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Early-onset Dementia v1.16 GLA Zornitza Stark Classified gene: GLA as Green List (high evidence)
Early-onset Dementia v1.16 GLA Zornitza Stark Gene: gla has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5793 CYHR1 Zornitza Stark Tag new gene name tag was added to gene: CYHR1.
Microcephaly v1.258 CYHR1 Zornitza Stark Tag new gene name tag was added to gene: CYHR1.
Mendeliome v1.1757 CYHR1 Zornitza Stark Tag new gene name tag was added to gene: CYHR1.
Early-onset Parkinson disease v2.1 RAB32 Bryony Thompson gene: RAB32 was added
gene: RAB32 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: RAB32 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB32 were set to 38614108
Phenotypes for gene: RAB32 were set to Parkinson disease MONDO:0005180
Mode of pathogenicity for gene: RAB32 was set to Other
Review for gene: RAB32 was set to AMBER
Added comment: A single variant in RAB32 - c.213C>G p.(Ser71Arg) with a significant association with PD (odds ratio [OR] 13.17, 95% CI 2.15-87.23; p=0.0055, 6,043 PD cases and 62,549 controls).
The variant cosegregated with autosomal dominant PD in 3 families (9 affected individuals), with incomplete penetrance. In vitro studies demonstrate that RAB32 Ser71Arg activates LRRK2 kinase.
Sources: Literature
Mendeliome v1.1757 CCDC91 Bryony Thompson Marked gene: CCDC91 as ready
Mendeliome v1.1757 CCDC91 Bryony Thompson Gene: ccdc91 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1757 CCDC91 Bryony Thompson Classified gene: CCDC91 as Amber List (moderate evidence)
Mendeliome v1.1757 CCDC91 Bryony Thompson Gene: ccdc91 has been classified as Amber List (Moderate Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.132 CCDC91 Bryony Thompson changed review comment from: A single 3 generation Chinese acrokeratoelastoidosis family segregates c.1101 + 1 G > A (causes exon 11 skipping). In vitro knockdown experiments in cell lines demonstrated distended Golgi cisternae, cytoplasmic vesicle accumulation, and lysosome presence.
Sources: Literature; to: A single 3-generation Chinese acrokeratoelastoidosis family segregates c.1101 + 1 G > A (causes exon 11 skipping). In vitro knockdown experiments in cell lines demonstrated distended Golgi cisternae, cytoplasmic vesicle accumulation, and lysosome presence. Immnunostaining of si-CCDC91-human skin fibroblasts cells demonstrated tropoelastin accumulation in the Golgi and abnormal extracellular aggregates.
Sources: Literature
Mendeliome v1.1756 CCDC91 Bryony Thompson gene: CCDC91 was added
gene: CCDC91 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC91 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCDC91 were set to 38627542
Phenotypes for gene: CCDC91 were set to Punctate palmoplantar keratoderma type III MONDO:0007047
Review for gene: CCDC91 was set to AMBER
Added comment: A single 3-generation Chinese acrokeratoelastoidosis family segregates c.1101 + 1 G > A (causes exon 11 skipping). In vitro knockdown experiments in cell lines demonstrated distended Golgi cisternae, cytoplasmic vesicle accumulation, and lysosome presence. Immnunostaining of si-CCDC91-human skin fibroblasts cells demonstrated tropoelastin accumulation in the Golgi and abnormal extracellular aggregates
Sources: Literature
Palmoplantar Keratoderma and Erythrokeratoderma v0.132 CCDC91 Bryony Thompson Marked gene: CCDC91 as ready
Palmoplantar Keratoderma and Erythrokeratoderma v0.132 CCDC91 Bryony Thompson Gene: ccdc91 has been classified as Amber List (Moderate Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.132 CCDC91 Bryony Thompson Classified gene: CCDC91 as Amber List (moderate evidence)
Palmoplantar Keratoderma and Erythrokeratoderma v0.132 CCDC91 Bryony Thompson Gene: ccdc91 has been classified as Amber List (Moderate Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.131 CCDC91 Bryony Thompson gene: CCDC91 was added
gene: CCDC91 was added to Palmoplantar Keratoderma and Erythrokeratoderma. Sources: Literature
Mode of inheritance for gene: CCDC91 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCDC91 were set to 38627542
Phenotypes for gene: CCDC91 were set to Punctate palmoplantar keratoderma type III MONDO:0007047
Review for gene: CCDC91 was set to AMBER
Added comment: A single 3 generation Chinese acrokeratoelastoidosis family segregates c.1101 + 1 G > A (causes exon 11 skipping). In vitro knockdown experiments in cell lines demonstrated distended Golgi cisternae, cytoplasmic vesicle accumulation, and lysosome presence.
Sources: Literature
Mendeliome v1.1755 CYHR1 Bryony Thompson Phenotypes for gene: CYHR1 were changed from Neurodevelopmental disorder and microcephaly, MONDO:0700092, CYHR1-related to Neurodevelopmental disorder, MONDO:0700092, ZTRAF1-related
Mendeliome v1.1754 CYHR1 Bryony Thompson Publications for gene: CYHR1 were set to
Intellectual disability syndromic and non-syndromic v0.5793 CYHR1 Bryony Thompson Classified gene: CYHR1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5793 CYHR1 Bryony Thompson Gene: cyhr1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5792 CYHR1 Bryony Thompson reviewed gene: CYHR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38641995; Phenotypes: neurodevelopmental disorder MONDO:0700092, ZTRAF1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.258 CYHR1 Bryony Thompson reviewed gene: CYHR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 38641995; Phenotypes: neurodevelopmental disorder MONDO:0700092, ZTRAF1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1753 CYHR1 Bryony Thompson Classified gene: CYHR1 as Green List (high evidence)
Mendeliome v1.1753 CYHR1 Bryony Thompson Gene: cyhr1 has been classified as Green List (High Evidence).
Mendeliome v1.1752 CYHR1 Bryony Thompson reviewed gene: CYHR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38641995; Phenotypes: neurodevelopmental disorder MONDO:0700092, ZTRAF1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v1.15 GLA Lynn Tan gene: GLA was added
gene: GLA was added to Early-onset Dementia. Sources: Literature
Mode of inheritance for gene: GLA 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: GLA were set to 36927868; 38254927; 9213072; 23949010; 32510623
Phenotypes for gene: GLA were set to Fabry disease MONDO:0010526
Review for gene: GLA was set to GREEN
gene: GLA was marked as current diagnostic
Added comment: PMID 36927868 (2023)
Index patient with GLA T410A (α-Gal A activity 32%) developed dementia and died of stroke in her 70s

PMID: 9213072 (1997)
47M biochemically confirmed Fabry’s with predominant manifestation being a dementing illness

PMID: 23949010 (2014)
Systematic review on cognitive dysfunction in Fabry's disease: patients with Fabry disease may be impaired in: executive functioning assessed by two standardised tests, the Stroop test and the Trail Making test part B, information processing speed and attention. Five case studies documenting neuropsychological impairment also described.

PMID: 32510623
Prospective cohort study to describe cognitive function changes in Fabry's over a year. Eighty‐one patients were included of which 76 patients (94%) completed both assessments (age: 44 years, 34% men, 75% classical phenotype). Four patients (5.3%) showed reliable decrease in cognitive functioning, two women and one man with classical disease and one woman with non‐classical disease (age range: 19‐41 years). Changes were from excellent to good/average and from good to average. None had a history of stroke or extensive WMLs. Follow‐up CESD scores were similar in two patients (+0 and +1) and increased in two others (+6, +11).

PMID: 38254927 (2023)
"This vasculopathy, along with elevating the risk of cerebral ischemia and stroke, is likely the pathophysiological basis for cognitive impairments in FD patients. Nevertheless, there is currently insufficient evidence indicating a direct association between neuropsychological findings and alterations in morphology in the CNS of FD patients as determined by brain imaging techniques such as magnetic resonance imaging."
Sources: Literature
Monogenic Diabetes v0.52 KCNJ11 Hali Van Niel reviewed gene: KCNJ11: 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: 30086875, 20922570, 28824061, 15115830, 23626843; Phenotypes: permanent neonatal diabetes mellitus MONDO:0100164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic Diabetes v0.52 AKT2 Hali Van Niel reviewed gene: AKT2: Rating: RED; Mode of pathogenicity: None; Publications: 37105912, 28341696, 15166380; Phenotypes: type 2 diabetes mellitus MONDO:0005148; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic Diabetes v0.52 HNF1B Hali Van Niel reviewed gene: HNF1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 25536396, 9703339, 10484768; Phenotypes: renal cysts and diabetes syndrome MONDO:0007669; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hydrops fetalis v0.311 EHBP1L1 Ain Roesley Phenotypes for gene: EHBP1L1 were changed from Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related to non-immune hydrops fetalis MONDO:0009369, EHBP1L1-related
Fetal anomalies v1.241 EHBP1L1 Ain Roesley Phenotypes for gene: EHBP1L1 were changed from Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related to non-immune hydrops fetalis MONDO:0009369, EHBP1L1-related
Mendeliome v1.1752 EHBP1L1 Ain Roesley Phenotypes for gene: EHBP1L1 were changed from non-immune hydrops fetalis MONDO:0009369, EHBP1L1-related to non-immune hydrops fetalis MONDO:0009369, EHBP1L1-related
Mendeliome v1.1751 EHBP1L1 Ain Roesley Phenotypes for gene: EHBP1L1 were changed from Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related to non-immune hydrops fetalis MONDO:0009369, EHBP1L1-related
Early-onset Dementia v1.15 NOTCH3 Ain Roesley Mode of inheritance for gene: NOTCH3 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
Early-onset Dementia v1.14 NOTCH3 Ain Roesley reviewed gene: NOTCH3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 MIM#125310; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Monogenic Diabetes v0.52 HNF4A Hali Van Niel reviewed gene: HNF4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 8945471, 11590126; Phenotypes: maturity-onset diabetes of the young type 1 MONDO:0007452; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Vasculitis v0.82 NOTCH3 Ain Roesley Phenotypes for gene: NOTCH3 were changed from Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 MIM#125310
Susceptibility to Viral Infections v0.117 IL27RA Ain Roesley Marked gene: IL27RA as ready
Susceptibility to Viral Infections v0.117 IL27RA Ain Roesley Gene: il27ra has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1750 IL27RA Ain Roesley Marked gene: IL27RA as ready
Mendeliome v1.1750 IL27RA Ain Roesley Gene: il27ra has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1750 IL27RA Ain Roesley Classified gene: IL27RA as Amber List (moderate evidence)
Mendeliome v1.1750 IL27RA Ain Roesley Gene: il27ra has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1749 IL27RA Ain Roesley gene: IL27RA was added
gene: IL27RA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IL27RA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL27RA were set to 38509369
Phenotypes for gene: IL27RA were set to Epstein-Barr virus infection MONDO:0005111 , IL27RA-related
Review for gene: IL27RA was set to AMBER
gene: IL27RA was marked as current diagnostic
Added comment: 3 children from 2 families with severe acute EBV infection.

fam1: homozygous for p.(Gln96*) (NMD-pred)
fam2: chet for p.(Arg446Gly) and c.1142-2A>C

the splice variant in fam2 was found to to result in an in-frame deletion p.(Gln381_Ala395del)
the missense in fam2 is hypothesised to be a hypomorphic allele:
- out of 15 Homs in the Finnish database, 2 had hospital diagnoses of EBV IM
- expression of this variant on its own results in a weak but detectable IL-27RA expression associated with significant increase in STAT1/3 phosphorus in response to IL-27 stimulation

borderline amber/green due to functional studies performed
Sources: Literature
Susceptibility to Viral Infections v0.117 IL27RA Ain Roesley Classified gene: IL27RA as Amber List (moderate evidence)
Susceptibility to Viral Infections v0.117 IL27RA Ain Roesley Gene: il27ra has been classified as Amber List (Moderate Evidence).
Susceptibility to Viral Infections v0.116 IL27RA Ain Roesley gene: IL27RA was added
gene: IL27RA was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: IL27RA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL27RA were set to 38509369
Phenotypes for gene: IL27RA were set to Epstein-Barr virus infection MONDO:0005111 , IL27RA-related
Review for gene: IL27RA was set to AMBER
gene: IL27RA was marked as current diagnostic
Added comment: 3 children from 2 families with severe acute EBV infection.

fam1: homozygous for p.(Gln96*) (NMD-pred)
fam2: chet for p.(Arg446Gly) and c.1142-2A>C

the splice variant in fam2 was found to to result in an in-frame deletion p.(Gln381_Ala395del)
the missense in fam2 is hypothesised to be a hypomorphic allele:
- out of 15 Homs in the Finnish database, 2 had hospital diagnoses of EBV IM
- expression of this variant on its own results in a weak but detectable IL-27RA expression associated with significant increase in STAT1/3 phosphorus in response to IL-27 stimulation

borderline amber/green due to functional studies performed
Sources: Literature
Monogenic Diabetes v0.52 HNF1A Hali Van Niel reviewed gene: HNF1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 11162430, 11575290, 36257325; Phenotypes: maturity-onset diabetes of the young type 3 MONDO:0010894, diabetes mellitus MONDO:0005015; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic Diabetes v0.52 PAX6 Hali Van Niel changed review comment from: PAX6 well established gene disease association for Aniridia
No evidence of association with monogenic diabetes
PMID: 22153401: out of 83 patients with Aniridia, did not find increased incidence of diabetes beyond normal population
PMID: 11756345: one family with cosegregation of T2D and arnidia with PAX6 SNP; to: PAX6 well established gene disease association for Aniridia
No evidence of association with monogenic diabetes
PMID: 22153401: out of 83 patients with Aniridia, did not find increased incidence of diabetes beyond normal population
PMID: 11756345: one family with cosegregation of T2D and Aniridia with PAX6 SNP
Monogenic Diabetes v0.52 PAX6 Hali Van Niel reviewed gene: PAX6: Rating: RED; Mode of pathogenicity: None; Publications: 22153401, 11756345; Phenotypes: aniridia MONDO:0019172; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2613 NOTCH3 Ain Roesley Phenotypes for gene: NOTCH3 were changed from neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 - 125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 - 125310
Genetic Epilepsy v0.2612 NOTCH3 Ain Roesley Phenotypes for gene: NOTCH3 were changed from Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 - 125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 - 125310
Genetic Epilepsy v0.2612 NOTCH3 Ain Roesley Mode of inheritance for gene: NOTCH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2612 NOTCH3 Ain Roesley Classified gene: NOTCH3 as Green List (high evidence)
Genetic Epilepsy v0.2612 NOTCH3 Ain Roesley Gene: notch3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2611 NOTCH3 Ain Roesley reviewed gene: NOTCH3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Vasculitis v0.81 NOTCH3 Ain Roesley Mode of inheritance for gene: NOTCH3 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 v0.5792 NOTCH3 Ain Roesley Phenotypes for gene: NOTCH3 were changed from neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310
Intellectual disability syndromic and non-syndromic v0.5791 NOTCH3 Ain Roesley Phenotypes for gene: NOTCH3 were changed from Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310
Intellectual disability syndromic and non-syndromic v0.5791 NOTCH3 Ain Roesley Mode of inheritance for gene: NOTCH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5791 NOTCH3 Ain Roesley Classified gene: NOTCH3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5791 NOTCH3 Ain Roesley Gene: notch3 has been classified as Green List (High Evidence).
Vasculitis v0.80 NOTCH3 Ain Roesley reviewed gene: NOTCH3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder MONDO:0700092, NOTCH3-related, Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 MIM#125310; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5790 NOTCH3 Ain Roesley changed review comment from: Pre-print (https://sciprofiles.com/publication/view/62eb776390415f0166f73fae7cd172ed)

Review of research and diagnostic databases and literature review found 50 individuals from 31 families with biallelic variants.

13 PTCS (including splice) and 15 missense resulting in gain or loss of Cys residue.

AR PTCs are associated with early onset leukoencephalopathy including cognitive decline, dev delay/ID and dysmorphism

AR missense are associated with CADASIL-like phenotype; to: Pre-print (https://sciprofiles.com/publication/view/62eb776390415f0166f73fae7cd172ed)

Review of research and diagnostic databases and literature review found 50 individuals from 31 families with biallelic variants.

13 PTCS (including splice) and 15 missense resulting in gain or loss of Cys residue.

AR PTCs are associated with early onset leukoencephalopathy including cognitive decline, dev delay/ID and dysmorphism; seizures, spasticity, hypotonia, ataxia

AR missense are associated with CADASIL-like phenotype
Intellectual disability syndromic and non-syndromic v0.5790 NOTCH3 Ain Roesley reviewed gene: NOTCH3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Early-onset Dementia v1.14 COL4A2 Lynn Tan edited their review of gene: COL4A2: Added comment: PMID: 35699195
The frequency of cognitive features in COL4A2 was 27% [11/41 individuals from 22 pedigrees]. These 11 patients all had developmental delay.

PMID: 37272523
Ontario Neurodegenerative Disease Research Initiative (ONDRI) sample size 510: 8 patients with COL4A1/2 variants had Alzheimer's disease/mild cognitive impairment, 3 patients with COL4A1/2 variants had frontotemporal dementia

PMID: 36300346
UK Biobank cohort study (n = 454 756): 2 patients with COL4A1/2 variants had vascular dementia, 8 patients with COL4A1/2 variants had all-cause dementia

Dev delay vs early-onset dementia
PMID: 37272523 and PMID: 36300346 -combined cohort with both COL4A1 and COL4A2

Sources: Literature; Changed rating: AMBER
Mendeliome v1.1748 SHH Ain Roesley Publications for gene: SHH were set to 21976454; 12503095; 22791840; 19057928; 19533790; 38562108; 29321670, 32703609
Mendeliome v1.1747 SHH Ain Roesley edited their review of gene: SHH: Changed publications: 38562108, 29321670, 32703609
Mendeliome v1.1747 SHH Ain Roesley Publications for gene: SHH were set to 21976454; 12503095; 22791840; 19057928; 19533790,38562108, 29321670, 32703609
Mendeliome v1.1746 SHH Ain Roesley Phenotypes for gene: SHH were changed from Holoprosencephaly 3, MIM#142945; Microphthalmia with coloboma 5, MIM#611638; Single median maxillary central incisor, MIM#147250 to Holoprosencephaly 3, MIM#142945; Microphthalmia with coloboma 5, MIM#611638; Single median maxillary central incisor, MIM#147250; Hypertelorism, ACC, intellectual disability
Mendeliome v1.1745 SHH Ain Roesley Publications for gene: SHH were set to 21976454; 12503095; 22791840; 19057928; 19533790
Mendeliome v1.1744 SHH Ain Roesley reviewed gene: SHH: Rating: GREEN; Mode of pathogenicity: None; Publications: 38562108, 29321670, 32703609; Phenotypes: Hypertelorism, ACC, intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Monogenic Diabetes v0.52 PPP1R15B Hali Van Niel reviewed gene: PPP1R15B: Rating: RED; Mode of pathogenicity: None; Publications: 26159176, 26307080, 27640355; Phenotypes: microcephaly MONDO:0001149; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v1.14 POLG Lynn Tan gene: POLG was added
gene: POLG was added to Early-onset Dementia. Sources: Literature
Mode of inheritance for gene: POLG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLG were set to 15477547; 14694057; 16638794
Phenotypes for gene: POLG were set to Mitochondrial DNA depletion syndrome 4a MONDO:0008758
Review for gene: POLG was set to AMBER
gene: POLG was marked as current diagnostic
Added comment: PMID: 15477547
5 patients with "cognitive impairment" in their 30s-50s, one male "had mild cognitive decline in the fifth decade".

PMID: 14694057
Biallelic POLG A467T variants: The 18-year-old patient is the elder son of nonconsanguineous parents, aged 45 and 41 years. The clinical features of myoclonus, seizure, axonal sensory ataxic neuropathy, and hepatotoxicity induced by valproate and mild cognitive decline and cardiomyopathy were indicative of a multisystem disorder and suggestive of mitochondrial disease.

PMID: 16638794
We studied 26 patients belonging to 20 families with a disorder caused by biallelic mutations in the POLG gene. Mild cognitive abnormalities were clinically suspected in eight patients. In four a mild cognitive impairment was confirmed by neuropsychological examination.

Cognitive impairment -developmental delay/regression/ID in childhood vs dementia (and decline from a baseline) later in life
Sources: Literature
Monogenic Diabetes v0.52 BSCL2 Hali Van Niel reviewed gene: BSCL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11479539, 26239609; Phenotypes: congenital generalized lipodystrophy type 2 MONDO:0010020, diabetes mellitus MONDO:0005015; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.52 SLC19A2 Hali Van Niel reviewed gene: SLC19A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10391221, 14994241, 22369132, 35114785; Phenotypes: thiamine-responsive megaloblastic anemia syndrome MONDO:0009575, neonatal diabetes mellitus MONDO:0016391, diabetes mellitus MONDO:0005015; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.52 SLC29A3 Hali Van Niel reviewed gene: SLC29A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19336477, 22238637, 38163427, 24894595; Phenotypes: H syndrome MONDO:0011273; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v1.14 COL4A2 Lynn Tan gene: COL4A2 was added
gene: COL4A2 was added to Early-onset Dementia. Sources: Literature
Mode of inheritance for gene: COL4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A2 were set to 35699195; 37272523; 36300346
Phenotypes for gene: COL4A2 were set to Familial porencephaly MONDO:0020496
Review for gene: COL4A2 was set to GREEN
gene: COL4A2 was marked as current diagnostic
Added comment: PMID: 35699195
The frequency of cognitive features in COL4A2 was 27% [11/41 individuals from 22 pedigrees]. Developmental delay was present in over 80% of individuals with COL4A1/2 with cognitive features.

PMID: 37272523
Ontario Neurodegenerative Disease Research Initiative (ONDRI) sample size 510: 8 patients with COL4A1/2 variants had Alzheimer's disease/mild cognitive impairment, 3 patients with COL4A1/2 variants had frontotemporal dementia

PMID: 36300346
UK Biobank cohort study (n = 454 756): 2 patients with COL4A1/2 variants had vascular dementia, 8 patients with COL4A1/2 variants had all-cause dementia
Sources: Literature
Monogenic Diabetes v0.52 SLC40A1 Hali Van Niel reviewed gene: SLC40A1: 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: 34601591, 33341511, 2258529; Phenotypes: hemochromatosis type 4 MONDO:0011631, diabetes mellitus MONDO:0005015; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v1.14 COL4A1 Lynn Tan gene: COL4A1 was added
gene: COL4A1 was added to Early-onset Dementia. Sources: Literature
Mode of inheritance for gene: COL4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A1 were set to 35699195; 37272523; 36300346; 30413629
Phenotypes for gene: COL4A1 were set to Brain small vessel disease 1 with or without ocular anomalies MONDO:0008289; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant MONDO:0032814
Review for gene: COL4A1 was set to GREEN
gene: COL4A1 was marked as current diagnostic
Added comment: PMID: 35699195
Systematic review: frequency of cognitive features in COL4A1 was 33% [128/390 individuals from 233 pedigrees]. Developmental delay was present in over 80% of individuals with COL4A1/2 with cognitive features.

PMID: 37272523
Ontario Neurodegenerative Disease Research Initiative (ONDRI) sample size 510: 8 patients with COL4A1/2 variants had Alzheimer's disease/mild cognitive impairment, 3 patients with COL4A1/2 variants had frontotemporal dementia

PMID: 36300346
UK Biobank cohort study (n = 454 756): 2 patients with COL4A1/2 variants had vascular dementia, 8 patients with COL4A1/2 variants had all-cause dementia

PMID: 30413629
Child with COL4A1 p. G601S variant: developmental delay, moderate cognitive impairment, autism, and normal neurologic examination. Focal-onset drug-resistant seizures started at 11 years of age.
3-year-old girl with de novo COL4A1 p.G1239R: Surgical delivery was performed because prenatal hydrocephalus was suspected. The child developed microcephaly, severe cognitive impairment, and drug-resistant epileptic spasms.
Sources: Literature
Monogenic Diabetes v0.52 AGPAT2 Hali Van Niel reviewed gene: AGPAT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33651552, 30296183, 35857714, 21847459; Phenotypes: diabetes mellitus MONDO:0005015, congenital generalized lipodystrophy type 1 MONDO:0012071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.240 PIP5K1C Zornitza Stark Publications for gene: PIP5K1C were set to 17701898
Fetal anomalies v1.239 PIP5K1C Zornitza Stark Classified gene: PIP5K1C as Green List (high evidence)
Fetal anomalies v1.239 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Green List (High Evidence).
Fetal anomalies v1.238 PIP5K1C Zornitza Stark reviewed gene: PIP5K1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 38491417; Phenotypes: Lethal congenital contractural syndrome 3, OMIM:611369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Multiple pterygium syndrome_Fetal akinesia sequence v1.5 PIP5K1C Zornitza Stark Classified gene: PIP5K1C as Green List (high evidence)
Multiple pterygium syndrome_Fetal akinesia sequence v1.5 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Green List (High Evidence).
Multiple pterygium syndrome_Fetal akinesia sequence v1.4 PIP5K1C Zornitza Stark edited their review of gene: PIP5K1C: Added comment: PMID 38491417: reported a novel variant (p.S318Ifs*28) and a different variant which has been reported in ClinVar (p.G230Qfs*114) has been identified in two foetuses with contractures and other joint abnormalities. The variants were confirmed to be in trans through parental testing.; Changed rating: GREEN; Changed publications: 17701898, 38491417
Arthrogryposis v0.409 PIP5K1C Zornitza Stark Publications for gene: PIP5K1C were set to 17701898
Arthrogryposis v0.408 PIP5K1C Zornitza Stark Classified gene: PIP5K1C as Green List (high evidence)
Arthrogryposis v0.408 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Green List (High Evidence).
Monogenic Diabetes v0.52 SLC2A2 Hali Van Niel changed review comment from: Rare presenting feature for recessive Fanconi-Bickel syndrome.
From 104 patients with neonatal diabetes, five (5%) were found to have homozygous SLC2A2 mutations (PMID: 22660720)
Three further patient with neonatal diabetes with SLC2A2 variant detected (PMID: 22060631, PMID: 23456528; 29116606); to: Rare presenting feature for recessive Fanconi-Bickel syndrome.
From 104 patients with neonatal diabetes, five (5%) were found to have homozygous SLC2A2 mutations (PMID: 22660720)
Three further patients with neonatal diabetes with SLC2A2 variant detected (PMID: 22060631, PMID: 23456528; 29116606)
Arthrogryposis v0.407 PIP5K1C Zornitza Stark Classified gene: PIP5K1C as Green List (high evidence)
Arthrogryposis v0.407 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Green List (High Evidence).
Monogenic Diabetes v0.52 SLC2A2 Hali Van Niel reviewed gene: SLC2A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22060631, 23456528, 29116606, 22660720; Phenotypes: neonatal diabetes mellitus MONDO:0016391; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5790 SLC35C1 Zornitza Stark Marked gene: SLC35C1 as ready
Intellectual disability syndromic and non-syndromic v0.5790 SLC35C1 Zornitza Stark Gene: slc35c1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5790 SLC35C1 Zornitza Stark Phenotypes for gene: SLC35C1 were changed from to Congenital disorder of glycosylation, type IIc, MIM# 266265, MONDO:0009953
Intellectual disability syndromic and non-syndromic v0.5789 SLC35C1 Zornitza Stark Publications for gene: SLC35C1 were set to
Intellectual disability syndromic and non-syndromic v0.5788 SLC35C1 Zornitza Stark Mode of inheritance for gene: SLC35C1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.114 P3H1 Zornitza Stark Publications for gene: P3H1 were set to 17277775; 18566967
Osteogenesis Imperfecta and Osteoporosis v0.113 P3H1 Zornitza Stark Tag founder tag was added to gene: P3H1.
Intellectual disability syndromic and non-syndromic v0.5787 PRMT9 Zornitza Stark Marked gene: PRMT9 as ready
Intellectual disability syndromic and non-syndromic v0.5787 PRMT9 Zornitza Stark Gene: prmt9 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5787 PRMT9 Zornitza Stark Phenotypes for gene: PRMT9 were changed from Neurodevelopmental disorder, MONDO:0100500 to Neurodevelopmental disorder, MONDO:0100500, PRMT9-related
Mendeliome v1.1744 PRMT9 Zornitza Stark Marked gene: PRMT9 as ready
Mendeliome v1.1744 PRMT9 Zornitza Stark Gene: prmt9 has been classified as Red List (Low Evidence).
Mendeliome v1.1744 PRMT9 Zornitza Stark Phenotypes for gene: PRMT9 were changed from Neurodevelopmental disorder, MONDO:0100500 to Neurodevelopmental disorder, MONDO:0100500, PRMT9-related
Lipodystrophy_Lipoatrophy v1.16 SUPT7L Zornitza Stark Marked gene: SUPT7L as ready
Lipodystrophy_Lipoatrophy v1.16 SUPT7L Zornitza Stark Gene: supt7l has been classified as Red List (Low Evidence).
Lipodystrophy_Lipoatrophy v1.16 SUPT7L Zornitza Stark Phenotypes for gene: SUPT7L were changed from lipodystrophy, MONDO:0006573 to lipodystrophy, MONDO:0006573, SUPT7L-related
Mendeliome v1.1743 SUPT7L Zornitza Stark Marked gene: SUPT7L as ready
Mendeliome v1.1743 SUPT7L Zornitza Stark Gene: supt7l has been classified as Red List (Low Evidence).
Mendeliome v1.1743 SUPT7L Zornitza Stark Phenotypes for gene: SUPT7L were changed from Lipodystrophy, MONDO:0006573 to Lipodystrophy, MONDO:0006573, SUPT7L-related
Retinitis pigmentosa v0.145 PQLC2 Zornitza Stark Marked gene: PQLC2 as ready
Retinitis pigmentosa v0.145 PQLC2 Zornitza Stark Gene: pqlc2 has been classified as Green List (High Evidence).
Retinitis pigmentosa v0.145 PQLC2 Zornitza Stark Phenotypes for gene: PQLC2 were changed from Retinitis pigmentosa, MONDO:0019200 to Retinitis pigmentosa, MONDO:0019200, PQLC2-related
Retinitis pigmentosa v0.144 PQLC2 Zornitza Stark Publications for gene: PQLC2 were set to PMID: 35486108; and online publication GiM Feb 2024
Retinitis pigmentosa v0.143 PQLC2 Zornitza Stark Tag new gene name tag was added to gene: PQLC2.
Mendeliome v1.1742 PQLC2 Zornitza Stark Marked gene: PQLC2 as ready
Mendeliome v1.1742 PQLC2 Zornitza Stark Gene: pqlc2 has been classified as Green List (High Evidence).
Mendeliome v1.1742 PQLC2 Zornitza Stark Phenotypes for gene: PQLC2 were changed from Retinitis pigmentosa, MONDO:0019200 to Retinitis pigmentosa, MONDO:0019200, PQLC2-related
Mendeliome v1.1741 PQLC2 Zornitza Stark Publications for gene: PQLC2 were set to PMID: 35486108; and online publication GiM Feb 2024
Mendeliome v1.1740 PQLC2 Zornitza Stark Tag new gene name tag was added to gene: PQLC2.
Retinitis pigmentosa v0.143 SLC39A12 Zornitza Stark Marked gene: SLC39A12 as ready
Retinitis pigmentosa v0.143 SLC39A12 Zornitza Stark Gene: slc39a12 has been classified as Red List (Low Evidence).
Retinitis pigmentosa v0.143 SLC39A12 Zornitza Stark Phenotypes for gene: SLC39A12 were changed from Retinitis pigmentosa, MONDO:0019200 to Retinitis pigmentosa, MONDO:0019200, SLC39A12-related
Mendeliome v1.1740 SLC39A12 Zornitza Stark Marked gene: SLC39A12 as ready
Mendeliome v1.1740 SLC39A12 Zornitza Stark Gene: slc39a12 has been classified as Red List (Low Evidence).
Mendeliome v1.1740 SLC39A12 Zornitza Stark Phenotypes for gene: SLC39A12 were changed from Retinitis pigmentosa, MONDO:0019200 to Retinitis pigmentosa, MONDO:0019200, SLC39A12-related
Early-onset Dementia v1.14 TREX1 Lynn Tan gene: TREX1 was added
gene: TREX1 was added to Early-onset Dementia. Sources: Literature
Mode of inheritance for gene: TREX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TREX1 were set to 29380913; 35699195; 36586737; 35307828
Phenotypes for gene: TREX1 were set to Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations MONDO:0008641
Review for gene: TREX1 was set to GREEN
gene: TREX1 was marked as current diagnostic
Added comment: PMID: 35699195
Systematic review: frequency of cognitive features in TREX1 was 29% [36/123 individuals from 34 pedigrees]

PMID: 29380913
Symptoms for this disorder start in adulthood and frequently include rapid loss of vision, multifocal strokes and dementia.

