29276005, 33150406) and also in a non-human animal model (PMID: 23426673) providing definitive evidence for the KMT2B gene relationship with autosomal dominant, Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516).In terms of dosage sensitivity, there is sufficient evidence this gene exhibits haploinsufficiency and is intolerant to LoF variation.
The G2P database (https://www.ebi.ac.uk/gene2phenotype/) only enlists the KMT2B gene in the Developmental Delay panel. The KMT2B is absent from the recently published publicly available resource, Cardiac G2P, which is designed to aid in the filtering and analysing of genetic variants of inherited cardiac conditions (ICC)(PMID 37872640).
The largest cohort with KMT2B variants (133 patients: 53 as the initial study cohort in addition to 80 published cases)(PMID:33150406) provides a detailed delineation of their clinical phenotype and molecular genetic features. Although this study emphasised that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants, it reported on new disease features ( i.e. atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype). It also identified co-morbidities ( i.e. risk of status dystonicus, intrauterine growth retardation, and endocrinopathies); however, it failed to associate the KMT2B gene with congenital abnormalities of the heart.; to: There is insufficient evidence in the published data to rate this gene as green in the context of congenital heart disease.
The Gene Cards summary emphasises the
The supporting evidence for rating this gene AMBER is as follows:
No heart abnormalities have been noted in the synopsis of two phenotypes listed in OMIM ( both reviewed in the year 2022).
The GenCC database( https://thegencc.org/) has summarised evidence from four reputable submitters: Genomic England Panel App, ClinGen, Ambry Genetics and Orphanet). Three classifications (two supportive, one strong) implicate KMT2B in two diseases: Dystonia,28, childhood-onset (MONDO:0015004; OMIM: 617284) and Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516) where the KMT2B variations are inherited in autosomal dominant mode.
The KMT2B gene has been evaluated in ClinGen (The Clinical Genome Resource), with ten variants (missense, nonsense, and frameshift) being reported in 10 probands in 2 publications (PMIDs: 29276005, 33150406) and also in a non-human animal model (PMID: 23426673) providing definitive evidence for the KMT2B gene relationship with autosomal dominant, Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516).In terms of dosage sensitivity, there is sufficient evidence this gene exhibits haploinsufficiency and is intolerant to LoF variation.
The G2P database (https://www.ebi.ac.uk/gene2phenotype/) only enlists the KMT2B gene in the Developmental Delay panel. The KMT2B is absent from the Cardiac G2P, a publicly available resource designed to aid in the filtering and analysing genetic variants of inherited cardiac conditions (ICC)(PMID 37872640).
The largest cohort with KMT2B variants (133 patients: 53 as the initial study cohort in addition to 80 published cases)(PMID:33150406) provides a detailed delineation of their clinical phenotype and molecular genetic features. Although this study emphasised that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants, it reported on new disease features ( i.e. atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype). It also identified co-morbidities ( i.e. risk of status dystonicus, intrauterine growth retardation, and endocrinopathies); however, it failed to associate the KMT2B gene with congenital abnormalities of the heart.
Congenital Heart Defect v0.315 KMT2B Violeta Velkoska-Ivanova reviewed gene: KMT2B: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID:29276005, 23426673, 33150406; Phenotypes: Dystonia 28,Childhood-onset, DYT28(617284), Intellectual Developmental disorder, Autosomal dominant, MRD68(619934); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.183 MADD Peter McNaughton gene: MADD was added
gene: MADD was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: MADD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MADD were set to PMID: 36206192
Phenotypes for gene: MADD were set to HLH, enteropathy
Review for gene: MADD was set to AMBER
Added comment: 2-month-old female infant born to consanguineous parents was admitted with complex syndromic features of dystrophy, endocrinological dysfunction, and developmental delay developed partial features of HLH with a postnatally acquired cytomegalovirus infection and a persistent secretory enteropathy. Her brother with similar symptoms had died at 2 years of life. Severe degranulation defect of resting and IL-2ā€“stimulated NK and cytotoxic T lymphocytes (CTLs) was detected. MADD knockout cell line showed same defect.
Another patient displayed reduced degranulation of cytotoxic cells (patient 2 PMID: 32761064)
Sources: Literature
Congenital Heart Defect v0.315 ARID1B Michelle Wu reviewed gene: ARID1B: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 35579625, 35445787, 29549119, 34324492; Phenotypes: Coffin-Siris syndrome 1, intellectual disability with or without nonspecific dysmorphic features; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.315 PKD1L1 Joce vd Bergen gene: PKD1L1 was added
gene: PKD1L1 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: PKD1L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PKD1L1 were set to PMID: 27616478; 31026592; 3079108; 30791085; 33655537
Phenotypes for gene: PKD1L1 were set to Heterotaxy, visceral, 8, autosomal; HTX8 (MIM617205)
Review for gene: PKD1L1 was set to GREEN
Added comment: Numerous families (6 families, 9 affected individuals) reported with heterotaxy and complex congenital heart defects, with biallelic variants (primarily nonsense, frameshift, splice site and a missense variant) in the PKD1L1 gene. Three reports with additional features (3079108, 30791085, 30791085), such as congenital asplenia, sideroblastic anemia, hydrops fetalis.

Several animal models suggest PKD1L1 plays a significant role in the development of L-R asymmetry and establish the L-R axis in vertebrate organisms, including mouse null and missense substitution models and a medaka knockout. Where complex congenital heart defects are often associated with laterality defects (ranging from situs inversus totalis (SIT) to situs

ClinVar: reports all published variants presented, plus 1 additional nonsense variant (not published). Summary: likely pathogenic/pathogenic (6 nonsense loss of function, 2 splice site and 1 missense variant), associated with autosomal visceral heterotaxy type 8, MIM 617205).
Sources: Literature
Cataract v0.361 DNA2 Elena Savva Publications for gene: DNA2 were set to 37133451
Congenital Heart Defect v0.315 MYBPC3 Yi-Wei Chao edited their review of gene: MYBPC3: Changed rating: GREEN
Congenital Heart Defect v0.315 MYBPC3 Yi-Wei Chao reviewed gene: MYBPC3: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 34097875, 25335496, 31877118, 22057632, 18467358, 36980931, 33209723; Phenotypes: Hypertrophic cardiomyopathy, bicuspid aortic valve, severe infantile cardiomyopathy, septal defect; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Heart Defect v0.315 LTBP2 Dion Paul gene: LTBP2 was added
gene: LTBP2 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: LTBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LTBP2 were set to 33098376; 35245370; 31512380; 22539340
Phenotypes for gene: LTBP2 were set to Atrioventricular septal defect (AVSD); Mitral valve prolapse; patent ductus arteriosus (PDA); secondary atrial septal defect; pulmonary hypertension; polydactyly
Penetrance for gene: LTBP2 were set to unknown
Mode of pathogenicity for gene: LTBP2 was set to Other
Review for gene: LTBP2 was set to RED
Added comment: OMIM (602091) LTBP2 encodes an extracellular matrix (ECM) protein that is expressed in elastic tissues and associates with fibrillin-1 (FBN1) containing microfibrils (PMID: 22539340). Due to this gene's wide association with fibrillin and elastin and corresponding ocular disorders, it is already included in the congenital glaucoma panel.

Animal model study - PMID: 31512380 LTBP2 silencing reduces myocardial oxidative stress injury, myocardial fibrosis and myocardial remodelling in rat models of dilated cardiomyopathy (DCM) by down-regulating the NF-ĪŗB signalling pathway.

PMID: 33098376 This study performed whole exome sequencing on a single 1.5-year-old female patient with complex CHD. The phenotype of this patient consisted of the following features: complete atrioventricular septal defect (AVSD), patent ductus arteriosus (PDA), secondary atrial septal defect, pulmonary hypertension, and polydactyly. WES revealed the following heterozygous variant in exon 12 of LTBP2: c.2206G>A (p.Asp736Asn), RefSeq NM_000428.2. Unfortunately, nil family data is available to power family studies. WES also identified another heterozygous variant within the TCTN3 gene. Sanger sequencing was employed to validate the variant. LTBP2 variants are associated with Weill-Marchesani syndrome 3 (WMS3, OMIM #614819), a rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, and eye abnormalities. 39% of these patients demonstrate pulmonary and aortic stenosis (PMID: 22539340). Furthermore this study generated human pluripotent stem cell lines (with the aforementioned LTBP2 variant) which differentiated into cardiomyocytes, yielding transcriptomic analysis. Relative to the wildtype, the LTBP2 variant delayed the development of cardiomyocytes and along with the TCTN3 variant may affect contractility of cardiac myocytes and the development of the heart.

PMID: 33098376 The allele frequency of LTBP2 c.2206G>A was 0.0009, 0.0035 and 0.0008 in population databases of dbSNP, 1000Genomes, and HGVD (BGI).

PMID: 35245370 Genome-wide association study identified six candidate genes associated with mitral valve prolapse (MVP) - one of which included LTBP2. LTBP2 at 14q24.3 demonstrated high levels of protein expression with RNA-Seq confirming corresponding gene expression as a main driver. Although this study labelled LTBP2 as one of the strongest candidate genes at a particular locus for MVP, it also pinpointed a lack of sufficient concordant evidence. This study suggests TGF-B signalling as a role in isolated MVP pathogenesis - TGF-B signalling is regulated by an extracellular matrix protein encoded by LTBP2.
Sources: Literature
Congenital Heart Defect v0.315 ZFPM2 Luke Tork changed review comment from: Missense variants (and sometimes truncations) in ZFPM2 segregate in individuals with multiple types of congenital heart disease. Development of cardiac related structures involve the GATA family member genes. The ZFPM2 gene encodes the FOG2 protein, a transcriptional regulator responsible for binding to GATA, as well as the deacetylation (NuRD) complex - moderating GATA-mediated gene regulation. Hence, mutations in important residues of ZFPM2 may disrupt FOG2's interaction with GATA4 or NuRD complexes, resulting in congenital heart defects [PMID:28372585]

Phenotypes such as DIAPHRAGMATIC HERNIA 3; DIH3 [MIM:610187], TETRALOGY OF FALLOT; TOF [MIM:187500], and DOUBLE-OUTLET RIGHT VENTRICLE; DORV [MIM:217095] are commonly seen in patients with pathogenic ZFPM2 variants.; to: Missense variants (and sometimes truncations) in ZFPM2 segregate in individuals with multiple types of congenital heart disease. Development of cardiac related structures involve the GATA family member genes. The ZFPM2 gene encodes the FOG2 protein, a transcriptional regulator responsible for binding to GATA, as well as the deacetylation (NuRD) complex - moderating GATA-mediated gene regulation. Hence, mutations in important residues of ZFPM2 may disrupt FOG2's interaction with GATA4 or NuRD complexes, resulting in congenital heart defects [PMID:28372585]

Phenotypes such as DIAPHRAGMATIC HERNIA 3; DIH3 [MIM:610187], TETRALOGY OF FALLOT; TOF [MIM:187500], and DOUBLE-OUTLET RIGHT VENTRICLE; DORV [MIM:217095] are commonly seen in patients with ZFPM2 variants.
Congenital Heart Defect v0.315 ZFPM2 Luke Tork reviewed gene: ZFPM2: Rating: AMBER; Mode of pathogenicity: Other; Publications: 29018978, 25025186, 28372585, 21919901, 24702427; Phenotypes: 217095, 87500, 610187; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Heart Defect v0.315 THOC6 Ling Sun edited their review of gene: THOC6: Changed phenotypes: Beaulieu-Boycott-Innes syndrome (OMIM#613680)
Congenital Heart Defect v0.315 THOC6 Ling Sun edited their review of gene: THOC6: Changed phenotypes: 613680
Congenital Heart Defect v0.315 THOC6 Ling Sun changed review comment from: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome (OMIM#613680). Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype, eg. see https://databases.lovd.nl/shared/diseases/03390).

PMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly) [compound het]

PMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C)
A girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu) [compount het]

PMID: 32282736: A boy with paternally inherited c.664T>C (p.Trp222Arg) and maternally inherited c.945+1 G>A [compound het]
Sources: Other; to: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome (OMIM#613680). Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype, eg. see https://databases.lovd.nl/shared/diseases/03390).

PMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly) [compound het]

PMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C)
A girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu) [compount het]

PMID: 32282736: A boy with paternally inherited c.664T>C (p.Trp222Arg) and maternally inherited c.945+1 G>A [compound het]

Cardiac anomalies described include VSD/ASD, severe aortic and left ventricular hypoplasia, mild dilation of the right chambers and a mild myocardial hypertrophy secondary to a chronic hypertension, ventriculomegaly

Sources: Other
Congenital Heart Defect v0.315 THOC6 Ling Sun changed review comment from: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome. Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype, eg. see https://databases.lovd.nl/shared/diseases/03390).

PMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly) [compound het]

PMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C)
A girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu) [compount het]

PMID: 32282736: A boy with paternally inherited c.664T>C (p.Trp222Arg) and maternally inherited c.945+1 G>A [compound het]
Sources: Other; to: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome (OMIM#613680). Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype, eg. see https://databases.lovd.nl/shared/diseases/03390).

PMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly) [compound het]

PMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C)
A girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu) [compount het]

PMID: 32282736: A boy with paternally inherited c.664T>C (p.Trp222Arg) and maternally inherited c.945+1 G>A [compound het]
Sources: Other
Mendeliome v1.1377 THOC6 Ling Sun Deleted their review
Mendeliome v1.1377 THOC6 Ling Sun Deleted their comment
Congenital Heart Defect v0.315 THOC6 Ling Sun gene: THOC6 was added
gene: THOC6 was added to Congenital Heart Defect. Sources: Other
Mode of inheritance for gene: THOC6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: THOC6 were set to 35426486; 30476144; 32282736
Phenotypes for gene: THOC6 were set to VSD/ASD; severe aortic and left ventricular hypoplasia; Mild dilation of the right chambers and a mild myocardial hypertrophy secondary to a chronic hypertension; ventriculomegaly
Penetrance for gene: THOC6 were set to Incomplete
Review for gene: THOC6 was set to AMBER
Added comment: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome. Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype, eg. see https://databases.lovd.nl/shared/diseases/03390).

PMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly) [compound het]

PMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C)
A girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu) [compount het]

PMID: 32282736: A boy with paternally inherited c.664T>C (p.Trp222Arg) and maternally inherited c.945+1 G>A [compound het]
Sources: Other
Overgrowth v1.9 MED12 Ling Sun Deleted their review
Overgrowth v1.9 MED12 Ling Sun Deleted their comment
Congenital Heart Defect v0.315 MED12 Ling Sun gene: MED12 was added
gene: MED12 was added to Congenital Heart Defect. Sources: Other
Mode of inheritance for gene: MED12 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: MED12 were set to 32682435; 18973276; 31255603; 28724790; 20301719
Phenotypes for gene: MED12 were set to Dilated cardiomyopathy (DCM); left ventricular non-compaction (LVNC); dilated cardiomyopathy (DCM); arrhythmia; ventricular septal defect (VSD)
Penetrance for gene: MED12 were set to unknown
Mode of pathogenicity for gene: MED12 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: MED12 was set to AMBER
Added comment: MED12-associated syndromes or genetic conditions resulting from MED12 loss of function variants can encompass aortic and heart conditions within their broader diagnostic spectrum. For instance, while not universally present in all individuals with Lujan-Fryns syndrome, some may indeed exhibit heart abnormalities as an integral part of their overall clinical profile (PMID: 18973276). Additionally, congenital heart defects and aortic dilation have been sporadically reported in patients with MED12-syndromic XLID. However, these cardiac issues tend to be more consistently observed in females with Hardikar syndrome, with aortic coarctation being the most prevalent cardiac abnormality in this group (PMID: 20301719).

Moreover, research has demonstrated that mice with a cardiac-specific deletion of the Med12 gene experience disruptions in calcium cycling, disturbances in cardiac electrical activity, and ultimately develop dilated cardiomyopathy (PMID: 2872470). This suggests a critical role for MED12 in cardiac function and highlights its relevance in both research and clinical contexts.