PMID: 36586737
1. Female patient displayed the first symptoms at a very early-age, 57 years old, and originated from Serbia. She presented with mild cognitive impairment.
2. 53-year old Dutch patient who displayed presenile dementia
3. 39-year old Finnish patient presenting migrane without aura, severe and pervasive cognitive impairment

PMID: 35307828
First stroke at age 39, diagnosed with severe amyloid angiopathy, and he also started suffering from migraines without aura and was later diagnosed with cognitive impairment
Sources: Literature
Bleeding and Platelet Disorders v1.43 CBS Zornitza Stark Publications for gene: CBS were set to
Bleeding and Platelet Disorders v1.42 CBS Zornitza Stark Classified gene: CBS as Green List (high evidence)
Bleeding and Platelet Disorders v1.42 CBS Zornitza Stark Gene: cbs has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.41 CBS Zornitza Stark edited their review of gene: CBS: Changed rating: GREEN
Retinitis pigmentosa v0.142 SLC4A7 Zornitza Stark Marked gene: SLC4A7 as ready
Retinitis pigmentosa v0.142 SLC4A7 Zornitza Stark Gene: slc4a7 has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa v0.142 SLC4A7 Zornitza Stark Phenotypes for gene: SLC4A7 were changed from Retinitis pigmentosa, MONDO:0019200 to Retinitis pigmentosa, MONDO:0019200, SLC4A7-related
Mendeliome v1.1739 SLC4A7 Zornitza Stark Marked gene: SLC4A7 as ready
Mendeliome v1.1739 SLC4A7 Zornitza Stark Gene: slc4a7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1739 SLC4A7 Zornitza Stark Phenotypes for gene: SLC4A7 were changed from Retinitis pigmentosa, MONDO:0019200 to Retinitis pigmentosa, MONDO:0019200, SLC4A7-related
Monogenic Diabetes v0.52 ABCC8 Zornitza Stark Marked gene: ABCC8 as ready
Monogenic Diabetes v0.52 ABCC8 Zornitza Stark Gene: abcc8 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.52 ABCC8 Zornitza Stark Phenotypes for gene: ABCC8 were changed from DIABETES MELLITUS, NONINSULIN-DEPENDENT; Transient Neonatal Diabetes, Dominant; Diabetes mellitus, permanent neonatal, 6; Hyperinsulinemic hypoglycemia, familial, 1, 256450; Diabetes mellitus, noninsulin-dependent, 125853; Permanent Neonatal Diabetes Mellitus; Permanent neonatal diabetes mellitus; transient neonatal diabetes (Dominant); Hypoglycemia of infancy, leucine-sensitive, 240800; Permanent Neonatal Diabetes Mellitus (recessive); Diabetes mellitus, transient neonatal 2, 610374; Hyperinsulinemic hypoglycemia, familial, 1, 256450Hypoglycemia of infancy, leucine-sensitive, 240800Diabetes mellitus, transient neonatal 2, 610374Diabetes mellitus, noninsulin-dependent, 125853Diabetes mellitus, permanent neonatal, 6 to permanent neonatal diabetes mellitus MONDO:0100164; transient neonatal diabetes mellitus MONDO:0020525
Monogenic Diabetes v0.51 ABCC8 Zornitza Stark Publications for gene: ABCC8 were set to
Bleeding and Platelet Disorders v1.41 PLG Zornitza Stark Publications for gene: PLG were set to
Bleeding and Platelet Disorders v1.40 PLG Zornitza Stark Mode of inheritance for gene: PLG was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.39 PLG Zornitza Stark Classified gene: PLG as Amber List (moderate evidence)
Bleeding and Platelet Disorders v1.39 PLG Zornitza Stark Gene: plg has been classified as Amber List (Moderate Evidence).
Bleeding and Platelet Disorders v1.38 PLG Zornitza Stark reviewed gene: PLG: Rating: AMBER; Mode of pathogenicity: None; Publications: 35244080, 27976734; Phenotypes: Dysplasminogenemia 217090; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic Diabetes v0.50 ABCC8 Hali Van Niel reviewed gene: ABCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: (PMID: 21054355, 32027066, 32376986); Phenotypes: permanent neonatal diabetes mellitus MONDO:0100164, transient neonatal diabetes mellitus MONDO:0020525; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.38 PLG Jane Lin gene: PLG was added
gene: PLG was added to Bleeding and Platelet Disorders. Sources: Expert Review
Mode of inheritance for gene: PLG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PLG were set to Plasminogen deficiency, type I; Dysplasminogenemia; MIM#217090
gene: PLG was marked as current diagnostic
Added comment: Included in Genomics England PanelApp "Thrombophilia with a likely monogenic cause" panel. Adding to this panel as this gene has a gene-disease association with thrombophilia.
Sources: Expert Review
Mendeliome v1.1738 SLC4A7 Chirag Patel Classified gene: SLC4A7 as Amber List (moderate evidence)
Mendeliome v1.1738 SLC4A7 Chirag Patel Gene: slc4a7 has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa v0.141 SLC4A7 Chirag Patel Classified gene: SLC4A7 as Amber List (moderate evidence)
Retinitis pigmentosa v0.141 SLC4A7 Chirag Patel Gene: slc4a7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1737 SLC4A7 Chirag Patel gene: SLC4A7 was added
gene: SLC4A7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC4A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A7 were set to PMID: 35486108, 32594822
Phenotypes for gene: SLC4A7 were set to Retinitis pigmentosa, MONDO:0019200
Review for gene: SLC4A7 was set to AMBER
Added comment: Total 4 individuals from 3 families (2 known to be from same ethnic origin: Oriental-Jewish) with adult onset retinitis pigmentosa. All individuals had same homozygous frameshift variant in SLC4A7 gene (p.P670Sfs*6). RNA seq analysis revealed retinal expression in human and mouse samples. Immunohistochemistry of human and mouse retina revealed relatively strong expression in various retinal layers. Western blot analysis in fibroblasts from 1 patient showed absence of encoded protein.
Sources: Literature
Retinitis pigmentosa v0.140 SLC4A7 Chirag Patel gene: SLC4A7 was added
gene: SLC4A7 was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: Literature
Mode of inheritance for gene: SLC4A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A7 were set to PMID: 35486108, 32594822
Phenotypes for gene: SLC4A7 were set to Retinitis pigmentosa, MONDO:0019200
Review for gene: SLC4A7 was set to AMBER
Added comment: Total 4 individuals from 3 families (2 known to be from same ethnic origin: Oriental-Jewish) with adult onset retinitis pigmentosa. All individuals had same homozygous frameshift variant in SLC4A7 gene (p.P670Sfs*6). RNA seq analysis revealed retinal expression in human and mouse samples. Immunohistochemistry of human and mouse retina revealed relatively strong expression in various retinal layers. Western blot analysis in fibroblasts from 1 patient showed absence of encoded protein.
Sources: Literature
Bleeding and Platelet Disorders v1.38 CBS Jane Lin reviewed gene: CBS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombosis, HOMOCYSTINURIA, MIM# 236200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1736 SLC39A12 Chirag Patel gene: SLC39A12 was added
gene: SLC39A12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC39A12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC39A12 were set to PMID: 35486108
Phenotypes for gene: SLC39A12 were set to Retinitis pigmentosa, MONDO:0019200
Review for gene: SLC39A12 was set to RED
Added comment: WES (with targeted analysis of SLC genes) in 913 cases from 785 families with inherited retinal dystrophy. They identified 1 homozygous variant in SLC39A12 in 1 individual with adult-onset mild widespread retinal degeneration with marked macular involvement. No functional data. RNA seq analysis revealed retinal expression in human samples. Immunohistochemistry of human and mouse retina revealed comprehensive expression in various retinal cells including retinal pigment epithelium.
Sources: Literature
Retinitis pigmentosa v0.139 SLC39A12 Chirag Patel gene: SLC39A12 was added
gene: SLC39A12 was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: Literature
Mode of inheritance for gene: SLC39A12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC39A12 were set to PMID: 35486108
Phenotypes for gene: SLC39A12 were set to Retinitis pigmentosa, MONDO:0019200
Review for gene: SLC39A12 was set to RED
Added comment: WES (with targeted analysis of SLC genes) in 913 cases from 785 families with inherited retinal dystrophy. They identified 1 homozygous variant in SLC39A12 in 1 individual with adult-onset mild widespread retinal degeneration with marked macular involvement. No functional data. RNA seq analysis revealed retinal expression in human samples. Immunohistochemistry of human and mouse retina revealed comprehensive expression in various retinal cells including retinal pigment epithelium.
Sources: Literature
Mendeliome v1.1735 PQLC2 Chirag Patel Classified gene: PQLC2 as Green List (high evidence)
Mendeliome v1.1735 PQLC2 Chirag Patel Gene: pqlc2 has been classified as Green List (High Evidence).
Retinitis pigmentosa v0.138 PQLC2 Chirag Patel Classified gene: PQLC2 as Green List (high evidence)
Retinitis pigmentosa v0.138 PQLC2 Chirag Patel Gene: pqlc2 has been classified as Green List (High Evidence).
Mendeliome v1.1734 PQLC2 Chirag Patel gene: PQLC2 was added
gene: PQLC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PQLC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PQLC2 were set to PMID: 35486108; and online publication GiM Feb 2024
Phenotypes for gene: PQLC2 were set to Retinitis pigmentosa, MONDO:0019200
Review for gene: PQLC2 was set to GREEN
gene: PQLC2 was marked as current diagnostic
Added comment: HGNC Gene Symbol: SLC66A1
Total 8 individuals from 6 families.

Millo et al. (2022)(PMID: 35486108) -
WES (with targeted analysis of SLC genes) in 913 cases from 785 families with inherited retinal dystrophy. They identified 2 different homozygous variants in SLC66A1 in 3 individuals from 2 families with adult-onset retinal dystrophy. No functional data.


Olinger et al. (2024)(https://www.sciencedirect.com/science/article/pii/S2949774424009804) -
CNV analysis of trio and non-trio WGS data from Genomics England 100K genomes project. They identified homozygous 21kb deletion spanning nearly entire SLC66A1 gene in 2 siblings with adult-onset rod-cone dystrophy (parents HTZ carriers). Review of cohort data then identified homozygous LOF variants (1 nonsense, 2 frameshift) in another 3 individuals with rod-cone dystrophy.
Sources: Literature
Retinitis pigmentosa v0.137 PQLC2 Chirag Patel gene: PQLC2 was added
gene: PQLC2 was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: Literature
Mode of inheritance for gene: PQLC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PQLC2 were set to PMID: 35486108; and online publication GiM Feb 2024
Phenotypes for gene: PQLC2 were set to Retinitis pigmentosa, MONDO:0019200
Review for gene: PQLC2 was set to GREEN
gene: PQLC2 was marked as current diagnostic
Added comment: HGNC Gene Symbol: SLC66A1
Total 8 individuals from 6 families.

Millo et al. (2022)(PMID: 35486108) -
WES (with targeted analysis of SLC genes) in 913 cases from 785 families with inherited retinal dystrophy. They identified 2 different homozygous variants in SLC66A1 in 3 individuals from 2 families with adult-onset retinal dystrophy. No functional data.


Olinger et al. (2024)(https://www.sciencedirect.com/science/article/pii/S2949774424009804) -
CNV analysis of trio and non-trio WGS data from Genomics England 100K genomes project. They identified homozygous 21kb deletion spanning nearly entire SLC66A1 gene in 2 siblings with adult-onset rod-cone dystrophy (parents HTZ carriers). Review of cohort data then identified homozygous LOF variants (1 nonsense, 2 frameshift) in another 3 individuals with rod-cone dystrophy.
Sources: Literature
Mendeliome v1.1733 SUPT7L Chirag Patel gene: SUPT7L was added
gene: SUPT7L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SUPT7L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUPT7L were set to PMID: 38592547
Phenotypes for gene: SUPT7L were set to Lipodystrophy, MONDO:0006573
Review for gene: SUPT7L was set to RED
Added comment: 1 case with generalised lipodystrophy, growth retardation, congenital cataracts, severe developmental delay and progeriod features. Trio WGS identified compound heterozygous variants in SUPT7L (missense causing abnormal splicing + frameshift). Variants validated with Sanger. SUPT7L encodes a component of the core structural module of the STAGA complex - a nuclear multifunctional protein complex that plays a role in various cellular processes (e.g. transcription factor binding, protein acetylation, splicing, and DNA damage control). Immunolabelling in fibroblasts from patient showed complete absence of SUPT7L protein. Transcriptome data from individual revealed downregulation of several gene sets associated with DNA replication, DNA repair, cell cycle, and transcription.
Sources: Literature
Mendeliome v1.1732 PRMT9 Chirag Patel gene: PRMT9 was added
gene: PRMT9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRMT9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRMT9 were set to PMID: 38561334
Phenotypes for gene: PRMT9 were set to Neurodevelopmental disorder, MONDO:0100500
Review for gene: PRMT9 was set to RED
Added comment: A homozygous variant (G189R) in PRMT9 is reported based on large WGS study in 136 consanguineous families - unclear if only found in 1 family and no clinical information on case(s).

PMRTs (protein arginine methyltransferases) catalyse post translational modification via arginine methylation. Functional studies showed that the G189R variant abolishes PRMT9's methyltransferase activity - specifically at the R508 residue of SF3B2 RNA (exclusively methylated by PRMT9) - and leads to heavy PRMT9 ubiquitination, and abnormal splicing activity of SF3B2. Knock out mouse model showed PRMT9 loss in excitatory neurons leads to aberrant synapse development and impaired learning and memory.
Sources: Literature
Lipodystrophy_Lipoatrophy v1.15 SUPT7L Chirag Patel gene: SUPT7L was added
gene: SUPT7L was added to Lipodystrophy_Lipoatrophy. Sources: Literature
Mode of inheritance for gene: SUPT7L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUPT7L were set to PMID: 38592547
Phenotypes for gene: SUPT7L were set to lipodystrophy, MONDO:0006573
Review for gene: SUPT7L was set to RED
Added comment: 1 case with generalised lipodystrophy, growth retardation, congenital cataracts, severe developmental delay and progeriod features. Trio WGS identified compound heterozygous variants in SUPT7L (missense causing abnormal splicing + frameshift). Variants validated with Sanger. SUPT7L encodes a component of the core structural module of the STAGA complex - a nuclear multifunctional protein complex that plays a role in various cellular processes (e.g. transcription factor binding, protein acetylation, splicing, and DNA damage control). Immunolabelling in fibroblasts from patient showed complete absence of SUPT7L protein. Transcriptome data from individual revealed downregulation of several gene sets associated with DNA replication, DNA repair, cell cycle, and transcription.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5786 PRMT9 Chirag Patel gene: PRMT9 was added
gene: PRMT9 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PRMT9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRMT9 were set to PMID: 38561334
Phenotypes for gene: PRMT9 were set to Neurodevelopmental disorder, MONDO:0100500
Review for gene: PRMT9 was set to RED
Added comment: A homozygous variant (G189R) in PRMT9 is reported based on large WGS study in 136 consanguineous families - unclear if only found in 1 family and no clinical information on case(s).

PMRTs (protein arginine methyltransferases) catalyse post translational modification via arginine methylation. Functional studies showed that the G189R variant abolishes PRMT9's methyltransferase activity - specifically at the R508 residue of SF3B2 RNA (exclusively methylated by PRMT9) - and leads to heavy PRMT9 ubiquitination, and abnormal splicing activity of SF3B2. Knock out mouse model showed PRMT9 loss in excitatory neurons leads to aberrant synapse development and impaired learning and memory.
Sources: Literature
Osteogenesis Imperfecta and Osteoporosis v0.113 P3H1 Tashunka Taylor-Miller reviewed gene: P3H1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 36833249; Phenotypes: Osteopenia HP:0000938, Platyspondyly HP:0000926, MONDO:0012581; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Autoinflammatory Disorders v1.47 JAK1 Zornitza Stark Marked gene: JAK1 as ready
Autoinflammatory Disorders v1.47 JAK1 Zornitza Stark Gene: jak1 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.47 JAK1 Zornitza Stark Classified gene: JAK1 as Green List (high evidence)
Autoinflammatory Disorders v1.47 JAK1 Zornitza Stark Gene: jak1 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.46 JAK1 Zornitza Stark gene: JAK1 was added
gene: JAK1 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: JAK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JAK1 were set to 38563820; 28111307
Phenotypes for gene: JAK1 were set to Autoinflammation, immunde dysregulation, and eosinophilia, MIM# 618999
Review for gene: JAK1 was set to GREEN
Added comment: PMID 38563820: 59 individuals presenting with autoimmunity, atopy, colitis, and/or dermatitis and one of four JAK1 variants.
Sources: Literature
Disorders of immune dysregulation v0.186 JAK1 Zornitza Stark Classified gene: JAK1 as Green List (high evidence)
Disorders of immune dysregulation v0.186 JAK1 Zornitza Stark Gene: jak1 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.185 JAK1 Zornitza Stark edited their review of gene: JAK1: Added comment: PMID 38563820: 59 individuals presenting with autoimmunity, atopy, colitis, and/or dermatitis and one of four JAK1 variants.; Changed rating: GREEN; Changed phenotypes: Autoinflammation, immunde dysregulation, and eosinophilia, MIM# 618999, Eosinophilia, Eosinophilic enteritis, Thyroid disease, Poor growth, Viral infections, Autoinflammation, immunde dysregulation, and eosinophilia, MIM# 618999
Mendeliome v1.1731 JAK1 Zornitza Stark Phenotypes for gene: JAK1 were changed from Eosinophilia; Eosinophilic enteritis; Thyroid disease; Poor growth; Viral infections; Susceptibility to mycobacteria and viruses to Autoinflammation, immunde dysregulation, and eosinophilia, MIM# 618999; Eosinophilia; Eosinophilic enteritis; Thyroid disease; Poor growth; Viral infections; Susceptibility to mycobacteria and viruses
Mendeliome v1.1730 JAK1 Zornitza Stark Publications for gene: JAK1 were set to 28111307; 28008925; 30671064
Mendeliome v1.1729 JAK1 Zornitza Stark Classified gene: JAK1 as Green List (high evidence)
Mendeliome v1.1729 JAK1 Zornitza Stark Gene: jak1 has been classified as Green List (High Evidence).
Mendeliome v1.1728 JAK1 Zornitza Stark edited their review of gene: JAK1: Added comment: PMID 38563820: 59 individuals presenting with autoimmunity, atopy, colitis, and/or dermatitis and one of four JAK1 variants.; Changed rating: GREEN; Changed publications: 28111307, 28008925, 30671064, 38563820; Changed phenotypes: Autoinflammatory syndrome, MONDO:0019751, JAK1-related, Eosinophilia, Eosinophilic enteritis, Thyroid disease, Poor growth, Viral infections, Susceptibility to mycobacteria and viruses, Autoinflammation, immunde dysregulation, and eosinophilia, MIM# 618999
Mendeliome v1.1728 SRPK3 Zornitza Stark Marked gene: SRPK3 as ready
Mendeliome v1.1728 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Green List (High Evidence).
Mendeliome v1.1728 SRPK3 Zornitza Stark Classified gene: SRPK3 as Green List (high evidence)
Mendeliome v1.1728 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Green List (High Evidence).
Mendeliome v1.1727 SRPK3 Zornitza Stark gene: SRPK3 was added
gene: SRPK3 was added to Mendeliome. Sources: Literature
digenic tags were added to gene: SRPK3.
Mode of inheritance for gene: SRPK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SRPK3 were set to 38429495
Phenotypes for gene: SRPK3 were set to Myopathy, MONDO:0005336, digenic SRPK3- and TTN-related
Review for gene: SRPK3 was set to GREEN
Added comment: 33 individuals reported with SRPK3 variants but myopathy only occurred when TTN variant also present (most truncating). Zebrafish model supports digenic model of inheritance.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.33 SRPK3 Zornitza Stark Marked gene: SRPK3 as ready
Muscular dystrophy and myopathy_Paediatric v1.33 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.33 SRPK3 Zornitza Stark Classified gene: SRPK3 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.33 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.32 SRPK3 Zornitza Stark Tag digenic tag was added to gene: SRPK3.
Muscular dystrophy and myopathy_Paediatric v1.32 SRPK3 Zornitza Stark gene: SRPK3 was added
gene: SRPK3 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: SRPK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SRPK3 were set to 38429495
Phenotypes for gene: SRPK3 were set to Myopathy, MONDO:0005336, digenic SRPK3- and TTN-related
Review for gene: SRPK3 was set to GREEN
Added comment: 33 individuals reported with SRPK3 variants but myopathy only occurred when TTN variant also present (most truncating). Zebrafish model supports digenic model of inheritance.
Sources: Literature
Mendeliome v1.1726 OTULIN Zornitza Stark Publications for gene: OTULIN were set to 27523608; 27559085; 35587511
Mendeliome v1.1725 OTULIN Zornitza Stark edited their review of gene: OTULIN: Added comment: Three individuals reported with de novo missense variants and auto inflammatory syndrome. Two had at the same variant, p.Cys129Ser. Experimental data supports dominant negative mechanism. Fourth individual with heterozygous variant in PMID 38129331 and severe fasciitis.; Changed publications: 27523608, 27559085, 35587511, 38630025, 38652464, 38129331
Autoinflammatory Disorders v1.45 OTULIN Zornitza Stark Publications for gene: OTULIN were set to 27523608; 27559085
Autoinflammatory Disorders v1.44 OTULIN Zornitza Stark Mode of inheritance for gene: OTULIN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Autoinflammatory Disorders v1.43 OTULIN Zornitza Stark edited their review of gene: OTULIN: Added comment: Three individuals reported with de novo missense variants and auto inflammatory syndrome. Two had at the same variant, p.Cys129Ser. Experimental data supports dominant negative mechanism. Fourth individual with heterozygous variant in PMID 38129331 and severe fasciitis.; Changed publications: 27523608, 27559085, 38630025, 38652464, 38129331; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.38 CFI Zornitza Stark Marked gene: CFI as ready
Bleeding and Platelet Disorders v1.38 CFI Zornitza Stark Gene: cfi has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.38 CFI Zornitza Stark Classified gene: CFI as Green List (high evidence)
Bleeding and Platelet Disorders v1.38 CFI Zornitza Stark Gene: cfi has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.37 CFI Zornitza Stark gene: CFI was added
gene: CFI was added to Bleeding and Platelet Disorders. Sources: Expert Review
Mode of inheritance for gene: CFI was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CFI were set to {Haemolytic uremic syndrome, atypical, susceptibility to, 3}, MIM# 612923
Review for gene: CFI was set to GREEN
Added comment: Thrombotic microangiopathy is part of the phenotype. Note this is a susceptibility locus.
Sources: Expert Review
Bleeding and Platelet Disorders v1.36 CFB Zornitza Stark Marked gene: CFB as ready
Bleeding and Platelet Disorders v1.36 CFB Zornitza Stark Gene: cfb has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.36 CFB Zornitza Stark Classified gene: CFB as Green List (high evidence)
Bleeding and Platelet Disorders v1.36 CFB Zornitza Stark Gene: cfb has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.35 CFB Zornitza Stark gene: CFB was added
gene: CFB was added to Bleeding and Platelet Disorders. Sources: Expert Review
Mode of inheritance for gene: CFB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CFB were set to {Hemolytic uremic syndrome, atypical, susceptibility to, 4}, MIM# 612924
Review for gene: CFB was set to GREEN
Added comment: Thrombotic microangiopathy is part of the phenotype. Note this is a susceptibility locus.
Sources: Expert Review
Bleeding and Platelet Disorders v1.34 C3 Zornitza Stark Marked gene: C3 as ready
Bleeding and Platelet Disorders v1.34 C3 Zornitza Stark Gene: c3 has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.34 C3 Zornitza Stark Classified gene: C3 as Green List (high evidence)
Bleeding and Platelet Disorders v1.34 C3 Zornitza Stark Gene: c3 has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.33 C3 Zornitza Stark gene: C3 was added
gene: C3 was added to Bleeding and Platelet Disorders. Sources: Expert Review
Mode of inheritance for gene: C3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: C3 were set to {Hemolytic uremic syndrome, atypical, susceptibility to, 5}, MIM# 612925
Review for gene: C3 was set to GREEN
Added comment: Thrombotic microangiopathy is part of the clinical presentation. Note this is a susceptibility locus.
Sources: Expert Review
Mitochondrial disease v0.922 SPG7 Zornitza Stark Marked gene: SPG7 as ready
Mitochondrial disease v0.922 SPG7 Zornitza Stark Gene: spg7 has been classified as Green List (High Evidence).
Mitochondrial disease v0.922 SPG7 Zornitza Stark Phenotypes for gene: SPG7 were changed from to Spastic paraplegia 7, autosomal recessive, MIM# 607259; Autosomal dominant optic atrophy, MONDO:0020250
Mitochondrial disease v0.921 SPG7 Zornitza Stark Publications for gene: SPG7 were set to 9635427; 9635427; 16534102; 18799786; 22571692; 34500365; 33598982; 32548275; 24727571
Mitochondrial disease v0.920 SPG7 Zornitza Stark Publications for gene: SPG7 were set to
Mitochondrial disease v0.919 SPG7 Zornitza Stark Mode of inheritance for gene: SPG7 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disease v0.918 SPG7 Zornitza Stark edited their review of gene: SPG7: Added comment: Please note PEO can be a feature +/- multiple mito deletions in skeletal muscle. PMID 24727571; Changed publications: 9635427, 9635427, 16534102, 18799786, 22571692, 34500365, 33598982, 32548275, 24727571
Autoinflammatory Disorders v1.43 SHARPIN Zornitza Stark Phenotypes for gene: SHARPIN were changed from Autoinflammatory syndrome, MONDO:0019751, SHARPIN-related to Autoinflammation with episodic fever and immune dysregulation, MIM# 620795
Autoinflammatory Disorders v1.42 SHARPIN Zornitza Stark edited their review of gene: SHARPIN: Changed phenotypes: Autoinflammation with episodic fever and immune dysregulation, MIM# 620795
Mendeliome v1.1725 SHARPIN Zornitza Stark Phenotypes for gene: SHARPIN were changed from Autoinflammatory syndrome, MONDO:0019751, SHARPIN-related to Autoinflammation with episodic fever and immune dysregulation, MIM# 620795
Mendeliome v1.1724 SHARPIN Zornitza Stark edited their review of gene: SHARPIN: Changed phenotypes: Autoinflammation with episodic fever and immune dysregulation, MIM# 620795
Intellectual disability syndromic and non-syndromic v0.5785 OTUD7A Zornitza Stark Phenotypes for gene: OTUD7A were changed from Intellectual disability; Epilepsy to Neurodevelopmental disorder with hypotonia and seizures, MIM# 620790
Intellectual disability syndromic and non-syndromic v0.5784 OTUD7A Zornitza Stark edited their review of gene: OTUD7A: Changed phenotypes: Neurodevelopmental disorder with hypotonia and seizures, MIM# 620790
Genetic Epilepsy v0.2611 OTUD7A Zornitza Stark Phenotypes for gene: OTUD7A were changed from Intellectual disability; Epilepsy to Neurodevelopmental disorder with hypotonia and seizures, MIM# 620790
Genetic Epilepsy v0.2610 OTUD7A Zornitza Stark edited their review of gene: OTUD7A: Changed phenotypes: Neurodevelopmental disorder with hypotonia and seizures, MIM# 620790
Mendeliome v1.1724 OTUD7A Zornitza Stark Phenotypes for gene: OTUD7A were changed from Intellectual disability; Epilepsy to Neurodevelopmental disorder with hypotonia and seizures, MIM# 620790
Mendeliome v1.1723 OTUD7A Zornitza Stark edited their review of gene: OTUD7A: Changed phenotypes: Neurodevelopmental disorder with hypotonia and seizures, MIM# 620790
Cardiomyopathy_Paediatric v0.190 MYPN Zornitza Stark Marked gene: MYPN as ready
Cardiomyopathy_Paediatric v0.190 MYPN Zornitza Stark Gene: mypn has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.190 MYPN Zornitza Stark Phenotypes for gene: MYPN were changed from Cardiomyopathy, dilated, 1KK, MIM# 615248; Cardiomyopathy, hypertrophic, 22, MIM# 615248 to Congenital myopathy 24, MIM# 617336; Cardiomyopathy, dilated, 1KK, MIM# 615248; Cardiomyopathy, hypertrophic, 22, MIM# 615248
Cardiomyopathy_Paediatric v0.189 MYPN Zornitza Stark Mode of inheritance for gene: MYPN was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.188 MYPN Zornitza Stark Classified gene: MYPN as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v0.188 MYPN Zornitza Stark Gene: mypn has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.187 MYPN Zornitza Stark edited their review of gene: MYPN: Added comment: However, note that the AR skeletal myopathy condition has some reports of HCM in association.; Changed rating: AMBER; Changed phenotypes: Congenital myopathy 24, MIM# 617336, Cardiomyopathy, dilated, 1KK, MIM# 615248, Cardiomyopathy, hypertrophic, 22, MIM# 615248; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.187 MYPN Zornitza Stark Phenotypes for gene: MYPN were changed from Cardiomyopathy, dilated, 1KK; Cardiomypathy, familial hypertrophic, 22, to Cardiomyopathy, dilated, 1KK, MIM# 615248; Cardiomyopathy, hypertrophic, 22, MIM# 615248
Cardiomyopathy_Paediatric v0.186 MYPN Zornitza Stark Mode of inheritance for gene: MYPN was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v0.185 MYPN Zornitza Stark Classified gene: MYPN as Red List (low evidence)
Cardiomyopathy_Paediatric v0.185 MYPN Zornitza Stark Gene: mypn has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v0.184 MYPN Zornitza Stark reviewed gene: MYPN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, dilated, 1KK, MIM# 615248, Cardiomyopathy, hypertrophic, 22, MIM# 615248; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5784 SLC35C1 Yixin JIANG reviewed gene: SLC35C1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33836758, 32313197, 34389986; Phenotypes: Congenital disorder of glycosylation, type IIc, MIM# 266265, MONDO:0009953; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1723 AMPD2 Bryony Thompson Deleted their review
Mendeliome v1.1723 AMPD2 Bryony Thompson commented on gene: AMPD2
Mendeliome v1.1723 AMPD2 Bryony Thompson Deleted their review
Metabolic Disorders Superpanel v8.143 Bryony Thompson Changed child panels to: Congenital Disorders of Glycosylation; Miscellaneous Metabolic Disorders; Calcium and Phosphate disorders; Fatty Acid Oxidation Defects; Hypertension and Aldosterone disorders; Lysosomal Storage Disorder; Neurotransmitter Defects; Disorders of branched chain amino acid metabolism; Glycogen Storage Diseases; Inherited vitamin B12 or cobalamin deficiency; Mitochondrial disease; Peroxisomal Disorders; Monogenic Diabetes; Iron metabolism disorders; Dyslipidaemia; Vitamin C Pathway Disorders; Porphyria; Hyperammonaemia
Mendeliome v1.1723 SAR1B Bryony Thompson Deleted their review
Mendeliome v1.1723 SAR1B Bryony Thompson commented on gene: SAR1B
Mendeliome v1.1723 SAR1B Bryony Thompson Deleted their review
Dyslipidaemia v0.37 STAP1 Bryony Thompson Marked gene: STAP1 as ready
Dyslipidaemia v0.37 STAP1 Bryony Thompson Gene: stap1 has been classified as Red List (Low Evidence).
Dyslipidaemia v0.37 STAP1 Bryony Thompson gene: STAP1 was added
gene: STAP1 was added to Dyslipidaemia. Sources: Literature
Mode of inheritance for gene: STAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STAP1 were set to 31809983; 31996024; 32208993
Phenotypes for gene: STAP1 were set to Familial hypercholesterolemia MONDO:0005439
Review for gene: STAP1 was set to RED
Added comment: The gene appears to fulfil the criteria for a refuted gene-disease association
Sources: Literature
Metal Metabolism Disorders v0.43 Bryony Thompson removed gene:PLA2G6 from the panel
Metal Metabolism Disorders v0.42 Bryony Thompson removed gene:PANK2 from the panel
Metal Metabolism Disorders v0.41 Bryony Thompson removed gene:FA2H from the panel
Metal Metabolism Disorders v0.40 Bryony Thompson removed gene:C19orf12 from the panel
Metal Metabolism Disorders v0.39 Bryony Thompson removed gene:ATP13A2 from the panel
Liverome Superpanel v1.6 Zornitza Stark Panel types changed to Melbourne Genomics; Victorian Clinical Genetics Services; Royal Melbourne Hospital
Intellectual disability syndromic and non-syndromic v0.5784 PTRH2 Bryony Thompson Publications for gene: PTRH2 were set to 25574476; 28175314; 28328138; 25558065; 27129381
Intellectual disability syndromic and non-syndromic v0.5783 PTRH2 Bryony Thompson Classified gene: PTRH2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5783 PTRH2 Bryony Thompson Gene: ptrh2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5782 PTRH2 Bryony Thompson reviewed gene: PTRH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33092935, 37239392; Phenotypes: neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1 MONDO:8000012; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuria v0.225 SCARB2 Bryony Thompson Marked gene: SCARB2 as ready
Proteinuria v0.225 SCARB2 Bryony Thompson Gene: scarb2 has been classified as Green List (High Evidence).
Proteinuria v0.225 SCARB2 Bryony Thompson Phenotypes for gene: SCARB2 were changed from to Progressive Myoclonus Epilepsy, MONDO:0020074; Epilepsy, progressive myoclonic 4, with or without renal failure, MIM #254900
Proteinuria v0.224 SCARB2 Bryony Thompson Publications for gene: SCARB2 were set to
Proteinuria v0.223 SCARB2 Bryony Thompson Mode of inheritance for gene: SCARB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Metal Metabolism Disorders v0.38 Bryony Thompson removed gene:WDR45 from the panel
Early-onset Dementia v1.14 VPS13C Bryony Thompson Marked gene: VPS13C as ready
Early-onset Dementia v1.14 VPS13C Bryony Thompson Gene: vps13c has been classified as Green List (High Evidence).
Early-onset Dementia v1.14 VPS13C Bryony Thompson Classified gene: VPS13C as Green List (high evidence)
Early-onset Dementia v1.14 VPS13C Bryony Thompson Gene: vps13c has been classified as Green List (High Evidence).
Early-onset Dementia v1.14 VPS13C Bryony Thompson Classified gene: VPS13C as Green List (high evidence)
Early-onset Dementia v1.14 VPS13C Bryony Thompson Gene: vps13c has been classified as Green List (High Evidence).
Early-onset Dementia v1.13 VPS13C Bryony Thompson gene: VPS13C was added
gene: VPS13C was added to Early-onset Dementia. Sources: Literature
Mode of inheritance for gene: VPS13C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS13C were set to 33579389; 37330543; 34875562
Phenotypes for gene: VPS13C were set to autosomal recessive early-onset Parkinson disease 23 MONDO:0014796
Review for gene: VPS13C was set to GREEN
gene: VPS13C was marked as current diagnostic
Added comment: Multiple cases with biallelic variants and dementia with Lewy bodies have been reported.
Sources: Literature
Arthrogryposis v0.406 PIP5K1C Achchuthan Shanmugasundram reviewed gene: PIP5K1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 38491417; Phenotypes: Lethal congenital contractural syndrome 3, OMIM:611369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1723 KIAA1024L Zornitza Stark Tag new gene name tag was added to gene: KIAA1024L.
Deafness_IsolatedAndComplex v1.180 KIAA1024L Zornitza Stark Marked gene: KIAA1024L as ready
Deafness_IsolatedAndComplex v1.180 KIAA1024L Zornitza Stark Gene: kiaa1024l has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.180 KIAA1024L Zornitza Stark Classified gene: KIAA1024L as Green List (high evidence)
Deafness_IsolatedAndComplex v1.180 KIAA1024L Zornitza Stark Gene: kiaa1024l has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.179 KIAA1024L Zornitza Stark gene: KIAA1024L was added
gene: KIAA1024L was added to Deafness_IsolatedAndComplex. Sources: Literature
new gene name tags were added to gene: KIAA1024L.
Mode of inheritance for gene: KIAA1024L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA1024L were set to 35727972
Phenotypes for gene: KIAA1024L were set to Deafness, autosomal recessive 120, OMIM:620238
Review for gene: KIAA1024L was set to GREEN
Added comment: New gene name - MINAR2

PMID:35727972 reported 13 patients from four unrelated families with non-syndromic sensorineural hearing loss. Four of these patients had prelingual onset of severe to profound, progressive bilateral hearing loss. The other nine patients had congenital onset of severe to profound bilateral hearing loss, which was not progressive on one patient, while data was not available for the other.

Three different homozygous variants (c.144G > A/ p.Trp48Ter, c.412_419delCGGTTTTG/ p.Arg138Valfs*10 and c.393G > T/ p.Lys131Asn) were identified in MINAR2/ KIAA1024L gene in these patients.

There is some functional evidence available for the p.Lys131Asn variant. In addition, mice with loss of function of the Minar2 protein present with rapidly progressive sensorineural hearing loss.
Sources: Literature
Mendeliome v1.1723 KIAA1024L Zornitza Stark Marked gene: KIAA1024L as ready
Mendeliome v1.1723 KIAA1024L Zornitza Stark Gene: kiaa1024l has been classified as Green List (High Evidence).
Mendeliome v1.1723 KIAA1024L Zornitza Stark Classified gene: KIAA1024L as Green List (high evidence)
Mendeliome v1.1723 KIAA1024L Zornitza Stark Gene: kiaa1024l has been classified as Green List (High Evidence).
Fetal anomalies v1.238 EHBP1L1 Zornitza Stark Phenotypes for gene: EHBP1L1 were changed from Non-immune hydrops fetalis MONDO:0009369 to Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related
Fetal anomalies v1.237 EHBP1L1 Zornitza Stark Classified gene: EHBP1L1 as Green List (high evidence)
Fetal anomalies v1.237 EHBP1L1 Zornitza Stark Gene: ehbp1l1 has been classified as Green List (High Evidence).
Fetal anomalies v1.236 EHBP1L1 Zornitza Stark reviewed gene: EHBP1L1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1722 EHBP1L1 Zornitza Stark Phenotypes for gene: EHBP1L1 were changed from Non-immune hydrops fetalis, MONDO:0015193, EHBP1l1-related to Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related
Mendeliome v1.1721 EHBP1L1 Zornitza Stark Classified gene: EHBP1L1 as Green List (high evidence)
Mendeliome v1.1721 EHBP1L1 Zornitza Stark Gene: ehbp1l1 has been classified as Green List (High Evidence).
Mendeliome v1.1720 EHBP1L1 Zornitza Stark reviewed gene: EHBP1L1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hydrops fetalis v0.310 EHBP1L1 Zornitza Stark Phenotypes for gene: EHBP1L1 were changed from Non-immune hydrops fetalis, MONDO:0015193, EHBP1l1-related to Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related
Hydrops fetalis v0.309 EHBP1L1 Zornitza Stark Classified gene: EHBP1L1 as Green List (high evidence)
Hydrops fetalis v0.309 EHBP1L1 Zornitza Stark Gene: ehbp1l1 has been classified as Green List (High Evidence).
Hydrops fetalis v0.308 EHBP1L1 Zornitza Stark reviewed gene: EHBP1L1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5782 DMAP1 Ben Lundie reviewed gene: DMAP1: Rating: AMBER; Mode of pathogenicity: Other; Publications: ; Phenotypes: Unknown.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2610 EFHC1 Zornitza Stark Tag disputed was removed from gene: EFHC1.
Tag refuted tag was added to gene: EFHC1.
Genetic Epilepsy v0.2610 SCN1A Zornitza Stark Publications for gene: SCN1A were set to 30368457; 12754708; 25754450; 32928894
Genetic Epilepsy v0.2609 SCN1A Zornitza Stark Publications for gene: SCN1A were set to
Genetic Epilepsy v0.2608 SCN1B Zornitza Stark Marked gene: SCN1B as ready
Genetic Epilepsy v0.2608 SCN1B Zornitza Stark Gene: scn1b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2608 SCN1B Zornitza Stark Phenotypes for gene: SCN1B were changed from Developmental and epileptic encephalopathy (MONDO:0100062); generalized epilepsy with febrile seizures plus (MONDO:0018214) to Developmental and epileptic encephalopathy (MONDO:0100062); generalized epilepsy with febrile seizures plus (MONDO:0018214)
Genetic Epilepsy v0.2607 SCN1B Zornitza Stark Phenotypes for gene: SCN1B were changed from to Developmental and epileptic encephalopathy (MONDO:0100062); generalized epilepsy with febrile seizures plus (MONDO:0018214)
Genetic Epilepsy v0.2606 SCN1B Zornitza Stark Publications for gene: SCN1B were set to
Genetic Epilepsy v0.2605 SCN1B Zornitza Stark Mode of inheritance for gene: SCN1B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2604 SLC12A5 Zornitza Stark Marked gene: SLC12A5 as ready
Genetic Epilepsy v0.2604 SLC12A5 Zornitza Stark Gene: slc12a5 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2604 SLC12A5 Zornitza Stark Phenotypes for gene: SLC12A5 were changed from Developmental and epileptic encephalopathy 34, MIM# 616645; {Epilepsy, idiopathic generalized, susceptibility to, 14}, MIM# 616685 to Developmental and epileptic encephalopathy 34, MIM# 616645; {Epilepsy, idiopathic generalized, susceptibility to, 14}, MIM# 616685
Genetic Epilepsy v0.2603 SLC12A5 Zornitza Stark Phenotypes for gene: SLC12A5 were changed from Developmental and epileptic encephalopathy 34, MIM# 616645; {Epilepsy, idiopathic generalized, susceptibility to, 14}, MIM# 616685 to Developmental and epileptic encephalopathy 34, MIM# 616645; {Epilepsy, idiopathic generalized, susceptibility to, 14}, MIM# 616685
Genetic Epilepsy v0.2602 SLC12A5 Zornitza Stark Phenotypes for gene: SLC12A5 were changed from to Developmental and epileptic encephalopathy 34, MIM# 616645; {Epilepsy, idiopathic generalized, susceptibility to, 14}, MIM# 616685
Genetic Epilepsy v0.2601 SLC12A5 Zornitza Stark Publications for gene: SLC12A5 were set to
Genetic Epilepsy v0.2600 SLC12A5 Zornitza Stark Mode of inheritance for gene: SLC12A5 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.113 ALPL Zornitza Stark Marked gene: ALPL as ready
Osteogenesis Imperfecta and Osteoporosis v0.113 ALPL Zornitza Stark Gene: alpl has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.113 ALPL Zornitza Stark Phenotypes for gene: ALPL were changed from to Hypophosphatasia, adult 146300 (AD, AR); Hypophosphatasia, childhood 241510 AR; Hypophosphatasia, infantile 241500 AR; Odontohypophosphatasia 146300 AD, AR
Osteogenesis Imperfecta and Osteoporosis v0.112 ALPL Zornitza Stark Publications for gene: ALPL were set to
Osteogenesis Imperfecta and Osteoporosis v0.111 ALPL Zornitza Stark Mode of inheritance for gene: ALPL was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Autonomic neuropathy v0.50 DST Zornitza Stark Publications for gene: DST were set to
Autonomic neuropathy v0.49 DST Zornitza Stark Classified gene: DST as Green List (high evidence)
Autonomic neuropathy v0.49 DST Zornitza Stark Gene: dst has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.42 PSMB9 Zornitza Stark Phenotypes for gene: PSMB9 were changed from Proteasome-associated autoinflammatory syndrome 3, digenic, MIM# 617591 to Proteasome-associated autoinflammatory syndrome 3, digenic, MIM# 617591; Proteasome-associated autoinflammatory syndrome 6, MIM# 620796
Autoinflammatory Disorders v1.41 PSMB9 Zornitza Stark edited their review of gene: PSMB9: Changed phenotypes: Proteasome-associated autoinflammatory syndrome 3, digenic, MIM# 617591, Proteasome-associated autoinflammatory syndrome 6, MIM# 620796
Mendeliome v1.1720 PSMB9 Zornitza Stark Phenotypes for gene: PSMB9 were changed from Proteasome-associated autoinflammatory syndrome 3, digenic, MIM# 617591 to Proteasome-associated autoinflammatory syndrome 3, digenic, MIM# 617591; Proteasome-associated autoinflammatory syndrome 6, MIM# 620796
Mendeliome v1.1719 PSMB9 Zornitza Stark edited their review of gene: PSMB9: Changed phenotypes: Proteasome-associated autoinflammatory syndrome 3, digenic, MIM# 617591, Proteasome-associated autoinflammatory syndrome 6, MIM# 620796
Autoinflammatory Disorders v1.41 OTULIN Peter McNaughton reviewed gene: OTULIN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38630025; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5782 SLC1A1 Bryony Thompson Classified gene: SLC1A1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5782 SLC1A1 Bryony Thompson Gene: slc1a1 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy v0.178 TCAP Bryony Thompson Tag disputed tag was added to gene: TCAP.
Hypertrophic cardiomyopathy v0.178 TCAP Bryony Thompson Classified gene: TCAP as Red List (low evidence)
Hypertrophic cardiomyopathy v0.178 TCAP Bryony Thompson Added comment: Comment on list classification: Now DISPUTED gene-disease association by ClinGen Hereditary Cardiovascular Disease GCEP
Hypertrophic cardiomyopathy v0.178 TCAP Bryony Thompson Gene: tcap has been classified as Red List (Low Evidence).
Autonomic neuropathy v0.48 DST Alison Yeung edited their review of gene: DST: Added comment: Since first family published in 2012, there have been two other families published. This is a green gene in the hereditary neuropathy panel.; Changed rating: GREEN; Changed publications: 30371979, 28468842
Rhabdomyolysis and Metabolic Myopathy v1.3 PACSIN3 Zornitza Stark Marked gene: PACSIN3 as ready
Rhabdomyolysis and Metabolic Myopathy v1.3 PACSIN3 Zornitza Stark Gene: pacsin3 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.3 PACSIN3 Zornitza Stark Classified gene: PACSIN3 as Amber List (moderate evidence)
Rhabdomyolysis and Metabolic Myopathy v1.3 PACSIN3 Zornitza Stark Gene: pacsin3 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.2 PACSIN3 Zornitza Stark gene: PACSIN3 was added
gene: PACSIN3 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Literature
Mode of inheritance for gene: PACSIN3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PACSIN3 were set to 38637313
Phenotypes for gene: PACSIN3 were set to Myopathy, MONDO:0005336, PACSIN3-related
Review for gene: PACSIN3 was set to AMBER
Added comment: Two unrelated families with LoF variants, one homozygous. Muscle phenotype including raised CK. Supportive mouse model.
Sources: Literature
Mendeliome v1.1719 PACSIN3 Zornitza Stark Marked gene: PACSIN3 as ready
Mendeliome v1.1719 PACSIN3 Zornitza Stark Gene: pacsin3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1719 PACSIN3 Zornitza Stark Classified gene: PACSIN3 as Amber List (moderate evidence)
Mendeliome v1.1719 PACSIN3 Zornitza Stark Gene: pacsin3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1718 PACSIN3 Zornitza Stark gene: PACSIN3 was added
gene: PACSIN3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PACSIN3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PACSIN3 were set to 38637313
Phenotypes for gene: PACSIN3 were set to Myopathy, MONDO:0005336, PACSIN3-related
Review for gene: PACSIN3 was set to AMBER
Added comment: Two unrelated families with LoF variants, one homozygous. Muscle phenotype including raised CK. Supportive mouse model.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.31 PACSIN3 Zornitza Stark Marked gene: PACSIN3 as ready
Muscular dystrophy and myopathy_Paediatric v1.31 PACSIN3 Zornitza Stark Gene: pacsin3 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.31 PACSIN3 Zornitza Stark Classified gene: PACSIN3 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.31 PACSIN3 Zornitza Stark Gene: pacsin3 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.30 PACSIN3 Zornitza Stark gene: PACSIN3 was added
gene: PACSIN3 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: PACSIN3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PACSIN3 were set to 38637313
Phenotypes for gene: PACSIN3 were set to Myopathy, MONDO:0005336, PACSIN3-related
Review for gene: PACSIN3 was set to AMBER
Added comment: Two unrelated families with LoF variants, one homozygous. Muscle phenotype including raised CK. Supportive mouse model.
Sources: Literature
Angelman Rett like syndromes v1.10 MECP2 Zornitza Stark changed review comment from: Well established gene-disease association, XLD.; to: Well established gene-disease association, XLD.
Metabolic Disorders Superpanel v8.132 Bryony Thompson Changed child panels to: Miscellaneous Metabolic Disorders; Congenital Disorders of Glycosylation; Calcium and Phosphate disorders; Fatty Acid Oxidation Defects; Hypertension and Aldosterone disorders; Lysosomal Storage Disorder; Neurotransmitter Defects; Disorders of branched chain amino acid metabolism; Glycogen Storage Diseases; Rhabdomyolysis and Metabolic Myopathy; Inherited vitamin B12 or cobalamin deficiency; Mitochondrial disease; Peroxisomal Disorders; Monogenic Diabetes; Iron metabolism disorders; Dyslipidaemia; Vitamin C Pathway Disorders; Porphyria; Hyperammonaemia
Intellectual disability syndromic and non-syndromic v0.5781 RNU4-2 Zornitza Stark changed review comment from: Emerging evidence that de novo variants in this gene cause ID.
Sources: Literature; to: Over 100 individuals with ID found to have de novo variants in this gene. Please note difficult to identify on ES.
Sources: Literature
Mendeliome v1.1717 RNU4-2 Zornitza Stark changed review comment from: Emerging evidence that de novo variants in this gene cause ID.
Sources: Literature; to: Over 100 individuals with ID found to have de novo variants in this gene. Please note difficult to identify on ES.
Sources: Literature
Mendeliome v1.1717 RNU4-2 Zornitza Stark Publications for gene: RNU4-2 were set to
Mendeliome v1.1716 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Changed publications: 38645094
Intellectual disability syndromic and non-syndromic v0.5781 RNU4-2 Zornitza Stark Publications for gene: RNU4-2 were set to
Intellectual disability syndromic and non-syndromic v0.5780 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Changed publications: 38645094
Intellectual disability syndromic and non-syndromic v0.5780 MAB21L1 Zornitza Stark reviewed gene: MAB21L1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebellar, ocular, craniofacial, and genital syndrome MIM#618479; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.110 ALPL Chirag Patel reviewed gene: ALPL: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19500388, 23688511; Phenotypes: Hypophosphatasia, adult 146300 (AD, AR), Hypophosphatasia, childhood 241510 AR, Hypophosphatasia, infantile 241500 AR, Odontohypophosphatasia 146300 AD, AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v0.2599 SLC12A5 Sangavi Sivagnanasundram reviewed gene: SLC12A5: Rating: AMBER; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006147; Phenotypes: developmental and epileptic encephalopathy MONDO:0100062; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2599 SERPINI1 Sangavi Sivagnanasundram reviewed gene: SERPINI1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006114; Phenotypes: progressive myoclonus epilepsy MONDO:0020074; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2599 SCN1B Sangavi Sivagnanasundram reviewed gene: SCN1B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19710327, 28218389, 23148524; Phenotypes: Developmental and epileptic encephalopathy (MONDO:0100062), generalized epilepsy with febrile seizures plus (MONDO:0018214); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2599 SCN1A Sangavi Sivagnanasundram reviewed gene: SCN1A: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: generalized epilepsy with febrile seizures plus (MONDO:0018214), Dravet syndrome (MONDO:0100135), developmental and epileptic encephalopathy (MONDO:0100062), familial hemiplegic migraine (MONDO:0000700); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2599 RORB Sangavi Sivagnanasundram reviewed gene: RORB: Rating: ; Mode of pathogenicity: None; Publications: 27352968; Phenotypes: epilepsy MONDO:0005027; Mode of inheritance: None
Genetic Epilepsy v0.2599 NECAP1 Sangavi Sivagnanasundram reviewed gene: NECAP1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 24399846, 30626896; Phenotypes: developmental and epileptic encephalopathy MONDO:0100062; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2599 KCNT1 Sangavi Sivagnanasundram reviewed gene: KCNT1: 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: 23086397, 26725113; Phenotypes: childhood-onset epilepsy syndrome MONDO:0020072; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2599 EFHC1 Sangavi Sivagnanasundram reviewed gene: EFHC1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 31056551, https://search.clinicalgenome.org/CCID:004730; Phenotypes: epilepsy MONDO:0005027; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Progressive Neurological Conditions v16.1 Bryony Thompson Changed child panels to: Early-onset Parkinson disease; Brain Calcification; Hereditary Spastic Paraplegia - paediatric; Hereditary Neuropathy_CMT - isolated; Congenital Disorders of Glycosylation; Miscellaneous Metabolic Disorders; Dystonia - isolated/combined; Limb-Girdle Muscular Dystrophy and Distal Myopathy; Motor Neurone Disease; Ataxia - paediatric; Fatty Acid Oxidation Defects; Early-onset Dementia; Hereditary Neuropathy - complex; Lysosomal Storage Disorder; Ataxia - adult onset; Hereditary Spastic Paraplegia - adult onset; Neurotransmitter Defects; Brain Channelopathies; Glycogen Storage Diseases; Rhabdomyolysis and Metabolic Myopathy; Genetic Epilepsy; Mitochondrial disease; Leukodystrophy - paediatric; Dystonia - complex; Leukodystrophy - adult onset; Peroxisomal Disorders; Cerebral vascular malformations; Iron metabolism disorders; Neurodegeneration with brain iron accumulation; Pain syndromes
Early-onset Parkinson disease v2.0 Bryony Thompson promoted panel to version 2.0
Early-onset Parkinson disease v1.0 Bryony Thompson promoted panel to version 1.0
Early-onset Parkinson disease v0.347 WDR45 Bryony Thompson Marked gene: WDR45 as ready
Early-onset Parkinson disease v0.347 WDR45 Bryony Thompson Gene: wdr45 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.347 WDR45 Bryony Thompson Phenotypes for gene: WDR45 were changed from to X-linked complex neurodevelopmental disorder MONDO:0100148
Early-onset Parkinson disease v0.346 WDR45 Bryony Thompson Publications for gene: WDR45 were set to
Early-onset Parkinson disease v0.345 WDR45 Bryony Thompson Mode of inheritance for gene: WDR45 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)
Early-onset Parkinson disease v0.344 VPS13A Bryony Thompson Marked gene: VPS13A as ready
Early-onset Parkinson disease v0.344 VPS13A Bryony Thompson Gene: vps13a has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.344 VPS13A Bryony Thompson Phenotypes for gene: VPS13A were changed from to chorea-acanthocytosis MONDO:0008695
Early-onset Parkinson disease v0.343 VPS13A Bryony Thompson Publications for gene: VPS13A were set to
Early-onset Parkinson disease v0.342 VPS13A Bryony Thompson Mode of inheritance for gene: VPS13A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.341 TUBB4A Bryony Thompson Mode of inheritance for gene: TUBB4A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.340 TUBB4A Bryony Thompson Marked gene: TUBB4A as ready
Early-onset Parkinson disease v0.340 TUBB4A Bryony Thompson Gene: tubb4a has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.340 TUBB4A Bryony Thompson Classified gene: TUBB4A as Red List (low evidence)
Early-onset Parkinson disease v0.340 TUBB4A Bryony Thompson Added comment: Comment on list classification: More suitable for the dystonia panel
Early-onset Parkinson disease v0.340 TUBB4A Bryony Thompson Gene: tubb4a has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.339 TH Bryony Thompson Marked gene: TH as ready
Early-onset Parkinson disease v0.339 TH Bryony Thompson Gene: th has been classified as Green List (High Evidence).
Motor Neurone Disease v1.21 OPTN Bryony Thompson Marked gene: OPTN as ready
Motor Neurone Disease v1.21 OPTN Bryony Thompson Gene: optn has been classified as Green List (High Evidence).
Motor Neurone Disease v1.21 OPTN Bryony Thompson Phenotypes for gene: OPTN were changed from to Amyotrophic lateral sclerosis 12 with or without frontotemporal dementia (MONDO: 0013264, MIM#613435)
Early-onset Parkinson disease v0.339 TH Bryony Thompson Phenotypes for gene: TH were changed from to Tyrosine hydroxylase deficiency MONDO:0100064
Motor Neurone Disease v1.20 OPTN Bryony Thompson Publications for gene: OPTN were set to
Early-onset Parkinson disease v0.338 TH Bryony Thompson Publications for gene: TH were set to 20301334; 20301610
Motor Neurone Disease v1.19 OPTN Bryony Thompson Mode of inheritance for gene: OPTN was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Early-onset Parkinson disease v0.337 TH Bryony Thompson Publications for gene: TH were set to
Motor Neurone Disease v1.19 OPTN Bryony Thompson Mode of inheritance for gene: OPTN 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 v0.336 TH Bryony Thompson Mode of inheritance for gene: TH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.335 SPR Bryony Thompson Marked gene: SPR as ready
Early-onset Parkinson disease v0.335 SPR Bryony Thompson Gene: spr has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.335 SPR Bryony Thompson Phenotypes for gene: SPR were changed from to Dopa-responsive dystonia due to sepiapterin reductase deficiency MONDO:0012994
Early-onset Parkinson disease v0.334 SPR Bryony Thompson Publications for gene: SPR were set to
Early-onset Parkinson disease v0.333 SPR Bryony Thompson Mode of inheritance for gene: SPR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.332 SLC30A10 Bryony Thompson Marked gene: SLC30A10 as ready
Early-onset Parkinson disease v0.332 SLC30A10 Bryony Thompson Gene: slc30a10 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.332 SLC30A10 Bryony Thompson Mode of inheritance for gene: SLC30A10 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v1.18 UBQLN2 Bryony Thompson Mode of inheritance for gene: UBQLN2 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, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early-onset Parkinson disease v0.332 SLC30A10 Bryony Thompson Mode of inheritance for gene: SLC30A10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v1.18 UBQLN2 Bryony Thompson Mode of inheritance for gene: UBQLN2 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)
Early-onset Parkinson disease v0.331 SLC30A10 Bryony Thompson Publications for gene: SLC30A10 were set to
Early-onset Parkinson disease v0.330 SLC30A10 Bryony Thompson Phenotypes for gene: SLC30A10 were changed from to cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome MONDO:0013208
Early-onset Parkinson disease v0.329 SPG11 Bryony Thompson Marked gene: SPG11 as ready
Early-onset Parkinson disease v0.329 SPG11 Bryony Thompson Gene: spg11 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.329 SPG11 Bryony Thompson Mode of inheritance for gene: SPG11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.328 SPG11 Bryony Thompson Publications for gene: SPG11 were set to
Early-onset Parkinson disease v0.328 SPG11 Bryony Thompson Phenotypes for gene: SPG11 were changed from hereditary spastic paraplegia 11 MONDO:0011445 to hereditary spastic paraplegia 11 MONDO:0011445
Early-onset Parkinson disease v0.327 SPG11 Bryony Thompson Phenotypes for gene: SPG11 were changed from hereditary spastic paraplegia 11 MONDO:0011445 to hereditary spastic paraplegia 11 MONDO:0011445
Early-onset Parkinson disease v0.327 SPG11 Bryony Thompson Phenotypes for gene: SPG11 were changed from to hereditary spastic paraplegia 11 MONDO:0011445
Early-onset Parkinson disease v0.326 RAB39B Bryony Thompson Marked gene: RAB39B as ready
Early-onset Parkinson disease v0.326 RAB39B Bryony Thompson Gene: rab39b has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.326 RAB39B Bryony Thompson Mode of inheritance for gene: RAB39B was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early-onset Parkinson disease v0.325 RAB39B Bryony Thompson Publications for gene: RAB39B were set to
Early-onset Parkinson disease v0.324 RAB39B Bryony Thompson Phenotypes for gene: RAB39B were changed from to Early-onset parkinsonism-intellectual disability syndrome MONDO:0010709
Motor Neurone Disease v1.17 NEFH Bryony Thompson Marked gene: NEFH as ready
Motor Neurone Disease v1.17 NEFH Bryony Thompson Gene: nefh has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.323 PSEN1 Bryony Thompson Marked gene: PSEN1 as ready
Early-onset Parkinson disease v0.323 PSEN1 Bryony Thompson Gene: psen1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.323 PSEN1 Bryony Thompson Mode of inheritance for gene: PSEN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.322 PSEN1 Bryony Thompson Mode of inheritance for gene: PSEN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v1.17 NEFH Bryony Thompson gene: NEFH was added
gene: NEFH was added to Motor Neurone Disease. Sources: ClinGen
Mode of inheritance for gene: NEFH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NEFH were set to amyotrophic lateral sclerosis MONDO:0004976
Review for gene: NEFH was set to RED
Added comment: Limited gene-disease validity classification by ClinGen ALS spectrum disorders GCEP - 23/03/2023
https://search.clinicalgenome.org/CCID:005612
Sources: ClinGen
Early-onset Parkinson disease v0.321 PSEN1 Bryony Thompson Publications for gene: PSEN1 were set to
Early-onset Parkinson disease v0.320 PSEN1 Bryony Thompson Phenotypes for gene: PSEN1 were changed from to Alzheimer disease 3 MONDO:0011913
Early-onset Parkinson disease v0.319 PRKN Bryony Thompson Marked gene: PRKN as ready
Early-onset Parkinson disease v0.319 PRKN Bryony Thompson Gene: prkn has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.319 PRKN Bryony Thompson Phenotypes for gene: PRKN were changed from to autosomal recessive juvenile Parkinson disease 2 MONDO:0010820
Early-onset Parkinson disease v0.318 PRKN Bryony Thompson Mode of inheritance for gene: PRKN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.317 PARK7 Bryony Thompson Marked gene: PARK7 as ready
Early-onset Parkinson disease v0.317 PARK7 Bryony Thompson Gene: park7 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.317 PARK7 Bryony Thompson Phenotypes for gene: PARK7 were changed from to autosomal recessive early-onset Parkinson disease 7 MONDO:0011658
Fetal anomalies v1.236 FOSL2 Zornitza Stark Phenotypes for gene: FOSL2 were changed from Neurodevelopmental disorder, MONDO:0700092, FOSL2-related to Aplasia cutis-enamel dysplasia syndrome, MIM# 620789
Fetal anomalies v1.235 FOSL2 Zornitza Stark reviewed gene: FOSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aplasia cutis-enamel dysplasia syndrome, MIM# 620789; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Growth failure v1.76 FOSL2 Zornitza Stark Phenotypes for gene: FOSL2 were changed from Neurodevelopmental disorder, MONDO:0700092, FOSL2-related to Aplasia cutis-enamel dysplasia syndrome, MIM# 620789
Growth failure v1.75 FOSL2 Zornitza Stark reviewed gene: FOSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aplasia cutis-enamel dysplasia syndrome, MIM# 620789; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ectodermal Dysplasia v0.86 FOSL2 Zornitza Stark Phenotypes for gene: FOSL2 were changed from Neurodevelopmental disorder, MONDO:0700092, FOSL2-related to Aplasia cutis-enamel dysplasia syndrome, MIM# 620789
Ectodermal Dysplasia v0.85 FOSL2 Zornitza Stark reviewed gene: FOSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aplasia cutis-enamel dysplasia syndrome, MIM# 620789; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5780 FOSL2 Zornitza Stark Phenotypes for gene: FOSL2 were changed from Neurodevelopmental disorder, MONDO:0700092, FOSL2-related to Aplasia cutis-enamel dysplasia syndrome, MIM# 620789
Intellectual disability syndromic and non-syndromic v0.5779 FOSL2 Zornitza Stark reviewed gene: FOSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aplasia cutis-enamel dysplasia syndrome, MIM# 620789; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1716 FOSL2 Zornitza Stark Phenotypes for gene: FOSL2 were changed from Neurodevelopmental disorder, MONDO:0700092, FOSL2-related to Aplasia cutis-enamel dysplasia syndrome, MIM# 620789
Mendeliome v1.1715 FOSL2 Zornitza Stark reviewed gene: FOSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aplasia cutis-enamel dysplasia syndrome, MIM# 620789; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.365 FOSL2 Zornitza Stark Phenotypes for gene: FOSL2 were changed from Neurodevelopmental disorder, MONDO:0700092, FOSL2-related to Aplasia cutis-enamel dysplasia syndrome, MIM# 620789
Cataract v0.364 FOSL2 Zornitza Stark reviewed gene: FOSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aplasia cutis-enamel dysplasia syndrome, MIM# 620789; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.316 PARK7 Bryony Thompson Publications for gene: PARK7 were set to
Early-onset Parkinson disease v0.315 PARK7 Bryony Thompson Mode of inheritance for gene: PARK7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v1.16 SETX Bryony Thompson Marked gene: SETX as ready
Motor Neurone Disease v1.16 SETX Bryony Thompson Gene: setx has been classified as Green List (High Evidence).
Motor Neurone Disease v1.16 SETX Bryony Thompson Phenotypes for gene: SETX were changed from to Amyotrophic Lateral Sclerosis 4, juvenile (MIM#602433)
Motor Neurone Disease v1.15 SETX Bryony Thompson Publications for gene: SETX were set to
Motor Neurone Disease v1.14 SETX Bryony Thompson Mode of inheritance for gene: SETX was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.314 ANG Bryony Thompson Marked gene: ANG as ready
Early-onset Parkinson disease v0.314 ANG Bryony Thompson Gene: ang has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.314 ANG Bryony Thompson gene: ANG was added
gene: ANG was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: ANG was set to Unknown
Publications for gene: ANG were set to 33875291; 25386690
Phenotypes for gene: ANG were set to Parkinson disease MONDO:0005180
Review for gene: ANG was set to RED
Added comment: Multiple large studies not finding an association with PD
Sources: Literature
Early-onset Parkinson disease v0.313 FUS Bryony Thompson changed review comment from: A single family reported p.Gln290* segregating (incomplete penetrance) with essential tremor, also two missense variants reported in 2 probands which are too common in gnomAD and have been classified as LB in ClinVar. A reported ET risk variant Met392Ile in a Chinese population - set 1 odds ratio = 4.72 [95% confidence interval = 1.90-11.71], p = 0.0037). Validation set 2 (joint analysis odds ratio = 3.92 [95% confidence interval = 1.57-9.82], p = 8.6 × 10(-4). This variant has been classified as LB in ClinVar.
Sources: Literature; to: A single family reported p.Gln290* segregating (incomplete penetrance) with essential tremor, also two missense variants reported in 2 probands which are too common in gnomAD and have been classified as LB in ClinVar. One of these (Pro431Leu) was also reported in an Italian family. A reported ET risk variant Met392Ile in a Chinese population - set 1 odds ratio = 4.72 [95% confidence interval = 1.90-11.71], p = 0.0037). Validation set 2 (joint analysis odds ratio = 3.92 [95% confidence interval = 1.57-9.82], p = 8.6 × 10(-4). This variant has been classified as LB in ClinVar.
Sources: Literature
Early-onset Parkinson disease v0.313 FUS Bryony Thompson edited their review of gene: FUS: Changed publications: 22863194, 23834483, 23825177, 38626532
Early-onset Parkinson disease v0.313 FUS Bryony Thompson Publications for gene: FUS were set to 22863194
Early-onset Parkinson disease v0.312 FUS Bryony Thompson Marked gene: FUS as ready
Early-onset Parkinson disease v0.312 FUS Bryony Thompson Gene: fus has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.312 FUS Bryony Thompson gene: FUS was added
gene: FUS was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: FUS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FUS were set to 22863194
Phenotypes for gene: FUS were set to tremor, hereditary essential, 4 MONDO:0013888
Review for gene: FUS was set to RED
Added comment: A single family reported p.Gln290* segregating (incomplete penetrance) with essential tremor, also two missense variants reported in 2 probands which are too common in gnomAD and have been classified as LB in ClinVar. A reported ET risk variant Met392Ile in a Chinese population - set 1 odds ratio = 4.72 [95% confidence interval = 1.90-11.71], p = 0.0037). Validation set 2 (joint analysis odds ratio = 3.92 [95% confidence interval = 1.57-9.82], p = 8.6 × 10(-4). This variant has been classified as LB in ClinVar.
Sources: Literature
Early-onset Parkinson disease v0.311 MAPT Bryony Thompson Marked gene: MAPT as ready
Early-onset Parkinson disease v0.311 MAPT Bryony Thompson Gene: mapt has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.311 MAPT Bryony Thompson Phenotypes for gene: MAPT were changed from to late-onset Parkinson disease MONDO:0008199
Early-onset Parkinson disease v0.310 MAPT Bryony Thompson Mode of inheritance for gene: MAPT was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.309 MAPT Bryony Thompson Mode of inheritance for gene: MAPT was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v1.13 FUS Bryony Thompson Marked gene: FUS as ready
Motor Neurone Disease v1.13 FUS Bryony Thompson Gene: fus has been classified as Green List (High Evidence).
Motor Neurone Disease v1.13 FUS Bryony Thompson Phenotypes for gene: FUS were changed from to Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia (MIM#608030)
Early-onset Parkinson disease v0.308 MAPT Bryony Thompson Publications for gene: MAPT were set to
Motor Neurone Disease v1.12 FUS Bryony Thompson Publications for gene: FUS were set to
Motor Neurone Disease v1.11 FUS Bryony Thompson Mode of inheritance for gene: FUS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.307 VCP Bryony Thompson Marked gene: VCP as ready
Early-onset Parkinson disease v0.307 VCP Bryony Thompson Gene: vcp has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.307 VCP Bryony Thompson Classified gene: VCP as Green List (high evidence)
Early-onset Parkinson disease v0.307 VCP Bryony Thompson Gene: vcp has been classified as Green List (High Evidence).
Neurodegeneration with brain iron accumulation v0.35 THAP1 Bryony Thompson Marked gene: THAP1 as ready
Neurodegeneration with brain iron accumulation v0.35 THAP1 Bryony Thompson Gene: thap1 has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.306 VCP Bryony Thompson gene: VCP was added
gene: VCP was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCP were set to 38283104; 38145206
Phenotypes for gene: VCP were set to Inclusion body myopathy with Paget disease of bone and frontotemporal dementia MONDO:0000507
Mode of pathogenicity for gene: VCP was set to Other
Review for gene: VCP was set to GREEN
gene: VCP was marked as current diagnostic
Added comment: Parkinsonism is a rare feature of VCP-related multisystem proteinopathy, but has been reported in at least 15 individuals with VCP variants.
Sources: Literature
Early-onset Parkinson disease v0.305 LYST Bryony Thompson Marked gene: LYST as ready
Early-onset Parkinson disease v0.305 LYST Bryony Thompson Gene: lyst has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.305 LYST Bryony Thompson Publications for gene: LYST were set to
Neurodegeneration with brain iron accumulation v0.35 THAP1 Bryony Thompson Classified gene: THAP1 as Amber List (moderate evidence)
Neurodegeneration with brain iron accumulation v0.35 THAP1 Bryony Thompson Gene: thap1 has been classified as Amber List (Moderate Evidence).
Neurodegeneration with brain iron accumulation v0.34 DDHD1 Bryony Thompson Marked gene: DDHD1 as ready
Neurodegeneration with brain iron accumulation v0.34 DDHD1 Bryony Thompson Gene: ddhd1 has been classified as Red List (Low Evidence).
Neurodegeneration with brain iron accumulation v0.34 DDHD1 Bryony Thompson Classified gene: DDHD1 as Red List (low evidence)
Neurodegeneration with brain iron accumulation v0.34 DDHD1 Bryony Thompson Added comment: Comment on list classification: Only single case reported with iron accumulation
Neurodegeneration with brain iron accumulation v0.34 DDHD1 Bryony Thompson Gene: ddhd1 has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.304 LYST Bryony Thompson Phenotypes for gene: LYST were changed from to Chediak-Higashi syndrome MONDO:0008963
Early-onset Parkinson disease v0.303 LYST Bryony Thompson Mode of inheritance for gene: LYST was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Neurodegeneration with brain iron accumulation v0.33 SQSTM1 Bryony Thompson Marked gene: SQSTM1 as ready
Neurodegeneration with brain iron accumulation v0.33 SQSTM1 Bryony Thompson Gene: sqstm1 has been classified as Red List (Low Evidence).
Neurodegeneration with brain iron accumulation v0.33 SQSTM1 Bryony Thompson Classified gene: SQSTM1 as Red List (low evidence)
Neurodegeneration with brain iron accumulation v0.33 SQSTM1 Bryony Thompson Added comment: Comment on list classification: Only single family reported with iron accumulation
Neurodegeneration with brain iron accumulation v0.33 SQSTM1 Bryony Thompson Gene: sqstm1 has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.302 LYST Bryony Thompson Classified gene: LYST as Green List (high evidence)
Early-onset Parkinson disease v0.302 LYST Bryony Thompson Added comment: Comment on list classification: Parkinsonism is a feature of the condition
Early-onset Parkinson disease v0.302 LYST Bryony Thompson Gene: lyst has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.301 EPM2A Bryony Thompson Publications for gene: EPM2A were set to PMID: 27574708
Early-onset Parkinson disease v0.300 KIF5A Bryony Thompson Phenotypes for gene: KIF5A were changed from to Spastic paraplegia 10, autosomal dominant MIM#604187
Early-onset Parkinson disease v0.299 KIF5A Bryony Thompson Publications for gene: KIF5A were set to
Early-onset Parkinson disease v0.298 KIF5A Bryony Thompson Mode of inheritance for gene: KIF5A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.297 NHLRC1 Bryony Thompson Publications for gene: NHLRC1 were set to PMID: 22425593
Mendeliome v1.1715 KIAA1024L Achchuthan Shanmugasundram gene: KIAA1024L was added
gene: KIAA1024L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIAA1024L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA1024L were set to 35727972
Phenotypes for gene: KIAA1024L were set to Deafness, autosomal recessive 120, OMIM:620238
Review for gene: KIAA1024L was set to GREEN
Added comment: New gene name - MINAR2

PMID:35727972 reported 13 patients from four unrelated families with non-syndromic sensorineural hearing loss. Four of these patients had prelingual onset of severe to profound, progressive bilateral hearing loss. The other nine patients had congenital onset of severe to profound bilateral hearing loss, which was not progressive on one patient, while data was not available for the other.

Three different homozygous variants (c.144G > A/ p.Trp48Ter, c.412_419delCGGTTTTG/ p.Arg138Valfs*10 and c.393G > T/ p.Lys131Asn) were identified in MINAR2/ KIAA1024L gene in these patients.

There is some functional evidence available for the p.Lys131Asn variant. In addition, mice with loss of function of the Minar2 protein present with rapidly progressive sensorineural hearing loss.