[Submitted on behalf of Essra Bartlett 20/11/2023]
Sources: Other
Autoinflammatory Disorders v1.28 ARPC5 Zornitza Stark Marked gene: ARPC5 as ready
Autoinflammatory Disorders v1.28 ARPC5 Zornitza Stark Gene: arpc5 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.28 ARPC5 Zornitza Stark Classified gene: ARPC5 as Green List (high evidence)
Autoinflammatory Disorders v1.28 ARPC5 Zornitza Stark Gene: arpc5 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.27 ARPC5 Zornitza Stark gene: ARPC5 was added
gene: ARPC5 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: ARPC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARPC5 were set to 37349293; 37382373
Phenotypes for gene: ARPC5 were set to Immunodeficiency 133 with autoimmunity and autoinflammation, MIM# 620565
Review for gene: ARPC5 was set to GREEN
Added comment: Four individuals from 3 families reported. In addition to recurrent infections, features of autoinflammation common: haemolytic anaemia, thrombocytopenia, hepatosplenomegaly, leukocytosis, neutrophilia, and elevated acute phase reactants. More variable systemic features may include coeliac disease or enteropathy, ileus, nephropathy, eczema, and dermatomyositis.
Sources: Literature
Combined Immunodeficiency v1.51 ARPC5 Zornitza Stark Phenotypes for gene: ARPC5 were changed from Combined immunodeficiency, ARPC5-related MONDO:0015131 to Immunodeficiency 133 with autoimmunity and autoinflammation, MIM# 620565
Combined Immunodeficiency v1.50 ARPC5 Zornitza Stark reviewed gene: ARPC5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 133 with autoimmunity and autoinflammation, MIM# 620565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1377 ARPC5 Zornitza Stark Phenotypes for gene: ARPC5 were changed from Combined immunodeficiency, ARPC5-related MONDO:0015131 to Immunodeficiency 133 with autoimmunity and autoinflammation, MIM# 620565
Mendeliome v1.1376 ARPC5 Zornitza Stark commented on gene: ARPC5: Features of autoinflammation common: haemolytic anaemia, thrombocytopenia, hepatosplenomegaly, leukocytosis, neutrophilia, and elevated acute phase reactants. More variable systemic features may include coeliac disease or enteropathy, ileus, nephropathy, eczema, and dermatomyositis.
Mendeliome v1.1376 ARPC5 Zornitza Stark reviewed gene: ARPC5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 133 with autoimmunity and autoinflammation, MIM# 620565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.315 BRAF Penny Snell changed review comment from: Well established gene-disease association.
Cardiofaciocutaneous and Noonan syndromes present with overlapping clinical features, including congenital heart defects.

There is limited evidence for loss-of-function as a mechanism of disease for either of these phenotypes.; to: Well established gene-disease association.
Cardiofaciocutaneous and Noonan syndromes present with overlapping clinical features, including congenital heart defects.

There is limited evidence for loss-of-function as a mechanism of disease for either of these phenotypes.
Congenital Heart Defect v0.315 BRAF Penny Snell reviewed gene: BRAF: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 19206169, 18042262; Phenotypes: Cardiofaciocutaneous syndrome, 115150, Noonan syndrome 7, 613706; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.315 GATA6 Sivaranjani Balachander reviewed gene: GATA6: Rating: GREEN; Mode of pathogenicity: None; Publications: (PMID: 22158542, 23223019, 23635550); Phenotypes: Congenital heart defects pancreatic agenesis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital Heart Defect v0.315 JAG1 Uditi Shah reviewed gene: JAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26580007, 19325125, 11139239, 9207787, 9585603, 11152664, 32065591, 12022040, 20437614, 36400760); Phenotypes: ?Deafness, congenital heart defects, and posterior embryotoxon #617992, Alagille syndrome 1 #118450, Charcot-Marie-Tooth disease, axonal, type 2HH #619574, Tetralogy of Fallot #187500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.315 JAG1 Uditi Shah Deleted their review
Congenital Heart Defect v0.315 JAG1 Uditi Shah changed review comment from: JAG1 is a gene that plays a crucial role in capillary morphogenesis, mesenchymal stem cell differentiation into cardiomyocytes, and the regulation of signaling pathways such as Notch and Wnt.

Mutations in the JAG1 gene are associated with Alagille Syndrome (ALGS), a disorder characterized by liver, heart, and other organ abnormalities. ALGS exhibits high genetic heterogeneity, with various types of mutations identified, including deletions, insertions, splice site mutations, and missense mutations. The majority of ALGS cases involve haploinsufficiency, where a single functional copy of the JAG1 gene is insufficient for normal development. However, some missense mutations may act in a dominant-negative manner, inhibiting Notch signaling.

In TOF, a missense mutation in JAG1 was identified in a kindred segregating autosomal dominant TOF with variable expressivity and characteristic facial features.

JAG1 mutations in axonal Charcot-Marie-Tooth disease type 2HH were associated with impaired peripheral nerve integrity and altered Notch signaling.

Another syndrome, DCHE, involving hearing loss, congenital heart defects, and posterior embryotoxon, was also linked to a JAG1 missense mutation. (PMID: 12022040 PMID: 20437614 PMID: 36400760); to: JAG1 is a gene that plays a crucial role in capillary morphogenesis, mesenchymal stem cell differentiation into cardiomyocytes, and the regulation of signaling pathways such as Notch and Wnt. (PMID: 26580007, PMID: 19325125)

Mutations in the JAG1 gene are associated with Alagille Syndrome (ALGS), a disorder characterized by liver, heart, and other organ abnormalities. ALGS exhibits high genetic heterogeneity, with various types of mutations identified, including deletions, insertions, splice site mutations, and missense mutations. The majority of ALGS cases involve haploinsufficiency, where a single functional copy of the JAG1 gene is insufficient for normal development. However, some missense mutations may act in a dominant-negative manner, inhibiting Notch signaling. (PMID: 11139239, PMID: 9207787, PMID: 9585603)

In TOF, a missense mutation in JAG1 was identified in a kindred segregating autosomal dominant TOF with variable expressivity and characteristic facial features. (PMID: 11152664)

JAG1 mutations in axonal Charcot-Marie-Tooth disease type 2HH were associated with impaired peripheral nerve integrity and altered Notch signaling. (PMID: 32065591)

Another syndrome, DCHE, involving hearing loss, congenital heart defects, and posterior embryotoxon, was also linked to a JAG1 missense mutation. (PMID: 12022040 PMID: 20437614 PMID: 36400760)
Congenital Heart Defect v0.315 JAG1 Uditi Shah reviewed gene: JAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 12022040 PMID: 20437614 PMID: 36400760; Phenotypes: ?Deafness, congenital heart defects, and posterior embryotoxon #617992, Alagille syndrome 1 #118450, Charcot-Marie-Tooth disease, axonal, type 2HH #619574, Tetralogy of Fallot #187500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v1.9 MED12 Ling Sun reviewed gene: MED12: Rating: AMBER; Mode of pathogenicity: None; Publications: 32682435, 18973276, 31255603, 28724790, 20301719; Phenotypes: Dilated cardiomyopathy (DCM), left ventricular non-compaction (LVNC), dilated cardiomyopathy (DCM), arrhythmia, ventricular septal defect (VSD); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Congenital Heart Defect v0.315 NUP188 GORJANA ROBEVSKA gene: NUP188 was added
gene: NUP188 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: NUP188 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP188 were set to PMID: 32021605; 32275884
Phenotypes for gene: NUP188 were set to Sandestig-Stefanova syndrome MIM 618804
Review for gene: NUP188 was set to GREEN
Added comment: Sandestig et al 2020/19:
two unrelated female infants from consanguineous families, each with homozygous nonsense gene variants of NUP188 (p.Tyr96* and p.Gln113*, respectively). Both patients showed close similarity and specificity of clinical features including the course of the disease and a poor prognosis.

Muir et al 2020:
Four unrelated families with six affected female infants with bi-allelic truncating variants in NUP188. all found to have very similar phenotypes
Functional studies showed:
1. Nuclear import of proteins was decreased in affected individualsā€™ fibroblasts, supporting a possible disease mechanism.
2. CRISPR-mediated knockout of NUP188 inā€ÆDrosophilaā€Ærevealed motor deficits and seizure susceptibility, partially recapitulating the neurological phenotype seen in affected individuals.
3. Removal of NUP188 also resulted in aberrant dendrite tiling, suggesting a potential role of NUP188 in dendritic development

Key clinical features of Sandestig-Stefanova syndrome MIM 618804:
- congenital cataracts
- hypotonia,
- prenatal-onset ventriculomegaly,
- white-matter abnormalities,
- hypoplastic corpus callosum,
- congenital heart defects, and
- central hypoventilation.ā€Æ
Characteristic dysmorphic features include:
- small palpebral fissures,
- a wide nasal bridge and nose,
- micrognathia, and
- digital anomalies.
Sources: Literature
Congenital Heart Defect v0.315 CHST14 Arthur Limawan reviewed gene: CHST14: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ehlers-Danlos syndrome, arterial septal defects, coarctation of the aorta, patent ductus arteriosus, dextrocardia, tricuspid atresia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.315 MAP3K7 Emma Northrop gene: MAP3K7 was added
gene: MAP3K7 was added to Congenital Heart Defect. Sources: Other
Mode of inheritance for gene: MAP3K7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP3K7 were set to PMID: 27426734; 29467388; 35730652; 27426733
Phenotypes for gene: MAP3K7 were set to Cardiospondylocarpofacial syndrome (CSCF) MIM# 157800; Frontometaphyseal dysplasia 2 (FMD2) MIM# 617137
Review for gene: MAP3K7 was set to GREEN
Added comment: CSCF - primarily caused by loss of function variants.
FMD2 - primarily caused by gain of function variants.

PMID: 27426734 - Monoallelic missense and in-frame deletion variants were identified in the MAP3K7 gene in six individuals affected with CSCF from four unrelated families. All met the clinical feature criteria of CSCF, including skeletal and facial features, and cardiac defects (including VSD (1/6), ASD (1/6) and valve dysplasia (6/6)). One family with 3 affected individuals across 2 generations was reported.

PMID: 29467388 - One case with a splice variant creating a new splice acceptor site causing an in-frame insertion of 2 amino acids. A heart ultrasound at birth revealed patent foramen ovale with left-right shunt and two small muscular ventricular septal defects, mitral and tricuspid valves dysplasia and mild, non-progressive aortic arch hypoplasia.

PMID: 35730652 - 14 novel patients with CSCF + 2 with FMD2. 9/15 with Congenital Heart Defects (including the 2 cases with FMD2), 2/12 Ventricular septal defects, 1/13 Atrial septal defects, 4/14 Cardiomyopathy. CSCF cases include one family with 2 individuals across 2 generations.
Sources: Other
Congenital Heart Defect v0.315 ARID1A Mary Huang reviewed gene: ARID1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 33803261; Phenotypes: Coffin-Siris syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.315 CRELD1 Rajini Sreenivasan reviewed gene: CRELD1: Rating: RED; Mode of pathogenicity: None; Publications: (PMID: 22740159, 12632326, 23040494, 25328912, 24697899, 33773999); Phenotypes: Atrioventricular septal defect, susceptibility to, 2, Atrioventricular septal defect, partial, with heterotaxy syndrome MIM#606217; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital Heart Defect v0.315 PIGV Jen Malcolm gene: PIGV was added
gene: PIGV was added to Congenital Heart Defect. Sources: Other
Mode of inheritance for gene: PIGV was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGV were set to PMID: 37372388; 24129430; 37390992; 20802478
Phenotypes for gene: PIGV were set to mental retardation; seizures and hypotonia; hyperphosphatasia; facial dysmorphism; variable degrees of brachytelephalangy
Penetrance for gene: PIGV were set to unknown
Mode of pathogenicity for gene: PIGV was set to Other
Review for gene: PIGV was set to RED
Added comment: Autosomal recessive. Multiple variants involved in Mabry syndrome (also known as Hyperphosphatasia)- intellectual disability, distinctive facial features, increased levels of an enzyme called alkaline phosphatase in the blood and other signs and symptoms.
Literature:
ā€¢ Xue et al PMID: 27177984 2 Chinese infants with Mabry syndrome variants PIGV:c.615C>G (p.Asn205Lys) and c.854A>G (p.Tyr285Cys)
ā€¢ Thompson et al, PMID: 22315194
3 patients (2 sibs with compound heterozygotes for c.467G > A and c.494C > A (novel variant) in exon 3 of PIGV gene. 3rd unrelated individual compound heterozygote for the known c.1022C > A/c.1022C > T (p.Ala341Glu/p.Ala341Val) mutation)
ā€¢ Hutny et al PMID: 37372388, 6 Polish Patients all with homozygotic mutation (c.1022C>A; p.Ala341Glu) variant hyperphosphatasia with impaired intellectual development syndrome 1 (HPMRS1), distinct from other CDGs in terms of hyperphosphatemia related to abnormal ALP activity and brachytelephalangy.
ā€¢ Horn et al PMID: 24129430
16 individuals with Mabrys syndrome, most common variant c.1022C>A , and also novel variants (c. 176T>G, c.53G>A, c.905T>C, and c.1405C>T) detected PIGV mutations and demonstrate that the severe end of the clinical spectrum presents as a multiple congenital malformation syndrome with a high frequency of Hirschsprung disease, vesicoureteral, and renal anomalies as well as anorectal malformations. PIGV mutations are the major cause of HPMRS, which displays a broad clinical variability regarding associated malformations and growth patterns. Severe developmental delays, particular facial anomalies, brachytelephalangy, and hyperphosphatasia are consistently found in PIGV-positive individuals.
No evidence of congenital heart defects found.
Sources: Other
Congenital Heart Defect v0.315 KDR Dee Lawlor reviewed gene: KDR: Rating: AMBER; Mode of pathogenicity: None; Publications: 34113005; Phenotypes: Tetralogy of Fallot; Mode of inheritance: Unknown
Congenital Heart Defect v0.315 KDR Dee Lawlor Deleted their review
Congenital Heart Defect v0.315 KDR Dee Lawlor reviewed gene: KDR: Rating: AMBER; Mode of pathogenicity: None; Publications: 34113005; Phenotypes: ; Mode of inheritance: Unknown
Congenital Heart Defect v0.315 PIGL Harshini Thiyagarajah reviewed gene: PIGL: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22444671; Phenotypes: colobomas, heart defects, ichthyosiform dermatosis, intellectual disability, ear anomalies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.315 WASHC5 Lucas Mitchell gene: WASHC5 was added
gene: WASHC5 was added to Congenital Heart Defect. Sources: ClinGen,Literature
Mode of inheritance for gene: WASHC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WASHC5 were set to PMID: 24065355; 37840956; 30896870; 32349777; 32349777
Phenotypes for gene: WASHC5 were set to Ritscher-Schinzel syndrome - MIM#220210; Ventricular septal defect; Atrial septal defect; Tetralogy of Fallot; Double outlet right ventricle; Hypoplastic left heart; Aortic stenosis; Pulmonic stenosis
Penetrance for gene: WASHC5 were set to unknown
Review for gene: WASHC5 was set to AMBER
Added comment: Homozygous/biallelic variants in WASHC5 (previous name KIAA0196) are associated with Ritscher-Schinzel syndrome (RSS) - A developmental malformation syndrome characterised by craniofacial abnormalities, congenital heart defects, and cerebellar brain malformations. Cardiac defects include septal defects and aortic stenosis, among others (OMIM: Leonardi et al., 2001; Elliott et al., 2013).

Victor Chang CHD gene registry reports on WASHC5, also stating unknown penetrance.
(https://chdgene.victorchang.edu.au/gene/9897)

Literature (humans):
Elliot et al, 2013 (24065355)
8 first nations patients, and 8 of their parents, and 5 unaffected people from same geographic region (northern Manitoba, Canada) underwent homozygosity mapping by SNP array and sanger sequencing. Variable phenotypic traits among affected members included atrial and ventricular septal defects. The only biallelic mutations identified occurred in KIAA0196 (WASHC5), where sequence analysis revealed homozygosity for three novel variants (c.3335+2T>A, c.3335 +4C>A and c.3335+8A>G) in each patient (figure 2A). All parents were heterozygous for the three sequence changes, and none of the five control subjects was homozygous for any of these changes. Comparison of normalised cycle threshold (Ct) values indicated a 6.98 to 8.72 (mean 7.85)-fold reduction in the relative amount of KIAA0196 transcript in the patient samples versus the control sample. Sanger sequencing of the cloned PCR product from a patient revealed that the primary product did not contain exon 27 (figure 2B). Suggesting altered KIAA0196 transcript produced by the patient might be targeted for nonsense mediated decay. Strumpellin, the product of KIAA0196, is a highly conserved glycoprotein from plants to humans, and ubiquitously expressed.

Harvey et al, 2023 (37840956), reports 2 probands with WASHC5 variants and CHD phenotype. Not clear if probands related, or from same geographical area. Zygosity not clear. No information provided about probands, family testing/segregation.
Landis 2023, (37681527) a cohort of 1362 with CHD, reports one with variant in WASHC5. No further information provided about variant, zygosity, or about participant in paper or supp data.
Bu. 2020 et al, (30896870)
Reports, 9mnth male in Changsha, China, with patent ductus arteriosus (PDA) - an opening between two blood vessels leading from the heart, patent foramen ovale (PFO) - hole between the left and right atria, and KIAA0196 (WASHC5) variant. No mention zygosity or biallelic. No supp data provided.
MĆøller Nielsen, 2021(https://doi.org/10.1016/j.ijcchd.2021.100164),
Danish cohort study with Atrial septal defects (ASD), 384 variants identified, three WASHC5 variants are considered pathogenic. Supplementary table 3 reports three WASHC5 variants, but no further information is provided about participants, zygosity of variants, or if blood-related. Limitations state only had singleton data and unable to clarify inheritance/de-novo. Supplementary table reported further info for the three WASHC5 variants, but no explicit mention if biallelic mutations. Excel column J reports 'reads (Ref:Alt)' and indicates participants are ?heterozygous variants which may conflict with RSS being a recessive/biallelic condition?
Hseih, 2020, (32349777)
Mentioned having two damaging germline and one mosaic mutations in their cohort that supports WASHC5 to be a candidate CHD gene. No further information about those variants or participants is provided. No supp data provided.

Animal models:
Mouse Genome Informatics MGI#2146110) : Homozygous knockout mice die well prior to E13.5 as no evidence of conceptus. In heterozygous knockout mice no cardiovascular defect recorded.
Bu, 2020 (32417190)
Mouse and zebrafish studies show potential evidence for WASHC5 biallelic variants cause CHD/. However CliniGen Commented "neither provide evidence to support the gene-disease relationship (Bu et al., PMID:32417190)"


In summary, Elliot et al provides detailed evidence, however looking further at recent literature, studies mention or report on WASHC5 variants and possible associations with CHD, but do not report enough detail to be confident and satisfy ClinGene/PanelApp criteria.
Sources: ClinGen, Literature
Congenital Heart Defect v0.315 PIGL Harshini Thiyagarajah gene: PIGL was added
gene: PIGL was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: PIGL was set to BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.315 ARID1A Kaitlyn Dianna Weldon reviewed gene: ARID1A: Rating: GREEN; Mode of pathogenicity: None; Publications: NBK131811; Phenotypes: Coffin-Siris syndrome MONDO:0015452; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v0.173 RRAGC Zornitza Stark Phenotypes for gene: RRAGC were changed from Dilated cardiomyopathy (MONDO:0005021), RRAGC-related to Long-Olsen syndrome, MIM# 620609
Mendeliome v1.1376 RRAGC Zornitza Stark Publications for gene: RRAGC were set to 27234373
Mendeliome v1.1375 RRAGC Zornitza Stark Phenotypes for gene: RRAGC were changed from Dilated cardiomyopathy (MONDO:0005021), RRAGC-related to Long-Olsen syndrome, MIM# 620609
Congenital Heart Defect v0.315 TXNL4A LUCAS GARCIA ALVES FERREIRA gene: TXNL4A was added
gene: TXNL4A was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: TXNL4A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TXNL4A were set to 25434003; 28905882
Phenotypes for gene: TXNL4A were set to Burn-McKeown syndrome - MIM#608572
Penetrance for gene: TXNL4A were set to unknown
Review for gene: TXNL4A was set to AMBER
Added comment: Homozygous or compound heterozygous mutation in the TXNL4A gene are associated to Burn-McKeown syndrome (BMKS). BMKS is a rare disorder in which individuals with normal intellectual development exhibit the characteristic combination of choanal atresia, sensorineural deafness, cardiac defects, and typical craniofacial dysmorphism consisting of narrow palpebral fissures, coloboma of the lower eyelids, prominent nose with high nasal bridge, short philtrum, cleft lip and/or palate, and large and protruding ears (Wieczorek et al 2014 - PMID 25434003).

Wieczorek et al (2014 - PMID: 25434003) report 9 families presenting individuals with BMKS and harboring biallelic variants in the TXNL4A gene. Four unrelated individuals presented cardiac defects.

Goos et al (2017 - PMID: 28905882) report an individual with BMKS including asymptomatic atrial and ventricular septal defects, and harboring biallelic variants in the TXNL4A gene.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5615 PBX1 Zornitza Stark Marked gene: PBX1 as ready
Intellectual disability syndromic and non-syndromic v0.5615 PBX1 Zornitza Stark Gene: pbx1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5615 PBX1 Zornitza Stark Phenotypes for gene: PBX1 were changed from to Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, OMIM #617641
Intellectual disability syndromic and non-syndromic v0.5614 PBX1 Zornitza Stark Mode of inheritance for gene: PBX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.315 SMG9 Laura S Deleted their comment
Congenital Heart Defect v0.315 SMG9 Laura S edited their review of gene: SMG9: Added comment: Autosomal recessive inheritance

Shaheen et al. in 2016 (27018474) published case reports about two consanguineous families in which a similar patter of congenital anomalies was found to be most likely caused by homozygous loss-of-function mutation in SMG9. This gene encodes an essential component of the SURF complex that generates phosphor-UPF1, the single most important step in nonsense-mediated decay (NMD). The authors generated a knock-out Smg9 mouse model using CRISPR/Cas9 and observed similar congenital anomaly syndrome to the one reported in humans. Additionally, human cells not expressing SMG9 had global transcriptional dysregulation, but not reduction of premature stop codon (PST)-containing transcripts.

The affected family members in these two families showed to have phenotypic overlap between Dandy-Walker malformation and congenital heart disease. Due to the consanguineous nature in both families and the geographical proximity (both cases in Arabia) indicate the possibility of a homozygous pathogenic variants in the same gene. These variants are c.520_521delCC and c.701+4A>G, both affecting the gene SMG9. The indel in family 1 predicts a frameshift and premature truncation, p.Pro174Argfs*12. In family 2, a complete skipping of exon 6 was revealed by RT-PCR. The resulting aberrant transcript predicts frameshift and premature truncation (p.Tyr197Aspfs*10).

In 2019, another case was reported by Lecoquierre et al. (31390136). The patient presented with a syndromic association of severe global developmental delay and diverse malformations. She carried a novel SMG9 homozygous variant NM_019108.3:c.1177C>T, p.(Gln393*), while her unaffected parents were both heterozygous and first-degree cousins. This absent variant in gnomaAD was predicted to result in a premature stop codon leading to nonsense-mediated decay within this single transcript gene.

In 2020, Lemire et al. (32412169) reported a case of 7-year-old female with severe intellectual disability, multiple congenital anomalies, including cardiovascular anomalies, and facial dysmorphisms. No known consanguinity, the parents were heterozygous for the variant and she had an unaffected brother. She carried a homozygous missense variant in the SMG9 gene (c.1508G > C; p.Trp503Ser) identified as the likely etiology. In silico analysis predicted this change to impact protein structure/function. This missense change is rare, with only one allele count in gnomAD and no homozygotes.

In 2021, Altuwaijri et al. (33609422) reported a new case in a research letter to the editor, in which a 25-month-old male had significant heart and brain malformations. Exome sequencing performed on the subject revealed the same homozygous splicing variant (NM_019108.4: exon7:c.701+4A>G) as their original report (Shaheen et al., 2016). Thus validating their previous findings.; Changed publications: 27018474 31390136 32412169 33609422; Changed phenotypes: Heart and brain malformation syndrome (HBMS)
Congenital Heart Defect v0.315 SMG9 Laura S changed review comment from: Autosomal recessive inheritance

Shaheen et al. in 2016 (27018474) published case reports about two consanguineous families in which a similar patter of congenital anomalies was found to be most likely caused by homozygous loss-of-function mutation in SMG9. This gene encodes an essential component of the SURF complex that generates phosphor-UPF1, the single most important step in nonsense-mediated decay (NMD). The authors generated a knock-out Smg9 mouse model using CRISPR/Cas9 and observed similar congenital anomaly syndrome to the one reported in humans. Additionally, human cells not expressing SMG9 had global transcriptional dysregulation, but not reduction of premature stop codon (PST)-containing transcripts.

The affected family members in these two families showed to have phenotypic overlap between Dandy-Walker malformation and congenital heart disease. Due to the consanguineous nature in both families and the geographical proximity (both cases in Arabia) indicate the possibility of a homozygous pathogenic variants in the same gene. These variants are c.520_521delCC and c.701+4A>G, both affecting the gene SMG9. The indel in family 1 predicts a frameshift and premature truncation, p.Pro174Argfs*12. In family 2, a complete skipping of exon 6 was revealed by RT-PCR. The resulting aberrant transcript predicts frameshift and premature truncation (p.Tyr197Aspfs*10).

In 2019, another case was reported by Lecoquierre et al. (31390136). The patient presented with a syndromic association of severe global developmental delay and diverse malformations. She carried a novel SMG9 homozygous variant NM_019108.3:c.1177C>T, p.(Gln393*), while her unaffected parents were both heterozygous and first-degree cousins. This absent variant in gnomaAD was predicted to result in a premature stop codon leading to nonsense-mediated decay within this single transcript gene.

In 2020, Lemire et al. (32412169) reported a case of 7-year-old female with severe intellectual disability, multiple congenital anomalies, including cardiovascular anomalies, and facial dysmorphisms. No known consanguinity, the parents were heterozygous for the variant and she had an unaffected brother. She carried a homozygous missense variant in the SMG9 gene (c.1508G > C; p.Trp503Ser) identified as the likely etiology. In silico analysis predicted this change to impact protein structure/function. This missense change is rare, with only one allele count in gnomAD and no homozygotes.

In 2021, Altuwaijri et al. (33609422) reported a new case in a research letter to the editor, in which a 25-month-old male had significant heart and brain malformations. Exome sequencing performed on the subject revealed the same homozygous splicing variant (NM_019108.4: exon7:c.701+4A>G) as their original report (Shaheen et al., 2016). Thus validating their previous findings.
Sources: Literature; to: Autosomal recessive inheritance

Shaheen et al. in 2016 (27018474) published case reports about two consanguineous families in which a similar patter of congenital anomalies was found to be most likely caused by homozygous loss-of-function mutation in SMG9. This gene encodes an essential component of the SURF complex that generates phosphor-UPF1, the single most important step in nonsense-mediated decay (NMD). The authors generated a knock-out Smg9 mouse model using CRISPR/Cas9 and observed similar congenital anomaly syndrome to the one reported in humans. Additionally, human cells not expressing SMG9 had global transcriptional dysregulation, but not reduction of premature stop codon (PST)-containing transcripts.

The affected family members in these two families showed to have phenotypic overlap between Dandy-Walker malformation and congenital heart disease. Due to the consanguineous nature in both families and the geographical proximity (both cases in Arabia) indicate the possibility of a homozygous pathogenic variants in the same gene. These variants are c.520_521delCC and c.701+4A>G, both affecting the gene SMG9. The indel in family 1 predicts a frameshift and premature truncation, p.Pro174Argfs*12. In family 2, a complete skipping of exon 6 was revealed by RT-PCR. The resulting aberrant transcript predicts frameshift and premature truncation (p.Tyr197Aspfs*10).

In 2019, another case was reported by Lecoquierre et al. (31390136). The patient presented with a syndromic association of severe global developmental delay and diverse malformations. She carried a novel SMG9 homozygous variant NM_019108.3:c.1177C>T, p.(Gln393*), while her unaffected parents were both heterozygous and first-degree cousins. This absent variant in gnomaAD was predicted to result in a premature stop codon leading to nonsense-mediated decay within this single transcript gene.

In 2020, Lemire et al. (32412169) reported a case of 7-year-old female with severe intellectual disability, multiple congenital anomalies, including cardiovascular anomalies, and facial dysmorphisms. No known consanguinity, the parents were heterozygous for the variant and she had an unaffected brother. She carried a homozygous missense variant in the SMG9 gene (c.1508G > C; p.Trp503Ser) identified as the likely etiology. In silico analysis predicted this change to impact protein structure/function. This missense change is rare, with only one allele count in gnomAD and no homozygotes.

In 2021, Altuwaijri et al. (33609422) reported a new case in a research letter to the editor, in which a 25-month-old male had significant heart and brain malformations. Exome sequencing performed on the subject revealed the same homozygous splicing variant (NM_019108.4: exon7:c.701+4A>G) as their original report (Shaheen et al., 2016). Thus validating their previous findings.
Sources: Literature
Congenital Heart Defect v0.315 SMG9 Laura S gene: SMG9 was added
gene: SMG9 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: SMG9 was set to Other
Publications for gene: SMG9 were set to 27018474
Review for gene: SMG9 was set to RED
Added comment: Autosomal recessive inheritance

Shaheen et al. in 2016 (27018474) published case reports about two consanguineous families in which a similar patter of congenital anomalies was found to be most likely caused by homozygous loss-of-function mutation in SMG9. This gene encodes an essential component of the SURF complex that generates phosphor-UPF1, the single most important step in nonsense-mediated decay (NMD). The authors generated a knock-out Smg9 mouse model using CRISPR/Cas9 and observed similar congenital anomaly syndrome to the one reported in humans. Additionally, human cells not expressing SMG9 had global transcriptional dysregulation, but not reduction of premature stop codon (PST)-containing transcripts.

The affected family members in these two families showed to have phenotypic overlap between Dandy-Walker malformation and congenital heart disease. Due to the consanguineous nature in both families and the geographical proximity (both cases in Arabia) indicate the possibility of a homozygous pathogenic variants in the same gene. These variants are c.520_521delCC and c.701+4A>G, both affecting the gene SMG9. The indel in family 1 predicts a frameshift and premature truncation, p.Pro174Argfs*12. In family 2, a complete skipping of exon 6 was revealed by RT-PCR. The resulting aberrant transcript predicts frameshift and premature truncation (p.Tyr197Aspfs*10).

In 2019, another case was reported by Lecoquierre et al. (31390136). The patient presented with a syndromic association of severe global developmental delay and diverse malformations. She carried a novel SMG9 homozygous variant NM_019108.3:c.1177C>T, p.(Gln393*), while her unaffected parents were both heterozygous and first-degree cousins. This absent variant in gnomaAD was predicted to result in a premature stop codon leading to nonsense-mediated decay within this single transcript gene.

In 2020, Lemire et al. (32412169) reported a case of 7-year-old female with severe intellectual disability, multiple congenital anomalies, including cardiovascular anomalies, and facial dysmorphisms. No known consanguinity, the parents were heterozygous for the variant and she had an unaffected brother. She carried a homozygous missense variant in the SMG9 gene (c.1508G > C; p.Trp503Ser) identified as the likely etiology. In silico analysis predicted this change to impact protein structure/function. This missense change is rare, with only one allele count in gnomAD and no homozygotes.