This gene has also been associated with relevant phenotype in OMIM (MIM #620238).
Sources: Literature
Pulmonary Arterial Hypertension v1.39 FLNA Zornitza Stark Marked gene: FLNA as ready
Pulmonary Arterial Hypertension v1.39 FLNA Zornitza Stark Gene: flna has been classified as Green List (High Evidence).
Pulmonary Arterial Hypertension v1.39 FLNA Zornitza Stark Classified gene: FLNA as Green List (high evidence)
Pulmonary Arterial Hypertension v1.39 FLNA Zornitza Stark Gene: flna has been classified as Green List (High Evidence).
Pulmonary Arterial Hypertension v1.38 FLNA Zornitza Stark gene: FLNA was added
gene: FLNA was added to Pulmonary Arterial Hypertension. Sources: Expert Review
Mode of inheritance for gene: FLNA 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: FLNA were set to 33143682
Phenotypes for gene: FLNA were set to congenital emphysematous lung disease due to Filamin A loss-of-function variant, MONDO:0800135; Melnick-Needles syndrome, MIM# 309350
Review for gene: FLNA was set to GREEN
Added comment: Severe PAH can be a rare feature of FLNA-related disorders.
Sources: Expert Review
Motor Neurone Disease v1.10 CYLD Zornitza Stark Marked gene: CYLD as ready
Motor Neurone Disease v1.10 CYLD Zornitza Stark Gene: cyld has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1715 CYLD Zornitza Stark Classified gene: CYLD as Green List (high evidence)
Mendeliome v1.1715 CYLD Zornitza Stark Gene: cyld has been classified as Green List (High Evidence).
Mendeliome v1.1714 CYLD Zornitza Stark Classified gene: CYLD as Amber List (moderate evidence)
Mendeliome v1.1714 CYLD Zornitza Stark Gene: cyld has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1713 CYLD Zornitza Stark commented on gene: CYLD: DEFINITIVE by ClinGen for the cutaneous disorder, Brooke-Spiegler syndrome, 605041.
LIMITED for FTD/ALS -- rated as Amber due to multiple affected individuals and experimental data.
Motor Neurone Disease v1.10 CYLD Zornitza Stark Marked gene: CYLD as ready
Motor Neurone Disease v1.10 CYLD Zornitza Stark Gene: cyld has been classified as Amber List (Moderate Evidence).
Incidentalome v0.301 SS18L1 Zornitza Stark Marked gene: SS18L1 as ready
Incidentalome v0.301 SS18L1 Zornitza Stark Gene: ss18l1 has been classified as Amber List (Moderate Evidence).
Incidentalome v0.301 SS18L1 Zornitza Stark Classified gene: SS18L1 as Amber List (moderate evidence)
Incidentalome v0.301 SS18L1 Zornitza Stark Gene: ss18l1 has been classified as Amber List (Moderate Evidence).
Incidentalome v0.300 SS18L1 Zornitza Stark gene: SS18L1 was added
gene: SS18L1 was added to Incidentalome. Sources: Expert Review
Mode of inheritance for gene: SS18L1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SS18L1 were set to 25888396; 24360741; 23708140; 30976389
Phenotypes for gene: SS18L1 were set to amyotrophic lateral sclerosis (MONDO:0004976)
Review for gene: SS18L1 was set to AMBER
Added comment: ClinGen has curated as LIMITED:

There are 5 variants (one nonsense, three missense, and one in-frame del) that have been reported in 5 probands in 3 publications (PMIDs: 23708140, 24360741, 31522742) that are included in this curation, one of which was not scored due to the patient harboring a variant in another ALS-causing gene and a high minor allele frequency in population databases. ALS-associated SS18L1 variants are suggested to dysregulate neuronal function by inhibiting dendrite outgrowth and microglial activation through a dominant-negative mechanism, however there is an absence of functional data from primary tissue of SS18L1 mutation carriers. This gene-disease relationship is also supported by experimental evidence (mouse models, expression, and protein interactions; PMIDs: 30976389, 14716005, 23708140). CREST knockout (Crest +/− ) and Q394X knock-in mice generated through CRISPR/Cas9 system displayed deficits in motor coordination and partially recapitulated ALS phenotypes (PMID: 30976389). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship.
Sources: Expert Review
Motor Neurone Disease v1.10 SS18L1 Zornitza Stark Phenotypes for gene: SS18L1 were changed from amyotrophic lateral sclerosis to amyotrophic lateral sclerosis (MONDO:0004976)
Motor Neurone Disease v1.9 SS18L1 Zornitza Stark Classified gene: SS18L1 as Amber List (moderate evidence)
Motor Neurone Disease v1.9 SS18L1 Zornitza Stark Gene: ss18l1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1713 MARS Zornitza Stark Mode of inheritance for gene: MARS was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1712 MARS Zornitza Stark edited their review of gene: MARS: Added comment: The mono-allelic gene-disease associations have LIMITED evidence.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Vascular Malformations_Somatic v1.13 PIK3R1 Bryony Thompson Phenotypes for gene: PIK3R1 were changed from capillary and lymphatic malformation to capillary malformation MONDO:0016231, PIK3R1-related
Vascular Malformations_Somatic v1.12 PIK3R1 Bryony Thompson Publications for gene: PIK3R1 were set to 29174369
Vascular Malformations_Somatic v1.11 PIK3R1 Bryony Thompson Classified gene: PIK3R1 as Green List (high evidence)
Vascular Malformations_Somatic v1.11 PIK3R1 Bryony Thompson Gene: pik3r1 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v1.10 PIK3R1 Bryony Thompson edited their review of gene: PIK3R1: Added comment: Many reports now of somatic variants in individuals with capillary malformation with dilated veins. Loss of function is the expected mechanism of malformation formation.; Changed rating: GREEN; Changed publications: 29174369, 34040190, 37641480, 38431221
Mendeliome v1.1712 PMP2 Zornitza Stark Mode of pathogenicity for gene: PMP2 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v1.1711 PMP2 Zornitza Stark Classified gene: PMP2 as Amber List (moderate evidence)
Mendeliome v1.1711 PMP2 Zornitza Stark Gene: pmp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1710 PMP2 Zornitza Stark reviewed gene: PMP2: Rating: AMBER; 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: 26257172, 27009151, 30249361, 31412900, 26828946, 32277537; Phenotypes: Charcot-Marie-Tooth disease, demyelinating, type 1G, 618279; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v1.111 ELANE Zornitza Stark Mode of pathogenicity for gene: ELANE 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
Genomic newborn screening: BabyScreen+ v1.110 ELANE Zornitza Stark commented on gene: ELANE: ClinGen: there is little evidence for haploinsufficiency. gnomAD pLI score is zero and there are NMD predicted variants in the population.

Entire gene deletion is not described in the context of neutropenia, including deletion of 19p terminal (encompassing ELANE) (PMID: 33968054).

Maturation arrest, the failure of the marrow myeloid progenitors to form mature neutrophils, is a consistent feature of ELANE associated congenital neutropenia. Knock-out of the mutant allele in hematopoietic stem cells derived from SCN patients restores neutrophils maturation (PMID: 3124897).
Genomic newborn screening: BabyScreen+ v1.110 ELANE Zornitza Stark edited their review of gene: ELANE: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
IBMDx study v0.23 ELANE Zornitza Stark Marked gene: ELANE as ready
IBMDx study v0.23 ELANE Zornitza Stark Gene: elane has been classified as Green List (High Evidence).
IBMDx study v0.23 ELANE Zornitza Stark Publications for gene: ELANE were set to
IBMDx study v0.22 ELANE Zornitza Stark Mode of pathogenicity for gene: ELANE 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
IBMDx study v0.21 ELANE Zornitza Stark Mode of inheritance for gene: ELANE was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
IBMDx study v0.20 ELANE Zornitza Stark edited their review of gene: ELANE: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Autoinflammatory Disorders v1.41 ELANE Zornitza Stark Mode of pathogenicity for gene: ELANE was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Autoinflammatory Disorders v1.40 ELANE Zornitza Stark edited their review of gene: ELANE: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Phagocyte Defects v1.26 ELANE Zornitza Stark Mode of pathogenicity for gene: ELANE was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Phagocyte Defects v1.25 ELANE Zornitza Stark edited their review of gene: ELANE: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v1.1710 ELANE Zornitza Stark Publications for gene: ELANE were set to 19036076
Mendeliome v1.1709 ELANE Zornitza Stark Mode of pathogenicity for gene: ELANE was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v1.1708 ELANE Zornitza Stark edited their review of gene: ELANE: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Bone Marrow Failure v1.89 ELANE Zornitza Stark Mode of pathogenicity for gene: ELANE was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Bone Marrow Failure v1.88 ELANE Zornitza Stark edited their review of gene: ELANE: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Early-onset Parkinson disease v0.296 LRRK2 Zornitza Stark Mode of inheritance for gene: LRRK2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Regression v0.551 ABCD1 Zornitza Stark Marked gene: ABCD1 as ready
Regression v0.551 ABCD1 Zornitza Stark Gene: abcd1 has been classified as Green List (High Evidence).
Regression v0.551 ABCD1 Zornitza Stark Phenotypes for gene: ABCD1 were changed from to adrenoleukodystrophy (MONDO:0018544)
Regression v0.550 ABCD1 Zornitza Stark Publications for gene: ABCD1 were set to
Regression v0.549 ABCD1 Zornitza Stark Mode of inheritance for gene: ABCD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Regression v0.548 ABCD1 Zornitza Stark reviewed gene: ABCD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15811009, 8651290, 7825602, 21700483; Phenotypes: adrenoleukodystrophy (MONDO:0018544); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Peroxisomal Disorders v0.53 ABCD1 Zornitza Stark Marked gene: ABCD1 as ready
Peroxisomal Disorders v0.53 ABCD1 Zornitza Stark Gene: abcd1 has been classified as Green List (High Evidence).
Peroxisomal Disorders v0.53 ABCD1 Zornitza Stark Publications for gene: ABCD1 were set to 15811009; 8651290; 7825602; 21700483
Peroxisomal Disorders v0.52 ABCD1 Zornitza Stark Publications for gene: ABCD1 were set to 15811009; 8651290; 7825602, 21700483
Peroxisomal Disorders v0.51 ABCD1 Zornitza Stark Publications for gene: ABCD1 were set to
Peroxisomal Disorders v0.50 ABCD1 Zornitza Stark Phenotypes for gene: ABCD1 were changed from to adrenoleukodystrophy (MONDO:0018544)
Peroxisomal Disorders v0.49 ABCD1 Zornitza Stark Mode of inheritance for gene: ABCD1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Peroxisomal Disorders v0.48 ABCD1 Zornitza Stark Mode of inheritance for gene: ABCD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v1.235 CNOT1 Zornitza Stark Classified gene: CNOT1 as Amber List (moderate evidence)
Fetal anomalies v1.235 CNOT1 Zornitza Stark Gene: cnot1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.234 CNOT1 Zornitza Stark edited their review of gene: CNOT1: Added comment: LIMITED by ClinGen for holoprosencephaly 12 with or without pancreatic agenesis, MONDO:0032787

ClinGen curation: CNOT1 was originally reported in cases of holoprosencephaly and/or pancreatic agenesis/insufficiency in 2019 (PMID: 31006513, 31006510). One of the papers included 3 individuals with heterozygous p.Arg535Cys (PMID: 31006513), confirmed to be de novo in 2 individuals. One of these individuals was not scored due to a lack of documentation of holoprosencephaly. The other paper included 2 individuals with de novo p.Arg535Cys, both of whom with holoprosencephaly. A knock-in mouse model of this variant showed neurological and pancreatic abnormalities at E14.5, and this evidence was used to augment the genetic evidence. A mouse brain expression study (PMID: 31006510) was scored as functional evidence. In total, there is Limited evidence to support the gene-disease relationship between CNOT1 and holoprosencephaly with or without pancreatic agenesis. Of note, this gene has also been implicated in Vissers-Bodmer syndrome, which is characterized by global developmental delay and behavioral abnormalities apparent from infancy. As the condition is clinically distinct from holoprosencephaly and/or pancreatic agenesis/insufficiency, lacks specific structural brain anomalies, and likely has different molecular mechanisms, this will be/have been assessed separately.; Changed rating: AMBER; Changed phenotypes: Holoprosencephaly 12 with or without pancreatic agenesis MONDO:0032787
Holoprosencephaly and septo-optic dysplasia v1.16 CNOT1 Zornitza Stark Phenotypes for gene: CNOT1 were changed from Holoprosencephaly 12 with or without pancreatic agenesis MONDO:0032787 to Holoprosencephaly 12 with or without pancreatic agenesis MONDO:0032787
Holoprosencephaly and septo-optic dysplasia v1.16 CNOT1 Zornitza Stark Phenotypes for gene: CNOT1 were changed from HOLOPROSENCEPHALY 12 WITH OR WITHOUT PANCREATIC AGENESIS; HPE12; OMIM# 618500 to Holoprosencephaly 12 with or without pancreatic agenesis MONDO:0032787
Holoprosencephaly and septo-optic dysplasia v1.15 CNOT1 Zornitza Stark Classified gene: CNOT1 as Amber List (moderate evidence)
Holoprosencephaly and septo-optic dysplasia v1.15 CNOT1 Zornitza Stark Gene: cnot1 has been classified as Amber List (Moderate Evidence).
Holoprosencephaly and septo-optic dysplasia v1.14 CNOT1 Zornitza Stark edited their review of gene: CNOT1: Changed rating: AMBER
Holoprosencephaly and septo-optic dysplasia v1.14 CNOT1 Zornitza Stark edited their review of gene: CNOT1: Added comment: LIMITED by ClinGen for holoprosencephaly 12 with or without pancreatic agenesis, MONDO:0032787

ClinGen curation:
CNOT1 was originally reported in cases of holoprosencephaly and/or pancreatic agenesis/insufficiency in 2019 (PMID: 31006513, 31006510). One of the papers included 3 individuals with heterozygous p.Arg535Cys (PMID: 31006513), confirmed to be de novo in 2 individuals. One of these individuals was not scored due to a lack of documentation of holoprosencephaly. The other paper included 2 individuals with de novo p.Arg535Cys, both of whom with holoprosencephaly. A knock-in mouse model of this variant showed neurological and pancreatic abnormalities at E14.5, and this evidence was used to augment the genetic evidence. A mouse brain expression study (PMID: 31006510) was scored as functional evidence. In total, there is Limited evidence to support the gene-disease relationship between CNOT1 and holoprosencephaly with or without pancreatic agenesis. Of note, this gene has also been implicated in Vissers-Bodmer syndrome, which is characterized by global developmental delay and behavioral abnormalities apparent from infancy. As the condition is clinically distinct from holoprosencephaly and/or pancreatic agenesis/insufficiency, lacks specific structural brain anomalies, and likely has different molecular mechanisms, this will be/have been assessed separately.; Changed phenotypes: Holoprosencephaly 12 with or without pancreatic agenesis MONDO:0032787
Mendeliome v1.1708 CNOT1 Zornitza Stark commented on gene: CNOT1: DEFINITIVE by ClinGen for Neurodevelopmental disorder.
Mendeliome v1.1708 SHARPIN Zornitza Stark Marked gene: SHARPIN as ready
Mendeliome v1.1708 SHARPIN Zornitza Stark Gene: sharpin has been classified as Green List (High Evidence).
Mendeliome v1.1708 SHARPIN Zornitza Stark Classified gene: SHARPIN as Green List (high evidence)
Mendeliome v1.1708 SHARPIN Zornitza Stark Gene: sharpin has been classified as Green List (High Evidence).
Mendeliome v1.1707 SHARPIN Zornitza Stark gene: SHARPIN was added
gene: SHARPIN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SHARPIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHARPIN were set to 38609546
Phenotypes for gene: SHARPIN were set to Autoinflammatory syndrome, MONDO:0019751, SHARPIN-related
Review for gene: SHARPIN was set to GREEN
Added comment: Two unrelated patients with homozygous frameshift variants presenting with: P1 - recurrent fever, parotitis, joint inflammation, colitis and chronic otitis media necessitating tympanoplasty P2 - recurrent fever episodes with lymphadenopathy and vomiting every 2–3 weeks. Extensive functional data and mouse model.
Sources: Literature
Autoinflammatory Disorders v1.40 SHARPIN Zornitza Stark Marked gene: SHARPIN as ready
Autoinflammatory Disorders v1.40 SHARPIN Zornitza Stark Gene: sharpin has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.40 SHARPIN Zornitza Stark Phenotypes for gene: SHARPIN were changed from recurrent fever to Autoinflammatory syndrome, MONDO:0019751, SHARPIN-related
Autoinflammatory Disorders v1.39 SHARPIN Zornitza Stark Classified gene: SHARPIN as Green List (high evidence)
Autoinflammatory Disorders v1.39 SHARPIN Zornitza Stark Gene: sharpin has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.38 SHARPIN Zornitza Stark reviewed gene: SHARPIN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoinflammatory syndrome, MONDO:0019751, SHARPIN-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1706 RTN2 Zornitza Stark Phenotypes for gene: RTN2 were changed from Spastic paraplegia 12, autosomal dominant, 604805; MONDO:0011489 to Spastic paraplegia 12, autosomal dominant, 604805; MONDO:0011489; distal hereditary motor neuropathy, MONDO:0018894
Mendeliome v1.1705 RTN2 Zornitza Stark Publications for gene: RTN2 were set to 22232211; 27165006
Mendeliome v1.1704 RTN2 Zornitza Stark Mode of inheritance for gene: RTN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Autoinflammatory Disorders v1.38 PTCRA Zornitza Stark Marked gene: PTCRA as ready
Autoinflammatory Disorders v1.38 PTCRA Zornitza Stark Gene: ptcra has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.38 PTCRA Zornitza Stark Classified gene: PTCRA as Green List (high evidence)
Autoinflammatory Disorders v1.38 PTCRA Zornitza Stark Gene: ptcra has been classified as Green List (High Evidence).
Autoinflammatory Disorders v1.37 PTCRA Zornitza Stark gene: PTCRA was added
gene: PTCRA was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: PTCRA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTCRA were set to 38422122
Phenotypes for gene: PTCRA were set to Autoinflammatory syndrome, MONDO:0019751, PTCRA-related
Review for gene: PTCRA was set to GREEN
Added comment: PMID:38422122 reported the identification of 10 individuals from seven kindreds from four different ethnicities with biallelic PTCRA variants (homozygous in five kindreds and compound heterozygous in two kindreds).

Six of these 10 patients were clinically asymptomatic at their most recent evaluation, while other four patients displayed infection, lymphoproliferation, and/or autoimmunity with an onset during their teens or in adulthood. One of these patients died from SARS-CoV-2 pneumonia at the age of 24 years. Patient 9 had a small thymus on MRI at the age of 2 years, whereas P5 and P6 had no visible thymus at the ages of 13 and 8 years, respectively. Three of the nine patients with pLOF PTCRA variants tested were found to produce autoantibodies, several of which were associated with clinical manifestations. Anti-thyroid autoantibodies and/or clinically overt thyroiditis were found in three of the nine patients. P7, who suffered from recurrent herpes infections, had autoantibodies against type I interferons.

Two of those identified variants are hypomorphic and are associated with autoimmunity. In addition, there is extensive functional and epidemiological data available.
Sources: Literature
Mendeliome v1.1703 PTCRA Zornitza Stark Marked gene: PTCRA as ready
Mendeliome v1.1703 PTCRA Zornitza Stark Gene: ptcra has been classified as Green List (High Evidence).
Mendeliome v1.1703 PTCRA Zornitza Stark Phenotypes for gene: PTCRA were changed from Autoimmunity, HP:0002960; lymphopenia, MONDO:0003783 to Autoinflammatory syndrome, MONDO:0019751, PTCRA-related
Mendeliome v1.1702 PTCRA Zornitza Stark Classified gene: PTCRA as Green List (high evidence)
Mendeliome v1.1702 PTCRA Zornitza Stark Gene: ptcra has been classified as Green List (High Evidence).
Mendeliome v1.1701 PTCRA Zornitza Stark reviewed gene: PTCRA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoinflammatory syndrome, MONDO:0019751, PTCRA-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinitis pigmentosa v0.136 SLC37A3 Zornitza Stark Marked gene: SLC37A3 as ready
Retinitis pigmentosa v0.136 SLC37A3 Zornitza Stark Gene: slc37a3 has been classified as Green List (High Evidence).
Retinitis pigmentosa v0.136 SLC37A3 Zornitza Stark Classified gene: SLC37A3 as Green List (high evidence)
Retinitis pigmentosa v0.136 SLC37A3 Zornitza Stark Gene: slc37a3 has been classified as Green List (High Evidence).
Retinitis pigmentosa v0.135 SLC37A3 Zornitza Stark gene: SLC37A3 was added
gene: SLC37A3 was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: Literature
Mode of inheritance for gene: SLC37A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC37A3 were set to 28041643; 35486108
Phenotypes for gene: SLC37A3 were set to Retinitis pigmentosa, MONDO:0019200, SLC37A3-related
Review for gene: SLC37A3 was set to GREEN
Added comment: Three unrelated cases reported with biallelic variants in SLC37A3 gene (One case in PMID:28041643 and two cases in PMID:35486108) and with autosomal recessive retinitis pigmentosa.
Sources: Literature
Mendeliome v1.1701 SLC37A3 Zornitza Stark Marked gene: SLC37A3 as ready
Mendeliome v1.1701 SLC37A3 Zornitza Stark Gene: slc37a3 has been classified as Green List (High Evidence).
Mendeliome v1.1701 SLC37A3 Zornitza Stark Classified gene: SLC37A3 as Green List (high evidence)
Mendeliome v1.1701 SLC37A3 Zornitza Stark Gene: slc37a3 has been classified as Green List (High Evidence).
Mendeliome v1.1700 CADM3 Zornitza Stark Publications for gene: CADM3 were set to PMID: 33889941
Mendeliome v1.1699 CADM3 Zornitza Stark Classified gene: CADM3 as Green List (high evidence)
Mendeliome v1.1699 CADM3 Zornitza Stark Gene: cadm3 has been classified as Green List (High Evidence).
Mendeliome v1.1698 CADM3 Zornitza Stark edited their review of gene: CADM3: Added comment: Two additional families reported with a different variant, de novo in one family.; Changed rating: GREEN; Changed publications: 38074074
Genetic Epilepsy v0.2599 CLCN2 Zornitza Stark Tag disputed was removed from gene: CLCN2.
Tag refuted tag was added to gene: CLCN2.
Mendeliome v1.1698 EMILIN1 Chern Lim reviewed gene: EMILIN1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuronopathy, distal hereditary motor, autosomal dominant 10, MIM#620080, Aortic aneurysm, MONDO:0005160, EMILIN1-related, AR.; Mode of inheritance: None
Aortopathy_Connective Tissue Disorders v1.84 EMILIN1 Chern Lim reviewed gene: EMILIN1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuronopathy, distal hereditary motor, autosomal dominant 10, MIM#620080, Aortic aneurysm, MONDO:0005160, EMILIN1-related, AR.; Mode of inheritance: None
Genetic Epilepsy v0.2599 CLCN2 Sangavi Sivagnanasundram reviewed gene: CLCN2: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004463; Phenotypes: epilepsy (MONDO:0005027); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe early-onset obesity v1.10 ACBD6 Zornitza Stark Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder (MONDO#0700092), ACBD6-related to Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785
Severe early-onset obesity v1.9 ACBD6 Zornitza Stark reviewed gene: ACBD6: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia and Chorea v0.235 ACBD6 Zornitza Stark Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder (MONDO#0700092), ACBD6-related to Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785
Dystonia and Chorea v0.234 ACBD6 Zornitza Stark reviewed gene: ACBD6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v1.19 ACBD6 Zornitza Stark Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder (MONDO#0700092), ACBD6-related to Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785
Ataxia v1.18 ACBD6 Zornitza Stark reviewed gene: ACBD6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5779 ACBD6 Zornitza Stark Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder (MONDO#0700092), ACBD6-related to Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785
Intellectual disability syndromic and non-syndromic v0.5778 ACBD6 Zornitza Stark reviewed gene: ACBD6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1698 ACBD6 Zornitza Stark Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder (MONDO#0700092), ACBD6-related to Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785
Mendeliome v1.1697 ACBD6 Zornitza Stark reviewed gene: ACBD6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Angelman Rett like syndromes v1.10 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Intellectual disability syndromic and non-syndromic v0.5778 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Intellectual disability syndromic and non-syndromic v0.5778 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Genetic Epilepsy v0.2599 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Autism v0.198 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Autism v0.198 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Mendeliome v1.1697 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Mendeliome v1.1696 SLC37A3 Achchuthan Shanmugasundram gene: SLC37A3 was added
gene: SLC37A3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC37A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC37A3 were set to 28041643; 35486108
Phenotypes for gene: SLC37A3 were set to retinitis pigmentosa, MONDO:0019200
Review for gene: SLC37A3 was set to GREEN
Added comment: Three unrelated cases reported with biallelic variants in SLC37A3 gene (One case in PMID:28041643 and two cases in PMID:35486108) and with autosomal recessive retinitis pigmentosa.
Sources: Literature
Mendeliome v1.1696 PTCRA Achchuthan Shanmugasundram gene: PTCRA was added
gene: PTCRA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTCRA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTCRA were set to 38422122
Phenotypes for gene: PTCRA were set to Autoimmunity, HP:0002960; lymphopenia, MONDO:0003783
Review for gene: PTCRA was set to GREEN
Added comment: PMID:38422122 reported the identification of 10 individuals from seven kindreds from four different ethnicities with biallelic PTCRA variants (homozygous in five kindreds and compound heterozygous in two kindreds).

Six of these 10 patients were clinically asymptomatic at their most recent evaluation, while other four patients displayed infection, lymphoproliferation, and/or autoimmunity with an onset during their teens or in adulthood. One of these patients died from SARS-CoV-2 pneumonia at the age of 24 years. Patient 9 had a small thymus on MRI at the age of 2 years, whereas P5 and P6 had no visible thymus at the ages of 13 and 8 years, respectively. Three of the nine patients with pLOF PTCRA variants tested were found to produce autoantibodies, several of which were associated with clinical manifestations. Anti-thyroid autoantibodies and/or clinically overt thyroiditis were found in three of the nine patients. P7, who suffered from recurrent herpes infections, had autoantibodies against type I interferons.

Two of those identified variants are hypomorphic and are associated with autoimmunity. In addition, there is extensive functional and epidemiological data available.
Sources: Literature
Regression v0.548 NAA60 Zornitza Stark Phenotypes for gene: NAA60 were changed from Basal ganglia calcification, MONDO:0008947, NAA60-related to Basal ganglia calcification, idiopathic, 9, autosomal recessive, MIM# 620786
Regression v0.547 NAA60 Zornitza Stark edited their review of gene: NAA60: Changed phenotypes: Basal ganglia calcification, idiopathic, 9, autosomal recessive, MIM# 620786
Mendeliome v1.1696 NAA60 Zornitza Stark Phenotypes for gene: NAA60 were changed from Basal ganglia calcification, MONDO:0008947, NAA60-related to Basal ganglia calcification, idiopathic, 9, autosomal recessive, MIM# 620786
Mendeliome v1.1695 NAA60 Zornitza Stark reviewed gene: NAA60: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Basal ganglia calcification, idiopathic, 9, autosomal recessive, MIM# 620786; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.95 NAA60 Zornitza Stark Phenotypes for gene: NAA60 were changed from Basal ganglia calcification, MONDO:0008947, NAA60-related to Basal ganglia calcification, idiopathic, 9, autosomal recessive, MIM# 620786
Brain Calcification v1.94 NAA60 Zornitza Stark reviewed gene: NAA60: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Basal ganglia calcification, idiopathic, 9, autosomal recessive, MIM# 620786; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1695 RTN2 Achchuthan Shanmugasundram changed review comment from: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.; to: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain, and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Mendeliome v1.1695 RTN2 Achchuthan Shanmugasundram changed review comment from: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals (seven males and seven females, aged 9-50 years) exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.; to: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Mendeliome v1.1695 RTN2 Achchuthan Shanmugasundram reviewed gene: RTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38527963; Phenotypes: distal hereditary motor neuropathy, MONDO:0018894; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2598 PEX19 Zornitza Stark Marked gene: PEX19 as ready
Genetic Epilepsy v0.2598 PEX19 Zornitza Stark Gene: pex19 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2598 PEX19 Zornitza Stark Phenotypes for gene: PEX19 were changed from to Peroxisome biogenesis disorder 12A (Zellweger) - MIM#614886
Genetic Epilepsy v0.2597 PEX19 Zornitza Stark Publications for gene: PEX19 were set to
Genetic Epilepsy v0.2596 PEX19 Zornitza Stark Mode of inheritance for gene: PEX19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2595 PEX19 Zornitza Stark reviewed gene: PEX19: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 12A (Zellweger) - MIM#614886; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2595 PEX12 Zornitza Stark Marked gene: PEX12 as ready
Genetic Epilepsy v0.2595 PEX12 Zornitza Stark Gene: pex12 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2595 PEX12 Zornitza Stark Phenotypes for gene: PEX12 were changed from to Peroxisome biogenesis disorder 3A (Zellweger) - MIM#614859; Peroxisome biogenesis disorder 3B - MIM#266510
Genetic Epilepsy v0.2594 PEX12 Zornitza Stark Mode of inheritance for gene: PEX12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2593 PEX12 Zornitza Stark reviewed gene: PEX12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 3A (Zellweger) - MIM#614859, Peroxisome biogenesis disorder 3B - MIM#266510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2593 PEX1 Zornitza Stark Marked gene: PEX1 as ready
Genetic Epilepsy v0.2593 PEX1 Zornitza Stark Gene: pex1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2593 PEX1 Zornitza Stark Phenotypes for gene: PEX1 were changed from to Peroxisome biogenesis disorder 1A (Zellweger) 214100
Genetic Epilepsy v0.2592 PEX1 Zornitza Stark Publications for gene: PEX1 were set to
Genetic Epilepsy v0.2591 PEX1 Zornitza Stark Mode of inheritance for gene: PEX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2590 PEX1 Zornitza Stark reviewed gene: PEX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 1A (Zellweger) 214100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2590 PDHX Zornitza Stark Marked gene: PDHX as ready
Genetic Epilepsy v0.2590 PDHX Zornitza Stark Gene: pdhx has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2590 PDHX Zornitza Stark Phenotypes for gene: PDHX were changed from to Lactic acidaemia due to PDX1 deficiency MIM#245349
Genetic Epilepsy v0.2589 PDHX Zornitza Stark Publications for gene: PDHX were set to
Genetic Epilepsy v0.2588 PDHX Zornitza Stark Mode of inheritance for gene: PDHX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2587 PDHX Zornitza Stark reviewed gene: PDHX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lactic acidaemia due to PDX1 deficiency MIM#245349; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2587 PDHA1 Zornitza Stark Marked gene: PDHA1 as ready
Genetic Epilepsy v0.2587 PDHA1 Zornitza Stark Gene: pdha1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2587 PDHA1 Zornitza Stark Phenotypes for gene: PDHA1 were changed from to Pyruvate dehydrogenase E1-alpha deficiency - MIM#312170
Genetic Epilepsy v0.2586 PDHA1 Zornitza Stark Publications for gene: PDHA1 were set to
Genetic Epilepsy v0.2585 PDHA1 Zornitza Stark Mode of inheritance for gene: PDHA1 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)
Genetic Epilepsy v0.2584 PDHA1 Zornitza Stark reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pyruvate dehydrogenase E1-alpha deficiency - MIM#312170; 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 v0.2584 PCDH12 Zornitza Stark Marked gene: PCDH12 as ready
Genetic Epilepsy v0.2584 PCDH12 Zornitza Stark Gene: pcdh12 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2584 PCDH12 Zornitza Stark Phenotypes for gene: PCDH12 were changed from to Diencephalic-mesencephalic junction dysplasia syndrome 1, MIM# 251280
Genetic Epilepsy v0.2583 PCDH12 Zornitza Stark Publications for gene: PCDH12 were set to
Genetic Epilepsy v0.2582 PCDH12 Zornitza Stark Mode of inheritance for gene: PCDH12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2581 PCCB Zornitza Stark Marked gene: PCCB as ready
Genetic Epilepsy v0.2581 PCCB Zornitza Stark Gene: pccb has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2581 PCCB Zornitza Stark Phenotypes for gene: PCCB were changed from to Propionicacidemia - MIM#606054
Genetic Epilepsy v0.2580 PCCB Zornitza Stark Publications for gene: PCCB were set to
Genetic Epilepsy v0.2579 PCCB Zornitza Stark Mode of inheritance for gene: PCCB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2578 PCCB Zornitza Stark reviewed gene: PCCB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Propionicacidemia - MIM#606054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2578 PCCA Zornitza Stark Marked gene: PCCA as ready
Genetic Epilepsy v0.2578 PCCA Zornitza Stark Gene: pcca has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2578 PCCA Zornitza Stark Phenotypes for gene: PCCA were changed from to Propionicacidemia - MIM#606054
Genetic Epilepsy v0.2577 PCCA Zornitza Stark Publications for gene: PCCA were set to
Genetic Epilepsy v0.2576 PCCA Zornitza Stark Mode of inheritance for gene: PCCA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2575 PCCA Zornitza Stark reviewed gene: PCCA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Propionicacidemia - MIM#606054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2575 OTUD6B Zornitza Stark Marked gene: OTUD6B as ready
Genetic Epilepsy v0.2575 OTUD6B Zornitza Stark Gene: otud6b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2575 OTUD6B Zornitza Stark Phenotypes for gene: OTUD6B were changed from to Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, OMIM #617452
Genetic Epilepsy v0.2574 OTUD6B Zornitza Stark Publications for gene: OTUD6B were set to
Genetic Epilepsy v0.2573 OTUD6B Zornitza Stark Mode of inheritance for gene: OTUD6B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2572 OPHN1 Zornitza Stark Marked gene: OPHN1 as ready
Genetic Epilepsy v0.2572 OPHN1 Zornitza Stark Gene: ophn1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2572 OPHN1 Zornitza Stark Phenotypes for gene: OPHN1 were changed from to Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance, MIM#300486
Genetic Epilepsy v0.2571 OPHN1 Zornitza Stark Publications for gene: OPHN1 were set to
Genetic Epilepsy v0.2570 OPHN1 Zornitza Stark Mode of inheritance for gene: OPHN1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.2569 OPHN1 Zornitza Stark changed review comment from: OPHN1 variants cause cerebellar hypoplasia and distinctive facial appearance, macrocephaly is a feature. At least 8 families reported.; to: OPHN1 variants cause cerebellar hypoplasia and distinctive facial appearance, macrocephaly is a feature. At least 8 families reported.

Seizures are a feature.
Genetic Epilepsy v0.2569 OCLN Zornitza Stark Marked gene: OCLN as ready
Genetic Epilepsy v0.2569 OCLN Zornitza Stark Gene: ocln has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2569 OCLN Zornitza Stark Phenotypes for gene: OCLN were changed from to Pseudo-TORCH syndrome 1, MIM#251290
Genetic Epilepsy v0.2568 OCLN Zornitza Stark Publications for gene: OCLN were set to
Genetic Epilepsy v0.2567 OCLN Zornitza Stark Mode of inheritance for gene: OCLN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2566 NSD1 Zornitza Stark Marked gene: NSD1 as ready
Genetic Epilepsy v0.2566 NSD1 Zornitza Stark Gene: nsd1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2566 NSD1 Zornitza Stark Phenotypes for gene: NSD1 were changed from to Sotos syndrome 1 (MIM#117550), AD
Genetic Epilepsy v0.2565 NSD1 Zornitza Stark Publications for gene: NSD1 were set to
Genetic Epilepsy v0.2564 NSD1 Zornitza Stark Mode of inheritance for gene: NSD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2563 NSD1 Zornitza Stark reviewed gene: NSD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Sotos syndrome 1 (MIM#117550), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2563 NGLY1 Zornitza Stark Marked gene: NGLY1 as ready
Genetic Epilepsy v0.2563 NGLY1 Zornitza Stark Gene: ngly1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2563 NGLY1 Zornitza Stark Phenotypes for gene: NGLY1 were changed from to Congenital disorder of deglycosylation, MIM# 615273
Genetic Epilepsy v0.2562 NGLY1 Zornitza Stark Publications for gene: NGLY1 were set to
Genetic Epilepsy v0.2561 NGLY1 Zornitza Stark Mode of inheritance for gene: NGLY1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2560 NDUFV1 Zornitza Stark Marked gene: NDUFV1 as ready
Genetic Epilepsy v0.2560 NDUFV1 Zornitza Stark Gene: ndufv1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2560 NDUFV1 Zornitza Stark Phenotypes for gene: NDUFV1 were changed from to Mitochondrial complex I deficiency, nuclear type 4 MIM#618225
Genetic Epilepsy v0.2559 NDUFV1 Zornitza Stark Publications for gene: NDUFV1 were set to
Genetic Epilepsy v0.2558 NDUFV1 Zornitza Stark Mode of inheritance for gene: NDUFV1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2557 NDUFV1 Zornitza Stark reviewed gene: NDUFV1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 4 MIM#618225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2557 NDUFS8 Zornitza Stark Marked gene: NDUFS8 as ready
Genetic Epilepsy v0.2557 NDUFS8 Zornitza Stark Gene: ndufs8 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2557 NDUFS8 Zornitza Stark Phenotypes for gene: NDUFS8 were changed from to Mitochondrial complex I deficiency, nuclear type 2 MIM#618222
Genetic Epilepsy v0.2556 NDUFS8 Zornitza Stark Publications for gene: NDUFS8 were set to
Genetic Epilepsy v0.2555 NDUFS8 Zornitza Stark Mode of inheritance for gene: NDUFS8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2554 NDUFS8 Zornitza Stark reviewed gene: NDUFS8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 2 MIM#618222; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2554 NDUFS4 Zornitza Stark Marked gene: NDUFS4 as ready
Genetic Epilepsy v0.2554 NDUFS4 Zornitza Stark Gene: ndufs4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2554 NDUFS4 Zornitza Stark Phenotypes for gene: NDUFS4 were changed from to Mitochondrial complex I deficiency, nuclear type 1 - MIM#252010
Genetic Epilepsy v0.2553 NDUFS4 Zornitza Stark Publications for gene: NDUFS4 were set to
Genetic Epilepsy v0.2552 NDUFS4 Zornitza Stark Mode of inheritance for gene: NDUFS4 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2551 NDUFS4 Zornitza Stark Mode of inheritance for gene: NDUFS4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5777 SOX2 Zornitza Stark Marked gene: SOX2 as ready
Intellectual disability syndromic and non-syndromic v0.5777 SOX2 Zornitza Stark Gene: sox2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5777 STRA6 Zornitza Stark Marked gene: STRA6 as ready
Intellectual disability syndromic and non-syndromic v0.5777 STRA6 Zornitza Stark Gene: stra6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5777 STRA6 Zornitza Stark Phenotypes for gene: STRA6 were changed from to Matthew-Wood syndrome MONDO:0011010
Intellectual disability syndromic and non-syndromic v0.5776 STRA6 Zornitza Stark Publications for gene: STRA6 were set to
Intellectual disability syndromic and non-syndromic v0.5775 STRA6 Zornitza Stark Mode of inheritance for gene: STRA6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5774 UFC1 Zornitza Stark Marked gene: UFC1 as ready
Intellectual disability syndromic and non-syndromic v0.5774 UFC1 Zornitza Stark Gene: ufc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5774 WARS2 Zornitza Stark Marked gene: WARS2 as ready
Intellectual disability syndromic and non-syndromic v0.5774 WARS2 Zornitza Stark Gene: wars2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5774 WDPCP Zornitza Stark Marked gene: WDPCP as ready
Intellectual disability syndromic and non-syndromic v0.5774 WDPCP Zornitza Stark Gene: wdpcp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5774 WDPCP Zornitza Stark Phenotypes for gene: WDPCP were changed from to Bardet-Biedl syndrome 15, MIM# 615992; OFD; Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085
Intellectual disability syndromic and non-syndromic v0.5773 ZIC1 Zornitza Stark Marked gene: ZIC1 as ready
Intellectual disability syndromic and non-syndromic v0.5773 ZIC1 Zornitza Stark Gene: zic1 has been classified as Green List (High Evidence).
Mendeliome v1.1695 FAM58A Zornitza Stark Mode of inheritance for gene: FAM58A was changed from Other to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v1.1694 FAM58A Zornitza Stark reviewed gene: FAM58A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; 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 v1.1694 TUBA8 Sangavi Sivagnanasundram reviewed gene: TUBA8: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006476; Phenotypes: polymicrogyria with optic nerve hypoplasia (MONDO:0013172); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1694 KIF1BP Sangavi Sivagnanasundram reviewed gene: KIF1BP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Autoinflammatory Disorders v1.36 SHARPIN Peter McNaughton gene: SHARPIN was added
gene: SHARPIN was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: SHARPIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHARPIN were set to PMID: 38609546
Phenotypes for gene: SHARPIN were set to recurrent fever
Review for gene: SHARPIN was set to GREEN
Added comment: Two unrelated patients with homozygous frameshift variants presenting with:
P1 - recurrent fever, parotitis, joint inflammation, colitis and chronic otitis media necessitating tympanoplasty
P2 - recurrent fever episodes with lymphadenopathy and vomiting every 2–3 weeks.