In 2021, Altuwaijri et al. (33609422) reported a new case in a research letter to the editor, in which a 25-month-old male had significant heart and brain malformations. Exome sequencing performed on the subject revealed the same homozygous splicing variant (NM_019108.4: exon7:c.701+4A>G) as their original report (Shaheen et al., 2016). Thus validating their previous findings.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5613 PBX1 Chirag Patel reviewed gene: PBX1: Rating: GREEN; Mode of pathogenicity: None; Publications: Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, OMIM #617641; Phenotypes: Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, OMIM #617641; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.1374 SLCO1B3 Zornitza Stark Publications for gene: SLCO1B3 were set to 33860121
Mendeliome v1.1373 SLCO1B3 Zornitza Stark Classified gene: SLCO1B3 as Green List (high evidence)
Mendeliome v1.1373 SLCO1B3 Zornitza Stark Gene: slco1b3 has been classified as Green List (High Evidence).
Mendeliome v1.1372 SLCO1B3 Zornitza Stark edited their review of gene: SLCO1B3: Added comment: Five additional individuals reported.; Changed rating: GREEN; Changed publications: 33860121, 36964102
Mendeliome v1.1372 SLCO1B1 Zornitza Stark Publications for gene: SLCO1B1 were set to 30250148; 24918167; 33860121
Mendeliome v1.1371 SLCO1B1 Zornitza Stark edited their review of gene: SLCO1B1: Changed publications: 36964102, 33860121
Mendeliome v1.1371 SLCO1B1 Zornitza Stark Classified gene: SLCO1B1 as Green List (high evidence)
Mendeliome v1.1371 SLCO1B1 Zornitza Stark Gene: slco1b1 has been classified as Green List (High Evidence).
Mendeliome v1.1370 SLCO1B1 Zornitza Stark edited their review of gene: SLCO1B1: Changed rating: GREEN
Mendeliome v1.1370 SLCO1B1 Zornitza Stark edited their review of gene: SLCO1B1: Added comment: Five additional individuals reported.; Changed publications: 33860121, 33860121
Intellectual disability syndromic and non-syndromic v0.5613 KCNJ11 Chirag Patel Classified gene: KCNJ11 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5613 KCNJ11 Chirag Patel Gene: kcnj11 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5612 KCNJ11 Chirag Patel reviewed gene: KCNJ11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Congenital Heart Defect v0.315 DOCK6 Zornitza Stark Marked gene: DOCK6 as ready
Congenital Heart Defect v0.315 DOCK6 Zornitza Stark Gene: dock6 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.315 DOCK6 Zornitza Stark Phenotypes for gene: DOCK6 were changed from to Adams-Oliver syndrome 2 MIM#614219
Congenital Heart Defect v0.314 DOCK6 Zornitza Stark Publications for gene: DOCK6 were set to
Congenital Heart Defect v0.314 DOCK6 Zornitza Stark Mode of inheritance for gene: DOCK6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.313 DOCK6 Zornitza Stark edited their review of gene: DOCK6: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.313 DOCK6 Zornitza Stark reviewed gene: DOCK6: Rating: GREEN; Mode of pathogenicity: None; Publications: 28160419; Phenotypes: Adams-Oliver syndrome 2 MIM#614219; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5612 KCNA3 Zornitza Stark Publications for gene: KCNA3 were set to
Intellectual disability syndromic and non-syndromic v0.5611 KCNA3 Zornitza Stark reviewed gene: KCNA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37964487; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, KCNA3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1947 KCNA3 Zornitza Stark Publications for gene: KCNA3 were set to
Genetic Epilepsy v0.1946 KCNA3 Zornitza Stark reviewed gene: KCNA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37964487; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, KCNA3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1370 KCNA3 Zornitza Stark Publications for gene: KCNA3 were set to
Mendeliome v1.1369 KCNA3 Zornitza Stark reviewed gene: KCNA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37964487; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, KCNA3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1369 ERG Zornitza Stark Phenotypes for gene: ERG were changed from primary lymphoedema MONDO#0019175, ERG-related to Lymphatic malformation 14, MIM# 620602
Fetal anomalies v1.166 PLS3 Zornitza Stark Phenotypes for gene: PLS3 were changed from Bone mineral density QTL18, osteoporosis - MIM#300910; congenital diaphragmatic hernia MONDO:0005711, PLS3-related to Bone mineral density QTL18, osteoporosis - MIM#300910; Diaphragmatic hernia 5, X-linked, MIM# 306950
Fetal anomalies v1.165 PLS3 Zornitza Stark reviewed gene: PLS3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diaphragmatic hernia 5, X-linked, MIM# 306950; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.1368 PLS3 Zornitza Stark Phenotypes for gene: PLS3 were changed from Bone mineral density QTL18, osteoporosis - MIM#300910; congenital diaphragmatic hernia MONDO:0005711, PLS3-related to Bone mineral density QTL18, osteoporosis - MIM#300910; Diaphragmatic hernia 5, X-linked, MIM# 306950
Mendeliome v1.1367 PLS3 Zornitza Stark edited their review of gene: PLS3: Changed phenotypes: Bone mineral density QTL18, osteoporosis - MIM#300910, Diaphragmatic hernia 5, X-linked, MIM# 306950
Congenital diaphragmatic hernia v1.14 PLS3 Zornitza Stark Phenotypes for gene: PLS3 were changed from congenital diaphragmatic hernia MONDO:0005711, PLS3-related to Diaphragmatic hernia 5, X-linked, MIM# 306950
Congenital diaphragmatic hernia v1.13 PLS3 Zornitza Stark reviewed gene: PLS3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diaphragmatic hernia 5, X-linked, MIM# 306950; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Congenital Heart Defect v0.313 DOCK6 Richard McCoy reviewed gene: DOCK6: Rating: RED; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 21820096, 23522784, 7606848, 25824905, 25824905, 36789878; Phenotypes: neurological disorders, impaired intellectual development, microcephaly, aplasia cutis congenita, terminal transverse limb defects; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bone Marrow Failure v1.59 POT1 Zornitza Stark Marked gene: POT1 as ready
Bone Marrow Failure v1.59 POT1 Zornitza Stark Gene: pot1 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.59 POT1 Zornitza Stark Classified gene: POT1 as Green List (high evidence)
Bone Marrow Failure v1.59 POT1 Zornitza Stark Gene: pot1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.893 TOMM7 Zornitza Stark Phenotypes for gene: TOMM7 were changed from Inborn mitochondrial disorder MONDO:0004069, TOMM7-related to Garg-Mishra progeroid syndrome, MIM# 620601
Mitochondrial disease v0.892 TOMM7 Zornitza Stark edited their review of gene: TOMM7: Changed phenotypes: Garg-Mishra progeroid syndrome, MIM# 620601
Mendeliome v1.1367 TOMM7 Zornitza Stark Phenotypes for gene: TOMM7 were changed from Inborn mitochondrial disorder MONDO:0004069, TOMM7-related to Garg-Mishra progeroid syndrome, MIM# 620601
Mendeliome v1.1366 TOMM7 Zornitza Stark edited their review of gene: TOMM7: Changed phenotypes: Garg-Mishra progeroid syndrome, MIM# 620601
Optic Atrophy v1.25 MCAT Zornitza Stark Phenotypes for gene: MCAT were changed from Leber hereditary optic neuropathy, autosomal recessive, MONDO:0030309 to Optic atrophy 15, MIM# 620583
Optic Atrophy v1.24 MCAT Zornitza Stark edited their review of gene: MCAT: Changed phenotypes: Optic atrophy 15, MIM# 620583
Mendeliome v1.1366 MCAT Zornitza Stark Phenotypes for gene: MCAT were changed from Leber hereditary optic neuropathy, autosomal recessive, MONDO:0030309 to Optic atrophy 15, MIM# 620583
Mendeliome v1.1365 MCAT Zornitza Stark Publications for gene: MCAT were set to 31915829
Mendeliome v1.1364 MCAT Zornitza Stark edited their review of gene: MCAT: Added comment: Second individual reported in PMID 33918393; Changed publications: 33918393
Mendeliome v1.1364 MCAT Zornitza Stark edited their review of gene: MCAT: Changed phenotypes: Optic atrophy 15, MIM# 620583
Congenital Heart Defect v0.313 GATA5 Ceecee Britten-Jones reviewed gene: GATA5: Rating: AMBER; Mode of pathogenicity: None; Publications: 21633169, 21839733, 23289003, 22961344, 24638895, 2329559, 23040494, 25515806, 35534675, 22641149, 26708639; Phenotypes: 617912; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Bone Marrow Failure v1.58 POT1 Bryony Thompson gene: POT1 was added
gene: POT1 was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: POT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POT1 were set to 33119245
Phenotypes for gene: POT1 were set to Hereditary neoplastic syndrome, MONDO:0015356, POT1-related
Review for gene: POT1 was set to GREEN
gene: POT1 was marked as current diagnostic
Added comment: Well-established telomere disorder with a variety of solid and haematological malignancies reported. The mechanism of disease is loss of function leading to overall telomere lengthening, and resulting in fragile and dysfunctional telomeres.
Sources: Expert list
Mendeliome v1.1364 MDM4 Bryony Thompson Marked gene: MDM4 as ready
Mendeliome v1.1364 MDM4 Bryony Thompson Gene: mdm4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1364 MDM4 Bryony Thompson Classified gene: MDM4 as Amber List (moderate evidence)
Mendeliome v1.1364 MDM4 Bryony Thompson Gene: mdm4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1363 MDM4 Bryony Thompson gene: MDM4 was added
gene: MDM4 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: MDM4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MDM4 were set to 32300648; 33104793
Phenotypes for gene: MDM4 were set to bone marrow failure syndrome MONDO:0000159, MDM4-related
Review for gene: MDM4 was set to AMBER
Added comment: A single family was reported to segregate a missense variant (p.Thr454Met) with features suggestive of dyskeratosis congenita, e.g., bone marrow hypocellularity, short telomeres, tongue squamous cell carcinoma, and acute myeloid leukemia. A mouse model of p.Thr454Met showed increased p53 activity, decreased telomere length, and bone marrow failure.
Sources: Other
Bone Marrow Failure v1.56 MDM4 Bryony Thompson Marked gene: MDM4 as ready
Bone Marrow Failure v1.56 MDM4 Bryony Thompson Gene: mdm4 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.56 MDM4 Bryony Thompson Classified gene: MDM4 as Amber List (moderate evidence)
Bone Marrow Failure v1.56 MDM4 Bryony Thompson Gene: mdm4 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.55 MDM4 Bryony Thompson gene: MDM4 was added
gene: MDM4 was added to Bone Marrow Failure. Sources: Other
Mode of inheritance for gene: MDM4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MDM4 were set to 32300648; 33104793
Phenotypes for gene: MDM4 were set to bone marrow failure syndrome MONDO:0000159, MDM4-related
Review for gene: MDM4 was set to AMBER
Added comment: A single family was reported to segregate a missense variant (p.Thr454Met) with features suggestive of dyskeratosis congenita, e.g., bone marrow hypocellularity, short telomeres, tongue squamous cell carcinoma, and acute myeloid leukemia. A mouse model of p.Thr454Met showed increased p53 activity, decreased telomere length, and bone marrow failure.
Sources: Other
Mendeliome v1.1362 THOC6 Ling Sun changed review comment from: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome. Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype).

PMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly) [compound het]

PMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C)
A girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu) [compount het]

PMID: 32282736: A boy with paternally inherited c.664T>C (p.Trp222Arg) and maternally inherited c.945+1 G>A [compound het]; to: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome. Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype, eg. see https://databases.lovd.nl/shared/diseases/03390).

PMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly) [compound het]

PMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C)
A girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu) [compount het]

PMID: 32282736: A boy with paternally inherited c.664T>C (p.Trp222Arg) and maternally inherited c.945+1 G>A [compound het]
Mendeliome v1.1362 THOC6 Ling Sun changed review comment from: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome. Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype).

PMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly)

PMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C)
A girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu); to: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome. Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype).

PMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly) [compound het]

PMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C)
A girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu) [compount het]

PMID: 32282736: A boy with paternally inherited c.664T>C (p.Trp222Arg) and maternally inherited c.945+1 G>A [compound het]
Mendeliome v1.1362 THOC6 Ling Sun changed review comment from: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome. Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies (syndromic phenotype).

PMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly)

PMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C)
A girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu); to: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome. Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype).

PMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly)

PMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C)
A girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu)
Mendeliome v1.1362 THOC6 Ling Sun reviewed gene: THOC6: Rating: AMBER; Mode of pathogenicity: None; Publications: 35426486, 30476144; Phenotypes: VSD/ASD, severe aortic and left ventricular hypoplasia, Mild dilation of the right chambers and a mild myocardial hypertrophy secondary to a chronic hypertension, ventriculomegaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.313 CHD4 Zornitza Stark Marked gene: CHD4 as ready
Congenital Heart Defect v0.313 CHD4 Zornitza Stark Gene: chd4 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.313 CHD4 Zornitza Stark Phenotypes for gene: CHD4 were changed from to Sifrim-Hitz-Weiss syndrome (MIM#617159)
Congenital Heart Defect v0.312 CHD4 Zornitza Stark Publications for gene: CHD4 were set to
Congenital Heart Defect v0.311 CHD4 Zornitza Stark Mode of inheritance for gene: CHD4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 500+ v1.0 Seb Lunke promoted panel to version 1.0
Prepair 500+ v0.1 Seb Lunke Panel status changed from internal to public
Panel types changed to Victorian Clinical Genetics Services
Congenital Heart Defect v0.310 CHD4 Polly McIntosh changed review comment from: OMIM 617159 Sifrim-Hitz-Weiss Syndrome (Also called CHD4 Neurodevelopmental Disorder)
31 de novo cases with Sifrim-Hitz-Weiss Syndrome PMID 31388190:
72% of patients assessed (21/29) had structural heart abnormalities inc. septal defects, tetrology of Fallot and truncus arteriosus.
Functional studies on engineered cells with CHD4 variants showed reduced ATPase activity and reduced chromatin remodeling (PMID 31388190). Mouse studies on another CHD4 variant showed ventricular hypertrabeculation in CHD4 variant mice (PMID 37254794); to: OMIM 617159 Sifrim-Hitz-Weiss Syndrome (Also called CHD4 Neurodevelopmental Disorder)
31 de novo cases with Sifrim-Hitz-Weiss Syndrome PMID 31388190:
72% of patients assessed (21/29) had structural heart abnormalities inc. septal defects, tetrology of Fallot and truncus arteriosus.
Functional studies on engineered cells with CHD4 variants showed reduced ATPase activity and reduced chromatin remodeling (PMID 31388190). Mouse studies on another CHD4 variant showed ventricular hypertrabeculation in CHD4 variant mice (PMID 37254794)
Congenital Heart Defect v0.310 CHD4 Polly McIntosh reviewed gene: CHD4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31388190, 31474762, 27479907, 27616479, 24348274, 37254794; Phenotypes: Developmental delay, intellectual disability, ophthalmological abnormalities, congenital heart defects, hypotonia, hearing impairment, cryptorchidism, macrocephaly, skeletal abnormalities, hypogonadism, short stature, hydrocephalus; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.310 LZTR1 Zornitza Stark Mode of inheritance for gene: LZTR1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Heart Defect v0.309 LZTR1 Zornitza Stark Classified gene: LZTR1 as Green List (high evidence)
Congenital Heart Defect v0.309 LZTR1 Zornitza Stark Gene: lztr1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.308 LZTR1 Zornitza Stark reviewed gene: LZTR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome 10, MIM# 616564, Noonan syndrome 2, MIM# 605275; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phagocyte Defects v1.23 TCIRG1 Zornitza Stark Marked gene: TCIRG1 as ready
Phagocyte Defects v1.23 TCIRG1 Zornitza Stark Gene: tcirg1 has been classified as Amber List (Moderate Evidence).
Phagocyte Defects v1.23 TCIRG1 Zornitza Stark Classified gene: TCIRG1 as Amber List (moderate evidence)
Phagocyte Defects v1.23 TCIRG1 Zornitza Stark Gene: tcirg1 has been classified as Amber List (Moderate Evidence).
Phagocyte Defects v1.22 TCIRG1 Zornitza Stark gene: TCIRG1 was added
gene: TCIRG1 was added to Phagocyte Defects. Sources: Expert Review
Mode of inheritance for gene: TCIRG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TCIRG1 were set to 24753205; 35573728
Phenotypes for gene: TCIRG1 were set to severe congenital neutropenia, MONDO:0018542
Review for gene: TCIRG1 was set to AMBER
Added comment: Biallelic variants in this gene have already been associated with Osteopetrosis (MIM #259700).

Newer reports of individuals with monoallelic TCIRG1 variants and congenital neutropenia.

PMID:24753205 reported a five generation family segregating a novel SNV in TCIRG1 (p.Arg736Ser) with congenital neutropenia.

PMID:35573728 - A seven years old patient suspected for Congenital Neutropenia, having symptoms related to chronic infections was reported with p.Val52Leu variant.
Sources: Expert Review
Mendeliome v1.1362 TCIRG1 Zornitza Stark edited their review of gene: TCIRG1: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1362 DAW1 Zornitza Stark Phenotypes for gene: DAW1 were changed from Primary ciliary dyskinesia, MONDO:0016575; Visceral heterotaxy, MONDO:0018677 to Primary ciliary dyskinesia, with or without heterotaxy, MIM#620570
Mendeliome v1.1361 DAW1 Zornitza Stark reviewed gene: DAW1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary ciliary dyskinesia, with or without heterotaxy, MIM#620570; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v1.31 DAW1 Zornitza Stark Phenotypes for gene: DAW1 were changed from Primary ciliary dyskinesia, MONDO:0016575; Visceral heterotaxy, MONDO:0018677 to Primary ciliary dyskinesia, with or without heterotaxy, MIM#620570
Heterotaxy v1.30 DAW1 Zornitza Stark reviewed gene: DAW1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary ciliary dyskinesia, with or without heterotaxy, MIM#620570; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v1.36 DAW1 Zornitza Stark Phenotypes for gene: DAW1 were changed from Primary ciliary dyskinesia, MONDO:0016575; Visceral heterotaxy, MONDO:0018677 to Primary ciliary dyskinesia, with or without heterotaxy, MIM#620570
Optic Atrophy v1.24 NDUFS2 Zornitza Stark Phenotypes for gene: NDUFS2 were changed from Mitochondrial complex I deficiency, nuclear type 6 - MIM#618228 to Mitochondrial complex I deficiency, nuclear type 6 - MIM#618228; Leber hereditary optic neuropathy, autosomal recessive 2, MIM# 620569
Optic Atrophy v1.23 NDUFS2 Zornitza Stark reviewed gene: NDUFS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28031252; Phenotypes: Leber hereditary optic neuropathy, autosomal recessive 2, MIM# 620569; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1361 TCIRG1 Achchuthan Shanmugasundram reviewed gene: TCIRG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24753205, 35573728; Phenotypes: severe congenital neutropenia, MONDO:0018542; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5611 FOXP4 Elena Savva Phenotypes for gene: FOXP4 were changed from Neurodevelopmental disorder (MONDO#0700092), FOXP4-related to Neurodevelopmental disorder (MONDO#0700092), FOXP4-related
Intellectual disability syndromic and non-syndromic v0.5611 FOXP4 Elena Savva Phenotypes for gene: FOXP4 were changed from Neurodevelopmental disorder (MONDO#0700092), FOXP4-related to Neurodevelopmental disorder (MONDO#0700092), FOXP4-related
Intellectual disability syndromic and non-syndromic v0.5610 FOXP4 Elena Savva Phenotypes for gene: FOXP4 were changed from Neurodevelopmental disorder; multiple congenital abnormalities to Neurodevelopmental disorder (MONDO#0700092), FOXP4-related
Intellectual disability syndromic and non-syndromic v0.5609 FOXP4 Elena Savva Publications for gene: FOXP4 were set to 33110267
Intellectual disability syndromic and non-syndromic v0.5609 FOXP4 Elena Savva Classified gene: FOXP4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5609 FOXP4 Elena Savva Gene: foxp4 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.308 LZTR1 Emanuel Birru gene: LZTR1 was added
gene: LZTR1 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: LZTR1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LZTR1 were set to PMID: 30368668; 34184824
Phenotypes for gene: LZTR1 were set to Cardiac defects; hypertrophic cardiomyopathy; atrial septal defect; pulmonary stenosis; short stature; intellectual disabilities
Penetrance for gene: LZTR1 were set to Incomplete
Review for gene: LZTR1 was set to GREEN
Added comment: Several variants of LZTR1 demonstrate compound heterozygosity, implying an autosomal recessive mode of inheritance. Patients with LZTR1 variants had cardiac defects, and these LZTR1 variants are linked to a spectrum of conditions, including Noonan syndrome (NS), Costello syndrome, cardiofaciocutaneous syndrome, and other related disorders.

Many patients carrying LZTR1 variants are clinically suspected to have Noonan syndrome due to the presence of shared clinical features associated with NS. These features encompass relative macrocephaly, NS-associated facial characteristics, heart defects, intellectual disability, and short stature.
Sources: Literature
Genetic Epilepsy v0.1946 PLA2G6 Zornitza Stark Marked gene: PLA2G6 as ready
Genetic Epilepsy v0.1946 PLA2G6 Zornitza Stark Gene: pla2g6 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1946 PLA2G6 Zornitza Stark Classified gene: PLA2G6 as Green List (high evidence)
Genetic Epilepsy v0.1946 PLA2G6 Zornitza Stark Gene: pla2g6 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1945 PLA2G6 Zornitza Stark gene: PLA2G6 was added
gene: PLA2G6 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: PLA2G6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLA2G6 were set to 30340910
Phenotypes for gene: PLA2G6 were set to Neurodegeneration with brain iron accumulation 2B MIM#610217
Review for gene: PLA2G6 was set to GREEN
Added comment: Sixteen cases of PLA2G6-associated neurodegeneration (PLAN) were examined in PMID: 30340910. Seizures were evident in 5/10 cases with infantile PLAN and in 3/6 cases with childhood PLAN. A total of nine PLA2G6 variants were associated with a phenotype that included seizures.
Sources: Expert Review
Fetal anomalies v1.165 TRIT1 Zornitza Stark Marked gene: TRIT1 as ready
Fetal anomalies v1.165 TRIT1 Zornitza Stark Gene: trit1 has been classified as Green List (High Evidence).
Fetal anomalies v1.165 TRIT1 Zornitza Stark Classified gene: TRIT1 as Green List (high evidence)
Fetal anomalies v1.165 TRIT1 Zornitza Stark Gene: trit1 has been classified as Green List (High Evidence).
Fetal anomalies v1.164 TRIT1 Zornitza Stark gene: TRIT1 was added
gene: TRIT1 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: TRIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIT1 were set to 36049610; 32088416
Phenotypes for gene: TRIT1 were set to Combined oxidative phosphorylation deficiency 35, MIM#617873
Review for gene: TRIT1 was set to GREEN
Added comment: Presentations with IUGR reported.
Sources: Expert Review
Mendeliome v1.1361 TUBGCP2 Zornitza Stark Phenotypes for gene: TUBGCP2 were changed from Lissencephaly; pachygyria; subcortical band heterotopia; microcephaly; intellectual disability to Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures, OMIM # 618737; Lissencephaly; pachygyria; subcortical band heterotopia; microcephaly; intellectual disability
Mendeliome v1.1360 TUBGCP2 Zornitza Stark edited their review of gene: TUBGCP2: Changed phenotypes: Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures, OMIM # 618737, Lissencephaly, pachygyria, subcortical band heterotopia, microcephaly, intellectual disability
Mendeliome v1.1360 PSMB10 Zornitza Stark Publications for gene: PSMB10 were set to 31783057
Mendeliome v1.1359 PSMB10 Zornitza Stark Classified gene: PSMB10 as Green List (high evidence)
Mendeliome v1.1359 PSMB10 Zornitza Stark Gene: psmb10 has been classified as Green List (High Evidence).
Mendeliome v1.1358 PSMB10 Zornitza Stark edited their review of gene: PSMB10: Added comment: PMID 37600812: 3 additional unrelated patients with compound heterozygous variants with structural modelling of proteasome assembly.; Changed rating: GREEN; Changed publications: 31783057, 37600812
Autoinflammatory Disorders v1.26 PSMB10 Zornitza Stark Publications for gene: PSMB10 were set to 31783057
Autoinflammatory Disorders v1.25 PSMB10 Zornitza Stark Classified gene: PSMB10 as Green List (high evidence)
Autoinflammatory Disorders v1.25 PSMB10 Zornitza Stark Gene: psmb10 has been classified as Green List (High Evidence).
Clefting disorders v0.245 ARCN1 Zornitza Stark Marked gene: ARCN1 as ready
Clefting disorders v0.245 ARCN1 Zornitza Stark Gene: arcn1 has been classified as Green List (High Evidence).
Clefting disorders v0.245 ARCN1 Zornitza Stark Publications for gene: ARCN1 were set to 27476655
Clefting disorders v0.244 ARCN1 Zornitza Stark Classified gene: ARCN1 as Green List (high evidence)
Clefting disorders v0.244 ARCN1 Zornitza Stark Gene: arcn1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.308 MYH11 Zoe Ward reviewed gene: MYH11: Rating: AMBER; Mode of pathogenicity: Other; Publications: 27418595, 16444274, 21937134, 17666408, 22968129, 37306888; Phenotypes: Patent Ductus Arteriosus (PDA); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.1358 FYB1 Zornitza Stark Marked gene: FYB1 as ready
Mendeliome v1.1358 FYB1 Zornitza Stark Gene: fyb1 has been classified as Green List (High Evidence).
Mendeliome v1.1358 FYB1 Zornitza Stark Classified gene: FYB1 as Green List (high evidence)
Mendeliome v1.1358 FYB1 Zornitza Stark Gene: fyb1 has been classified as Green List (High Evidence).
Mendeliome v1.1357 FYB1 Zornitza Stark gene: FYB1 was added
gene: FYB1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: FYB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FYB1 were set to 25516138; 25876182
Phenotypes for gene: FYB1 were set to Thrombocytopenia 3, MIM# 273900
Review for gene: FYB1 was set to GREEN
Added comment: Two families with LoF variants and segregation reported in the literature. Aware of two additional cases through clinical testing (Prevention Genetics).

Good functional evidence, including mouse models.

Moderate by ClinGen, though note score was in 'Strong' range and downgraded due to two families in the literature only.
Sources: Expert Review
Bleeding and Platelet Disorders v1.27 FYB1 Zornitza Stark Classified gene: FYB1 as Green List (high evidence)
Bleeding and Platelet Disorders v1.27 FYB1 Zornitza Stark Gene: fyb1 has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.26 FYB1 Zornitza Stark edited their review of gene: FYB1: Added comment: Two further cases through clinical testing (Prevention Genetics) with homozygous LoF variant.; Changed rating: GREEN; Changed phenotypes: Thrombocytopenia 3, MIM# 273900
Mendeliome v1.1356 MCTS1 Zornitza Stark Marked gene: MCTS1 as ready
Mendeliome v1.1356 MCTS1 Zornitza Stark Gene: mcts1 has been classified as Green List (High Evidence).
Mendeliome v1.1356 MCTS1 Zornitza Stark Classified gene: MCTS1 as Green List (high evidence)
Mendeliome v1.1356 MCTS1 Zornitza Stark Gene: mcts1 has been classified as Green List (High Evidence).
Mendeliome v1.1355 MCTS1 Zornitza Stark gene: MCTS1 was added
gene: MCTS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MCTS1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MCTS1 were set to 37875108
Phenotypes for gene: MCTS1 were set to Inherited susceptibility to mycobacterial diseases, MONDO:0019146, MCTS1-related
Review for gene: MCTS1 was set to GREEN
Added comment: 6 male subjects from 5 kindreds with LOF MCTS-1 variants with MSMD.
Extensive ex-vivo functional validation and mouse model.
Sources: Literature
Cardiomyopathy_Paediatric v0.172 ABCC9 Zornitza Stark Marked gene: ABCC9 as ready
Cardiomyopathy_Paediatric v0.172 ABCC9 Zornitza Stark Gene: abcc9 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.172 ABCC9 Zornitza Stark Phenotypes for gene: ABCC9 were changed from Cardiomyopathy, dilated, 1O; Dilated Cardiomyopathy, Dominant to Hypertrichotic osteochondrodysplasia (Cantu syndrome), MIM# 239850; Cardiomyopathy, dilated, 1O; Dilated Cardiomyopathy, Dominant
Cardiomyopathy_Paediatric v0.171 ABCC9 Zornitza Stark Publications for gene: ABCC9 were set to 15034580
Cardiomyopathy_Paediatric v0.170 ABCC9 Zornitza Stark reviewed gene: ABCC9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertrichotic osteochondrodysplasia (Cantu syndrome), MIM# 239850; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.308 EFTUD2 Zornitza Stark Marked gene: EFTUD2 as ready
Congenital Heart Defect v0.308 EFTUD2 Zornitza Stark Gene: eftud2 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.308 EFTUD2 Zornitza Stark Phenotypes for gene: EFTUD2 were changed from to Mandibulofacial dysostosis, Guion-Almeida type (MIM#610536; MONDO:0012516)
Congenital Heart Defect v0.307 EFTUD2 Zornitza Stark Publications for gene: EFTUD2 were set to
Congenital Heart Defect v0.306 EFTUD2 Zornitza Stark Mode of inheritance for gene: EFTUD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1354 DLG2 Zornitza Stark Tag SV/CNV tag was added to gene: DLG2.
Intellectual disability syndromic and non-syndromic v0.5608 DLG2 Zornitza Stark Tag SV/CNV tag was added to gene: DLG2.
Fetal anomalies v1.163 CASP2 Zornitza Stark Marked gene: CASP2 as ready
Fetal anomalies v1.163 CASP2 Zornitza Stark Gene: casp2 has been classified as Green List (High Evidence).
Fetal anomalies v1.163 CASP2 Zornitza Stark Classified gene: CASP2 as Green List (high evidence)
Fetal anomalies v1.163 CASP2 Zornitza Stark Gene: casp2 has been classified as Green List (High Evidence).
Fetal anomalies v1.162 CASP2 Zornitza Stark gene: CASP2 was added
gene: CASP2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CASP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CASP2 were set to 37880421
Phenotypes for gene: CASP2 were set to neurodevelopmental disorder MONDO:0700092, CASP2-related
Review for gene: CASP2 was set to GREEN
Added comment: 7 individuals from 5 families:
- 4 families homozygous for PTC.
- 1 family compound heterozygote for splice site + PTC. RNA studies indicate usage of 2 cryptic splice donor sites.