Extensive functional data and mouse model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5773 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Developmental and epileptic encephalopathy 115, MIM#620783 to Developmental and epileptic encephalopathy 115, MIM#620783; Neurodevelopmental disorder plus optic atrophy, MIM# 620784
Intellectual disability syndromic and non-syndromic v0.5772 SNF8 Zornitza Stark commented on gene: SNF8: Four individuals from 3 families with NDD plus OA, rather than DEE.
Intellectual disability syndromic and non-syndromic v0.5772 SNF8 Zornitza Stark edited their review of gene: SNF8: Changed phenotypes: Developmental and epileptic encephalopathy 115, MIM#620783, Neurodevelopmental disorder plus optic atrophy, MIM# 620784
Optic Atrophy v1.32 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Developmental and epileptic encephalopathy 115, MIM#620783 to Neurodevelopmental disorder plus optic atrophy, MIM# 620784
Optic Atrophy v1.31 SNF8 Zornitza Stark edited their review of gene: SNF8: Changed phenotypes: Neurodevelopmental disorder plus optic atrophy, MIM# 620784
Mendeliome v1.1694 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Developmental and epileptic encephalopathy 115, MIM#620783 to Developmental and epileptic encephalopathy 115, MIM#620783; Neurodevelopmental disorder plus optic atrophy, MIM# 620784
Mendeliome v1.1693 SNF8 Zornitza Stark edited their review of gene: SNF8: Added comment: Four individuals from 3 families with NDD plus OA, rather than DEE.; Changed phenotypes: Developmental and epileptic encephalopathy 115, MIM#620783, Neurodevelopmental disorder plus optic atrophy, MIM# 620784
Intellectual disability syndromic and non-syndromic v0.5772 NSUN6 Zornitza Stark Phenotypes for gene: NSUN6 were changed from neurodevelopmental disorder MONDO:0700092, NSUN6-related to Intellectual developmental disorder, autosomal recessive 82, MIM# 620779
Intellectual disability syndromic and non-syndromic v0.5771 NSUN6 Zornitza Stark reviewed gene: NSUN6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 82, MIM# 620779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1693 NSUN6 Zornitza Stark Phenotypes for gene: NSUN6 were changed from neurodevelopmental disorder MONDO:0700092, NSUN6-related to Intellectual developmental disorder, autosomal recessive 82, MIM# 620779
Mendeliome v1.1692 NSUN6 Zornitza Stark reviewed gene: NSUN6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 82, MIM# 620779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1692 CANVAS_ACAGG Bryony Thompson Classified STR: CANVAS_ACAGG as Green List (high evidence)
Mendeliome v1.1692 CANVAS_ACAGG Bryony Thompson Str: canvas_acagg has been classified as Green List (High Evidence).
Mendeliome v1.1691 CANVAS_ACAGG Bryony Thompson edited their review of STR: CANVAS_ACAGG: Added comment: Additional 4 unrelated cases homozygous for the (ACAGG)exp and one compound het with AAGGG/ACAGG expansion in a Japanese neuropathy cohort.; Changed rating: GREEN; Changed publications: 33103729, 36061987; Changed phenotypes: cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome MONDO:0044720; Set clinically relevant: yes
Intellectual disability syndromic and non-syndromic v0.5771 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 with language impairment, autism, and attention deficit-hyperactivity disorder, MIM# 620782; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Genetic Epilepsy v0.2550 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 with language impairment, autism, and attention deficit-hyperactivity disorder, MIM# 620782; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Mendeliome v1.1691 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 with language impairment, autism, and attention deficit-hyperactivity disorder, MIM# 620782; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Congenital Heart Defect v0.418 BMP2 Ain Roesley Marked gene: BMP2 as ready
Congenital Heart Defect v0.418 BMP2 Ain Roesley Gene: bmp2 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.418 BMP2 Ain Roesley reviewed gene: BMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37572998, 29198724; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Congenital Heart Defect v0.418 BMP2 Ain Roesley Deleted their review
Congenital Heart Defect v0.418 BMP2 Ain Roesley Deleted their comment
Congenital Heart Defect v0.418 BMP2 Ain Roesley Classified gene: BMP2 as Green List (high evidence)
Congenital Heart Defect v0.418 BMP2 Ain Roesley Gene: bmp2 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.417 BMP2 Ain Roesley gene: BMP2 was added
gene: BMP2 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: BMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP2 were set to 29198724
Phenotypes for gene: BMP2 were set to Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1, MIM# 617877
Review for gene: BMP2 was set to GREEN
gene: BMP2 was marked as current diagnostic
Added comment: 8 families with 12 affecteds

4 with CHD
Transposition of the great arteries HP:0001669
Mild pulmonary valve stenosis HP:0001642
Ebstein's anomaly HP:0010316
Wolff-Parkinson-White syndrome HP:0001716, perimembranous VSD HP:0011682
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.29 COMP Ain Roesley Marked gene: COMP as ready
Muscular dystrophy and myopathy_Paediatric v1.29 COMP Ain Roesley Gene: comp has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.29 COMP Ain Roesley Classified gene: COMP as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.29 COMP Ain Roesley Gene: comp has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.28 COMP Ain Roesley gene: COMP was added
gene: COMP was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: COMP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COMP were set to 20508815; 14684695; 15880723
Phenotypes for gene: COMP were set to Epiphyseal dysplasia, multiple, 1 MIM#132400
Review for gene: COMP was set to AMBER
gene: COMP was marked as current diagnostic
Added comment: Not a common feature of MED.
Amber so as not to miss a diagnosis

PMID: 14684695
2 families only 1 with mild myopathy
Fam1: 1 father + 3 sibs, only 1 reported muscle weakness
Fam2: no muscle weakness reported

PMID: 15880723
10 families but only 1 reported mild myopathy

PMID: 20508815
additional 2 unrelated individuals from European Skeletal Dysplasia Network
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.27 COL9A2 Ain Roesley Marked gene: COL9A2 as ready
Muscular dystrophy and myopathy_Paediatric v1.27 COL9A2 Ain Roesley Gene: col9a2 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.27 COL9A2 Ain Roesley Classified gene: COL9A2 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.27 COL9A2 Ain Roesley Gene: col9a2 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.26 COL9A2 Ain Roesley gene: COL9A2 was added
gene: COL9A2 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: COL9A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL9A2 were set to 20508815; 20358595
Phenotypes for gene: COL9A2 were set to Epiphyseal dysplasia, multiple, 2 MIM#600204
Review for gene: COL9A2 was set to AMBER
gene: COL9A2 was marked as current diagnostic
Added comment: not a common feature. only 1 paper found in pubmed and google (search terms COL9A2 AND myopathy)
Amber so as not to miss a diagnosis

PMID: 20358595
2 families with multiple affecteds but only 1 from each reporting muscle weakness

PMID: 20508815
additional individual from European Skeletal Dysplasia Network
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.25 COL9A3 Ain Roesley Marked gene: COL9A3 as ready
Muscular dystrophy and myopathy_Paediatric v1.25 COL9A3 Ain Roesley Gene: col9a3 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.25 COL9A3 Ain Roesley Classified gene: COL9A3 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.25 COL9A3 Ain Roesley Gene: col9a3 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.24 COL9A3 Ain Roesley gene: COL9A3 was added
gene: COL9A3 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: COL9A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL9A3 were set to 10655510
Phenotypes for gene: COL9A3 were set to Epiphyseal dysplasia, multiple, 3, with or without myopathy MIM#600969
Review for gene: COL9A3 was set to AMBER
gene: COL9A3 was marked as current diagnostic
Added comment: Not a common feature of MED, only one paper found in pubmed (search terms COL9A3 AND myopathy).
Amber so as not to miss a diagnosis

PMID: 10655510
1x male with proximal muscle weakness
Sources: Literature
Genetic Epilepsy v0.2549 KDM5C Ain Roesley Phenotypes for gene: KDM5C were changed from Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355 to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355
Mendeliome v1.1690 KDM5C Ain Roesley Phenotypes for gene: KDM5C were changed from Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534; MONDO:0010355 to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355
Genetic Epilepsy v0.2549 KDM5C Ain Roesley Phenotypes for gene: KDM5C were changed from Epilepsy; Intellectual Disability; microcephaly; Spasticity; hypothyroidism; Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534; MONDO:0010355 to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355
Hereditary Spastic Paraplegia v1.73 KDM5C Ain Roesley Phenotypes for gene: KDM5C were changed from Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534; MONDO:0010355; progressive spasticity; hypothyroidism; developmental delay; epilepsy to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355
Cerebral Palsy v1.192 KDM5C Ain Roesley Phenotypes for gene: KDM5C were changed from Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534; MONDO:0010355 to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355
Intellectual disability syndromic and non-syndromic v0.5770 KDM5C Ain Roesley Phenotypes for gene: KDM5C were changed from Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534; MONDO:0010355 to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355
Fetal anomalies v1.234 KDM5C Ain Roesley Phenotypes for gene: KDM5C were changed from Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534; MONDO:0010355 to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355
Mendeliome v1.1689 PSMA5 Zornitza Stark Marked gene: PSMA5 as ready
Mendeliome v1.1689 PSMA5 Zornitza Stark Gene: psma5 has been classified as Red List (Low Evidence).
Mendeliome v1.1689 PSMA5 Zornitza Stark gene: PSMA5 was added
gene: PSMA5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMA5 was set to Other
Publications for gene: PSMA5 were set to 37600812
Phenotypes for gene: PSMA5 were set to Inborn error of immunity, MONDO:0003778, PSMA5-related; PRAAS/CANDLE
Review for gene: PSMA5 was set to RED
Added comment: Single patient with heterozygous PSMB8 variant and de-novo PSMA5 truncating variant (p.Arg168*) with clinical features of CANDLE. Patient also had splice site variant in PSMC5. In silico modelling showing interaction of PSMB8 and PSMA5. PSMA5/a5 is a constitutive component of the 20S core proteasome, ? digenic model of disease.
Sources: Literature
Autoinflammatory Disorders v1.36 PSMA5 Zornitza Stark Marked gene: PSMA5 as ready
Autoinflammatory Disorders v1.36 PSMA5 Zornitza Stark Gene: psma5 has been classified as Red List (Low Evidence).
Autoinflammatory Disorders v1.36 PSMA5 Zornitza Stark Phenotypes for gene: PSMA5 were changed from PRAAS/CANDLE to Inborn error of immunity, MONDO:0003778, PSMA5-related; PRAAS/CANDLE
Autoinflammatory Disorders v1.35 PSMA5 Zornitza Stark Classified gene: PSMA5 as Red List (low evidence)
Autoinflammatory Disorders v1.35 PSMA5 Zornitza Stark Gene: psma5 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5769 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Developmental and epileptic encephalopathy 115, MIM#620783
Intellectual disability syndromic and non-syndromic v0.5768 SNF8 Zornitza Stark reviewed gene: SNF8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 115, MIM#620783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.522 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Developmental and epileptic encephalopathy 115, MIM#620783
Callosome v0.521 SNF8 Zornitza Stark reviewed gene: SNF8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 115, MIM#620783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2548 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Developmental and epileptic encephalopathy 115, MIM#620783 to Developmental and epileptic encephalopathy 115, MIM#620783
Genetic Epilepsy v0.2547 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Developmental and epileptic encephalopathy 115, MIM#620783
Genetic Epilepsy v0.2546 SNF8 Zornitza Stark Classified gene: SNF8 as Green List (high evidence)
Genetic Epilepsy v0.2546 SNF8 Zornitza Stark Gene: snf8 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2545 SNF8 Zornitza Stark reviewed gene: SNF8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 115, MIM#620783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic Atrophy v1.31 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Developmental and epileptic encephalopathy 115, MIM#620783
Optic Atrophy v1.30 SNF8 Zornitza Stark edited their review of gene: SNF8: Changed rating: AMBER
Optic Atrophy v1.30 SNF8 Zornitza Stark reviewed gene: SNF8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 115, MIM#620783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1688 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Developmental and epileptic encephalopathy 115, MIM#620783
Mendeliome v1.1687 SNF8 Zornitza Stark reviewed gene: SNF8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 115, MIM#620783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1687 CNOT1 Sangavi Sivagnanasundram reviewed gene: CNOT1: Rating: AMBER; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004485; Phenotypes: holoprosencephaly 12 with or without pancreatic agenesis MONDO:0032787; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1687 CENPE Sangavi Sivagnanasundram reviewed gene: CENPE: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004413; Phenotypes: autosomal recessive primary microcephaly MONDO:0016660; Mode of inheritance: None
Peroxisomal Disorders v0.47 ABCD1 Sangavi Sivagnanasundram reviewed gene: ABCD1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004013c; Phenotypes: adrenoleukodystrophy (MONDO:0018544); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early-onset Parkinson disease v0.295 LRRK2 Sangavi Sivagnanasundram reviewed gene: LRRK2: 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: 1626954, https://search.clinicalgenome.org/CCID:005305; Phenotypes: Parkinson disease (MONDO:0005180); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2545 PURA Ain Roesley Phenotypes for gene: PURA were changed from Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158) to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Intellectual disability syndromic and non-syndromic v0.5768 PURA Ain Roesley Phenotypes for gene: PURA were changed from Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158) to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Intellectual disability syndromic and non-syndromic v0.5768 PURA Ain Roesley Phenotypes for gene: PURA were changed from Mental retardation, autosomal dominant 31, MIM# 616158 to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Genetic Epilepsy v0.2545 PURA Ain Roesley Phenotypes for gene: PURA were changed from Mental retardation, autosomal dominant 31, MIM# 616158 to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Fetal anomalies v1.233 PURA Ain Roesley Phenotypes for gene: PURA were changed from Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158) to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Fetal anomalies v1.232 PURA Ain Roesley Phenotypes for gene: PURA were changed from Mental retardation, autosomal dominant 31, MIM# 616158 to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Mendeliome v1.1687 PURA Ain Roesley Phenotypes for gene: PURA were changed from Mental retardation, autosomal dominant 31, MIM# 616158 to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Motor Neurone Disease v1.8 SS18L1 Sangavi Sivagnanasundram reviewed gene: SS18L1: Rating: AMBER; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006276; Phenotypes: amyotrophic lateral sclerosis (MONDO:0004976); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v1.8 CYLD Sangavi Sivagnanasundram reviewed gene: CYLD: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004615; Phenotypes: frontotemporal dementia and/or amyotrophic lateral sclerosis 8 (MONDO:0030872); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v1.8 CHMP2B Sangavi Sivagnanasundram reviewed gene: CHMP2B: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004450; Phenotypes: frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (MONDO:0010936); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Repeat Disorders v0.167 DMD Bryony Thompson Publications for STR: DMD were set to 27417533
Repeat Disorders v0.166 FAME7 Bryony Thompson Publications for STR: FAME7 were set to 29507423
Repeat Disorders v0.165 FAME7 Bryony Thompson Classified STR: FAME7 as Amber List (moderate evidence)
Repeat Disorders v0.165 FAME7 Bryony Thompson Str: fame7 has been classified as Amber List (Moderate Evidence).
Repeat Disorders v0.164 FAME7 Bryony Thompson edited their review of STR: FAME7: Added comment: TTTCA expansion (without TTTTA expansion) identified in 3 affected individuals in a Chinese FAME family and another unrelated Japanese proband. Now 3 families reported.; Changed rating: AMBER; Changed publications: 29507423, 30351492, 33791773
Mendeliome v1.1686 EFEMP1 Zornitza Stark Phenotypes for gene: EFEMP1 were changed from Glaucoma 1, open angle, H, MIM# 611276; Doyne honeycomb degeneration of retina, MIM# 126600; EFEMP1-related connective tissue disorder to Doyne honeycomb degeneration of retina, MIM# 126600; Cutis laxa, autosomal recessive, type ID, MIM# 620780; Glaucoma 1, open angle, H, MIM# 611276
Mendeliome v1.1685 EFEMP1 Zornitza Stark edited their review of gene: EFEMP1: Changed phenotypes: Doyne honeycomb degeneration of retina, MIM# 126600, Cutis laxa, autosomal recessive, type ID, MIM# 620780, Glaucoma 1, open angle, H, MIM# 611276
Aortopathy_Connective Tissue Disorders v1.84 EFEMP1 Zornitza Stark Phenotypes for gene: EFEMP1 were changed from EFEMP1-related connective tissue disorder; cutis laxa to Cutis laxa, autosomal recessive, type ID, MIM# 620780
Aortopathy_Connective Tissue Disorders v1.83 EFEMP1 Zornitza Stark edited their review of gene: EFEMP1: Changed phenotypes: Cutis laxa, autosomal recessive, type ID, MIM# 620780
Bone Marrow Failure v1.88 GALE Zornitza Stark Marked gene: GALE as ready
Bone Marrow Failure v1.88 GALE Zornitza Stark Gene: gale has been classified as Green List (High Evidence).
Bone Marrow Failure v1.88 GALE Zornitza Stark Classified gene: GALE as Green List (high evidence)
Bone Marrow Failure v1.88 GALE Zornitza Stark Gene: gale has been classified as Green List (High Evidence).
Bone Marrow Failure v1.87 GALE Zornitza Stark gene: GALE was added
gene: GALE was added to Bone Marrow Failure. Sources: Expert Review
Mode of inheritance for gene: GALE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALE were set to 30247636; 34159722; 36395340
Phenotypes for gene: GALE were set to Thrombocytopenia 12, syndromic, MIM#620776
Review for gene: GALE was set to GREEN
Added comment: 10 individuals from 5 families reported with bi-allelic variants in this gene and congenital thrombocytopenia resulting in increased bleeding. Platelets were enlarged (macrothrombocytopenia) and/or gray and had functional defects. Some individuals have infection-induced leukopenia or anaemia and pancytopenia. Additional more variable features have also been reported, including mitral valve malformations, pyloric stenosis, and impaired intellectual development.
Sources: Expert Review
Mendeliome v1.1685 GALE Zornitza Stark Phenotypes for gene: GALE were changed from Galactose epimerase deficiency MIM#230350; Disorders of galactose metabolism to Galactose epimerase deficiency MIM#230350; Thrombocytopenia 12, syndromic, MIM#620776
Mendeliome v1.1684 GALE Zornitza Stark Publications for gene: GALE were set to 27604308; 9700591
Mendeliome v1.1683 GALE Zornitza Stark reviewed gene: GALE: Rating: GREEN; Mode of pathogenicity: None; Publications: 30247636, 34159722, 36395340; Phenotypes: Thrombocytopenia 12, syndromic, MIM#620776; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.31 GALE Zornitza Stark Marked gene: GALE as ready
Bleeding and Platelet Disorders v1.31 GALE Zornitza Stark Gene: gale has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.31 GALE Zornitza Stark Classified gene: GALE as Green List (high evidence)
Bleeding and Platelet Disorders v1.31 GALE Zornitza Stark Gene: gale has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.30 GALE Zornitza Stark gene: GALE was added
gene: GALE was added to Bleeding and Platelet Disorders. Sources: Expert list
Mode of inheritance for gene: GALE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALE were set to 30247636; 34159722; 36395340
Phenotypes for gene: GALE were set to Thrombocytopenia 12, syndromic, MIM#620776
Review for gene: GALE was set to GREEN
Added comment: 10 individuals from 5 families reported with bi-allelic variants in this gene and congenital thrombocytopenia resulting in increased bleeding. Platelets were enlarged (macrothrombocytopenia) and/or gray and had functional defects. Some individuals have infection-induced leukopenia or anaemia and pancytopenia. Additional more variable features have also been reported, including mitral valve malformations, pyloric stenosis, and impaired intellectual development.
Sources: Expert list
Repeat Disorders v0.164 DMD Bryony Thompson changed review comment from: Another case with BMD (patient 18) form a Japanese registry was reported with an expansion of 1381–1502 repeats in intron 62.; to: Another case with BMD (patient 18) form a Japanese registry was reported with an expansion of 1381–1502 repeats in intron 62. Repeat expansion causes a splicing aberration
Repeat Disorders v0.164 DMD Bryony Thompson Classified STR: DMD as Amber List (moderate evidence)
Repeat Disorders v0.164 DMD Bryony Thompson Str: dmd has been classified as Amber List (Moderate Evidence).
Repeat Disorders v0.163 DMD Bryony Thompson edited their review of STR: DMD: Added comment: Another case with BMD (patient 18) form a Japanese registry was reported with an expansion of 1381–1502 repeats in intron 62.; Changed rating: AMBER; Changed publications: 27417533, 36048237
Repeat Disorders v0.163 HFGS_tract2 Bryony Thompson Marked STR: HFGS_tract2 as ready
Repeat Disorders v0.163 HFGS_tract2 Bryony Thompson Str: hfgs_tract2 has been classified as Green List (High Evidence).
Repeat Disorders v0.163 SCA_THAP11_CAG Bryony Thompson Marked STR: SCA_THAP11_CAG as ready
Repeat Disorders v0.163 SCA_THAP11_CAG Bryony Thompson Str: sca_thap11_cag has been classified as Amber List (Moderate Evidence).
Repeat Disorders v0.163 SCA_THAP11_CAG Bryony Thompson Classified STR: SCA_THAP11_CAG as Amber List (moderate evidence)
Repeat Disorders v0.163 SCA_THAP11_CAG Bryony Thompson Str: sca_thap11_cag has been classified as Amber List (Moderate Evidence).
Repeat Disorders v0.162 SCA_THAP11_CAG Bryony Thompson STR: SCA_THAP11_CAG was added
STR: SCA_THAP11_CAG was added to Repeat Disorders. Sources: Other
Mode of inheritance for STR: SCA_THAP11_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA_THAP11_CAG were set to 15368101; 24677642; 34165550; 38113319
Phenotypes for STR: SCA_THAP11_CAG were set to autosomal dominant cerebellar ataxia MONDO:0020380
Review for STR: SCA_THAP11_CAG was set to AMBER
Added comment: 7 individuals from 2 Chinese families with SCA (1 was pre-ataxic) and a THAP11 CAG (polyQ) expansion. 45 repeats was the lowest number of repeats in an affected individual. A 46/29 CAG THAP11 genotype has also been identified in an individual with ataxia of European ancestry, that also had a CACNA1A pathogenic expansion which causes SCA6. Analysis of the 1000 genomes cohort (n=2504), suggests a normal range between 19-39. Also, a supporting mouse model and functional assays support a toxic aggregation mechanism of disease.
Further probands/families are required to confirm the gene-disease association.
Sources: Other
Mendeliome v1.1683 BANF1 Zornitza Stark Phenotypes for gene: BANF1 were changed from Nestor-Guillermo progeria syndrome, MIM# 614008 to Nestor-Guillermo progeria syndrome, MIM# 614008; Neurodevelopmental disorder, MONDO:0700092, BANF1-related; Hereditary peripheral neuropathy, MONDO:0020127, BANF1-related
Mendeliome v1.1682 BANF1 Zornitza Stark Publications for gene: BANF1 were set to 32783369; 21549337
Mendeliome v1.1681 BANF1 Zornitza Stark Mode of inheritance for gene: BANF1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1680 BANF1 Zornitza Stark changed review comment from: Two Spanish families reported but likely founder effect. One additional family. Lipoatrophy reported.; to: Bi-allelic disease: Two Spanish families reported with progeria but likely founder effect. One additional family. Lipoatrophy reported.
Mendeliome v1.1680 BANF1 Zornitza Stark edited their review of gene: BANF1: Added comment: PMID 35982159: Single individual reported with a de novo variant, p.Ala87Thr, and a neurodevelopmental disorder.

PMID 36980188: Hereditary peripheral neuropathy, MONDO:0020127, BANF1-related; Changed publications: 32783369, 21549337, 35982159, 36980188; Changed phenotypes: Nestor-Guillermo progeria syndrome, MIM# 614008, Neurodevelopmental disorder, MONDO:0700092, BANF1-related, Hereditary peripheral neuropathy, MONDO:0020127, BANF1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5767 BANF1 Zornitza Stark Marked gene: BANF1 as ready
Intellectual disability syndromic and non-syndromic v0.5767 BANF1 Zornitza Stark Gene: banf1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5767 BANF1 Zornitza Stark gene: BANF1 was added
gene: BANF1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: BANF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BANF1 were set to 35982159
Phenotypes for gene: BANF1 were set to Neurodevelopmental disorder, MONDO:0700092, BANF1-related
Review for gene: BANF1 was set to RED
Added comment: Single individual reported with a de novo variant, p.Ala87Thr, and a neurodevelopmental disorder.
Sources: Literature
Repeat Disorders v0.161 OPDM_ABCD3_GCC Bryony Thompson Marked STR: OPDM_ABCD3_GCC as ready
Repeat Disorders v0.161 OPDM_ABCD3_GCC Bryony Thompson Str: opdm_abcd3_gcc has been classified as Green List (High Evidence).
Repeat Disorders v0.161 OPDM_ABCD3_GCC Bryony Thompson Classified STR: OPDM_ABCD3_GCC as Green List (high evidence)
Repeat Disorders v0.161 OPDM_ABCD3_GCC Bryony Thompson Str: opdm_abcd3_gcc has been classified as Green List (High Evidence).
Repeat Disorders v0.160 OPDM_ABCD3_GCC Bryony Thompson STR: OPDM_ABCD3_GCC was added
STR: OPDM_ABCD3_GCC was added to Repeat Disorders. Sources: Other
Mode of inheritance for STR: OPDM_ABCD3_GCC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: OPDM_ABCD3_GCC were set to https://doi.org/10.1101/2023.10.09.23296582
Phenotypes for STR: OPDM_ABCD3_GCC were set to Oculopharyngodistal myopathy MONDO:0025193
Review for STR: OPDM_ABCD3_GCC was set to GREEN
STR: OPDM_ABCD3_GCC was marked as clinically relevant
Added comment: 35 OPDM individuals from 8 unrelated families from Australia, the UK, and France with an ABCD3 5’UTR CGG repeat. Affected individuals had repeat expansions ranging from 118-694 (n=19). 7 repeats is the median repeat size in non-neurological controls from the GE 100,000 Genome Project. 10 controls had estimated repeats >50, up to ~93. 50 repeats would be a safe cut-off for normal
Sources: Other
Muscular dystrophy and myopathy_Paediatric v1.23 FILIP1 Zornitza Stark Marked gene: FILIP1 as ready
Muscular dystrophy and myopathy_Paediatric v1.23 FILIP1 Zornitza Stark Gene: filip1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.23 FILIP1 Zornitza Stark Classified gene: FILIP1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.23 FILIP1 Zornitza Stark Gene: filip1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.22 FILIP1 Zornitza Stark gene: FILIP1 was added
gene: FILIP1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Expert Review
Mode of inheritance for gene: FILIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FILIP1 were set to 36943452; 37163662
Phenotypes for gene: FILIP1 were set to Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775
Review for gene: FILIP1 was set to GREEN
Added comment: Congenital neuromuscular disorder with dysmorphic facies (NMDF) is an autosomal recessive disorder characterized by impaired skeletal muscle development, usually resulting in hypotonia and secondary joint contractures, and dysmorphic facial features. Features are apparent from birth. Affected individuals may show motor delay, speech delay, and impaired intellectual development.

Seven families reported.
Sources: Expert Review
Fetal anomalies v1.231 FILIP1 Zornitza Stark Phenotypes for gene: FILIP1 were changed from Arthrogryposis multiplex congenita MONDO:0015168, FILIP1 related to ANeuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775
Fetal anomalies v1.230 FILIP1 Zornitza Stark reviewed gene: FILIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.258 FILIP1 Zornitza Stark Phenotypes for gene: FILIP1 were changed from Arthrogryposis multiplex congenita MONDO:0015168, FILIP1 related to Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775
Microcephaly v1.257 FILIP1 Zornitza Stark reviewed gene: FILIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1680 FILIP1 Zornitza Stark Phenotypes for gene: FILIP1 were changed from Arthrogryposis multiplex congenita MONDO:0015168, FILIP1 related to Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775
Mendeliome v1.1679 FILIP1 Zornitza Stark reviewed gene: FILIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.406 FILIP1 Zornitza Stark Phenotypes for gene: FILIP1 were changed from Arthrogryposis multiplex congenita MONDO:0015168, FILIP1-related to Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775
Arthrogryposis v0.405 FILIP1 Zornitza Stark reviewed gene: FILIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1679 RNU4-2 Zornitza Stark Marked gene: RNU4-2 as ready
Mendeliome v1.1679 RNU4-2 Zornitza Stark Gene: rnu4-2 has been classified as Green List (High Evidence).
Mendeliome v1.1679 RNU4-2 Zornitza Stark Classified gene: RNU4-2 as Green List (high evidence)
Mendeliome v1.1679 RNU4-2 Zornitza Stark Gene: rnu4-2 has been classified as Green List (High Evidence).
Mendeliome v1.1678 RNU4-2 Zornitza Stark gene: RNU4-2 was added
gene: RNU4-2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNU4-2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RNU4-2 were set to Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related
Review for gene: RNU4-2 was set to GREEN
Added comment: Emerging evidence that de novo variants in this gene cause ID.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5766 RNU4-2 Zornitza Stark Marked gene: RNU4-2 as ready
Intellectual disability syndromic and non-syndromic v0.5766 RNU4-2 Zornitza Stark Gene: rnu4-2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5766 RNU4-2 Zornitza Stark Classified gene: RNU4-2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5766 RNU4-2 Zornitza Stark Gene: rnu4-2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5765 RNU4-2 Zornitza Stark gene: RNU4-2 was added
gene: RNU4-2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RNU4-2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RNU4-2 were set to Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related
Review for gene: RNU4-2 was set to GREEN
Added comment: Emerging evidence that de novo variants in this gene cause ID.
Sources: Literature
Liver Failure_Paediatric v1.24 YKT6 Zornitza Stark Marked gene: YKT6 as ready
Liver Failure_Paediatric v1.24 YKT6 Zornitza Stark Gene: ykt6 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v1.24 YKT6 Zornitza Stark Classified gene: YKT6 as Amber List (moderate evidence)
Liver Failure_Paediatric v1.24 YKT6 Zornitza Stark Gene: ykt6 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v1.23 YKT6 Zornitza Stark gene: YKT6 was added
gene: YKT6 was added to Liver Failure_Paediatric. Sources: Literature
Mode of inheritance for gene: YKT6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YKT6 were set to 38522068
Phenotypes for gene: YKT6 were set to Syndromic disease, MONDO:0002254, YKT6-related
Review for gene: YKT6 was set to AMBER
Added comment: Two individuals homozygous for YKT6 [NM_006555.3:c.554A>G p.(Tyr185Cys)] exhibited normal prenatal course followed by failure to thrive, developmental delay and progressive liver disease. Haplotype analysis identified a shared homozygous region flanking the variant, suggesting a common ancestry. The third individual homozygous for YKT6 [NM_006555.3:c.191A>G p.(Tyr64Cys)] exhibited neurodevelopmental disorders and optic atrophy. Supportive functional data in Drosophila. Amber rating due to homozygous missense variants and founder effect in two of the families.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5764 YKT6 Zornitza Stark Marked gene: YKT6 as ready
Intellectual disability syndromic and non-syndromic v0.5764 YKT6 Zornitza Stark Gene: ykt6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5764 YKT6 Zornitza Stark Classified gene: YKT6 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5764 YKT6 Zornitza Stark Gene: ykt6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5763 YKT6 Zornitza Stark gene: YKT6 was added
gene: YKT6 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: YKT6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YKT6 were set to 38522068
Phenotypes for gene: YKT6 were set to Syndromic disease, MONDO:0002254, YKT6-related
Review for gene: YKT6 was set to AMBER
Added comment: Two individuals homozygous for YKT6 [NM_006555.3:c.554A>G p.(Tyr185Cys)] exhibited normal prenatal course followed by failure to thrive, developmental delay and progressive liver disease. Haplotype analysis identified a shared homozygous region flanking the variant, suggesting a common ancestry. The third individual homozygous for YKT6 [NM_006555.3:c.191A>G p.(Tyr64Cys)] exhibited neurodevelopmental disorders and optic atrophy. Supportive functional data in Drosophila. Amber rating due to homozygous missense variants and founder effect in two of the families.
Sources: Literature
Mendeliome v1.1677 YKT6 Zornitza Stark Marked gene: YKT6 as ready
Mendeliome v1.1677 YKT6 Zornitza Stark Gene: ykt6 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1677 YKT6 Zornitza Stark Classified gene: YKT6 as Amber List (moderate evidence)
Mendeliome v1.1677 YKT6 Zornitza Stark Gene: ykt6 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1676 YKT6 Zornitza Stark gene: YKT6 was added
gene: YKT6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: YKT6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YKT6 were set to 38522068
Phenotypes for gene: YKT6 were set to Syndromic disease, MONDO:0002254, YKT6-related
Review for gene: YKT6 was set to AMBER
Added comment: Two individuals homozygous for YKT6 [NM_006555.3:c.554A>G p.(Tyr185Cys)] exhibited normal prenatal course followed by failure to thrive, developmental delay and progressive liver disease. Haplotype analysis identified a shared homozygous region flanking the variant, suggesting a common ancestry. The third individual homozygous for YKT6 [NM_006555.3:c.191A>G p.(Tyr64Cys)] exhibited neurodevelopmental disorders and optic atrophy. Supportive functional data in Drosophila.