5/5 have ID/dev delay
1/5 seizures
2/5 hypotonia
3/5 Lissencephaly (pachygyria + cortical thickening)
Sources: Literature
Mendeliome v1.1354 SGSM3 Zornitza Stark Tag founder tag was added to gene: SGSM3.
Mendeliome v1.1354 SGSM3 Zornitza Stark Marked gene: SGSM3 as ready
Mendeliome v1.1354 SGSM3 Zornitza Stark Gene: sgsm3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1354 SGSM3 Zornitza Stark Classified gene: SGSM3 as Amber List (moderate evidence)
Mendeliome v1.1354 SGSM3 Zornitza Stark Gene: sgsm3 has been classified as Amber List (Moderate Evidence).
Macrocephaly_Megalencephaly v0.137 VCP Zornitza Stark Marked gene: VCP as ready
Macrocephaly_Megalencephaly v0.137 VCP Zornitza Stark Gene: vcp has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.137 VCP Zornitza Stark Classified gene: VCP as Green List (high evidence)
Macrocephaly_Megalencephaly v0.137 VCP Zornitza Stark Gene: vcp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5608 VCP Zornitza Stark Marked gene: VCP as ready
Intellectual disability syndromic and non-syndromic v0.5608 VCP Zornitza Stark Gene: vcp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5608 VCP Zornitza Stark Classified gene: VCP as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5608 VCP Zornitza Stark Gene: vcp has been classified as Green List (High Evidence).
Congenital Heart Defect v0.305 RERE Zornitza Stark Marked gene: RERE as ready
Congenital Heart Defect v0.305 RERE Zornitza Stark Gene: rere has been classified as Green List (High Evidence).
Congenital Heart Defect v0.305 RERE Zornitza Stark Publications for gene: RERE were set to 29330883, 27087320, 33772547, 36053530
Congenital Heart Defect v0.304 RERE Zornitza Stark Classified gene: RERE as Green List (high evidence)
Congenital Heart Defect v0.304 RERE Zornitza Stark Gene: rere has been classified as Green List (High Evidence).
Prepair 500+ v0.0 ZNF711 Seb Lunke gene: ZNF711 was added
gene: ZNF711 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: ZNF711 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ZNF711 were set to Mental retardation, X-linked 97, 300803 (3)
Prepair 500+ v0.0 ZFYVE26 Seb Lunke gene: ZFYVE26 was added
gene: ZFYVE26 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: ZFYVE26 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ZFYVE26 were set to Spastic paraplegia 15, autosomal recessive, 270700 (3)
Prepair 500+ v0.0 ZDHHC9 Seb Lunke gene: ZDHHC9 was added
gene: ZDHHC9 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: ZDHHC9 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ZDHHC9 were set to Mental retardation, X-linked syndromic, Raymond type, 300799 (3)
Prepair 500+ v0.0 ZBTB24 Seb Lunke gene: ZBTB24 was added
gene: ZBTB24 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: ZBTB24 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ZBTB24 were set to Immunodeficiency-centromeric instability-facial anomalies syndrome-2, 614069 (3)
Prepair 500+ v0.0 YARS2 Seb Lunke gene: YARS2 was added
gene: YARS2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: YARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: YARS2 were set to Myopathy, lactic acidosis, and sideroblastic anemia 2, 613561 (3)
Prepair 500+ v0.0 XPC Seb Lunke gene: XPC was added
gene: XPC was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: XPC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: XPC were set to Xeroderma pigmentosum, group C, 278720 (3)
Prepair 500+ v0.0 XPA Seb Lunke gene: XPA was added
gene: XPA was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: XPA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: XPA were set to Xeroderma pigmentosum, group A, 278700 (3)
Prepair 500+ v0.0 XIAP Seb Lunke gene: XIAP was added
gene: XIAP was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: XIAP was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: XIAP were set to Lymphoproliferative syndrome, X-linked, 2, 300635 (3)
Prepair 500+ v0.0 WWOX Seb Lunke gene: WWOX was added
gene: WWOX was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WWOX was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WWOX were set to Epileptic encephalopathy, early infantile, 28, 616211 (3)
Prepair 500+ v0.0 WRN Seb Lunke gene: WRN was added
gene: WRN was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WRN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WRN were set to Werner syndrome, 277700 (3)
Prepair 500+ v0.0 WISP3 Seb Lunke gene: WISP3 was added
gene: WISP3 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WISP3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WISP3 were set to Arthropathy, progressive pseudorheumatoid, of childhood, 208230 (3)
Prepair 500+ v0.0 WHRN Seb Lunke gene: WHRN was added
gene: WHRN was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WHRN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WHRN were set to Usher syndrome, type 2D, 611383 (3)
Prepair 500+ v0.0 WDR81 Seb Lunke gene: WDR81 was added
gene: WDR81 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WDR81 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR81 were set to Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2, 610185 (3)
Prepair 500+ v0.0 WDR62 Seb Lunke gene: WDR62 was added
gene: WDR62 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WDR62 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR62 were set to Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, 604317 (3)
Prepair 500+ v0.0 WDR34 Seb Lunke gene: WDR34 was added
gene: WDR34 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WDR34 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR34 were set to Short-rib thoracic dysplasia 11 with or without polydactyly, 615633 (3)
Prepair 500+ v0.0 WAS Seb Lunke gene: WAS was added
gene: WAS was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WAS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: WAS were set to Wiskott-Aldrich syndrome, 301000 (3)
Prepair 500+ v0.0 VSX2 Seb Lunke gene: VSX2 was added
gene: VSX2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VSX2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VSX2 were set to Microphthalmia with coloboma 3, 610092 (3)
Prepair 500+ v0.0 VRK1 Seb Lunke gene: VRK1 was added
gene: VRK1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VRK1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VRK1 were set to Pontocerebellar hypoplasia type 1A, 607596 (3)
Prepair 500+ v0.0 VPS53 Seb Lunke gene: VPS53 was added
gene: VPS53 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VPS53 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS53 were set to Pontocerebellar hypoplasia, type 2E, 615851 (3)
Prepair 500+ v0.0 VPS45 Seb Lunke gene: VPS45 was added
gene: VPS45 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VPS45 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS45 were set to Neutropenia, severe congenital, 5, autosomal recessive, 615285 (3)
Prepair 500+ v0.0 VPS13B Seb Lunke gene: VPS13B was added
gene: VPS13B was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VPS13B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS13B were set to Cohen syndrome, 216550 (3)
Prepair 500+ v0.0 VPS11 Seb Lunke gene: VPS11 was added
gene: VPS11 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VPS11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS11 were set to 27473128; 26307567; 27120463
Phenotypes for gene: VPS11 were set to Leukodystrophy, hypomyelinating, 12, 616683 (3), Autosomal recessive
Prepair 500+ v0.0 VLDLR Seb Lunke gene: VLDLR was added
gene: VLDLR was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VLDLR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VLDLR were set to Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1, 224050 (3)
Prepair 500+ v0.0 USP9X Seb Lunke gene: USP9X was added
gene: USP9X was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: USP9X was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: USP9X were set to Mental retardation, X-linked 99, 300919 (3)
Prepair 500+ v0.0 USH2A Seb Lunke gene: USH2A was added
gene: USH2A was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: USH2A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: USH2A were set to Usher syndrome, type 2A, 276901 (3)
Prepair 500+ v0.0 USH1G Seb Lunke gene: USH1G was added
gene: USH1G was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: USH1G was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: USH1G were set to Usher syndrome, type 1G, 606943 (3)
Prepair 500+ v0.0 USH1C Seb Lunke gene: USH1C was added
gene: USH1C was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: USH1C was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: USH1C were set to Usher syndrome, type 1C, 276904 (3)
Prepair 500+ v0.0 UPF3B Seb Lunke gene: UPF3B was added
gene: UPF3B was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UPF3B was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: UPF3B were set to Mental retardation, X-linked, syndromic 14, 300676 (3)
Prepair 500+ v0.0 UNC13D Seb Lunke gene: UNC13D was added
gene: UNC13D was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UNC13D was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UNC13D were set to Hemophagocytic lymphohistiocytosis, familial, 3, 608898 (3)
Prepair 500+ v0.0 UGT1A1 Seb Lunke gene: UGT1A1 was added
gene: UGT1A1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UGT1A1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UGT1A1 were set to Crigler-Najjar syndrome, type I, 218800 (3)
Prepair 500+ v0.0 UBR1 Seb Lunke gene: UBR1 was added
gene: UBR1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UBR1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UBR1 were set to Johanson-Blizzard syndrome, 243800 (3)
Prepair 500+ v0.0 UBE2T Seb Lunke gene: UBE2T was added
gene: UBE2T was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UBE2T was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UBE2T were set to Fanconi anemia, complementation group T, 616435 (3)
Prepair 500+ v0.0 UBA5 Seb Lunke gene: UBA5 was added
gene: UBA5 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UBA5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UBA5 were set to Epileptic encephalopathy, early infantile, 44, 617132 (3), Autosomal recessive
Prepair 500+ v0.0 TYRP1 Seb Lunke gene: TYRP1 was added
gene: TYRP1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TYRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TYRP1 were set to Albinism, oculocutaneous, type III, 203290 (3)
Prepair 500+ v0.0 TYR Seb Lunke gene: TYR was added
gene: TYR was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TYR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TYR were set to Albinism, oculocutaneous, type IA, 203100 (3)
Prepair 500+ v0.0 TYMP Seb Lunke gene: TYMP was added
gene: TYMP was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TYMP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TYMP were set to Mitochondrial DNA depletion syndrome 1 (MNGIE type), 603041 (3)
Prepair 500+ v0.0 TWNK Seb Lunke gene: TWNK was added
gene: TWNK was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TWNK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TWNK were set to Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), 271245 (3)
Prepair 500+ v0.0 TULP1 Seb Lunke gene: TULP1 was added
gene: TULP1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TULP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TULP1 were set to Retinitis pigmentosa 14, 600132 (3)
Prepair 500+ v0.0 TTPA Seb Lunke gene: TTPA was added
gene: TTPA was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TTPA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTPA were set to Ataxia with isolated vitamin E deficiency, 277460 (3)
Prepair 500+ v0.0 TTC8 Seb Lunke gene: TTC8 was added
gene: TTC8 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TTC8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTC8 were set to Bardet-Biedl syndrome 8, 615985 (3)
Prepair 500+ v0.0 TTC7A Seb Lunke gene: TTC7A was added
gene: TTC7A was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TTC7A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTC7A were set to Gastrointestinal defects and immunodeficiency syndrome, 243150 (3)
Prepair 500+ v0.0 TTC37 Seb Lunke gene: TTC37 was added
gene: TTC37 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TTC37 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTC37 were set to Trichohepatoenteric syndrome 1, 222470 (3)
Prepair 500+ v0.0 TSHB Seb Lunke gene: TSHB was added
gene: TSHB was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TSHB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TSHB were set to Hypothryoidism, congenital, nongoitrous 4, 275100 (3)
Prepair 500+ v0.0 TSFM Seb Lunke gene: TSFM was added
gene: TSFM was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TSFM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TSFM were set to Combined oxidative phosphorylation deficiency 3, 610505 (3)
Prepair 500+ v0.0 TSEN54 Seb Lunke gene: TSEN54 was added
gene: TSEN54 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TSEN54 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TSEN54 were set to Pontocerebellar hypoplasia type 2A, 277470 (3)
Prepair 500+ v0.0 TSEN2 Seb Lunke gene: TSEN2 was added
gene: TSEN2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TSEN2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TSEN2 were set to Pontocerebellar hypoplasia type 2B, 612389 (3)
Prepair 500+ v0.0 TRPM6 Seb Lunke gene: TRPM6 was added
gene: TRPM6 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TRPM6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRPM6 were set to Hypomagnesemia 1, intestinal, 602014 (3)
Prepair 500+ v0.0 TRMU Seb Lunke gene: TRMU was added
gene: TRMU was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TRMU was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRMU were set to Liver failure, transient infantile, 613070 (3)
Prepair 500+ v0.0 TRIM37 Seb Lunke gene: TRIM37 was added
gene: TRIM37 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TRIM37 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRIM37 were set to Mulibrey nanism, 253250 (3)
Prepair 500+ v0.0 TRIM32 Seb Lunke gene: TRIM32 was added
gene: TRIM32 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TRIM32 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRIM32 were set to Muscular dystrophy, limb-girdle, type 2H, 254110 (3)
Prepair 500+ v0.0 TREX1 Seb Lunke gene: TREX1 was added
gene: TREX1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TREX1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TREX1 were set to Aicardi-Goutieres syndrome 1, dominant and recessive, 225750 (3)
Prepair 500+ v0.0 TRDN Seb Lunke gene: TRDN was added
gene: TRDN was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TRDN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRDN were set to Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness, 615441 (3)
Prepair 500+ v0.0 TPP1 Seb Lunke gene: TPP1 was added
gene: TPP1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TPP1 were set to Ceroid lipofuscinosis, neuronal, 2, 204500 (3)
Prepair 500+ v0.0 TOE1 Seb Lunke gene: TOE1 was added
gene: TOE1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TOE1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TOE1 were set to Pontocerebellar hypoplasia, type 7, 614969 (3), Autosomal recessive
Prepair 500+ v0.0 TMTC3 Seb Lunke gene: TMTC3 was added
gene: TMTC3 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TMTC3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMTC3 were set to Lissencephaly 8, 617255 (3), Autosomal recessive
Prepair 500+ v0.0 TMEM67 Seb Lunke gene: TMEM67 was added
gene: TMEM67 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TMEM67 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM67 were set to Joubert syndrome 6, 610688 (3)
Prepair 500+ v0.0 TMEM237 Seb Lunke gene: TMEM237 was added
gene: TMEM237 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TMEM237 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM237 were set to Joubert syndrome 14, 614424 (3)
Prepair 500+ v0.0 TMEM231 Seb Lunke gene: TMEM231 was added
gene: TMEM231 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TMEM231 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM231 were set to Joubert syndrome 20, 614970 (3)
Prepair 500+ v0.0 TMEM216 Seb Lunke gene: TMEM216 was added
gene: TMEM216 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TMEM216 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM216 were set to Joubert syndrome 2, 608091 (3)
Prepair 500+ v0.0 TMEM138 Seb Lunke gene: TMEM138 was added
gene: TMEM138 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TMEM138 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM138 were set to Joubert syndrome 16, 614465 (3)
Prepair 500+ v0.0 TK2 Seb Lunke gene: TK2 was added
gene: TK2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TK2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TK2 were set to Mitochondrial DNA depletion syndrome 2 (myopathic type), 609560 (3)
Prepair 500+ v0.0 THOC2 Seb Lunke gene: THOC2 was added
gene: THOC2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: THOC2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: THOC2 were set to Mental retardation, X-linked 12/35, 300957 (3), X-linked recessive
Prepair 500+ v0.0 TH Seb Lunke gene: TH was added
gene: TH was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TH were set to Segawa syndrome, recessive, MIM# 605407
Prepair 500+ v0.0 TGM1 Seb Lunke gene: TGM1 was added
gene: TGM1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TGM1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TGM1 were set to Ichthyosis, congenital, autosomal recessive 1, 242300 (3)
Prepair 500+ v0.0 TF Seb Lunke gene: TF was added
gene: TF was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TF was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TF were set to Atransferrinemia, 209300 (3)
Prepair 500+ v0.0 TELO2 Seb Lunke gene: TELO2 was added
gene: TELO2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TELO2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TELO2 were set to You-Hoover-Fong syndrome, 616954 (3), Autosomal recessive
Prepair 500+ v0.0 TECPR2 Seb Lunke gene: TECPR2 was added
gene: TECPR2 was added to Prepair 500+. Sources: Literature,Expert Review Green
Mode of inheritance for gene: TECPR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TECPR2 were set to 23176824; 35130874; 26542466
Phenotypes for gene: TECPR2 were set to Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay, MIM#615031
Prepair 500+ v0.0 TCTN3 Seb Lunke gene: TCTN3 was added
gene: TCTN3 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TCTN3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TCTN3 were set to Joubert syndrome 18, 614815 (3)
Prepair 500+ v0.0 TCTN2 Seb Lunke gene: TCTN2 was added
gene: TCTN2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TCTN2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TCTN2 were set to Joubert syndrome 24
Prepair 500+ v0.0 TCN2 Seb Lunke gene: TCN2 was added
gene: TCN2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TCN2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TCN2 were set to Transcobalamin II deficiency, 275350 (3)
Prepair 500+ v0.0 TCIRG1 Seb Lunke gene: TCIRG1 was added
gene: TCIRG1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TCIRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TCIRG1 were set to Osteopetrosis, autosomal recessive 1, 259700 (3)
Prepair 500+ v0.0 TBCE Seb Lunke gene: TBCE was added
gene: TBCE was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TBCE were set to Kenny-Caffey syndrome-1, 244460 (3)
Prepair 500+ v0.0 TBCD Seb Lunke gene: TBCD was added
gene: TBCD was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TBCD was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TBCD were set to Encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum, 617193 (3), Autosomal recessive
Prepair 500+ v0.0 TBC1D24 Seb Lunke gene: TBC1D24 was added
gene: TBC1D24 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TBC1D24 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TBC1D24 were set to Epileptic encephalopathy, early infantile, 16, 615338 (3)
Prepair 500+ v0.0 TBC1D23 Seb Lunke gene: TBC1D23 was added
gene: TBC1D23 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TBC1D23 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TBC1D23 were set to Pontocerebellar hypoplasia, type 11, 617695 (3), Autosomal recessive
Prepair 500+ v0.0 TAZ Seb Lunke gene: TAZ was added
gene: TAZ was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TAZ was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: TAZ were set to Barth syndrome, 302060 (3)
Prepair 500+ v0.0 TAT Seb Lunke gene: TAT was added
gene: TAT was added to Prepair 500+. Sources: Literature,Expert Review Green
Mode of inheritance for gene: TAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAT were set to 16574453
Phenotypes for gene: TAT were set to Tyrosinemia, type II (MIM#276600)
Prepair 500+ v0.0 TANGO2 Seb Lunke gene: TANGO2 was added
gene: TANGO2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TANGO2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TANGO2 were set to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration
Prepair 500+ v0.0 SYN1 Seb Lunke gene: SYN1 was added
gene: SYN1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SYN1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: SYN1 were set to Epilepsy, X-linked, with variable learning disabilities and behavior disorders, 300491 (3)
Prepair 500+ v0.0 SURF1 Seb Lunke gene: SURF1 was added
gene: SURF1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SURF1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SURF1 were set to Leigh syndrome, due to COX deficiency, 256000 (3)
Prepair 500+ v0.0 SUOX Seb Lunke gene: SUOX was added
gene: SUOX was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SUOX was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SUOX were set to Sulfite oxidase deficiency, 272300 (3)
Prepair 500+ v0.0 SUMF1 Seb Lunke gene: SUMF1 was added
gene: SUMF1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SUMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SUMF1 were set to Multiple sulfatase deficiency, 272200 (3)
Prepair 500+ v0.0 STXBP2 Seb Lunke gene: STXBP2 was added
gene: STXBP2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: STXBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STXBP2 were set to Hemophagocytic lymphohistiocytosis, familial, 5, 613101 (3)
Prepair 500+ v0.0 STX11 Seb Lunke gene: STX11 was added
gene: STX11 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: STX11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STX11 were set to Hemophagocytic lymphohistiocytosis, familial, 4, 603552 (3)
Prepair 500+ v0.0 STAR Seb Lunke gene: STAR was added
gene: STAR was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: STAR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STAR were set to Lipoid adrenal hyperplasia, 201710 (3)
Prepair 500+ v0.0 ST3GAL5 Seb Lunke gene: ST3GAL5 was added
gene: ST3GAL5 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: ST3GAL5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ST3GAL5 were set to Salt and pepper developmental regression syndrome, 609056 (3), Autosomal recessive
Prepair 500+ v0.0 SPR Seb Lunke gene: SPR was added
gene: SPR was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SPR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SPR were set to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, 612716 (3)
Prepair 500+ v0.0 SPINK5 Seb Lunke gene: SPINK5 was added
gene: SPINK5 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SPINK5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SPINK5 were set to Netherton syndrome, 256500 (3)
Prepair 500+ v0.0 SPG11 Seb Lunke gene: SPG11 was added
gene: SPG11 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SPG11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPG11 were set to 33581793
Phenotypes for gene: SPG11 were set to Spastic paraplegia 11, autosomal recessive, MIM# 604360
Prepair 500+ v0.0 SPATA5 Seb Lunke gene: SPATA5 was added
gene: SPATA5 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SPATA5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SPATA5 were set to Epilepsy, hearing loss, and mental retardation syndrome, 616577 (3), Autosomal recessive
Prepair 500+ v0.0 SNAP29 Seb Lunke gene: SNAP29 was added
gene: SNAP29 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SNAP29 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SNAP29 were set to Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome, 609528 (3)
Prepair 500+ v0.0 SMPD1 Seb Lunke gene: SMPD1 was added
gene: SMPD1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SMPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMPD1 were set to Niemann-Pick disease, type A, 257200 (3)
Prepair 500+ v0.0 SMN1 Seb Lunke gene: SMN1 was added
gene: SMN1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SMN1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMN1 were set to Spinal muscular atrophy-1, 253300 (3)
Prepair 500+ v0.0 SMARCAL1 Seb Lunke gene: SMARCAL1 was added
gene: SMARCAL1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SMARCAL1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMARCAL1 were set to Schimke immunoosseous dysplasia, 242900 (3)
Prepair 500+ v0.0 SLC7A7 Seb Lunke gene: SLC7A7 was added
gene: SLC7A7 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC7A7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC7A7 were set to Lysinuric protein intolerance, 222700 (3)
Prepair 500+ v0.0 SLC6A8 Seb Lunke gene: SLC6A8 was added
gene: SLC6A8 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC6A8 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: SLC6A8 were set to Cerebral creatine deficiency syndrome 1, 300352 (3)
Prepair 500+ v0.0 SLC6A5 Seb Lunke gene: SLC6A5 was added
gene: SLC6A5 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC6A5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC6A5 were set to Hyperekplexia 3, 614618 (3)
Prepair 500+ v0.0 SLC52A3 Seb Lunke gene: SLC52A3 was added
gene: SLC52A3 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC52A3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC52A3 were set to Brown-Vialetto-Van Laere syndrome 1, 211530 (3)
Prepair 500+ v0.0 SLC52A2 Seb Lunke gene: SLC52A2 was added
gene: SLC52A2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC52A2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC52A2 were set to Brown-Vialetto-Van Laere syndrome 2, 614707 (3)
Prepair 500+ v0.0 SLC46A1 Seb Lunke gene: SLC46A1 was added
gene: SLC46A1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC46A1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC46A1 were set to Folate malabsorption, hereditary, 229050 (3)
Prepair 500+ v0.0 SLC45A2 Seb Lunke gene: SLC45A2 was added
gene: SLC45A2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC45A2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC45A2 were set to Albinism, oculocutaneous, type IV, 606574 (3)
Prepair 500+ v0.0 SLC39A4 Seb Lunke gene: SLC39A4 was added
gene: SLC39A4 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC39A4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC39A4 were set to Acrodermatitis enteropathica, 201100 (3)
Prepair 500+ v0.0 SLC38A8 Seb Lunke gene: SLC38A8 was added
gene: SLC38A8 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC38A8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC38A8 were set to Foveal hypoplasia 2, with or without optic nerve misrouting and/or anterior segment dysgenesis, 609218 (3)
Prepair 500+ v0.0 SLC37A4 Seb Lunke gene: SLC37A4 was added
gene: SLC37A4 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC37A4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC37A4 were set to Glycogen storage disease Ib, 232220 (3)
Prepair 500+ v0.0 SLC35A3 Seb Lunke gene: SLC35A3 was added
gene: SLC35A3 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC35A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC35A3 were set to 28777481; 24031089; 28328131
Phenotypes for gene: SLC35A3 were set to Arthrogryposis, mental retardation, and seizures (MIM615553)
Prepair 500+ v0.0 SLC26A3 Seb Lunke gene: SLC26A3 was added
gene: SLC26A3 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC26A3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC26A3 were set to Diarrhea 1, secretory chloride, congenital, 214700 (3)
Prepair 500+ v0.0 SLC26A2 Seb Lunke gene: SLC26A2 was added
gene: SLC26A2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC26A2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC26A2 were set to Achondrogenesis Ib, 600972 (3)
Prepair 500+ v0.0 SLC25A15 Seb Lunke gene: SLC25A15 was added
gene: SLC25A15 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC25A15 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC25A15 were set to Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome, 238970 (3)
Prepair 500+ v0.0 SLC25A13 Seb Lunke gene: SLC25A13 was added
gene: SLC25A13 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC25A13 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC25A13 were set to Citrullinemia, type II, neonatal-onset, 605814 (3)
Prepair 500+ v0.0 SLC25A1 Seb Lunke gene: SLC25A1 was added
gene: SLC25A1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC25A1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC25A1 were set to Combined D-2- and L-2-hydroxyglutaric aciduria, 615182 (3)
Prepair 500+ v0.0 SLC22A5 Seb Lunke gene: SLC22A5 was added
gene: SLC22A5 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC22A5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC22A5 were set to Carnitine deficiency, systemic primary, 212140 (3)
Prepair 500+ v0.0 SLC1A4 Seb Lunke gene: SLC1A4 was added
gene: SLC1A4 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC1A4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC1A4 were set to Spastic tetraplegia, thin corpus callosum, and progressive microcephaly, 616657 (3)
Prepair 500+ v0.0 SLC19A3 Seb Lunke gene: SLC19A3 was added
gene: SLC19A3 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC19A3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC19A3 were set to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2), 607483 (3)
Prepair 500+ v0.0 SLC19A2 Seb Lunke gene: SLC19A2 was added
gene: SLC19A2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC19A2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC19A2 were set to Thiamine-responsive megaloblastic anemia syndrome, 249270 (3)
Prepair 500+ v0.0 SLC17A5 Seb Lunke gene: SLC17A5 was added
gene: SLC17A5 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC17A5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC17A5 were set to Sialic acid storage disorder, infantile, 269920 (3)
Prepair 500+ v0.0 SLC16A2 Seb Lunke gene: SLC16A2 was added
gene: SLC16A2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC16A2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: SLC16A2 were set to Allan-Herndon-Dudley syndrome
Prepair 500+ v0.0 SLC12A6 Seb Lunke gene: SLC12A6 was added
gene: SLC12A6 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC12A6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC12A6 were set to Agenesis of the corpus callosum with peripheral neuropathy, 218000 (3)
Prepair 500+ v0.0 SLC12A1 Seb Lunke gene: SLC12A1 was added
gene: SLC12A1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC12A1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC12A1 were set to Bartter syndrome, type 1, 601678 (3)
Prepair 500+ v0.0 SKIV2L Seb Lunke gene: SKIV2L was added
gene: SKIV2L was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SKIV2L was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SKIV2L were set to Trichohepatoenteric syndrome 2, 614602 (3)
Prepair 500+ v0.0 SH3TC2 Seb Lunke gene: SH3TC2 was added
gene: SH3TC2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SH3TC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SH3TC2 were set to Charcot-Marie-Tooth disease, type 4C, 601596 (3)
Prepair 500+ v0.0 SGSH Seb Lunke gene: SGSH was added
gene: SGSH was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SGSH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SGSH were set to Mucopolysaccharidisis type IIIA (Sanfilippo A), 252900 (3)
Prepair 500+ v0.0 SGCG Seb Lunke gene: SGCG was added
gene: SGCG was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SGCG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SGCG were set to Muscular dystrophy, limb-girdle, type 2C, 253700 (3)
Prepair 500+ v0.0 SGCD Seb Lunke gene: SGCD was added
gene: SGCD was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SGCD was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SGCD were set to Muscular dystrophy, limb-girdle, type 2F, 601287 (3)
Prepair 500+ v0.0 SGCB Seb Lunke gene: SGCB was added
gene: SGCB was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SGCB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SGCB were set to Muscular dystrophy, limb-girdle, type 2E, 604286 (3)
Prepair 500+ v0.0 SGCA Seb Lunke gene: SGCA was added
gene: SGCA was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SGCA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SGCA were set to Muscular dystrophy, limb-girdle, type 2D, 608099 (3)
Prepair 500+ v0.0 SERPINH1 Seb Lunke gene: SERPINH1 was added
gene: SERPINH1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SERPINH1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SERPINH1 were set to Orofaciodigital syndrome VI, 277170 (3)
Prepair 500+ v0.0 SERAC1 Seb Lunke gene: SERAC1 was added
gene: SERAC1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SERAC1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SERAC1 were set to 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, 614739 (3)
Prepair 500+ v0.0 SEPSECS Seb Lunke gene: SEPSECS was added
gene: SEPSECS was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SEPSECS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SEPSECS were set to Pontocerebellar hypoplasia type 2D, 613811 (3)
Prepair 500+ v0.0 SEC23B Seb Lunke gene: SEC23B was added
gene: SEC23B was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SEC23B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SEC23B were set to Dyserythropoietic anemia, congenital, type II, 224100 (3)
Prepair 500+ v0.0 SDCCAG8 Seb Lunke gene: SDCCAG8 was added
gene: SDCCAG8 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SDCCAG8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SDCCAG8 were set to Bardet-Biedl syndrome 16, 615993 (3)
Prepair 500+ v0.0 SCO2 Seb Lunke gene: SCO2 was added
gene: SCO2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SCO2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SCO2 were set to Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, 604377 (3)
Prepair 500+ v0.0 SC5D Seb Lunke gene: SC5D was added
gene: SC5D was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SC5D was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SC5D were set to Lathosterolosis, 607330 (3)
Prepair 500+ v0.0 SAMHD1 Seb Lunke gene: SAMHD1 was added
gene: SAMHD1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SAMHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SAMHD1 were set to Aicardi-Goutieres syndrome 5, 612952 (3)
Prepair 500+ v0.0 SACS Seb Lunke gene: SACS was added
gene: SACS was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SACS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SACS were set to Spastic ataxia, Charlevoix-Saguenay type, 270550 (3)
Prepair 500+ v0.0 RYR1 Seb Lunke gene: RYR1 was added
gene: RYR1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RYR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RYR1 were set to PMID: 16917943, PMID: 23919265, PMID: 30155738, PMID: 27855725
Phenotypes for gene: RYR1 were set to Central core disease, MIM# 117000; Neuromuscular disease, congenital, with uniform type 1 fiber, MIM# 117000
Prepair 500+ v0.0 RTEL1 Seb Lunke gene: RTEL1 was added
gene: RTEL1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RTEL1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RTEL1 were set to Dyskeratosis congenita, autosomal recessive 5, 615190 (3)
Prepair 500+ v0.0 RPS6KA3 Seb Lunke gene: RPS6KA3 was added
gene: RPS6KA3 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RPS6KA3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: RPS6KA3 were set to Coffin-Lowry syndrome
Prepair 500+ v0.0 RPGRIP1L Seb Lunke gene: RPGRIP1L was added
gene: RPGRIP1L was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RPGRIP1L was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RPGRIP1L were set to Meckel syndrome 5, 611561 (3)
Prepair 500+ v0.0 RPE65 Seb Lunke gene: RPE65 was added
gene: RPE65 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RPE65 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RPE65 were set to Leber congenital amaurosis 2, 204100 (3)
Prepair 500+ v0.0 RP2 Seb Lunke gene: RP2 was added
gene: RP2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RP2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: RP2 were set to Retinitis pigmentosa 2, 312600 (3)
Prepair 500+ v0.0 RNASEH2C Seb Lunke gene: RNASEH2C was added
gene: RNASEH2C was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RNASEH2C was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RNASEH2C were set to Aicardi-Goutieres syndrome 3, 610329 (3)
Prepair 500+ v0.0 RNASEH2B Seb Lunke gene: RNASEH2B was added
gene: RNASEH2B was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RNASEH2B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RNASEH2B were set to Aicardi-Goutieres syndrome 2, 610181 (3)
Prepair 500+ v0.0 RNASEH2A Seb Lunke gene: RNASEH2A was added
gene: RNASEH2A was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RNASEH2A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RNASEH2A were set to Aicardi-Goutieres syndrome 4, 610333 (3)
Prepair 500+ v0.0 RMRP Seb Lunke gene: RMRP was added
gene: RMRP was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RMRP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RMRP were set to Cartilage-hair hypoplasia, 250250 (3)
Prepair 500+ v0.0 RMND1 Seb Lunke gene: RMND1 was added
gene: RMND1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RMND1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RMND1 were set to Combined oxidative phosphorylation deficiency 11, 614922 (3)
Prepair 500+ v0.0 RDH12 Seb Lunke gene: RDH12 was added
gene: RDH12 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RDH12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RDH12 were set to Leber congenital amaurosis 13, 612712 (3)
Prepair 500+ v0.0 RBBP8 Seb Lunke gene: RBBP8 was added
gene: RBBP8 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RBBP8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RBBP8 were set to Seckel syndrome 2, 606744 (3)
Prepair 500+ v0.0 RAX Seb Lunke gene: RAX was added
gene: RAX was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RAX was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RAX were set to Microphthalmia, isolated 3, 611038 (3)
Prepair 500+ v0.0 RARS2 Seb Lunke gene: RARS2 was added
gene: RARS2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RARS2 were set to Pontocerebellar hypoplasia, type 6, 611523 (3)
Prepair 500+ v0.0 RAPSN Seb Lunke gene: RAPSN was added
gene: RAPSN was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RAPSN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RAPSN were set to Fetal akinesia deformation sequence, 208150 (3)
Prepair 500+ v0.0 RAG2 Seb Lunke gene: RAG2 was added
gene: RAG2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RAG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAG2 were set to 26996199; 30046960
Phenotypes for gene: RAG2 were set to Severe combined immunodeficiency, B cell-negative, 601457 (3)
Prepair 500+ v0.0 RAG1 Seb Lunke gene: RAG1 was added
gene: RAG1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RAG1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RAG1 were set to Severe combined immunodeficiency, B cell-negative, 601457 (3)
Prepair 500+ v0.0 RAB3GAP2 Seb Lunke gene: RAB3GAP2 was added
gene: RAB3GAP2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RAB3GAP2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RAB3GAP2 were set to Warburg micro syndrome 2, 614225 (3)
Prepair 500+ v0.0 RAB3GAP1 Seb Lunke gene: RAB3GAP1 was added
gene: RAB3GAP1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RAB3GAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RAB3GAP1 were set to Warburg micro syndrome 1, 600118 (3)
Prepair 500+ v0.0 RAB23 Seb Lunke gene: RAB23 was added
gene: RAB23 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RAB23 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RAB23 were set to Carpenter syndrome, 201000 (3)
Prepair 500+ v0.0 RAB18 Seb Lunke gene: RAB18 was added
gene: RAB18 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: RAB18 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RAB18 were set to Warburg micro syndrome 3, 614222 (3)
Prepair 500+ v0.0 QDPR Seb Lunke gene: QDPR was added
gene: QDPR was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: QDPR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: QDPR were set to Hyperphenylalaninemia, BH4-deficient, C, 261630 (3)
Prepair 500+ v0.0 PUS1 Seb Lunke gene: PUS1 was added
gene: PUS1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PUS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PUS1 were set to Mitochondrial myopathy and sideroblastic anemia 1, 600462 (3)
Prepair 500+ v0.0 PTS Seb Lunke gene: PTS was added
gene: PTS was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PTS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PTS were set to Hyperphenylalaninemia, BH4-deficient, A, 261640 (3)
Prepair 500+ v0.0 PSAP Seb Lunke gene: PSAP was added
gene: PSAP was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PSAP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PSAP were set to Metachromatic leukodystrophy due to SAP-b deficiency, 249900 (3)
Prepair 500+ v0.0 PRPS1 Seb Lunke gene: PRPS1 was added
gene: PRPS1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PRPS1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: PRPS1 were set to Arts syndrome, 301835 (3)
Prepair 500+ v0.0 PROP1 Seb Lunke gene: PROP1 was added
gene: PROP1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PROP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PROP1 were set to Pituitary hormone deficiency, combined, 2, 262600 (3)
Prepair 500+ v0.0 PRF1 Seb Lunke gene: PRF1 was added
gene: PRF1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PRF1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PRF1 were set to Hemophagocytic lymphohistiocytosis, familial, 2, 603553 (3)
Prepair 500+ v0.0 PRDM5 Seb Lunke gene: PRDM5 was added
gene: PRDM5 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PRDM5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PRDM5 were set to Brittle cornea syndrome 2, 614170 (3)
Prepair 500+ v0.0 PQBP1 Seb Lunke gene: PQBP1 was added
gene: PQBP1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PQBP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: PQBP1 were set to Renpenning syndrome, 309500 (3)
Prepair 500+ v0.0 PPT1 Seb Lunke gene: PPT1 was added
gene: PPT1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PPT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PPT1 were set to Ceroid lipofuscinosis, neuronal, 1, 256730 (3)
Prepair 500+ v0.0 POU1F1 Seb Lunke gene: POU1F1 was added
gene: POU1F1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: POU1F1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POU1F1 were set to Pituitary hormone deficiency, combined, 1, 613038 (3)
Prepair 500+ v0.0 POR Seb Lunke gene: POR was added
gene: POR was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: POR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POR were set to Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, 201750 (3)
Prepair 500+ v0.0 POMT2 Seb Lunke gene: POMT2 was added
gene: POMT2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: POMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POMT2 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2, 613150 (3)
Prepair 500+ v0.0 POMT1 Seb Lunke gene: POMT1 was added
gene: POMT1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: POMT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POMT1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1, 236670 (3)
Prepair 500+ v0.0 POMGNT1 Seb Lunke gene: POMGNT1 was added
gene: POMGNT1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: POMGNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POMGNT1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3, 253280 (3)
Prepair 500+ v0.0 POLR3B Seb Lunke gene: POLR3B was added
gene: POLR3B was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: POLR3B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POLR3B were set to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, 614381 (3)
Prepair 500+ v0.0 POLR1C Seb Lunke gene: POLR1C was added
gene: POLR1C was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: POLR1C was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POLR1C were set to Treacher Collins syndrome 3, 248390 (3)
Prepair 500+ v0.0 POLG Seb Lunke gene: POLG was added
gene: POLG was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: POLG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POLG were set to Mitochondrial DNA depletion syndrome 4A (Alpers type), 203700 (3)
Prepair 500+ v0.0 PNPO Seb Lunke gene: PNPO was added
gene: PNPO was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PNPO was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PNPO were set to Pyridoxamine 5'-phosphate oxidase deficiency, 610090 (3)
Prepair 500+ v0.0 PNKP Seb Lunke gene: PNKP was added
gene: PNKP was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PNKP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PNKP were set to Microcephaly, seizures, and developmental delay, 613402 (3)
Prepair 500+ v0.0 PMM2 Seb Lunke gene: PMM2 was added
gene: PMM2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PMM2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PMM2 were set to Congenital disorder of glycosylation, type Ia, 212065 (3)
Prepair 500+ v0.0 PLPBP Seb Lunke gene: PLPBP was added
gene: PLPBP was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PLPBP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PLPBP were set to Epilepsy, early-onset, vitamin B6-dependent, 617290 (3), Autosomal recessive