Amber rating due to homozygous missense variants and founder effect in two of the families.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5762 SEPHS1 Zornitza Stark Marked gene: SEPHS1 as ready
Intellectual disability syndromic and non-syndromic v0.5762 SEPHS1 Zornitza Stark Gene: sephs1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5762 SEPHS1 Zornitza Stark Classified gene: SEPHS1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5762 SEPHS1 Zornitza Stark Gene: sephs1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5761 SEPHS1 Zornitza Stark gene: SEPHS1 was added
gene: SEPHS1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SEPHS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEPHS1 were set to 38531365
Phenotypes for gene: SEPHS1 were set to Neurodevelopmental disorder, MONDO:0700092, SEPHS1-related
Review for gene: SEPHS1 was set to GREEN
Added comment: Nine individuals from eight families with developmental delay, growth and feeding problems, hypotonia, and dysmorphic features, all with heterozygous missense variants in SEPHS1. Eight of these individuals had a recurrent variant at amino acid position 371 of SEPHS1 (p.Arg371Trp, p.Arg371Gln, and p.Arg371Gly); seven of these variants were known to be de novo.
Sources: Literature
Mendeliome v1.1675 SEPHS1 Zornitza Stark Marked gene: SEPHS1 as ready
Mendeliome v1.1675 SEPHS1 Zornitza Stark Gene: sephs1 has been classified as Green List (High Evidence).
Mendeliome v1.1675 SEPHS1 Zornitza Stark Classified gene: SEPHS1 as Green List (high evidence)
Mendeliome v1.1675 SEPHS1 Zornitza Stark Gene: sephs1 has been classified as Green List (High Evidence).
Mendeliome v1.1674 SEPHS1 Zornitza Stark gene: SEPHS1 was added
gene: SEPHS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEPHS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEPHS1 were set to 38531365
Phenotypes for gene: SEPHS1 were set to Neurodevelopmental disorder, MONDO:0700092, SEPHS1-related
Review for gene: SEPHS1 was set to GREEN
Added comment: Nine individuals from eight families with developmental delay, growth and feeding problems, hypotonia, and dysmorphic features, all with heterozygous missense variants in SEPHS1. Eight of these individuals had a recurrent variant at amino acid position 371 of SEPHS1 (p.Arg371Trp, p.Arg371Gln, and p.Arg371Gly); seven of these variants were known to be de novo.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5760 GLUL Zornitza Stark Marked gene: GLUL as ready
Intellectual disability syndromic and non-syndromic v0.5760 GLUL Zornitza Stark Gene: glul has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5760 GLUL Zornitza Stark Phenotypes for gene: GLUL were changed from to Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related; Glutamine deficiency, congenital MIM#610015
Intellectual disability syndromic and non-syndromic v0.5759 GLUL Zornitza Stark Publications for gene: GLUL were set to
Intellectual disability syndromic and non-syndromic v0.5758 GLUL Zornitza Stark Mode of inheritance for gene: GLUL was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5757 GLUL Zornitza Stark reviewed gene: GLUL: Rating: GREEN; Mode of pathogenicity: None; Publications: 16267323, 21353613, 33150193; Phenotypes: Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related, Glutamine deficiency, congenital MIM#610015, disorder of amino acid metabolism; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2544 GLUL Zornitza Stark Phenotypes for gene: GLUL were changed from Glutamine deficiency, congenital MIM#610015 to Glutamine deficiency, congenital MIM#610015; Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related
Genetic Epilepsy v0.2543 GLUL Zornitza Stark Mode of inheritance for gene: GLUL was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2542 GLUL Zornitza Stark edited their review of gene: GLUL: Added comment: Nine individuals with de novo variants in this gene and DEE. Seven out of nine were start-loss variants and two out of nine disrupted 5′ UTR splicing resulting in splice exclusion of the initiation codon.; Changed phenotypes: Glutamine deficiency, congenital MIM#610015, Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1673 GLUL Zornitza Stark Phenotypes for gene: GLUL were changed from Glutamine deficiency, congenital MIM#610015; disorder of amino acid metabolism to Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related; Glutamine deficiency, congenital MIM#610015; disorder of amino acid metabolism
Mendeliome v1.1672 GLUL Zornitza Stark Mode of inheritance for gene: GLUL was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1671 GLUL Zornitza Stark reviewed gene: GLUL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy v1.12 SCA4_ZFHX3_GGC Bryony Thompson Marked STR: SCA4_ZFHX3_GGC as ready
Hereditary Neuropathy v1.12 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Hereditary Neuropathy v1.12 SCA4_ZFHX3_GGC Bryony Thompson Classified STR: SCA4_ZFHX3_GGC as Green List (high evidence)
Hereditary Neuropathy v1.12 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Mendeliome v1.1671 SCA4_ZFHX3_GGC Bryony Thompson Marked STR: SCA4_ZFHX3_GGC as ready
Mendeliome v1.1671 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Mendeliome v1.1671 SCA4_ZFHX3_GGC Bryony Thompson Classified STR: SCA4_ZFHX3_GGC as Green List (high evidence)
Mendeliome v1.1671 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Hereditary Neuropathy v1.11 SCA4_ZFHX3_GGC Bryony Thompson STR: SCA4_ZFHX3_GGC was added
STR: SCA4_ZFHX3_GGC was added to Hereditary Neuropathy - complex. Sources: Literature
Mode of inheritance for STR: SCA4_ZFHX3_GGC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA4_ZFHX3_GGC were set to 38035881; 38197134
Phenotypes for STR: SCA4_ZFHX3_GGC were set to spinocerebellar ataxia type 4 MONDO:0010847
Review for STR: SCA4_ZFHX3_GGC was set to GREEN
STR: SCA4_ZFHX3_GGC was marked as clinically relevant
Added comment: PMID: 38035881 - repeat expansion is identified in 5 Swedish ataxia families that developed balance and gait disturbances at 15 to 60 years of age and had sensory neuropathy and slow saccades.
PMID: 38197134 - Poly-glycine GGC expansion in the last coding exon of ZFHX3 was identified in the original SCA4 Utah pedigree (Swedish origin) in the region of high linkage identified on 16q22. The expansion was also identified in an Iowa ataxia pedigree of Swedish ancestry. The expansion wasn’t identified in 11,258 exomes, 7,650 WGS probands without neurological phenotype, or 803 individuals with ataxia. Grch38 chr16:72787695–72787758
Normal allele <30 repeats, 21 repeats is the most common (derived from 33,094 individuals)
Undefined pathogenic 30-48 repeats
Definitive pathogenicity 48+ repeats
Sources: Literature
Mendeliome v1.1670 SCA4_ZFHX3_GGC Bryony Thompson STR: SCA4_ZFHX3_GGC was added
STR: SCA4_ZFHX3_GGC was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: SCA4_ZFHX3_GGC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA4_ZFHX3_GGC were set to 38035881; 38197134
Phenotypes for STR: SCA4_ZFHX3_GGC were set to spinocerebellar ataxia type 4 MONDO:0010847
Review for STR: SCA4_ZFHX3_GGC was set to GREEN
STR: SCA4_ZFHX3_GGC was marked as clinically relevant
Added comment: PMID: 38035881 - repeat expansion is identified in 5 Swedish ataxia families that developed balance and gait disturbances at 15 to 60 years of age and had sensory neuropathy and slow saccades.
PMID: 38197134 - Poly-glycine GGC expansion in the last coding exon of ZFHX3 was identified in the original SCA4 Utah pedigree (Swedish origin) in the region of high linkage identified on 16q22. The expansion was also identified in an Iowa ataxia pedigree of Swedish ancestry. The expansion wasn’t identified in 11,258 exomes, 7,650 WGS probands without neurological phenotype, or 803 individuals with ataxia. Grch38 chr16:72787695–72787758
Normal allele <30 repeats, 21 repeats is the most common (derived from 33,094 individuals)
Undefined pathogenic 30-48 repeats
Definitive pathogenicity 48+ repeats
Sources: Literature
Repeat Disorders v0.159 SCA4_ZFHX3_GGC Bryony Thompson Marked STR: SCA4_ZFHX3_GGC as ready
Repeat Disorders v0.159 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Repeat Disorders v0.159 SCA4_ZFHX3_GGC Bryony Thompson Classified STR: SCA4_ZFHX3_GGC as Green List (high evidence)
Repeat Disorders v0.159 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Repeat Disorders v0.158 SCA4_ZFHX3_GGC Bryony Thompson STR: SCA4_ZFHX3_GGC was added
STR: SCA4_ZFHX3_GGC was added to Repeat Disorders. Sources: Literature
Mode of inheritance for STR: SCA4_ZFHX3_GGC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA4_ZFHX3_GGC were set to 38035881; 38197134
Phenotypes for STR: SCA4_ZFHX3_GGC were set to spinocerebellar ataxia type 4 MONDO:0010847
Review for STR: SCA4_ZFHX3_GGC was set to GREEN
STR: SCA4_ZFHX3_GGC was marked as clinically relevant
Added comment: PMID: 38035881 - repeat expansion is identified in 5 Swedish ataxia families that developed balance and gait disturbances at 15 to 60 years of age and had sensory neuropathy and slow saccades.
PMID: 38197134 - Poly-glycine GGC expansion in the last coding exon of ZFHX3 was identified in the original SCA4 Utah pedigree (Swedish origin) in the region of high linkage identified on 16q22. The expansion was also identified in an Iowa ataxia pedigree of Swedish ancestry. The expansion wasn’t identified in 11,258 exomes, 7,650 WGS probands without neurological phenotype, or 803 individuals with ataxia. Grch38 chr16:72787695–72787758
Normal allele <30 repeats, 21 repeats is the most common (derived from 33,094 individuals)
Undefined pathogenic 30-48 repeats
Definitive pathogenicity 48+ repeats
Sources: Literature
Genetic Epilepsy v0.2542 ZFHX3 Bryony Thompson Marked gene: ZFHX3 as ready
Genetic Epilepsy v0.2542 ZFHX3 Bryony Thompson Gene: zfhx3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2542 ZFHX3 Bryony Thompson Classified gene: ZFHX3 as Green List (high evidence)
Genetic Epilepsy v0.2542 ZFHX3 Bryony Thompson Gene: zfhx3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2541 ZFHX3 Bryony Thompson gene: ZFHX3 was added
gene: ZFHX3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ZFHX3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZFHX3 were set to 38508705
Phenotypes for gene: ZFHX3 were set to developmental and epileptic encephalopathy MONDO:0100062
Review for gene: ZFHX3 was set to GREEN
gene: ZFHX3 was marked as current diagnostic
Added comment: 8 unrelated probands with biallelic variants and a phenotype consistent with DEE and childhood partial epilepsy. Also a supporting Drosophila Zfh2 knockdown model with seizure-like behaviour.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5757 GTF3C5 Bryony Thompson Marked gene: GTF3C5 as ready
Intellectual disability syndromic and non-syndromic v0.5757 GTF3C5 Bryony Thompson Gene: gtf3c5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5757 GTF3C5 Bryony Thompson Classified gene: GTF3C5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5757 GTF3C5 Bryony Thompson Gene: gtf3c5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5756 GTF3C5 Bryony Thompson gene: GTF3C5 was added
gene: GTF3C5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GTF3C5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C5 were set to 38520561; 35503477
Phenotypes for gene: GTF3C5 were set to neurodevelopmental disorder MONDO:0700092, GTF3C5-related
Review for gene: GTF3C5 was set to GREEN
gene: GTF3C5 was marked as current diagnostic
Added comment: 4 families/probands with syndromic ID. Loss of function is the expected
PMID: 38520561 - Biallelic variants identified (3 missense & 1 stopgain) in 4 individuals from 3 families presenting with multisystem developmental syndrome including the features: growth retardation, developmental delay, intellectual disability, dental anomalies, cerebellar malformations, delayed bone age, skeletal anomalies, and facial dysmorphism. Gene-disease relationship supported by: reduced protein expression in patient cells, yeast assays, and a zebrafish model
PMID: 35503477 - 1 proband with biallelic missense variants and hypomelanosis of Ito, seizures, growth retardation, abnormal brain MRI, developmental delay, and facial dysmorphism
Sources: Literature
Mendeliome v1.1669 GTF3C5 Bryony Thompson Marked gene: GTF3C5 as ready
Mendeliome v1.1669 GTF3C5 Bryony Thompson Gene: gtf3c5 has been classified as Green List (High Evidence).
Mendeliome v1.1669 GTF3C5 Bryony Thompson Classified gene: GTF3C5 as Green List (high evidence)
Mendeliome v1.1669 GTF3C5 Bryony Thompson Gene: gtf3c5 has been classified as Green List (High Evidence).
Mendeliome v1.1668 GTF3C5 Bryony Thompson gene: GTF3C5 was added
gene: GTF3C5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GTF3C5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C5 were set to 38520561; 35503477
Phenotypes for gene: GTF3C5 were set to neurodevelopmental disorder MONDO:0700092, GTF3C5-related
Review for gene: GTF3C5 was set to GREEN
Added comment: 4 families/probands with syndromic ID. Loss of function is the expected
PMID: 38520561 - Biallelic variants identified (3 missense & 1 stopgain) in 4 individuals from 3 families presenting with multisystem developmental syndrome including the features: growth retardation, developmental delay, intellectual disability, dental anomalies, cerebellar malformations, delayed bone age, skeletal anomalies, and facial dysmorphism. Gene-disease relationship supported by: reduced protein expression in patient cells, yeast assays, and a zebrafish model
PMID: 35503477 - 1 proband with biallelic missense variants and hypomelanosis of Ito, seizures, growth retardation, abnormal brain MRI, developmental delay, and facial dysmorphism
Sources: Literature
Mendeliome v1.1667 MCOLN1 Zornitza Stark Phenotypes for gene: MCOLN1 were changed from Mucolipidosis IV, MIM# 252650; MONDO:0009653 to Mucolipidosis IV, MIM# 252650; MONDO:0009653; Lisch epithelial corneal dystrophy, OMIM# 620763
Mendeliome v1.1666 MCOLN1 Zornitza Stark Publications for gene: MCOLN1 were set to
Mendeliome v1.1665 MCOLN1 Zornitza Stark Mode of inheritance for gene: MCOLN1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1664 MCOLN1 Zornitza Stark edited their review of gene: MCOLN1: Added comment: PMID 37972748: 23 affected individuals from 13 families with Lisch epithelial corneal dystrophy. WGS in 2 families and then targeted Sanger sequencing in the other families identified 9 rare heterozygous loss of function variants in MCOLN1. Homozygous and compound-heterozygous state of 4 of 9 LECD-associated variants cause Mucolipidosis IV (MLIV), which comprises neurodegeneration as well as corneal opacity of infantile-onset with epithelial autofluorescent lysosomal inclusions. Six parents of 3 patients with MLIV confirmed to carry pathogenic MCOLN1 variants did not have the LECD phenotype. Heterozygous MCOLN1 variants can be associated with incomplete penetrance and variable expressivity of LECD with an estimated penetrance of 0.2% for MCOLN1 loss-of-function variants based on gnomAD.; Changed publications: 37972748; Changed phenotypes: Mucolipidosis IV, MIM# 252650, MONDO:0009653, Lisch epithelial corneal dystrophy, OMIM# 620763; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Corneal Dystrophy v1.10 MCOLN1 Zornitza Stark Marked gene: MCOLN1 as ready
Corneal Dystrophy v1.10 MCOLN1 Zornitza Stark Gene: mcoln1 has been classified as Green List (High Evidence).
Growth failure v1.75 CEP295 Zornitza Stark Marked gene: CEP295 as ready
Growth failure v1.75 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5755 CEP295 Zornitza Stark Marked gene: CEP295 as ready
Intellectual disability syndromic and non-syndromic v0.5755 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Microcephaly v1.257 CEP295 Zornitza Stark Marked gene: CEP295 as ready
Microcephaly v1.257 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Mendeliome v1.1664 CEP295 Zornitza Stark Marked gene: CEP295 as ready
Mendeliome v1.1664 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Amelogenesis imperfecta v1.10 PLXNB2 Zornitza Stark Phenotypes for gene: PLXNB2 were changed from Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related to Syndromic disease MONDO:0002254, PLXNB2 -related
Deafness_IsolatedAndComplex v1.178 PLXNB2 Zornitza Stark Phenotypes for gene: PLXNB2 were changed from Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related to Syndromic disease MONDO:0002254, PLXNB2 -related
Mendeliome v1.1664 PLXNB2 Zornitza Stark Phenotypes for gene: PLXNB2 were changed from Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related to Syndromic disease MONDO:0002254, PLXNB2 -related
Intellectual disability syndromic and non-syndromic v0.5755 PLXNB2 Zornitza Stark Phenotypes for gene: PLXNB2 were changed from Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related to Syndromic disease MONDO:0002254, PLXNB2 -related
Intellectual disability syndromic and non-syndromic v0.5754 PLXNB2 Zornitza Stark Marked gene: PLXNB2 as ready
Intellectual disability syndromic and non-syndromic v0.5754 PLXNB2 Zornitza Stark Gene: plxnb2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.177 PLXNB2 Zornitza Stark Marked gene: PLXNB2 as ready
Deafness_IsolatedAndComplex v1.177 PLXNB2 Zornitza Stark Gene: plxnb2 has been classified as Green List (High Evidence).
Amelogenesis imperfecta v1.9 PLXNB2 Zornitza Stark Marked gene: PLXNB2 as ready
Amelogenesis imperfecta v1.9 PLXNB2 Zornitza Stark Gene: plxnb2 has been classified as Green List (High Evidence).
Mendeliome v1.1663 PLXNB2 Zornitza Stark Marked gene: PLXNB2 as ready
Mendeliome v1.1663 PLXNB2 Zornitza Stark Gene: plxnb2 has been classified as Green List (High Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v0.35 KCNJ2 Zornitza Stark Phenotypes for gene: KCNJ2 were changed from Andersen Tawil syndrome, LQTS to catecholaminergic polymorphic ventricular tachycardia MONDO:0017990
Catecholaminergic Polymorphic Ventricular Tachycardia v0.34 KCNJ2 Zornitza Stark Classified gene: KCNJ2 as Red List (low evidence)
Catecholaminergic Polymorphic Ventricular Tachycardia v0.34 KCNJ2 Zornitza Stark Gene: kcnj2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2540 KCNB2 Zornitza Stark Marked gene: KCNB2 as ready
Genetic Epilepsy v0.2540 KCNB2 Zornitza Stark Gene: kcnb2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2540 KCNB2 Zornitza Stark Classified gene: KCNB2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2540 KCNB2 Zornitza Stark Gene: kcnb2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2539 KCNB2 Zornitza Stark gene: KCNB2 was added
gene: KCNB2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KCNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNB2 were set to 38503299
Phenotypes for gene: KCNB2 were set to neurodevelopmental disorder MONDO:0700092, KCNB2-related
Review for gene: KCNB2 was set to AMBER
Added comment: 7 individuals, all missense
5 de novo + 1x inherited from father who has hypotonia + 1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature
Fetal anomalies v1.230 FRYL Zornitza Stark Classified gene: FRYL as Green List (high evidence)
Fetal anomalies v1.230 FRYL Zornitza Stark Gene: fryl has been classified as Green List (High Evidence).
Fetal anomalies v1.229 FRYL Zornitza Stark reviewed gene: FRYL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder MONDO:0700092, FRYL-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Tubulopathies and related disorders v1.12 TRPV5 Zornitza Stark Marked gene: TRPV5 as ready
Renal Tubulopathies and related disorders v1.12 TRPV5 Zornitza Stark Gene: trpv5 has been classified as Red List (Low Evidence).
Renal Tubulopathies and related disorders v1.12 TRPV5 Zornitza Stark gene: TRPV5 was added
gene: TRPV5 was added to Renal Tubulopathies and related disorders. Sources: Literature
Mode of inheritance for gene: TRPV5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRPV5 were set to 38528055; 14679186
Phenotypes for gene: TRPV5 were set to TRPV5-related hypercalciuria (MONDO:0009550)
Review for gene: TRPV5 was set to RED
Added comment: Not a well-established gene-disease association. Has only been reported in one consanguineous family.

PMID: 38528055
3 individuals from the same family affected with hypercalciuria.
Biallelic Met598Val variant was identified in the proband and his two affect sibs

Functional assay using WT and mutant plasmid vectors were transfected into HEK293T cells. The assay showed that the mutant vector had a non-functional TRPV5 channel as compared to the WT however no positive control was used.

PMID: 14679186
TRPV5 knockout mice model was used to assess whether the abolishment of TRPV5 led to a disruption in Ca2+ handling. The effects of the disruption in Ca2+ handling resulted in bone abnormalities in the mice and is likely the cause of idiopathic hypercalciuria.
Sources: Literature
Fetal anomalies v1.229 DISP1 Zornitza Stark Phenotypes for gene: DISP1 were changed from Holoprosencephaly, MONDO:0016296 to Holoprosencephaly (MONDO:0016296), DISP1-related
Fetal anomalies v1.228 DISP1 Zornitza Stark Publications for gene: DISP1 were set to 27363716; 19184110; 26748417; 23542665
Fetal anomalies v1.227 DISP1 Zornitza Stark Mode of inheritance for gene: DISP1 was changed from Other to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.226 DISP1 Zornitza Stark Classified gene: DISP1 as Green List (high evidence)
Fetal anomalies v1.226 DISP1 Zornitza Stark Gene: disp1 has been classified as Green List (High Evidence).
Fetal anomalies v1.225 DISP1 Zornitza Stark edited their review of gene: DISP1: Added comment: PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).
14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families).

HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP.; Changed rating: GREEN; Changed publications: 19184110, 26748417, 23542665, 38529886; Changed phenotypes: Holoprosencephaly (MONDO:0016296), DISP1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5754 DISP1 Zornitza Stark Phenotypes for gene: DISP1 were changed from Holoprosencephaly, MONDO:0016296 to Holoprosencephaly (MONDO:0016296), DISP1-related
Intellectual disability syndromic and non-syndromic v0.5753 DISP1 Zornitza Stark Publications for gene: DISP1 were set to 19184110; 26748417; 23542665
Intellectual disability syndromic and non-syndromic v0.5752 DISP1 Zornitza Stark Mode of inheritance for gene: DISP1 was changed from Other to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5751 DISP1 Zornitza Stark Classified gene: DISP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5751 DISP1 Zornitza Stark Gene: disp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5750 DISP1 Zornitza Stark edited their review of gene: DISP1: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.5750 DISP1 Zornitza Stark edited their review of gene: DISP1: Added comment: PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).
14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families).

HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP.; Changed publications: 19184110, 26748417, 23542665, 38529886; Changed phenotypes: Holoprosencephaly (MONDO:0016296), DISP1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1663 DOCK4 Zornitza Stark Marked gene: DOCK4 as ready
Mendeliome v1.1663 DOCK4 Zornitza Stark Gene: dock4 has been classified as Green List (High Evidence).
Mendeliome v1.1663 DOCK4 Zornitza Stark Classified gene: DOCK4 as Green List (high evidence)
Mendeliome v1.1663 DOCK4 Zornitza Stark Gene: dock4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5750 DOCK4 Bryony Thompson Phenotypes for gene: DOCK4 were changed from to DOCK4-related neurodevelopmental disorder (MONDO:0060490)
Intellectual disability syndromic and non-syndromic v0.5749 DOCK4 Bryony Thompson Publications for gene: DOCK4 were set to
Holoprosencephaly and septo-optic dysplasia v1.14 DISP1 Bryony Thompson Publications for gene: DISP1 were set to 19184110; 26748417; 23542665
Intellectual disability syndromic and non-syndromic v0.5748 DOCK4 Bryony Thompson Mode of inheritance for gene: DOCK4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Holoprosencephaly and septo-optic dysplasia v1.13 DISP1 Bryony Thompson Mode of inheritance for gene: DISP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5747 DOCK4 Bryony Thompson Classified gene: DOCK4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5747 DOCK4 Bryony Thompson Gene: dock4 has been classified as Green List (High Evidence).
Mendeliome v1.1662 TRPV5 Bryony Thompson Marked gene: TRPV5 as ready
Mendeliome v1.1662 TRPV5 Bryony Thompson Gene: trpv5 has been classified as Red List (Low Evidence).
Mendeliome v1.1662 TRPV5 Bryony Thompson Publications for gene: TRPV5 were set to PMID: 38528055
Holoprosencephaly and septo-optic dysplasia v1.12 DISP1 Bryony Thompson Classified gene: DISP1 as Green List (high evidence)
Holoprosencephaly and septo-optic dysplasia v1.12 DISP1 Bryony Thompson Gene: disp1 has been classified as Green List (High Evidence).
Mendeliome v1.1661 TRPV5 Bryony Thompson Classified gene: TRPV5 as Red List (low evidence)
Mendeliome v1.1661 TRPV5 Bryony Thompson Gene: trpv5 has been classified as Red List (Low Evidence).
Mendeliome v1.1660 TRPV5 Sangavi Sivagnanasundram edited their review of gene: TRPV5: Changed publications: PMID: 38528055, 14679186
Mendeliome v1.1660 TRPV5 Sangavi Sivagnanasundram changed review comment from: Not a well-established gene-disease association. Has only been reported in one consanguineous family.

PMID: 38528055
3 individuals from the same family affected with hypercalciuria.
Biallelic Met598Val variant was identified in the proband and his two affect sibs

Functional assay using WT and mutant plasmid vectors were transfected into HEK293T cells. The assay showed that the mutant vector had a non-functional TRPV5 channel as compared to the WT however no positive control was used.
Sources: Other; to: Not a well-established gene-disease association. Has only been reported in one consanguineous family.

PMID: 38528055
3 individuals from the same family affected with hypercalciuria.
Biallelic Met598Val variant was identified in the proband and his two affect sibs

Functional assay using WT and mutant plasmid vectors were transfected into HEK293T cells. The assay showed that the mutant vector had a non-functional TRPV5 channel as compared to the WT however no positive control was used.

PMID: 14679186
TRPV5 knockout mice model was used to assess whether the abolishment of TRPV5 led to a disruption in Ca2+ handling. The effects of the disruption in Ca2+ handling resulted in bone abnormalities in the mice and is likely the cause of idiopathic hypercalciuria.

Sources: Other
Mendeliome v1.1660 DOCK4 Sangavi Sivagnanasundram gene: DOCK4 was added
gene: DOCK4 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: DOCK4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DOCK4 were set to PMID: 38526744
Phenotypes for gene: DOCK4 were set to DOCK4-related neurodevelopmental disorder (MONDO:0060490)
Review for gene: DOCK4 was set to GREEN
Added comment: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities. Two of the individuals are reportedly compound heterozygous.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5746 DOCK4 Sangavi Sivagnanasundram changed review comment from: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).; to: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities. Two of the individuals are reportedly compound heterozygous.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).
Intellectual disability syndromic and non-syndromic v0.5746 DOCK4 Sangavi Sivagnanasundram changed review comment from: Well-established gene-disease association

7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).; to: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).
Mendeliome v1.1660 DISP1 Bryony Thompson Publications for gene: DISP1 were set to 19184110; 26748417; 23542665
Mendeliome v1.1659 DISP1 Bryony Thompson Mode of inheritance for gene: DISP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1658 DISP1 Bryony Thompson Classified gene: DISP1 as Green List (high evidence)
Mendeliome v1.1658 DISP1 Bryony Thompson Gene: disp1 has been classified as Green List (High Evidence).
Mendeliome v1.1657 DISP1 Sangavi Sivagnanasundram changed review comment from: Well-establised gene disease association with differing mechanism of disease depending on the type of causative variant.
Monoallelic truncating variants that resulted in haploinsufficiency in DISP1 led to mild HPE. However biallelic missense variants that results in a partial loss of function of DISP1 cause HPE as well.

PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).
14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families).

HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP.

; to: Gene disease association with differing mechanism of disease depending on the type of causative variant.
Monoallelic truncating variants that resulted in haploinsufficiency in DISP1 led to mild HPE. However biallelic missense variants that results in a partial loss of function of DISP1 cause HPE as well.

PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).
14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families).

HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP.

Mendeliome v1.1657 DISP1 Sangavi Sivagnanasundram changed review comment from: Well-establised gene disease association with differing mechanism of disease depending on the type of causative variant.

PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).

Monoallelic truncating variants that resulted in haploinsufficiency in DISP1 led to mild HPE. However biallelic missense variants that results in a partial loss of function f DISP1 cause HPE as well.; to: Well-establised gene disease association with differing mechanism of disease depending on the type of causative variant.
Monoallelic truncating variants that resulted in haploinsufficiency in DISP1 led to mild HPE. However biallelic missense variants that results in a partial loss of function of DISP1 cause HPE as well.

PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).
14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families).

HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP.

Fetal anomalies v1.225 FRYL Ain Roesley Marked gene: FRYL as ready
Fetal anomalies v1.225 FRYL Ain Roesley Gene: fryl has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.225 FRYL Ain Roesley Classified gene: FRYL as Amber List (moderate evidence)
Fetal anomalies v1.225 FRYL Ain Roesley Gene: fryl has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.224 FRYL Ain Roesley gene: FRYL was added
gene: FRYL was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRYL were set to 38479391
Phenotypes for gene: FRYL were set to neurodevelopmental disorder MONDO:0700092, FRYL-related
Review for gene: FRYL was set to AMBER
gene: FRYL was marked as current diagnostic
Added comment: 14 individuals, all de novo except 1x duo testing (not present in tested father)
5x missense + 8x fs/stopgain + 1x canonical splice

7/14 with cardiac anomalies

Of interest to this panel: 1x tetralogy of fallot (TOF) with pulmonary atresia (PA), 2x dextrocardia, 1x hypoplastic left heart syndrome

Other reported features AVSD, VSD, PDA
Sources: Literature
Congenital Heart Defect v0.416 FRYL Ain Roesley Classified gene: FRYL as Green List (high evidence)
Congenital Heart Defect v0.416 FRYL Ain Roesley Gene: fryl has been classified as Green List (High Evidence).
Congenital Heart Defect v0.415 FRYL Ain Roesley gene: FRYL was added
gene: FRYL was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRYL were set to 38479391
Phenotypes for gene: FRYL were set to neurodevelopmental disorder MONDO:0700092, FRYL-related
Review for gene: FRYL was set to GREEN
gene: FRYL was marked as current diagnostic
Added comment: 14 individuals, all de novo except 1x duo testing (not present in tested father)
5x missense + 8x fs/stopgain + 1x canonical splice

13/13 with ID/DD (1x deceased)
4/14 seizures
7/14 with cardiac anomalies such as PDA, TOF, VSD, dextrocardia

1x also has a de novo fs variant in SF3B4
1x also has a de novo stop gain variant in SDHA

functional studies using flies were performed
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5746 FRYL Ain Roesley Marked gene: FRYL as ready
Intellectual disability syndromic and non-syndromic v0.5746 FRYL Ain Roesley Gene: fryl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5746 FRYL Ain Roesley Classified gene: FRYL as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5746 FRYL Ain Roesley Gene: fryl has been classified as Green List (High Evidence).
Mendeliome v1.1657 FRYL Ain Roesley Marked gene: FRYL as ready
Mendeliome v1.1657 FRYL Ain Roesley Gene: fryl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5745 FRYL Ain Roesley gene: FRYL was added
gene: FRYL was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRYL were set to 38479391
Phenotypes for gene: FRYL were set to neurodevelopmental disorder MONDO:0700092, FRYL-related
Review for gene: FRYL was set to GREEN
gene: FRYL was marked as current diagnostic
Added comment: 14 individuals, all de novo except 1x duo testing (not present in tested father)
5x missense + 8x fs/stopgain + 1x canonical splice

13/13 with ID/DD (1x deceased)
4/14 seizures
7/14 with cardiac anomalies such as PDA, TOF, VSD, dextrocardia

1x also has a de novo fs variant in SF3B4
1x also has a de novo stop gain variant in SDHA

functional studies using flies were performed
Sources: Literature
Mendeliome v1.1657 FRYL Ain Roesley Classified gene: FRYL as Green List (high evidence)
Mendeliome v1.1657 FRYL Ain Roesley Gene: fryl has been classified as Green List (High Evidence).
Mendeliome v1.1656 FRYL Ain Roesley gene: FRYL was added
gene: FRYL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRYL were set to 38479391
Phenotypes for gene: FRYL were set to neurodevelopmental disorder MONDO:0700092, FRYL-related
Review for gene: FRYL was set to GREEN
gene: FRYL was marked as current diagnostic
Added comment: 14 individuals, all de novo except 1x duo testing (not present in tested father)
5x missense + 8x fs/stopgain + 1x canonical splice

13/13 with ID/DD (1x deceased)
4/14 seizures
7/14 with cardiac anomalies such as PDA, TOF, VSD, dextrocardia

1x also has a de novo fs variant in SF3B4
1x also has a de novo stop gain variant in SDHA

functional studies using flies were performed
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5744 KCNB2 Ain Roesley Marked gene: KCNB2 as ready
Intellectual disability syndromic and non-syndromic v0.5744 KCNB2 Ain Roesley Gene: kcnb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5744 KCNB2 Ain Roesley Classified gene: KCNB2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5744 KCNB2 Ain Roesley Gene: kcnb2 has been classified as Green List (High Evidence).
Mendeliome v1.1655 KCNB2 Ain Roesley Marked gene: KCNB2 as ready
Mendeliome v1.1655 KCNB2 Ain Roesley Gene: kcnb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5743 KCNB2 Ain Roesley gene: KCNB2 was added
gene: KCNB2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: KCNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNB2 were set to 38503299
Phenotypes for gene: KCNB2 were set to neurodevelopmental disorder MONDO:0700092, KCNB2-related
Review for gene: KCNB2 was set to GREEN
gene: KCNB2 was marked as current diagnostic
Added comment: 7 individuals, all missense
5 de novo + 1x inherited from father who has hypotonia + 1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature
Sources: Literature
Mendeliome v1.1655 KCNB2 Ain Roesley Classified gene: KCNB2 as Green List (high evidence)
Mendeliome v1.1655 KCNB2 Ain Roesley Gene: kcnb2 has been classified as Green List (High Evidence).
Mendeliome v1.1654 KCNB2 Ain Roesley changed review comment from: 7 individuals, all missense
1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature; to: 7 individuals, all missense
5 de novo + 1x inherited from father who has hypotonia + 1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature
Mendeliome v1.1654 KCNB2 Ain Roesley gene: KCNB2 was added
gene: KCNB2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KCNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNB2 were set to 38503299
Phenotypes for gene: KCNB2 were set to neurodevelopmental disorder MONDO:0700092, KCNB2-related
Review for gene: KCNB2 was set to GREEN
gene: KCNB2 was marked as current diagnostic
Added comment: 7 individuals, all missense
1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5742 DOCK4 Sangavi Sivagnanasundram edited their review of gene: DOCK4: Changed rating: GREEN
Catecholaminergic Polymorphic Ventricular Tachycardia v0.33 KCNJ2 Sangavi Sivagnanasundram reviewed gene: KCNJ2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: catecholaminergic polymorphic ventricular tachycardia MONDO:0017990; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.223 MAP3K20 Zornitza Stark edited their review of gene: MAP3K20: Added comment: PMID 38451290: five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20.; Changed publications: 38451290; Changed phenotypes: Syndromic disease, MONDO:0002254, MAP3K20-related, Centronuclear myopathy 6 with fiber-type disproportion MIM#617760, Split-foot malformation with mesoaxial polydactyly MIM#616890; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ectodermal Dysplasia v0.85 MAP3K20 Zornitza Stark Marked gene: MAP3K20 as ready
Ectodermal Dysplasia v0.85 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Ectodermal Dysplasia v0.85 MAP3K20 Zornitza Stark Classified gene: MAP3K20 as Green List (high evidence)
Ectodermal Dysplasia v0.85 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Ectodermal Dysplasia v0.84 MAP3K20 Zornitza Stark gene: MAP3K20 was added
gene: MAP3K20 was added to Ectodermal Dysplasia. Sources: Literature
Mode of inheritance for gene: MAP3K20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP3K20 were set to 38451290
Phenotypes for gene: MAP3K20 were set to Syndromic disease, MONDO:0002254, MAP3K20-related
Review for gene: MAP3K20 was set to GREEN
Added comment: PMID 38451290: five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20.
Sources: Literature
Deafness_IsolatedAndComplex v1.177 MAP3K20 Zornitza Stark Marked gene: MAP3K20 as ready
Deafness_IsolatedAndComplex v1.177 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.177 MAP3K20 Zornitza Stark Classified gene: MAP3K20 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.177 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.176 MAP3K20 Zornitza Stark gene: MAP3K20 was added
gene: MAP3K20 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: MAP3K20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP3K20 were set to 38451290
Phenotypes for gene: MAP3K20 were set to Syndromic disease, MONDO:0002254, MAP3K20-related
Review for gene: MAP3K20 was set to GREEN
Added comment: PMID 38451290: five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20.
Sources: Literature
Craniosynostosis v1.68 MAP3K20 Zornitza Stark Marked gene: MAP3K20 as ready
Craniosynostosis v1.68 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Craniosynostosis v1.68 MAP3K20 Zornitza Stark Classified gene: MAP3K20 as Green List (high evidence)
Craniosynostosis v1.68 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Craniosynostosis v1.67 MAP3K20 Zornitza Stark gene: MAP3K20 was added
gene: MAP3K20 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: MAP3K20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP3K20 were set to 38451290
Phenotypes for gene: MAP3K20 were set to Syndromic disease, MONDO:0002254, MAP3K20-related
Review for gene: MAP3K20 was set to GREEN
Added comment: PMID 38451290: five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20.
Sources: Literature
Mendeliome v1.1653 MAP3K20 Zornitza Stark Phenotypes for gene: MAP3K20 were changed from Centronuclear myopathy 6 with fiber-type disproportion MIM#617760; Split-foot malformation with mesoaxial polydactyly MIM#616890 to Syndromic disease, MONDO:0002254, MAP3K20-related; Centronuclear myopathy 6 with fiber-type disproportion MIM#617760; Split-foot malformation with mesoaxial polydactyly MIM#616890
Mendeliome v1.1652 MAP3K20 Zornitza Stark Publications for gene: MAP3K20 were set to 27816943; 26755636
Mendeliome v1.1651 MAP3K20 Zornitza Stark Mode of inheritance for gene: MAP3K20 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1650 MAP3K20 Zornitza Stark reviewed gene: MAP3K20: Rating: GREEN; Mode of pathogenicity: None; Publications: 38451290; Phenotypes: Syndromic disease, MONDO:0002254, MAP3K20-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.257 SASS6 Ain Roesley Publications for gene: SASS6 were set to 24951542; 30639237; 38501757; 36739862
Microcephaly v1.256 SASS6 Ain Roesley Publications for gene: SASS6 were set to 24951542; 30639237
Mendeliome v1.1650 PLXNB2 Chirag Patel Classified gene: PLXNB2 as Green List (high evidence)
Mendeliome v1.1650 PLXNB2 Chirag Patel Gene: plxnb2 has been classified as Green List (High Evidence).
Microcephaly v1.256 SASS6 Ain Roesley Classified gene: SASS6 as Green List (high evidence)
Microcephaly v1.256 SASS6 Ain Roesley Gene: sass6 has been classified as Green List (High Evidence).
Mendeliome v1.1649 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Mendeliome v1.1649 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Fetal anomalies v1.223 SASS6 Ain Roesley Publications for gene: SASS6 were set to 24951542; 30639237
Mendeliome v1.1649 PLXNB2 Chirag Patel gene: PLXNB2 was added
gene: PLXNB2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to PMID: 38458752
Phenotypes for gene: PLXNB2 were set to Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related
Review for gene: PLXNB2 was set to GREEN
gene: PLXNB2 was marked as current diagnostic
Added comment: 8 individuals from 6 families with core features of amelogenesis imperfecta and sensorineural hearing loss. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. WES and WGS identified biallelic pathogenic variants in PLXNB2 (missense, nonsense, splice and a multiexon deletion variants). Variants segregated with disease.

PLXNB2 is a large transmembrane semaphorin receptor protein, and semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Plxnb2 expression was detected in differentiating ameloblasts in mice. Human phenotype overlaps with that seen in Plxnb2 knockout mice.
Sources: Literature
Fetal anomalies v1.223 SASS6 Ain Roesley Classified gene: SASS6 as Green List (high evidence)
Fetal anomalies v1.223 SASS6 Ain Roesley Gene: sass6 has been classified as Green List (High Evidence).
Microcephaly v1.255 SASS6 Ain Roesley reviewed gene: SASS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 38501757, 36739862; Phenotypes: Microcephaly 14, primary, autosomal recessive, MIM# 616402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v1.222 SASS6 Ain Roesley reviewed gene: SASS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 38501757, 36739862; Phenotypes: Microcephaly 14, primary, autosomal recessive, MIM# 616402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1648 CEP295 Chirag Patel gene: CEP295 was added
gene: CEP295 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to PMID: 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Review for gene: CEP295 was set to GREEN
gene: CEP295 was marked as current diagnostic
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Literature
Mendeliome v1.1647 SASS6 Ain Roesley Publications for gene: SASS6 were set to 24951542; 30639237
Mendeliome v1.1647 SASS6 Ain Roesley Classified gene: SASS6 as Green List (high evidence)
Mendeliome v1.1647 SASS6 Ain Roesley Gene: sass6 has been classified as Green List (High Evidence).
Mendeliome v1.1646 SASS6 Ain Roesley Deleted their comment
Mendeliome v1.1646 SASS6 Ain Roesley commented on gene: SASS6: PMID: 38501757
1x compound het for a fs and +3 splice variant.

Using cDNA RT-ed from mother's RNA, exons 13-15 were amplified and exon 14 was found to be skipped resulting in c.1546_1674del and p.516_558del

PMID: 36739862
1x family, compound het for 2 missense
Functional studies not performed
Mendeliome v1.1646 SASS6 Ain Roesley reviewed gene: SASS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 38501757, 36739862; Phenotypes: Microcephaly 14, primary, autosomal recessive, MIM# 616402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1646 FANCI Ain Roesley Phenotypes for gene: FANCI were changed from Fanconi anemia, complementation group I, MIM# 609053; MONDO:0012186 to Fanconi anemia, complementation group I, MIM# 609053; MONDO:0012186; primary ovarian failure MONDO:0005387, FANCI-related
Mendeliome v1.1645 FANCI Ain Roesley reviewed gene: FANCI: Rating: AMBER; Mode of pathogenicity: None; Publications: 38483614; Phenotypes: primary ovarian failure MONDO:0005387, FANCI-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.325 FANCI Ain Roesley edited their review of gene: FANCI: Changed phenotypes: primary ovarian failure MONDO:0005387, FANCI-related
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.325 FANCI Ain Roesley Marked gene: FANCI as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.325 FANCI Ain Roesley Gene: fanci has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.325 FANCI Ain Roesley Classified gene: FANCI as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.325 FANCI Ain Roesley Gene: fanci has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.324 FANCI Ain Roesley gene: FANCI was added
gene: FANCI was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature
Mode of inheritance for gene: FANCI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCI were set to 38483614
Review for gene: FANCI was set to AMBER
gene: FANCI was marked as current diagnostic
Added comment: WES however FANCI was specifically looked at based on KO mouse model which had premature exhaustion of primordial follicles leading to complete sterility.

2x compound hets: 2x missense + 1x canonical splice+1x missense

Minigene performed on the splice variant
Functional assays using KO cells + expression of variant demonstrated reduced ubiquitination of FANCI and increased DNA damage under replication stress
Sources: Literature
Corneal Dystrophy v1.10 MCOLN1 Chirag Patel Classified gene: MCOLN1 as Green List (high evidence)
Corneal Dystrophy v1.10 MCOLN1 Chirag Patel Gene: mcoln1 has been classified as Green List (High Evidence).
Corneal Dystrophy v1.10 MCOLN1 Chirag Patel Classified gene: MCOLN1 as Green List (high evidence)
Corneal Dystrophy v1.10 MCOLN1 Chirag Patel Gene: mcoln1 has been classified as Green List (High Evidence).
Corneal Dystrophy v1.9 MCOLN1 Chirag Patel gene: MCOLN1 was added
gene: MCOLN1 was added to Corneal Dystrophy. Sources: Literature
Mode of inheritance for gene: MCOLN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MCOLN1 were set to PMID: 37972748,
Phenotypes for gene: MCOLN1 were set to Lisch epithelial corneal dystrophy, OMIM# 620763
Review for gene: MCOLN1 was set to GREEN
gene: MCOLN1 was marked as current diagnostic
Added comment: 23 affected individuals from 13 families with Lisch epithelial corneal dystrophy. WGS in 2 families and then targeted Sanger sequencing in the other families identified 9 rare heterozygous loss of function variants in MCOLN1.

Homozygous and compound-heterozygous state of 4 of 9 LECD-associated variants cause Mucolipidosis IV (MLIV), which comprises neurodegeneration as well as corneal opacity of infantile-onset with epithelial autofluorescent lysosomal inclusions. Six parents of 3 patients with MLIV confirmed to carry pathogenic MCOLN1 variants did not have the LECD phenotype.

Heterozygous MCOLN1 variants can be associated with incomplete penetrance and variable expressivity of LECD with an estimated penetrance of 0.2% for MCOLN1 loss-of-function variants based on gnomAD.
Sources: Literature
Deafness_IsolatedAndComplex v1.175 PLXNB2 Chirag Patel Classified gene: PLXNB2 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.175 PLXNB2 Chirag Patel Gene: plxnb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5742 PLXNB2 Chirag Patel Classified gene: PLXNB2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5742 PLXNB2 Chirag Patel Gene: plxnb2 has been classified as Green List (High Evidence).
Amelogenesis imperfecta v1.9 PLXNB2 Chirag Patel Classified gene: PLXNB2 as Green List (high evidence)
Amelogenesis imperfecta v1.9 PLXNB2 Chirag Patel Gene: plxnb2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.174 PLXNB2 Chirag Patel gene: PLXNB2 was added
gene: PLXNB2 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to PMID: 38458752
Phenotypes for gene: PLXNB2 were set to Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related
Review for gene: PLXNB2 was set to GREEN
gene: PLXNB2 was marked as current diagnostic
Added comment: 8 individuals from 6 families with core features of amelogenesis imperfecta and sensorineural hearing loss. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. WES and WGS identified biallelic pathogenic variants in PLXNB2 (missense, nonsense, splice and a multiexon deletion variants). Variants segregated with disease.

PLXNB2 is a large transmembrane semaphorin receptor protein, and semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Plxnb2 expression was detected in differentiating ameloblasts in mice. Human phenotype overlaps with that seen in Plxnb2 knockout mice.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5741 PLXNB2 Chirag Patel gene: PLXNB2 was added
gene: PLXNB2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to PMID: 38458752
Phenotypes for gene: PLXNB2 were set to Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related
Review for gene: PLXNB2 was set to GREEN
gene: PLXNB2 was marked as current diagnostic
Added comment: 8 individuals from 6 families with core features of amelogenesis imperfecta and sensorineural hearing loss. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. WES and WGS identified biallelic pathogenic variants in PLXNB2 (missense, nonsense, splice and a multiexon deletion variants). Variants segregated with disease.

PLXNB2 is a large transmembrane semaphorin receptor protein, and semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Plxnb2 expression was detected in differentiating ameloblasts in mice. Human phenotype overlaps with that seen in Plxnb2 knockout mice.
Sources: Literature
Amelogenesis imperfecta v1.8 PLXNB2 Chirag Patel gene: PLXNB2 was added
gene: PLXNB2 was added to Amelogenesis imperfecta. Sources: Literature
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to PMID: 38458752
Phenotypes for gene: PLXNB2 were set to Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related
Review for gene: PLXNB2 was set to GREEN
gene: PLXNB2 was marked as current diagnostic
Added comment: 8 individuals from 6 families with core features of amelogenesis imperfecta and sensorineural hearing loss. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. WES and WGS identified biallelic pathogenic variants in PLXNB2 (missense, nonsense, splice and a multiexon deletion variants). Variants segregated with disease.

PLXNB2 is a large transmembrane semaphorin receptor protein, and semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Plxnb2 expression was detected in differentiating ameloblasts in mice. Human phenotype overlaps with that seen in Plxnb2 knockout mice.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5740 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5740 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5740 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5740 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5739 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5739 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Microcephaly v1.255 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Microcephaly v1.255 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5739 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5739 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Microcephaly v1.254 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Microcephaly v1.254 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Growth failure v1.75 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Growth failure v1.75 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5738 CEP295 Chirag Patel gene: CEP295 was added
gene: CEP295 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to PMID: 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Review for gene: CEP295 was set to GREEN
gene: CEP295 was marked as current diagnostic
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Literature
Microcephaly v1.253 CEP295 Chirag Patel gene: CEP295 was added
gene: CEP295 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to PMID: 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Review for gene: CEP295 was set to GREEN
gene: CEP295 was marked as current diagnostic
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Literature
Growth failure v1.74 CEP295 Chirag Patel gene: CEP295 was added
gene: CEP295 was added to Growth failure. Sources: Literature
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to PMID: 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Review for gene: CEP295 was set to GREEN
gene: CEP295 was marked as current diagnostic
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Literature
Mendeliome v1.1645 CAPNS1 Zornitza Stark Marked gene: CAPNS1 as ready
Mendeliome v1.1645 CAPNS1 Zornitza Stark Gene: capns1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1645 CAPNS1 Zornitza Stark Classified gene: CAPNS1 as Amber List (moderate evidence)
Mendeliome v1.1645 CAPNS1 Zornitza Stark Gene: capns1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1644 CAPNS1 Zornitza Stark gene: CAPNS1 was added
gene: CAPNS1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CAPNS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAPNS1 were set to 38230350
Phenotypes for gene: CAPNS1 were set to Hereditary pulmonary arterial hypertension MONDO:0017148, CAPNS1-related
Review for gene: CAPNS1 was set to AMBER
Added comment: Three individuals from two families reported with homozygous splice site variants.
Sources: Expert list
Pulmonary Arterial Hypertension v1.37 CAPNS1 Zornitza Stark Marked gene: CAPNS1 as ready
Pulmonary Arterial Hypertension v1.37 CAPNS1 Zornitza Stark Gene: capns1 has been classified as Amber List (Moderate Evidence).
Pulmonary Arterial Hypertension v1.37 CAPNS1 Zornitza Stark Classified gene: CAPNS1 as Amber List (moderate evidence)
Pulmonary Arterial Hypertension v1.37 CAPNS1 Zornitza Stark Gene: capns1 has been classified as Amber List (Moderate Evidence).
Pulmonary Arterial Hypertension v1.36 CAPNS1 Zornitza Stark gene: CAPNS1 was added
gene: CAPNS1 was added to Pulmonary Arterial Hypertension. Sources: Expert list
Mode of inheritance for gene: CAPNS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAPNS1 were set to 38230350
Phenotypes for gene: CAPNS1 were set to Hereditary pulmonary arterial hypertension MONDO:0017148, CAPNS1-related
Review for gene: CAPNS1 was set to AMBER
Added comment: Three individuals from two families reported with homozygous splice site variants.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5737 USP27X Zornitza Stark Phenotypes for gene: USP27X were changed from Mental retardation, X-linked 105, MIM#300984 to Intellectual disability, X-linked 105, MIM#300984
Intellectual disability syndromic and non-syndromic v0.5736 USP27X Zornitza Stark Publications for gene: USP27X were set to 25644381
Intellectual disability syndromic and non-syndromic v0.5735 USP27X Zornitza Stark Classified gene: USP27X as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5735 USP27X Zornitza Stark Gene: usp27x has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5734 USP27X Zornitza Stark edited their review of gene: USP27X: Added comment: Ten additional individuals and further experimental data reported.; Changed rating: GREEN; Changed publications: 25644381, 38182161; Changed phenotypes: Intellectual disability, X-linked 105, MIM#300984
Mendeliome v1.1643 USP27X Zornitza Stark Phenotypes for gene: USP27X were changed from Mental retardation, X-linked 105, MIM#300984 to Intellectual disability, X-linked 105, MIM#300984
Mendeliome v1.1642 USP27X Zornitza Stark Publications for gene: USP27X were set to 25644381
Mendeliome v1.1641 USP27X Zornitza Stark Classified gene: USP27X as Green List (high evidence)
Mendeliome v1.1641 USP27X Zornitza Stark Gene: usp27x has been classified as Green List (High Evidence).
Mendeliome v1.1640 USP27X Zornitza Stark edited their review of gene: USP27X: Added comment: Ten additional individuals and further experimental data reported.; Changed rating: GREEN; Changed publications: 25644381, 38182161; Changed phenotypes: Intellectual disability, X-linked 105, MIM#300984
Mendeliome v1.1640 ZNF143 Bryony Thompson Classified gene: ZNF143 as Amber List (moderate evidence)
Mendeliome v1.1640 ZNF143 Bryony Thompson Gene: znf143 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1639 ZNF143 Bryony Thompson reviewed gene: ZNF143: Rating: AMBER; Mode of pathogenicity: None; Publications: 27349184, 33845046, 9009278, 22268977, 27349184, 27349184; Phenotypes: methylmalonic aciduria and homocystinuria MONDO:0016826; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1639 TCN1 Bryony Thompson Marked gene: TCN1 as ready
Mendeliome v1.1639 TCN1 Bryony Thompson Gene: tcn1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1639 TCN1 Bryony Thompson Classified gene: TCN1 as Amber List (moderate evidence)
Mendeliome v1.1639 TCN1 Bryony Thompson Gene: tcn1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1638 TCN1 Bryony Thompson gene: TCN1 was added
gene: TCN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TCN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TCN1 were set to 29764838; 19686235
Phenotypes for gene: TCN1 were set to transcobalamin I deficiency MONDO:0008659
Review for gene: TCN1 was set to AMBER
Added comment: Unclear if TC1 deficiency is associated with a clinical phenotype and only found 2 families with genetic findings. 1 confirmed chet (2 truncating variants) with severe TC 1 deficiency (depression and anxiety only reported symptoms, had sickle cell trait) & another family with 2 siblings that are presumed homozygous for a truncating variant (no plasma or serum TC 1 levels but no DNA available for genetic testing) which was found heterozygous in multiple first-degree relatives. Unclear if there is a clinical phenotype. Heterozygous individuals displayed mildly low or low-normal TC 1 serum levels. Also, 4 homozygotes were identified in a study of a loss-of-function variant associated with lower vitamin B12 concentration in African Americans but there was limited ability to assess the clinical impact of the recessive disease
Sources: Literature
Mendeliome v1.1637 FEM1B Zornitza Stark Classified gene: FEM1B as Green List (high evidence)
Mendeliome v1.1637 FEM1B Zornitza Stark Gene: fem1b has been classified as Green List (High Evidence).
Mendeliome v1.1636 FEM1B Zornitza Stark Publications for gene: FEM1B were set to PMID: 31036916
Mendeliome v1.1635 FEM1B Zornitza Stark Phenotypes for gene: FEM1B were changed from Syndromic intellectual disability to Syndromic disease MONDO:0002254, FEM1B-related
Intellectual disability syndromic and non-syndromic v0.5734 FEM1B Zornitza Stark Phenotypes for gene: FEM1B were changed from Syndromic intellectual disability to Syndromic disease MONDO:0002254, FEM1B-related
Intellectual disability syndromic and non-syndromic v0.5733 FEM1B Zornitza Stark Publications for gene: FEM1B were set to 31036916
Mendeliome v1.1634 FEM1B Zornitza Stark edited their review of gene: FEM1B: Added comment: Five individuals reported now with same recurrent missense variant, NM_015322.5:c.377G>A NP_056137.1:p.(Arg126Gln). Affected individuals shared a severe neurodevelopmental disorder with behavioral phenotypes and a variable set of malformations, including brain anomalies, clubfeet, skeletal abnormalities, and facial dysmorphism. Overexpression of the the FEM1BR126Q variant but not FEM1B wild-type protein, during mouse brain development, resulted in delayed neuronal migration of the target cells.; Changed rating: GREEN; Changed publications: 31036916, 38465576; Changed phenotypes: Syndromic disease MONDO:0002254, FEM1B-related; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5732 FEM1B Zornitza Stark Classified gene: FEM1B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5732 FEM1B Zornitza Stark Gene: fem1b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5731 FEM1B Zornitza Stark edited their review of gene: FEM1B: Added comment: Five individuals reported now with same recurrent missense variant, NM_015322.5:c.377G>A NP_056137.1:p.(Arg126Gln). Affected individuals shared a severe neurodevelopmental disorder with behavioral phenotypes and a variable set of malformations, including brain anomalies, clubfeet, skeletal abnormalities, and facial dysmorphism. Overexpression of the the FEM1BR126Q variant but not FEM1B wild-type protein, during mouse brain development, resulted in delayed neuronal migration of the target cells.; Changed rating: GREEN; Changed publications: 31036916, 38465576; Changed phenotypes: Syndromic disease MONDO:0002254, FEM1B-related
Intellectual disability syndromic and non-syndromic v0.5731 USP14 Zornitza Stark Marked gene: USP14 as ready
Intellectual disability syndromic and non-syndromic v0.5731 USP14 Zornitza Stark Gene: usp14 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5731 USP14 Zornitza Stark Classified gene: USP14 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5731 USP14 Zornitza Stark Gene: usp14 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5730 USP14 Zornitza Stark Classified gene: USP14 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5730 USP14 Zornitza Stark Gene: usp14 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5729 USP14 Zornitza Stark gene: USP14 was added
gene: USP14 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: USP14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP14 were set to 38469793; 35066879
Phenotypes for gene: USP14 were set to Syndromic disease MONDO:0002254, USP14-related
Review for gene: USP14 was set to AMBER
Added comment: AMBER rating as two of the families had affected fetuses, one had a severely affected newborn, and fourth had a progressive course: none fit well with ID, though there's likely to be a continuum.

PMID 35066879: 3 fetuses from 2 different branches of a consanguineous family, presenting with distal arthrogryposis, underdevelopment of the corpus callosum, and dysmorphic facial features. Exome sequencing identified a biallelic 4-bp deletion (c.233_236delTTCC; p.Leu78Glnfs*11) in USP14, and sequencing of family members showed segregation with the phenotype. Ubiquitin-specific protease 14 (USP14) encodes a major proteasome-associated deubiquitinating enzyme with an established dual role as an inhibitor and an activator of proteolysis, maintaining protein homeostasis. Usp14-deficient mice show a phenotype similar to lethal human multiple congenital contractures phenotypes, with callosal anomalies, muscle wasting, and early lethality, attributed to neuromuscular junction defects due to decreased monomeric ubiquitin pool. RT-qPCR experiment in an unaffected heterozygote revealed that mutant USP14 was expressed, indicating that abnormal transcript escapes nonsense-mediated mRNA decay.

PMID 38469793: biallelic USP14 variants in four individuals from three unrelated families: one fetus, a newborn with a syndromic NDD, and two siblings affected by a progressive neurological disease. Specifically, the two siblings from the latter family carried two compound heterozygous variants c.8T>C p.(Leu3Pro) and c.988C>T p.(Arg330*), while the fetus had a homozygous frameshift c.899_902del p.(Lys300Serfs*24) variant and the newborn patient harbored a homozygous frameshift c.233_236del p.(Leu78Glnfs*11) variant. The fetus and the newborn had extensive brain malformations.
Sources: Literature
Mendeliome v1.1634 DISP1 Sangavi Sivagnanasundram reviewed gene: DISP1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 38529886; Phenotypes: Holoprosencephaly (MONDO:0016296); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1634 TRPV5 Sangavi Sivagnanasundram gene: TRPV5 was added
gene: TRPV5 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: TRPV5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRPV5 were set to PMID: 38528055
Phenotypes for gene: TRPV5 were set to TRPV5-related hypercalciuria (MONDO:0009550)
Review for gene: TRPV5 was set to RED
Added comment: Not a well-established gene-disease association. Has only been reported in one consanguineous family.

PMID: 38528055
3 individuals from the same family affected with hypercalciuria.
Biallelic Met598Val variant was identified in the proband and his two affect sibs

Functional assay using WT and mutant plasmid vectors were transfected into HEK293T cells. The assay showed that the mutant vector had a non-functional TRPV5 channel as compared to the WT however no positive control was used.
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5728 DOCK4 Sangavi Sivagnanasundram reviewed gene: DOCK4: Rating: ; Mode of pathogenicity: None; Publications: PMID: 38526744; Phenotypes: DOCK4-related neurodevelopmental disorder (MONDO:0060490); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Metabolic Disorders Superpanel v8.125 Bryony Thompson Changed child panels to: Congenital Disorders of Glycosylation; Miscellaneous Metabolic Disorders; Calcium and Phosphate disorders; Fatty Acid Oxidation Defects; Hypertension and Aldosterone disorders; Lysosomal Storage Disorder; Neurotransmitter Defects; Disorders of branched chain amino acid metabolism; Glycogen Storage Diseases; Rhabdomyolysis and Metabolic Myopathy; Inherited vitamin B12 or cobalamin deficiency; Mitochondrial disease; Peroxisomal Disorders; Iron metabolism disorders; Dyslipidaemia; Vitamin C Pathway Disorders; Porphyria; Hyperammonaemia
Miscellaneous Metabolic Disorders v1.44 DPYD Bryony Thompson Tag pharmacogenomic tag was added to gene: DPYD.
Callosome v0.521 USP14 Zornitza Stark Publications for gene: USP14 were set to PMID: 35066879
Callosome v0.520 USP14 Zornitza Stark Classified gene: USP14 as Green List (high evidence)
Callosome v0.520 USP14 Zornitza Stark Gene: usp14 has been classified as Green List (High Evidence).
Callosome v0.519 USP14 Zornitza Stark reviewed gene: USP14: Rating: GREEN; Mode of pathogenicity: None; Publications: 38469793; Phenotypes: Syndromic disease MONDO:0002254, USP14-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.222 USP14 Zornitza Stark Publications for gene: USP14 were set to PMID: 35066879
Fetal anomalies v1.221 USP14 Zornitza Stark Classified gene: USP14 as Green List (high evidence)
Fetal anomalies v1.221 USP14 Zornitza Stark Gene: usp14 has been classified as Green List (High Evidence).
Fetal anomalies v1.220 USP14 Zornitza Stark reviewed gene: USP14: Rating: GREEN; Mode of pathogenicity: None; Publications: 38469793; Phenotypes: Syndromic disease MONDO:0002254, USP14-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1634 USP14 Zornitza Stark Marked gene: USP14 as ready
Mendeliome v1.1634 USP14 Zornitza Stark Gene: usp14 has been classified as Green List (High Evidence).
Mendeliome v1.1634 USP14 Zornitza Stark Classified gene: USP14 as Green List (high evidence)
Mendeliome v1.1634 USP14 Zornitza Stark Gene: usp14 has been classified as Green List (High Evidence).
Mendeliome v1.1633 USP14 Zornitza Stark gene: USP14 was added
gene: USP14 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: USP14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP14 were set to 38469793; 35066879
Phenotypes for gene: USP14 were set to Syndromic disease MONDO:0002254, USP14-related
Review for gene: USP14 was set to GREEN
Added comment: PMID 35066879: 3 fetuses from 2 different branches of a consanguineous family, presenting with distal arthrogryposis, underdevelopment of the corpus callosum, and dysmorphic facial features. Exome sequencing identified a biallelic 4-bp deletion (c.233_236delTTCC; p.Leu78Glnfs*11) in USP14, and sequencing of family members showed segregation with the phenotype. Ubiquitin-specific protease 14 (USP14) encodes a major proteasome-associated deubiquitinating enzyme with an established dual role as an inhibitor and an activator of proteolysis, maintaining protein homeostasis. Usp14-deficient mice show a phenotype similar to lethal human multiple congenital contractures phenotypes, with callosal anomalies, muscle wasting, and early lethality, attributed to neuromuscular junction defects due to decreased monomeric ubiquitin pool. RT-qPCR experiment in an unaffected heterozygote revealed that mutant USP14 was expressed, indicating that abnormal transcript escapes nonsense-mediated mRNA decay.