Prepair 500+ v0.0 PLP1 Seb Lunke gene: PLP1 was added
gene: PLP1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PLP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: PLP1 were set to Pelizaeus-Merzbacher disease, 312080 (3)
Prepair 500+ v0.0 PLOD1 Seb Lunke gene: PLOD1 was added
gene: PLOD1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PLOD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PLOD1 were set to Ehlers-Danlos syndrome, type VI, 225400 (3)
Prepair 500+ v0.0 PLA2G6 Seb Lunke gene: PLA2G6 was added
gene: PLA2G6 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PLA2G6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLA2G6 were set to 35803092
Phenotypes for gene: PLA2G6 were set to Neurodegeneration with brain iron accumulation 2B MIM#610217; Infantile neuroaxonal dystrophy 1 MIM#256600
Prepair 500+ v0.0 PKHD1 Seb Lunke gene: PKHD1 was added
gene: PKHD1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PKHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PKHD1 were set to Polycystic kidney and hepatic disease, 263200 (3)
Prepair 500+ v0.0 PIGT Seb Lunke gene: PIGT was added
gene: PIGT was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PIGT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PIGT were set to Multiple congenital anomalies-hypotonia-seizures syndrome 3
Prepair 500+ v0.0 PIGN Seb Lunke gene: PIGN was added
gene: PIGN was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PIGN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PIGN were set to Multiple congenital anomalies-hypotonia-seizures syndrome 1, 614080 (3)
Prepair 500+ v0.0 PIGG Seb Lunke gene: PIGG was added
gene: PIGG was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PIGG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PIGG were set to Mental retardation, autosomal recessive 53, 616917 (3)
Prepair 500+ v0.0 PIBF1 Seb Lunke gene: PIBF1 was added
gene: PIBF1 was added to Prepair 500+. Sources: Literature,Expert Review Green
Mode of inheritance for gene: PIBF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIBF1 were set to 26167768; 30858804; 29695797; 33004012
Phenotypes for gene: PIBF1 were set to Joubert syndrome 33 (MIM#617767)
Prepair 500+ v0.0 PHYH Seb Lunke gene: PHYH was added
gene: PHYH was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PHYH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PHYH were set to Refsum disease, 266500 (3)
Prepair 500+ v0.0 PHGDH Seb Lunke gene: PHGDH was added
gene: PHGDH was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PHGDH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PHGDH were set to Neu-Laxova syndrome1, 256520 (3)
Prepair 500+ v0.0 PHF8 Seb Lunke gene: PHF8 was added
gene: PHF8 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PHF8 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: PHF8 were set to Mental retardation syndrome, X-linked, Siderius type, 300263 (3)
Prepair 500+ v0.0 PGM3 Seb Lunke gene: PGM3 was added
gene: PGM3 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PGM3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PGM3 were set to Immunodeficiency 23, 615816 (3)
Prepair 500+ v0.0 PGM1 Seb Lunke gene: PGM1 was added
gene: PGM1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PGM1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PGM1 were set to Congenital disorder of glycosylation, type It, 614921 (3)
Prepair 500+ v0.0 PGK1 Seb Lunke gene: PGK1 was added
gene: PGK1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PGK1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PGK1 were set to 28580215; 16567715; 22348148; 30887539
Phenotypes for gene: PGK1 were set to Phosphoglycerate kinase 1 deficiency, 300653 (3)
Prepair 500+ v0.0 PGAP2 Seb Lunke gene: PGAP2 was added
gene: PGAP2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PGAP2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PGAP2 were set to Hyperphosphatasia with mental retardation syndrome 3, 614207 (3)
Prepair 500+ v0.0 PFKM Seb Lunke gene: PFKM was added
gene: PFKM was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PFKM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PFKM were set to Glycogen storage disease VII, 232800 (3)
Prepair 500+ v0.0 PEX7 Seb Lunke gene: PEX7 was added
gene: PEX7 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PEX7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX7 were set to Chondrodysplasia punctata, rhizomelic, type 1, 215100 (3)
Prepair 500+ v0.0 PEX6 Seb Lunke gene: PEX6 was added
gene: PEX6 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PEX6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX6 were set to Peroxisome biogenesis disorder 4A (Zellweger), 614862
Prepair 500+ v0.0 PEX5 Seb Lunke gene: PEX5 was added
gene: PEX5 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PEX5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX5 were set to Peroxisome biogenesis disorder 2A (Zellweger), 214110
Prepair 500+ v0.0 PEX26 Seb Lunke gene: PEX26 was added
gene: PEX26 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PEX26 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX26 were set to Peroxisome biogenesis disorder 7A (Zellweger), 614872
Prepair 500+ v0.0 PEX2 Seb Lunke gene: PEX2 was added
gene: PEX2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PEX2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX2 were set to Peroxisome biogenesis disorder 5A (Zellweger), 614866
Prepair 500+ v0.0 PEX16 Seb Lunke gene: PEX16 was added
gene: PEX16 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PEX16 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX16 were set to Peroxisome biogenesis disorder 8A, (Zellweger), 614876
Prepair 500+ v0.0 PEX13 Seb Lunke gene: PEX13 was added
gene: PEX13 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PEX13 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX13 were set to Peroxisome biogenesis disorder 11A (Zellweger), 614883
Prepair 500+ v0.0 PEX12 Seb Lunke gene: PEX12 was added
gene: PEX12 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PEX12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX12 were set to Peroxisome biogenesis disorder 3A (Zellweger), 614859
Prepair 500+ v0.0 PEX10 Seb Lunke gene: PEX10 was added
gene: PEX10 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PEX10 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX10 were set to Peroxisome biogenesis disorder 6A (Zellweger), 614870
Prepair 500+ v0.0 PEX1 Seb Lunke gene: PEX1 was added
gene: PEX1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PEX1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX1 were set to Peroxisome biogenesis disorder 1A (Zellweger), 214100
Prepair 500+ v0.0 PET100 Seb Lunke gene: PET100 was added
gene: PET100 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PET100 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PET100 were set to Mitochondrial complex IV deficiency, 220110 (3)
Prepair 500+ v0.0 PEPD Seb Lunke gene: PEPD was added
gene: PEPD was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PEPD was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEPD were set to Prolidase deficiency, 170100 (3)
Prepair 500+ v0.0 PDHB Seb Lunke gene: PDHB was added
gene: PDHB was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PDHB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PDHB were set to Pyruvate dehydrogenase E1-beta deficiency, 614111 (3)
Prepair 500+ v0.0 PDHA1 Seb Lunke gene: PDHA1 was added
gene: PDHA1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PDHA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PDHA1 were set to 28584645; 22142326
Phenotypes for gene: PDHA1 were set to Pyruvate dehydrogenase E1-alpha deficiency (MIM#312170)
Prepair 500+ v0.0 PCNT Seb Lunke gene: PCNT was added
gene: PCNT was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PCNT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PCNT were set to Microcephalic osteodysplastic primordial dwarfism, type II, 210720 (3)
Prepair 500+ v0.0 PCDH19 Seb Lunke gene: PCDH19 was added
gene: PCDH19 was added to Prepair 500+. Sources: Literature,Expert Review Green
Mode of inheritance for gene: PCDH19 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: PCDH19 were set to 18469813; 30287595
Phenotypes for gene: PCDH19 were set to Developmental and epileptic encephalopathy 9 (MIM#300088)
Prepair 500+ v0.0 PCDH15 Seb Lunke gene: PCDH15 was added
gene: PCDH15 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PCDH15 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PCDH15 were set to Usher syndrome, type 1F, 602083 (3)
Prepair 500+ v0.0 PCCB Seb Lunke gene: PCCB was added
gene: PCCB was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PCCB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PCCB were set to Propionicacidemia, 606054 (3)
Prepair 500+ v0.0 PCCA Seb Lunke gene: PCCA was added
gene: PCCA was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PCCA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PCCA were set to Propionicacidemia, 606054 (3)
Prepair 500+ v0.0 PC Seb Lunke gene: PC was added
gene: PC was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PC were set to Pyruvate carboxylase deficiency, 266150 (3)
Prepair 500+ v0.0 PANK2 Seb Lunke gene: PANK2 was added
gene: PANK2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PANK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PANK2 were set to 15911822
Phenotypes for gene: PANK2 were set to Neurodegeneration with brain iron accumulation 1, MIM#234200
Prepair 500+ v0.0 PAK3 Seb Lunke gene: PAK3 was added
gene: PAK3 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PAK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: PAK3 were set to Mental retardation, X-linked 30/47, 300558 (3)
Prepair 500+ v0.0 PAH Seb Lunke gene: PAH was added
gene: PAH was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: PAH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PAH were set to Phenylketonuria, 261600 (3)
Prepair 500+ v0.0 P3H1 Seb Lunke gene: P3H1 was added
gene: P3H1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: P3H1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: P3H1 were set to Osteogenesis imperfecta, type VIII, 610915 (3)
Prepair 500+ v0.0 OTC Seb Lunke gene: OTC was added
gene: OTC was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: OTC was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: OTC were set to Ornithine transcarbamylase deficiency, 311250 (3)
Prepair 500+ v0.0 OSTM1 Seb Lunke gene: OSTM1 was added
gene: OSTM1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: OSTM1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: OSTM1 were set to Osteopetrosis, autosomal recessive 5, 259720 (3)
Prepair 500+ v0.0 OSGEP Seb Lunke gene: OSGEP was added
gene: OSGEP was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: OSGEP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: OSGEP were set to Galloway-Mowat syndrome 3, 617729 (3), Autosomal recessive
Prepair 500+ v0.0 OPHN1 Seb Lunke gene: OPHN1 was added
gene: OPHN1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: OPHN1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: OPHN1 were set to Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance, 300486 (3)
Prepair 500+ v0.0 OPA3 Seb Lunke gene: OPA3 was added
gene: OPA3 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: OPA3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: OPA3 were set to 3-methylglutaconic aciduria, type III, 258501 (3)
Prepair 500+ v0.0 OPA1 Seb Lunke gene: OPA1 was added
gene: OPA1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: OPA1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: OPA1 were set to Behr syndrome, 210000 (3), Autosomal recessive
Prepair 500+ v0.0 OFD1 Seb Lunke gene: OFD1 was added
gene: OFD1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: OFD1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: OFD1 were set to Joubert syndrome 10, 300804 (3)
Prepair 500+ v0.0 OCRL Seb Lunke gene: OCRL was added
gene: OCRL was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: OCRL was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: OCRL were set to Lowe syndrome, 309000 (3)
Prepair 500+ v0.0 NTRK1 Seb Lunke gene: NTRK1 was added
gene: NTRK1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NTRK1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NTRK1 were set to Insensitivity to pain, congenital, with anhidrosis, 256800 (3)
Prepair 500+ v0.0 NR0B1 Seb Lunke gene: NR0B1 was added
gene: NR0B1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NR0B1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: NR0B1 were set to 46XY sex reversal 2, dosage-sensitive, 300018 (3)
Prepair 500+ v0.0 NPHS2 Seb Lunke gene: NPHS2 was added
gene: NPHS2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NPHS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NPHS2 were set to Nephrotic syndrome, type 2, 600995 (3)
Prepair 500+ v0.0 NPHS1 Seb Lunke gene: NPHS1 was added
gene: NPHS1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NPHS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NPHS1 were set to Nephrotic syndrome, type 1, 256300 (3)
Prepair 500+ v0.0 NPHP3 Seb Lunke gene: NPHP3 was added
gene: NPHP3 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NPHP3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NPHP3 were set to Meckel syndrome 7, 267010 (3)
Prepair 500+ v0.0 NPHP1 Seb Lunke gene: NPHP1 was added
gene: NPHP1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NPHP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NPHP1 were set to Joubert syndrome 4, 609583 (3)
Prepair 500+ v0.0 NPC2 Seb Lunke gene: NPC2 was added
gene: NPC2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NPC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPC2 were set to 29625568; 17470133
Phenotypes for gene: NPC2 were set to Niemann-pick disease, type C2, MIM#607625
Prepair 500+ v0.0 NPC1 Seb Lunke gene: NPC1 was added
gene: NPC1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPC1 were set to 11333381; 26910362
Phenotypes for gene: NPC1 were set to Niemann-Pick disease, type C1, MIM#257220
Prepair 500+ v0.0 NNT Seb Lunke gene: NNT was added
gene: NNT was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NNT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NNT were set to Glucocorticoid deficiency 4, 614736 (3)
Prepair 500+ v0.0 NGLY1 Seb Lunke gene: NGLY1 was added
gene: NGLY1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NGLY1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NGLY1 were set to Congenital disorder of deglycosylation, 615273 (3)
Prepair 500+ v0.0 NEU1 Seb Lunke gene: NEU1 was added
gene: NEU1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NEU1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NEU1 were set to Sialidosis, type I, 256550 (3)
Prepair 500+ v0.0 NEB Seb Lunke gene: NEB was added
gene: NEB was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NEB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEB were set to 27228465
Phenotypes for gene: NEB were set to Arthrogryposis multiplex congenita 6 (MIM#619334); Nemaline myopathy 2, autosomal recessive (MIM#256030)
Prepair 500+ v0.0 NDUFV1 Seb Lunke gene: NDUFV1 was added
gene: NDUFV1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NDUFV1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFV1 were set to Mitochondrial complex I deficiency, 252010 (3)
Prepair 500+ v0.0 NDUFS7 Seb Lunke gene: NDUFS7 was added
gene: NDUFS7 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NDUFS7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFS7 were set to Leigh syndrome, 256000 (3)
Prepair 500+ v0.0 NDUFS6 Seb Lunke gene: NDUFS6 was added
gene: NDUFS6 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NDUFS6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFS6 were set to Mitochondrial complex I deficiency, 252010 (3)
Prepair 500+ v0.0 NDUFS4 Seb Lunke gene: NDUFS4 was added
gene: NDUFS4 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NDUFS4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFS4 were set to Leigh syndrome, 256000 (3)
Prepair 500+ v0.0 NDUFAF5 Seb Lunke gene: NDUFAF5 was added
gene: NDUFAF5 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NDUFAF5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFAF5 were set to Mitochondrial complex 1 deficiency, 252010 (3)
Prepair 500+ v0.0 NDUFAF2 Seb Lunke gene: NDUFAF2 was added
gene: NDUFAF2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NDUFAF2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFAF2 were set to Leigh syndrome, 256000 (3)
Prepair 500+ v0.0 NDRG1 Seb Lunke gene: NDRG1 was added
gene: NDRG1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NDRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDRG1 were set to Charcot-Marie-Tooth disease, type 4D, 601455 (3)
Prepair 500+ v0.0 NDP Seb Lunke gene: NDP was added
gene: NDP was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NDP was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: NDP were set to Norrie disease, 310600 (3)
Prepair 500+ v0.0 NDE1 Seb Lunke gene: NDE1 was added
gene: NDE1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NDE1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDE1 were set to Lissencephaly 4 (with microcephaly), 614019 (3)
Prepair 500+ v0.0 NCF2 Seb Lunke gene: NCF2 was added
gene: NCF2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NCF2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NCF2 were set to Chronic granulomatous disease due to deficiency of NCF-2, 233710 (3)
Prepair 500+ v0.0 NBN Seb Lunke gene: NBN was added
gene: NBN was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NBN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NBN were set to Nijmegen breakage syndrome, 251260 (3)
Prepair 500+ v0.0 NARS2 Seb Lunke gene: NARS2 was added
gene: NARS2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NARS2 were set to Combined oxidative phosphorylation deficiency 24, 616239 (3)
Prepair 500+ v0.0 NALCN Seb Lunke gene: NALCN was added
gene: NALCN was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NALCN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NALCN were set to Hypotonia, infantile, with psychomotor retardation and characteristic facies, 615419 (3)
Prepair 500+ v0.0 NAGS Seb Lunke gene: NAGS was added
gene: NAGS was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NAGS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NAGS were set to N-acetylglutamate synthase deficiency, 237310 (3)
Prepair 500+ v0.0 NAGLU Seb Lunke gene: NAGLU was added
gene: NAGLU was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NAGLU was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NAGLU were set to Mucopolysaccharidosis type IIIB (Sanfilippo B), 252920 (3)
Prepair 500+ v0.0 NAGA Seb Lunke gene: NAGA was added
gene: NAGA was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NAGA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NAGA were set to Schindler disease, type I, 609241 (3)
Prepair 500+ v0.0 MYO7A Seb Lunke gene: MYO7A was added
gene: MYO7A was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: MYO7A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MYO7A were set to Usher syndrome, type 1B, 276900 (3)
Prepair 500+ v0.0 MYO5B Seb Lunke gene: MYO5B was added
gene: MYO5B was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: MYO5B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MYO5B were set to Microvillus inclusion disease, 251850 (3)
Prepair 500+ v0.0 MVK Seb Lunke gene: MVK was added
gene: MVK was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: MVK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MVK were set to Mevalonic aciduria, 610377 (3)
Prepair 500+ v0.0 MUT Seb Lunke gene: MUT was added
gene: MUT was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: MUT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MUT were set to Methylmalonic aciduria, mut(0) type, 251000 (3)
Prepair 500+ v0.0 MUSK Seb Lunke gene: MUSK was added
gene: MUSK was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: MUSK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MUSK were set to Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency, 616325 (3)
Prepair 500+ v0.0 MTTP Seb Lunke gene: MTTP was added
gene: MTTP was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: MTTP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MTTP were set to Abetalipoproteinemia, 200100 (3)
Prepair 500+ v0.0 MTRR Seb Lunke gene: MTRR was added
gene: MTRR was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: MTRR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MTRR were set to Homocystinuria-megaloblastic anemia, cbl E type, 236270 (3)
Prepair 500+ v0.0 MTR Seb Lunke gene: MTR was added
gene: MTR was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: MTR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MTR were set to Homocystinuria-megaloblastic anemia, cblG complementation type, 250940 (3)
Prepair 500+ v0.0 MTMR2 Seb Lunke gene: MTMR2 was added
gene: MTMR2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: MTMR2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MTMR2 were set to Charcot-Marie-Tooth disease, type 4B1, 601382 (3)
Prepair 500+ v0.0 MTM1 Seb Lunke gene: MTM1 was added
gene: MTM1 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: MTM1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: MTM1 were set to Myotubular myopathy, X-linked, 310400 (3)
Prepair 500+ v0.0 MTHFR Seb Lunke gene: MTHFR was added
gene: MTHFR was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: MTHFR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MTHFR were set to Homocystinuria due to MTHFR deficiency, 236250 (3)
Prepair 500+ v0.0 MTFMT Seb Lunke gene: MTFMT was added
gene: MTFMT was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: MTFMT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MTFMT were set to Combined oxidative phosphorylation deficiency 15, 614947 (3)
Prepair 500+ v0.0 MRE11 Seb Lunke gene: MRE11 was added
gene: MRE11 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: MRE11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MRE11 were set to Ataxia-telangiectasia-like disorder, 604391 (3)
Prepair 500+ v0.0 MPV17 Seb Lunke gene: MPV17 was added
gene: MPV17 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: MPV17 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MPV17 were set to Mitochondrial DNA depletion syndrome 6 (hepatocerebral type), 256810 (3)
Prepair 500+ v0.0 MPL Seb Lunke gene: MPL was added
gene: MPL was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: MPL was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MPL were set to Thrombocytopenia, congenital amegakaryocytic, 604498 (3)
Prepair 500+ v0.0 MPI Seb Lunke gene: MPI was added
gene: MPI was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: MPI was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MPI were set to Congenital disorder of glycosylation, type Ib, 602579 (3)
Prepair 500+ v0.0 MOCS2 Seb Lunke gene: MOCS2 was added
gene: MOCS2 was added to Prepair 500+. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: MOCS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MOCS2 were set to Molybdenum cofactor deficiency B, 252160 (3)