PMID 38469793: biallelic USP14 variants in four individuals from three unrelated families: one fetus, a newborn with a syndromic NDD, and two siblings affected by a progressive neurological disease. Specifically, the two siblings from the latter family carried two compound heterozygous variants c.8T>C p.(Leu3Pro) and c.988C>T p.(Arg330*), while the fetus had a homozygous frameshift c.899_902del p.(Lys300Serfs*24) variant and the newborn patient harbored a homozygous frameshift c.233_236del p.(Leu78Glnfs*11) variant. The fetus and the newborn had extensive brain malformations.
Sources: Literature
Vitamin metabolism disorders v1.0 Bryony Thompson promoted panel to version 1.0
Miscellaneous Metabolic Disorders v1.44 Bryony Thompson removed gene:THAP11 from the panel
Miscellaneous Metabolic Disorders v1.43 Bryony Thompson removed gene:ZNF143 from the panel
Miscellaneous Metabolic Disorders v1.42 Bryony Thompson removed gene:TCN2 from the panel
Miscellaneous Metabolic Disorders v1.41 Bryony Thompson removed gene:MTR from the panel
Miscellaneous Metabolic Disorders v1.40 Bryony Thompson removed gene:MMADHC from the panel
Vitamin metabolism disorders v0.36 MMADHC Bryony Thompson Tag treatable tag was added to gene: MMADHC.
Miscellaneous Metabolic Disorders v1.39 Bryony Thompson removed gene:MMACHC from the panel
Vitamin metabolism disorders v0.36 MMACHC Bryony Thompson Tag treatable tag was added to gene: MMACHC.
Miscellaneous Metabolic Disorders v1.38 Bryony Thompson removed gene:LMBRD1 from the panel
Vitamin metabolism disorders v0.36 LMBRD1 Bryony Thompson Tag treatable tag was added to gene: LMBRD1.
Miscellaneous Metabolic Disorders v1.37 Bryony Thompson removed gene:HCFC1 from the panel
Miscellaneous Metabolic Disorders v1.36 Bryony Thompson removed gene:GIF from the panel
Miscellaneous Metabolic Disorders v1.35 Bryony Thompson removed gene:CUBN from the panel
Vitamin metabolism disorders v0.36 CUBN Bryony Thompson Tag treatable tag was added to gene: CUBN.
Miscellaneous Metabolic Disorders v1.34 CBS Bryony Thompson Phenotypes for gene: CBS were changed from Homocystinuria, B6-responsive and nonresponsive types MIM#236200; disorder of intracellular cobalamin metabolism to Homocystinuria, B6-responsive and nonresponsive types MIM#236200; disorder of intracellular cobalamin metabolism; metabolic disorder of sulfur metabolism
Miscellaneous Metabolic Disorders v1.33 Bryony Thompson removed gene:AMN from the panel
Miscellaneous Metabolic Disorders v1.32 Bryony Thompson removed gene:ABCD4 from the panel
Vitamin metabolism disorders v0.36 ABCD4 Bryony Thompson Phenotypes for gene: ABCD4 were changed from Methylmalonic aciduria and homocystinuria, cblJ type MIM#614857 to Methylmalonic aciduria and homocystinuria, cblJ type MIM#614857; disorder of vitamin B12 metabolism
Vitamin metabolism disorders v0.35 Bryony Thompson Panel status changed from internal to public
Vitamin metabolism disorders v0.34 TCN1 Bryony Thompson Marked gene: TCN1 as ready
Vitamin metabolism disorders v0.34 TCN1 Bryony Thompson Gene: tcn1 has been classified as Amber List (Moderate Evidence).
Vitamin metabolism disorders v0.34 TCN1 Bryony Thompson changed review comment from: Unclear if TC1 deficiency is associated with a clinical phenotype and only found 2 families with genetic findings. 1 confirmed chet (2 truncating variants) with severe TC 1 deficiency (depression and anxiety only reported symptoms, had sickle cell trait) & another family with 2 siblings that are presumed homozygous for a truncating variant (no plasma or serum TC 1 levels but no DNA available for genetic testing) which was found heterozygous in multiple first degree relatives. Unclear if there is a clinical phenotype. Heterozygous individuals displayed mildly low or low-normal TC 1 serum levels
Sources: Literature; to: Unclear if TC1 deficiency is associated with a clinical phenotype and only found 2 families with genetic findings. 1 confirmed chet (2 truncating variants) with severe TC 1 deficiency (depression and anxiety only reported symptoms, had sickle cell trait) & another family with 2 siblings that are presumed homozygous for a truncating variant (no plasma or serum TC 1 levels but no DNA available for genetic testing) which was found heterozygous in multiple first-degree relatives. Unclear if there is a clinical phenotype. Heterozygous individuals displayed mildly low or low-normal TC 1 serum levels. Also, 4 homozygotes were identified in a study of a loss-of-function variant associated with lower vitamin B12 concentration in African Americans but there was limited ability to assess the clinical impact of the recessive disease
Sources: Literature
Vitamin metabolism disorders v0.34 TCN1 Bryony Thompson edited their review of gene: TCN1: Changed publications: 29764838, 19686235
Vitamin metabolism disorders v0.34 TCN1 Bryony Thompson Classified gene: TCN1 as Amber List (moderate evidence)
Vitamin metabolism disorders v0.34 TCN1 Bryony Thompson Gene: tcn1 has been classified as Amber List (Moderate Evidence).
Vitamin metabolism disorders v0.33 TCN1 Bryony Thompson gene: TCN1 was added
gene: TCN1 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: TCN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TCN1 were set to 19686235
Phenotypes for gene: TCN1 were set to transcobalamin I deficiency MONDO:0008659
Review for gene: TCN1 was set to AMBER
Added comment: Unclear if TC1 deficiency is associated with a clinical phenotype and only found 2 families with genetic findings. 1 confirmed chet (2 truncating variants) with severe TC 1 deficiency (depression and anxiety only reported symptoms, had sickle cell trait) & another family with 2 siblings that are presumed homozygous for a truncating variant (no plasma or serum TC 1 levels but no DNA available for genetic testing) which was found heterozygous in multiple first degree relatives. Unclear if there is a clinical phenotype. Heterozygous individuals displayed mildly low or low-normal TC 1 serum levels
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5728 ZFX Zornitza Stark Phenotypes for gene: ZFX were changed from Neurodevelopmental disorder, MONDO:0700092, ZFX-related to Intellectual developmental disorder, X-linked syndromic 37, MIM# 301118
Mendeliome v1.1632 ZFX Zornitza Stark Phenotypes for gene: ZFX were changed from Neurodevelopmental disorder, MONDO:0700092, ZFX-related to Intellectual developmental disorder, X-linked syndromic 37, MIM# 301118
Mendeliome v1.1631 ZFX Zornitza Stark edited their review of gene: ZFX: Changed phenotypes: Intellectual developmental disorder, X-linked syndromic 37, MIM# 301118
Vitamin metabolism disorders v0.32 MTRR Bryony Thompson Marked gene: MTRR as ready
Vitamin metabolism disorders v0.32 MTRR Bryony Thompson Gene: mtrr has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.32 MTRR Bryony Thompson Classified gene: MTRR as Green List (high evidence)
Vitamin metabolism disorders v0.32 MTRR Bryony Thompson Gene: mtrr has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.31 MTR Bryony Thompson Marked gene: MTR as ready
Vitamin metabolism disorders v0.31 MTR Bryony Thompson Gene: mtr has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.31 MTR Bryony Thompson Classified gene: MTR as Green List (high evidence)
Vitamin metabolism disorders v0.31 MTR Bryony Thompson Gene: mtr has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.30 MMADHC Bryony Thompson Marked gene: MMADHC as ready
Vitamin metabolism disorders v0.30 MMADHC Bryony Thompson Gene: mmadhc has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.30 MMADHC Bryony Thompson Classified gene: MMADHC as Green List (high evidence)
Vitamin metabolism disorders v0.30 MMADHC Bryony Thompson Gene: mmadhc has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.29 MMACHC Bryony Thompson Marked gene: MMACHC as ready
Vitamin metabolism disorders v0.29 MMACHC Bryony Thompson Gene: mmachc has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.29 MMACHC Bryony Thompson Classified gene: MMACHC as Green List (high evidence)
Vitamin metabolism disorders v0.29 MMACHC Bryony Thompson Gene: mmachc has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.28 LMBRD1 Bryony Thompson Marked gene: LMBRD1 as ready
Vitamin metabolism disorders v0.28 LMBRD1 Bryony Thompson Gene: lmbrd1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.28 LMBRD1 Bryony Thompson Classified gene: LMBRD1 as Green List (high evidence)
Vitamin metabolism disorders v0.28 LMBRD1 Bryony Thompson Gene: lmbrd1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.27 HCFC1 Bryony Thompson Marked gene: HCFC1 as ready
Vitamin metabolism disorders v0.27 HCFC1 Bryony Thompson Gene: hcfc1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.27 HCFC1 Bryony Thompson Classified gene: HCFC1 as Green List (high evidence)
Vitamin metabolism disorders v0.27 HCFC1 Bryony Thompson Gene: hcfc1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.26 GIF Bryony Thompson Marked gene: GIF as ready
Vitamin metabolism disorders v0.26 GIF Bryony Thompson Gene: gif has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.26 GIF Bryony Thompson Classified gene: GIF as Green List (high evidence)
Vitamin metabolism disorders v0.26 GIF Bryony Thompson Gene: gif has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.25 CUBN Bryony Thompson Marked gene: CUBN as ready
Vitamin metabolism disorders v0.25 CUBN Bryony Thompson Gene: cubn has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.25 CUBN Bryony Thompson Classified gene: CUBN as Green List (high evidence)
Vitamin metabolism disorders v0.25 CUBN Bryony Thompson Gene: cubn has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.24 AMN Bryony Thompson Marked gene: AMN as ready
Vitamin metabolism disorders v0.24 AMN Bryony Thompson Gene: amn has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.24 AMN Bryony Thompson Classified gene: AMN as Green List (high evidence)
Vitamin metabolism disorders v0.24 AMN Bryony Thompson Gene: amn has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.23 ABCD4 Bryony Thompson Marked gene: ABCD4 as ready
Vitamin metabolism disorders v0.23 ABCD4 Bryony Thompson Gene: abcd4 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.23 ABCD4 Bryony Thompson Classified gene: ABCD4 as Green List (high evidence)
Vitamin metabolism disorders v0.23 ABCD4 Bryony Thompson Gene: abcd4 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.21 THAP11 Bryony Thompson Marked gene: THAP11 as ready
Vitamin metabolism disorders v0.21 THAP11 Bryony Thompson Gene: thap11 has been classified as Red List (Low Evidence).
Vitamin metabolism disorders v0.21 TCN2 Bryony Thompson Marked gene: TCN2 as ready
Vitamin metabolism disorders v0.21 TCN2 Bryony Thompson Gene: tcn2 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.21 TCN2 Bryony Thompson Classified gene: TCN2 as Green List (high evidence)
Vitamin metabolism disorders v0.21 TCN2 Bryony Thompson Gene: tcn2 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.20 MTRR Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 MTR Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 MMADHC Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 MMACHC Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 LMBRD1 Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 HCFC1 Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 GIF Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 CUBN Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 AMN Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 ABCD4 Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.19 TCN2 Bryony Thompson gene: TCN2 was added
gene: TCN2 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: TCN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TCN2 were set to 19373259
Phenotypes for gene: TCN2 were set to Transcobalamin II deficiency, 275350
Vitamin metabolism disorders v0.18 ZNF143 Bryony Thompson Marked gene: ZNF143 as ready
Vitamin metabolism disorders v0.18 ZNF143 Bryony Thompson Gene: znf143 has been classified as Amber List (Moderate Evidence).
Vitamin metabolism disorders v0.18 ZNF143 Bryony Thompson Classified gene: ZNF143 as Amber List (moderate evidence)
Vitamin metabolism disorders v0.18 ZNF143 Bryony Thompson Gene: znf143 has been classified as Amber List (Moderate Evidence).
Vitamin metabolism disorders v0.17 ZNF143 Bryony Thompson gene: ZNF143 was added
gene: ZNF143 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: ZNF143 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF143 were set to 27349184; 33845046; 9009278; 22268977; 27349184; 27349184
Phenotypes for gene: ZNF143 were set to methylmalonic aciduria and homocystinuria MONDO:0016826
Review for gene: ZNF143 was set to AMBER
Added comment: Only a single case with biallelic variants reported. However, given a Moderate gene-disease validity classification by the General Inborn Errors of Metabolism GCEP (assessed 05/03/2024). The gene-disease relationship is also supported by biochemical evidence, functional alteration assays, model systems, and rescue experiments
Sources: Literature
Vitamin metabolism disorders v0.16 THAP11 Bryony Thompson Classified gene: THAP11 as Red List (low evidence)
Vitamin metabolism disorders v0.16 THAP11 Bryony Thompson Added comment: Comment on list classification: Limited gene-disease validity classification on 09/02/2024 by General Inborn Errors of Metabolism GCEP
Vitamin metabolism disorders v0.16 THAP11 Bryony Thompson Gene: thap11 has been classified as Red List (Low Evidence).
Vitamin metabolism disorders v0.15 THAP11 Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.15 THAP11 Bryony Thompson gene: THAP11 was added
gene: THAP11 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: THAP11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: THAP11 were set to 28449119
Phenotypes for gene: THAP11 were set to Methylmalonic aciduria and homocystinuria MONDO:0016826
Review for gene: THAP11 was set to RED
Added comment: Sources: Literature
Vitamin metabolism disorders v0.14 HCFC1 Bryony Thompson gene: HCFC1 was added
gene: HCFC1 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: HCFC1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: HCFC1 were set to 24011988
Phenotypes for gene: HCFC1 were set to methylmalonic acidemia with homocystinuria, type cblX MONDO:0010657; disorder of cobalamin metabolism
Review for gene: HCFC1 was set to GREEN
gene: HCFC1 was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.13 ABCD4 Bryony Thompson gene: ABCD4 was added
gene: ABCD4 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: ABCD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCD4 were set to 22922874; 31113616; 30651581; 28572511
Phenotypes for gene: ABCD4 were set to Methylmalonic aciduria and homocystinuria, cblJ type MIM#614857
Review for gene: ABCD4 was set to GREEN
gene: ABCD4 was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.12 MTR Bryony Thompson gene: MTR was added
gene: MTR was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: MTR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTR were set to 8968735; 27604308
Phenotypes for gene: MTR were set to Homocystinuria-megaloblastic anemia, cblG complementation type MIM#250940; Organic aciduria
Review for gene: MTR was set to GREEN
gene: MTR was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.11 LMBRD1 Bryony Thompson gene: LMBRD1 was added
gene: LMBRD1 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: LMBRD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LMBRD1 were set to 19136951; 27604308
Phenotypes for gene: LMBRD1 were set to Methylmalonic aciduria and homocystinuria, cblF type MIM#277380; Disorders of cobalamin absorption, transport and metabolism
Review for gene: LMBRD1 was set to GREEN
gene: LMBRD1 was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.10 MTRR Bryony Thompson gene: MTRR was added
gene: MTRR was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: MTRR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTRR were set to 27604308; 9501215
Phenotypes for gene: MTRR were set to Homocystinuria-megaloblastic anemia, cbl E type MIM#236270; Disorders of the metabolism of sulphur amino acids
Review for gene: MTRR was set to GREEN
gene: MTRR was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.9 MMADHC Bryony Thompson gene: MMADHC was added
gene: MMADHC was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: MMADHC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMADHC were set to 27604308; 18385497
Phenotypes for gene: MMADHC were set to Homocystinuria, cblD type, variant 1 MIM#277410; Methylmalonic aciduria and homocystinuria, cblD type MIM#277410; Methylmalonic aciduria, cblD type, variant 2 MIM#277410; Disorders of cobalamin absorption, transport and metabolism
Review for gene: MMADHC was set to GREEN
gene: MMADHC was marked as current diagnostic
Added comment: Sources: Literature
Mendeliome v1.1631 PRDX1 Bryony Thompson Marked gene: PRDX1 as ready
Mendeliome v1.1631 PRDX1 Bryony Thompson Gene: prdx1 has been classified as Green List (High Evidence).
Mendeliome v1.1631 PRDX1 Bryony Thompson Classified gene: PRDX1 as Green List (high evidence)
Mendeliome v1.1631 PRDX1 Bryony Thompson Gene: prdx1 has been classified as Green List (High Evidence).
Mendeliome v1.1630 PRDX1 Bryony Thompson gene: PRDX1 was added
gene: PRDX1 was added to Mendeliome. Sources: Literature
digenic tags were added to gene: PRDX1.
Mode of inheritance for gene: PRDX1 was set to Other
Publications for gene: PRDX1 were set to 29302025; 35190856
Phenotypes for gene: PRDX1 were set to methylmalonic aciduria and homocystinuria type cblC MONDO:0010184
Mode of pathogenicity for gene: PRDX1 was set to Other
Review for gene: PRDX1 was set to GREEN
Added comment: Only variants affecting the canonical splice acceptor site of intron 5 (e.g. c.515-1G-T, c.515-2A-T) that cause skipping of exon 6 and the polyA termination signal of PRDX1 produce an MMACHC epimutation. The resulting read-through transcript extends through the adjacent MMACHC locus in the antisense orientation. These PRDX1 exon 6 acceptor splice site variants cause disease through digenic inheritance with a pathogenic MMACHC on the other allele.
Sources: Literature
Vitamin metabolism disorders v0.8 PRDX1 Bryony Thompson Marked gene: PRDX1 as ready
Vitamin metabolism disorders v0.8 PRDX1 Bryony Thompson Gene: prdx1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.8 PRDX1 Bryony Thompson Classified gene: PRDX1 as Green List (high evidence)
Vitamin metabolism disorders v0.8 PRDX1 Bryony Thompson Gene: prdx1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.7 PRDX1 Bryony Thompson Tag digenic tag was added to gene: PRDX1.
Vitamin metabolism disorders v0.7 PRDX1 Bryony Thompson gene: PRDX1 was added
gene: PRDX1 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: PRDX1 was set to Other
Publications for gene: PRDX1 were set to 29302025; 35190856
Phenotypes for gene: PRDX1 were set to methylmalonic aciduria and homocystinuria type cblC MONDO:0010184
Mode of pathogenicity for gene: PRDX1 was set to Other
Review for gene: PRDX1 was set to GREEN
Added comment: Only variants affecting the canonical splice acceptor site of intron 5 (e.g. c.515-1G-T, c.515-2A-T) that cause skipping of exon 6 and the polyA termination signal of PRDX1 produce an MMACHC epimutation. The resulting read-through transcript extends through the adjacent MMACHC locus in the antisense orientation. These PRDX1 exon 6 acceptor splice site variants cause disease through digenic inheritance with a pathogenic MMACHC on the other allele.
Sources: Literature
Vitamin metabolism disorders v0.6 MMACHC Bryony Thompson gene: MMACHC was added
gene: MMACHC was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: MMACHC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMACHC were set to 27604308; 16311595
Phenotypes for gene: MMACHC were set to Methylmalonic aciduria and homocystinuria, cblC type MIM#277400; Disorders of cobalamin absorption, transport and metabolism
Review for gene: MMACHC was set to GREEN
gene: MMACHC was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.5 MMAB Bryony Thompson Marked gene: MMAB as ready
Vitamin metabolism disorders v0.5 MMAB Bryony Thompson Gene: mmab has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.5 MMAB Bryony Thompson Classified gene: MMAB as Green List (high evidence)
Vitamin metabolism disorders v0.5 MMAB Bryony Thompson Gene: mmab has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.4 MMAB Bryony Thompson gene: MMAB was added
gene: MMAB was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: MMAB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMAB were set to 12471062; 20556797; 35712814; 24813872
Phenotypes for gene: MMAB were set to methylmalonic aciduria, cblB type MONDO:0009614
Review for gene: MMAB was set to GREEN
gene: MMAB was marked as current diagnostic
Added comment: Well-established gene-disease association. Inborn error of cobalamin metabolism.
Sources: Literature
Vitamin metabolism disorders v0.3 AMN Bryony Thompson gene: AMN was added
gene: AMN was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: AMN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMN were set to 12590260; 27604308
Phenotypes for gene: AMN were set to Imerslund-Grasbeck syndrome 2 MIM#618882; Disorders of cobalamin absorption, transport and metabolism
Review for gene: AMN was set to GREEN
gene: AMN was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.2 CUBN Bryony Thompson gene: CUBN was added
gene: CUBN was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: CUBN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CUBN were set to 10080186; 31613795
Phenotypes for gene: CUBN were set to Proteinuria, chronic benign MIM#618884; Imerslund-Grasbeck syndrome 1 MIM#261100; Intrinsic factor receptor deficiency due to CUBN mutations (Disorders of cobalamin absorption, transport and metabolism)
Review for gene: CUBN was set to GREEN
Added comment: Sources: Literature
Mendeliome v1.1629 PSMB10 Zornitza Stark Phenotypes for gene: PSMB10 were changed from Proteasome-associated autoinflammatory syndrome 5, MIM# 619175 to Proteasome-associated autoinflammatory syndrome 5, MIM# 619175; Severe combined immunodeficiency, MONDO:0015974, PSMB10-related
Mendeliome v1.1628 PSMB10 Zornitza Stark Publications for gene: PSMB10 were set to 31783057; 37600812
Mendeliome v1.1627 PSMB10 Zornitza Stark Mode of inheritance for gene: PSMB10 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1626 PSMB10 Zornitza Stark edited their review of gene: PSMB10: Added comment: PMID 38503300: Six individuals with three de novo missense variants. Individuals presented with T-B-NK± severe combined immunodeficiency (SCID) and clinical features suggestive of Omenn syndrome, including diarrhea, alopecia, and desquamating erythematous rash.; Changed publications: 31783057, 37600812, 38503300; Changed phenotypes: Proteasome-associated autoinflammatory syndrome 5, MIM# 619175, Severe combined immunodeficiency, MONDO:0015974, PSMB10-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Vitamin metabolism disorders v0.1 GIF Bryony Thompson gene: GIF was added
gene: GIF was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
new gene name tags were added to gene: GIF.
Mode of inheritance for gene: GIF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GIF were set to 27604308; 14695536; 14576042
Phenotypes for gene: GIF were set to Intrinsic factor deficiency MIM#261000; Disorders of cobalamin absorption, transport and metabolism
Review for gene: GIF was set to GREEN
gene: GIF was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.0 Bryony Thompson Added Panel Inherited vitamin B12 or cobalamin deficiency
Set list of related panels to Abnormality of vitamin B12 metabolism; HP:0004341
Set panel types to: Royal Melbourne Hospital; Rare Disease
Transplant Co-Morbidity v0.18 Bryony Thompson removed gene:IFNL3 from the panel
Mendeliome v1.1626 CST3 Bryony Thompson Classified gene: CST3 as Green List (high evidence)
Mendeliome v1.1626 CST3 Bryony Thompson Gene: cst3 has been classified as Green List (High Evidence).
Mendeliome v1.1625 CST3 Bryony Thompson reviewed gene: CST3: Rating: GREEN; Mode of pathogenicity: Other; Publications: 38489591; Phenotypes: leukodystrophy MONDO:0019046, CST3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.57 CST3 Bryony Thompson Marked gene: CST3 as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.57 CST3 Bryony Thompson Gene: cst3 has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.57 CST3 Bryony Thompson Classified gene: CST3 as Green List (high evidence)
Alternating Hemiplegia and Hemiplegic Migraine v0.57 CST3 Bryony Thompson Gene: cst3 has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.56 CST3 Bryony Thompson gene: CST3 was added
gene: CST3 was added to Alternating Hemiplegia and Hemiplegic Migraine. Sources: Literature
Mode of inheritance for gene: CST3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CST3 were set to 38489591
Phenotypes for gene: CST3 were set to leukodystrophy MONDO:0019046, CST3-related
Mode of pathogenicity for gene: CST3 was set to Other
Review for gene: CST3 was set to GREEN
Added comment: 16 patients from 8 leukodystrophy families carrying one of four different stop-gain or frameshift dominant variants in the C-terminal (in the NMD-exclusion zone) of the CST3 gene. Suggested mechanism of disease by rendering the protein more prone to aggregation. The clinical phenotype consists of recurrent episodes of hemiplegic migraine associated with transient unilateral focal deficits and slowly progressing motor symptoms and cognitive decline in mid-old adult ages. Clinical & radiological features differ from Cerebral Amyloid Angiopathy.
Sources: Literature
Early-onset Dementia v1.12 CST3 Bryony Thompson Phenotypes for gene: CST3 were changed from Cerebral amyloid angiopathy MIM#105150 to Cerebral amyloid angiopathy MIM#105150; leukodystrophy MONDO:0019046
Early-onset Dementia v1.11 CST3 Bryony Thompson Publications for gene: CST3 were set to 22435454; 8866434; 2602413; 8108423
Early-onset Dementia v1.10 CST3 Bryony Thompson Classified gene: CST3 as Green List (high evidence)
Early-onset Dementia v1.10 CST3 Bryony Thompson Added comment: Comment on list classification: Cognitive decline is a feature of CST3-leukodystrophy
Early-onset Dementia v1.10 CST3 Bryony Thompson Gene: cst3 has been classified as Green List (High Evidence).
Early-onset Dementia v1.9 CST3 Bryony Thompson edited their review of gene: CST3: Added comment: New gene-disease association: 16 patients from 8 leukodystrophy families carrying one of four different stop-gain or frameshift dominant variants in the C-terminal (in the NMD-exclusion zone) of the CST3 gene. Suggested mechanism of disease by rendering the protein more prone to aggregation. The clinical phenotype consists of recurrent episodes of hemiplegic migraine associated with transient unilateral focal deficits and slowly progressing motor symptoms and cognitive decline in mid-old adult ages. Clinical & radiological features differ from Cerebral Amyloid Angiopathy.; Changed publications: 22435454, 8866434, 2602413, 8108423, 38489591; Changed phenotypes: Cerebral amyloid angiopathy MIM#105150, leukodystrophy MONDO:0019046
Intellectual disability syndromic and non-syndromic v0.5727 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755 to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755; Developmental and epileptic encephalopathy 114, MIM# 620774
Intellectual disability syndromic and non-syndromic v0.5726 SLC32A1 Zornitza Stark reviewed gene: SLC32A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 114, MIM# 620774; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2538 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755 to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755; Developmental and epileptic encephalopathy 114, MIM# 620774
Genetic Epilepsy v0.2537 SLC32A1 Zornitza Stark edited their review of gene: SLC32A1: Changed phenotypes: Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755, Developmental and epileptic encephalopathy 114, MIM# 620774
Mendeliome v1.1625 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755 to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755; Developmental and epileptic encephalopathy 114, MIM# 620774
Mendeliome v1.1624 SLC32A1 Zornitza Stark edited their review of gene: SLC32A1: Changed phenotypes: Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755, Developmental and epileptic encephalopathy 114, MIM# 620774
Intellectual disability syndromic and non-syndromic v0.5726 CRELD1 Zornitza Stark Phenotypes for gene: CRELD1 were changed from Neurodevelopmental disorder (MONDO:0700092), CRELD1-related to Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771
Intellectual disability syndromic and non-syndromic v0.5725 CRELD1 Zornitza Stark reviewed gene: CRELD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2537 CRELD1 Zornitza Stark Phenotypes for gene: CRELD1 were changed from Developmental and epileptic encephalopathy, MONDO:0100062, CRELD1-related to Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771
Genetic Epilepsy v0.2536 CRELD1 Zornitza Stark edited their review of gene: CRELD1: Changed phenotypes: Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771
Mendeliome v1.1624 CRELD1 Zornitza Stark Phenotypes for gene: CRELD1 were changed from Developmental and epileptic encephalopathy, MONDO:0100062, CRELD1-related; Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217 to Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771; Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217
Mendeliome v1.1623 CRELD1 Zornitza Stark edited their review of gene: CRELD1: Changed phenotypes: Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771, Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217
Calcium and Phosphate disorders v1.23 EHHADH Zornitza Stark Marked gene: EHHADH as ready
Calcium and Phosphate disorders v1.23 EHHADH Zornitza Stark Gene: ehhadh has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.23 EHHADH Zornitza Stark Classified gene: EHHADH as Green List (high evidence)
Calcium and Phosphate disorders v1.23 EHHADH Zornitza Stark Gene: ehhadh has been classified as Green List (High Evidence).
Early-onset Dementia v1.9 APP Bryony Thompson Marked gene: APP as ready
Early-onset Dementia v1.9 APP Bryony Thompson Gene: app has been classified as Green List (High Evidence).
Early-onset Dementia v1.9 APP Bryony Thompson Mode of pathogenicity for gene: APP was changed from to Other
Early-onset Dementia v1.8 APP Bryony Thompson Publications for gene: APP were set to
Early-onset Dementia v1.7 APP Bryony Thompson Phenotypes for gene: APP were changed from to Alzheimer disease MONDO:0007088
Early-onset Dementia v1.6 APP Bryony Thompson Mode of inheritance for gene: APP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Calcium and Phosphate disorders v1.22 NRAS Bryony Thompson Marked gene: NRAS as ready
Calcium and Phosphate disorders v1.22 NRAS Bryony Thompson Gene: nras has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.22 NRAS Bryony Thompson Classified gene: NRAS as Green List (high evidence)
Calcium and Phosphate disorders v1.22 NRAS Bryony Thompson Gene: nras has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.21 NRAS Bryony Thompson gene: NRAS was added
gene: NRAS was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: NRAS was set to Other
Publications for gene: NRAS were set to 24006476; 35999193; 32157705; 27900779
Phenotypes for gene: NRAS were set to Costello syndrome MONDO:0009026
Mode of pathogenicity for gene: NRAS was set to Other
Review for gene: NRAS was set to GREEN
gene: NRAS was marked as current diagnostic
Added comment: 5 cases with cutaneous skeletal hypophosphatemia syndrome and all with somatic mosaic activating NRAS Q61R
Sources: Literature
Calcium and Phosphate disorders v1.20 HRAS Bryony Thompson Marked gene: HRAS as ready
Calcium and Phosphate disorders v1.20 HRAS Bryony Thompson Gene: hras has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.20 HRAS Bryony Thompson Classified gene: HRAS as Green List (high evidence)
Calcium and Phosphate disorders v1.20 HRAS Bryony Thompson Gene: hras has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.19 HRAS Bryony Thompson gene: HRAS was added
gene: HRAS was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: HRAS was set to Other
Publications for gene: HRAS were set to 35738466; 36943390; 30373874; 27444071
Phenotypes for gene: HRAS were set to Costello syndrome MONDO:0009026
Mode of pathogenicity for gene: HRAS was set to Other
Review for gene: HRAS was set to GREEN
gene: HRAS was marked as current diagnostic
Added comment: Gain of function is the mechanism of disease and only somatic mosaic variants have been reported in association with hypophosphataemia
PMID: 35738466 - 1 case with a VUS & vitamin dependent rickets as a feature of the phenotype
PMID: 36943390 - mouse model with hypophosphataemia
PMID: 30373874 - 1 somatic mosaic HRAS c.182A>G (p.Gln61Arg) case with cutaneous skeletal hypophosphatemia syndrome (CSHS)
PMID: 27444071 - review with 4 cases of CSHS with somatic mosaic variants (G13R or Q61R)
Sources: Literature
Calcium and Phosphate disorders v1.18 ATP6V0A4 Bryony Thompson Marked gene: ATP6V0A4 as ready
Calcium and Phosphate disorders v1.18 ATP6V0A4 Bryony Thompson Gene: atp6v0a4 has been classified as Red List (Low Evidence).
Calcium and Phosphate disorders v1.18 ATP6V0A4 Bryony Thompson gene: ATP6V0A4 was added
gene: ATP6V0A4 was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: ATP6V0A4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V0A4 were set to 35738466
Phenotypes for gene: ATP6V0A4 were set to renal tubular acidosis, distal, 3, with or without sensorineural hearing loss MONDO:0011268
Review for gene: ATP6V0A4 was set to RED
Added comment: 1 homozygous case with hypophosphataemic rickets and renal tubular dysfunction
Sources: Literature
Calcium and Phosphate disorders v1.17 ATP6V1B1 Bryony Thompson Marked gene: ATP6V1B1 as ready
Calcium and Phosphate disorders v1.17 ATP6V1B1 Bryony Thompson Gene: atp6v1b1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.17 ATP6V1B1 Bryony Thompson Classified gene: ATP6V1B1 as Green List (high evidence)
Calcium and Phosphate disorders v1.17 ATP6V1B1 Bryony Thompson Gene: atp6v1b1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.16 ATP6V1B1 Bryony Thompson gene: ATP6V1B1 was added
gene: ATP6V1B1 was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: ATP6V1B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V1B1 were set to 35738466; 18386070
Phenotypes for gene: ATP6V1B1 were set to renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss MONDO:0009968
Review for gene: ATP6V1B1 was set to GREEN
gene: ATP6V1B1 was marked as current diagnostic
Added comment: Hypophosphataemic rickets can be a feature of the condition
PMID: 35738466 - 2 homozygous & 1 Chet case with hypophosphataemic rickets and renal tubular dysfunction
PMID: 18386070 - 2 siblings with distal renal tubular acidosis and hypophosphataemic rickets homozygous for a missense variant (c.242T>C p.Leu81Pro)
Sources: Literature
Calcium and Phosphate disorders v1.10 EHHADH Bryony Thompson gene: EHHADH was added
gene: EHHADH was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: EHHADH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EHHADH were set to 24401050; 35738466; 38310177
Phenotypes for gene: EHHADH were set to Fanconi renotubular syndrome 3 MONDO:0014275
Review for gene: EHHADH was set to GREEN
Added comment: Now 3 different variants from 4 families/cases were reported with consistent phenotypes. Assessed as Limited by ClinGen in March 2023. However, this assessment doesn't include: PMID: 35738466, 38310177; https://clinmedjournals.org/articles/jcnrc/journal-of-clinical-nephrology-and-renal-care-jcnrc-3-027.pdf
Additional info:
PMID: 35738466 - 1 family (proband and mother) with missense (c.385C>G, p.Leu129Val) with hypophosphataemic rickets and renal tubular dysfunction
PMID: 38310177 - case with a diagnosis of Fanconi renotubular syndrome with a whole gene deletion. Hypophosphataemic rickets was part of the clinical presentation
Sources: Literature
Calcium and Phosphate disorders v1.10 EHHADH Bryony Thompson gene: EHHADH was added
gene: EHHADH was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: EHHADH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EHHADH were set to 24401050; 35738466; 38310177
Phenotypes for gene: EHHADH were set to Fanconi renotubular syndrome 3 MONDO:0014275
Review for gene: EHHADH was set to GREEN
Added comment: Now 3 different variants from 4 families/cases were reported with consistent phenotypes. Assessed as Limited by ClinGen in March 2023. However, this assessment doesn't include: PMID: 35738466, 38310177; https://clinmedjournals.org/articles/jcnrc/journal-of-clinical-nephrology-and-renal-care-jcnrc-3-027.pdf
Additional info:
PMID: 35738466 - 1 family (proband and mother) with missense (c.385C>G, p.Leu129Val) with hypophosphataemic rickets and renal tubular dysfunction
PMID: 38310177 - case with a diagnosis of Fanconi renotubular syndrome with a whole gene deletion. Hypophosphataemic rickets was part of the clinical presentation
Sources: Literature
Renal Tubulopathies and related disorders v1.11 EHHADH Bryony Thompson Marked gene: EHHADH as ready
Renal Tubulopathies and related disorders v1.11 EHHADH Bryony Thompson Gene: ehhadh has been classified as Green List (High Evidence).
Renal Tubulopathies and related disorders v1.11 EHHADH Bryony Thompson Publications for gene: EHHADH were set to 24401050
Renal Tubulopathies and related disorders v1.10 EHHADH Bryony Thompson Classified gene: EHHADH as Green List (high evidence)
Renal Tubulopathies and related disorders v1.10 EHHADH Bryony Thompson Gene: ehhadh has been classified as Green List (High Evidence).
Renal Tubulopathies and related disorders v1.9 EHHADH Bryony Thompson reviewed gene: EHHADH: Rating: GREEN; Mode of pathogenicity: None; Publications: 24401050, 35738466, 38310177; Phenotypes: Fanconi renotubular syndrome 3 MONDO:0014275; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1623 EHHADH Bryony Thompson Publications for gene: EHHADH were set to 24401050
Mendeliome v1.1622 EHHADH Bryony Thompson Classified gene: EHHADH as Green List (high evidence)
Mendeliome v1.1622 EHHADH Bryony Thompson Gene: ehhadh has been classified as Green List (High Evidence).
Mendeliome v1.1621 EHHADH Bryony Thompson reviewed gene: EHHADH: Rating: GREEN; Mode of pathogenicity: None; Publications: 35738466, 38310177, 24401050; Phenotypes: Fanconi renotubular syndrome 3 MONDO:0014275; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Calcium and Phosphate disorders v1.9 FGFR1 Bryony Thompson Marked gene: FGFR1 as ready
Calcium and Phosphate disorders v1.9 FGFR1 Bryony Thompson Gene: fgfr1 has been classified as Amber List (Moderate Evidence).
Calcium and Phosphate disorders v1.9 FGFR1 Bryony Thompson Classified gene: FGFR1 as Amber List (moderate evidence)
Calcium and Phosphate disorders v1.9 FGFR1 Bryony Thompson Gene: fgfr1 has been classified as Amber List (Moderate Evidence).
Calcium and Phosphate disorders v1.8 FGFR1 Bryony Thompson gene: FGFR1 was added
gene: FGFR1 was added to Calcium and Phosphate disorders. Sources: Other
Mode of inheritance for gene: FGFR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGFR1 were set to 35738466; 36999651; 29147600; 26839958
Phenotypes for gene: FGFR1 were set to osteoglophonic dwarfism MONDO:0008150
Review for gene: FGFR1 was set to AMBER
gene: FGFR1 was marked as current diagnostic
Added comment: PMID: 35738466 - 1 case with vitamin dependent rickets & osteoglophonic dysplasia
PMID: 36999651 - 1 missense (VUS) in a case with hypophosphataemia
PMID: 29147600 - 1 case with Osteoglophonic dysplasia including hypophosphataemia, with c.1115G > A [p.(Cys372Tyr)]
PMID: 26839958 - mouse model demonstrates role for Fgrf1 in phosphate transport
Sources: Other
Calcium and Phosphate disorders v1.7 INPPL1 Bryony Thompson Marked gene: INPPL1 as ready
Calcium and Phosphate disorders v1.7 INPPL1 Bryony Thompson Gene: inppl1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.7 INPPL1 Bryony Thompson Classified gene: INPPL1 as Green List (high evidence)
Calcium and Phosphate disorders v1.7 INPPL1 Bryony Thompson Gene: inppl1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.6 INPPL1 Bryony Thompson gene: INPPL1 was added
gene: INPPL1 was added to Calcium and Phosphate disorders. Sources: Other
Mode of inheritance for gene: INPPL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INPPL1 were set to 23273567
Phenotypes for gene: INPPL1 were set to opsismodysplasia MONDO:0009785
Review for gene: INPPL1 was set to GREEN
gene: INPPL1 was marked as current diagnostic
Added comment: Hypophosphataemia can be a feature of the condition and has been reported in at least 5 individuals with chet/homozygous variants from 4 families.
Sources: Other
Calcium and Phosphate disorders v1.5 SLC4A1 Bryony Thompson Marked gene: SLC4A1 as ready
Calcium and Phosphate disorders v1.5 SLC4A1 Bryony Thompson Gene: slc4a1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.5 SLC4A1 Bryony Thompson changed review comment from: Hypophosphataemic rickets can be a feature of condition
PMID: 35738466 - 5 monoallelic & 2 biallelic cases with hypophosphataemic rickets and renal tubular dysfunction
Sources: Literature; to: Hypophosphataemic rickets can be a feature of the condition
PMID: 35738466 - 5 monoallelic & 2 biallelic cases with hypophosphataemic rickets and renal tubular dysfunction
Sources: Literature
Calcium and Phosphate disorders v1.5 SLC4A1 Bryony Thompson edited their review of gene: SLC4A1: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Calcium and Phosphate disorders v1.5 SLC4A1 Bryony Thompson Mode of inheritance for gene: SLC4A1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Calcium and Phosphate disorders v1.4 SLC4A1 Bryony Thompson edited their review of gene: SLC4A1: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Calcium and Phosphate disorders v1.4 SLC4A1 Bryony Thompson Classified gene: SLC4A1 as Green List (high evidence)
Calcium and Phosphate disorders v1.4 SLC4A1 Bryony Thompson Gene: slc4a1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.3 SLC4A1 Bryony Thompson gene: SLC4A1 was added
gene: SLC4A1 was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: SLC4A1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SLC4A1 were set to 35738466
Phenotypes for gene: SLC4A1 were set to renal tubular acidosis, distal, 4, with hemolytic anemia MONDO:0012700
Review for gene: SLC4A1 was set to GREEN
gene: SLC4A1 was marked as current diagnostic
Added comment: Hypophosphataemic rickets can be a feature of condition
PMID: 35738466 - 5 monoallelic & 2 biallelic cases with hypophosphataemic rickets and renal tubular dysfunction
Sources: Literature
Calcium and Phosphate disorders v1.2 SLC2A2 Bryony Thompson Marked gene: SLC2A2 as ready
Calcium and Phosphate disorders v1.2 SLC2A2 Bryony Thompson Gene: slc2a2 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.2 SLC2A2 Bryony Thompson Classified gene: SLC2A2 as Green List (high evidence)
Calcium and Phosphate disorders v1.2 SLC2A2 Bryony Thompson Gene: slc2a2 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.1 SLC2A2 Bryony Thompson gene: SLC2A2 was added
gene: SLC2A2 was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: SLC2A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC2A2 were set to 35738466
Phenotypes for gene: SLC2A2 were set to glycogen storage disease due to GLUT2 deficiency MONDO:0009216
Review for gene: SLC2A2 was set to GREEN
gene: SLC2A2 was marked as current diagnostic
Added comment: Hypophosphataemic rickets can be a feature of the condition.
PMID: 35738466 - 4 homozygous & 1 Chet case with hypophosphataemic rickets and renal tubular dysfunction
Sources: Literature
Mendeliome v1.1621 RXFP2 Katie Ayers reviewed gene: RXFP2: 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: 37208861, 38430325; Phenotypes: Infertility, cryptorchidism, non-obstructive azoospermia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.293 RXFP2 Katie Ayers edited their review of gene: RXFP2: Added comment: One individual with bilateral cryptorchidism and infertility had homozygous c.1406delT in RXFP2 (NM_130806.5), leading to a frameshift p.(Phe469Serfs*8). From consanguinous family.

Two affected brothers with homozygous missense variant c.1015A>G in RXFP2 (NM_130806.5) resulting in an amino acid substitution p.(Asn339Asp) with bilateral cryptorchidism.; Changed publications: 37208861; Changed phenotypes: Infertility, cryptorchidism, non-obstructive azoospermia
Differences of Sex Development v0.293 RXFP2 Katie Ayers edited their review of gene: RXFP2: Added comment: Homozygous non-canonical splicing variant by whole-exome sequencing and Sanger sequencing . NM_130806: c.1376-12A > G; Changed rating: GREEN; Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Changed publications: 38430325; Changed phenotypes: cryptorchidism and non-obstructive azoospermia; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.293 RXFP2 Katie Ayers commented on gene: RXFP2
Genetic Epilepsy v0.2536 NDUFAF5 Zornitza Stark Marked gene: NDUFAF5 as ready
Genetic Epilepsy v0.2536 NDUFAF5 Zornitza Stark Gene: ndufaf5 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2536 NDUFAF5 Zornitza Stark Phenotypes for gene: NDUFAF5 were changed from to Mitochondrial complex I deficiency, nuclear type 3 MIM#618224
Genetic Epilepsy v0.2535 NDUFAF5 Zornitza Stark Publications for gene: NDUFAF5 were set to
Genetic Epilepsy v0.2534 NDUFAF5 Zornitza Stark Mode of inheritance for gene: NDUFAF5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2533 NDUFAF5 Zornitza Stark reviewed gene: NDUFAF5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 3 MIM#618224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2533 NDUFA1 Zornitza Stark Marked gene: NDUFA1 as ready
Genetic Epilepsy v0.2533 NDUFA1 Zornitza Stark Gene: ndufa1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2533 NDUFA1 Zornitza Stark Phenotypes for gene: NDUFA1 were changed from to Mitochondrial complex I deficiency, nuclear type 12 MIM#301020
Genetic Epilepsy v0.2532 NDUFA1 Zornitza Stark Publications for gene: NDUFA1 were set to
Genetic Epilepsy v0.2531 NDUFA1 Zornitza Stark Mode of inheritance for gene: NDUFA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.2530 NDUFA1 Zornitza Stark reviewed gene: NDUFA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 12 MIM#301020; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.2530 NDE1 Zornitza Stark Marked gene: NDE1 as ready
Genetic Epilepsy v0.2530 NDE1 Zornitza Stark Gene: nde1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2530 NDE1 Zornitza Stark Phenotypes for gene: NDE1 were changed from to Microhydranencephaly 605013; Lissencephaly 4 (with microcephaly) 614019
Genetic Epilepsy v0.2529 NDE1 Zornitza Stark Publications for gene: NDE1 were set to
Genetic Epilepsy v0.2528 NDE1 Zornitza Stark Mode of inheritance for gene: NDE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2527 NAGA Zornitza Stark Marked gene: NAGA as ready
Genetic Epilepsy v0.2527 NAGA Zornitza Stark Gene: naga has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2527 NAGA Zornitza Stark Phenotypes for gene: NAGA were changed from to Schindler disease, type I and type II 609241
Genetic Epilepsy v0.2526 NAGA Zornitza Stark Publications for gene: NAGA were set to
Genetic Epilepsy v0.2525 NAGA Zornitza Stark Mode of inheritance for gene: NAGA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2524 NAGA Zornitza Stark Classified gene: NAGA as Amber List (moderate evidence)
Genetic Epilepsy v0.2524 NAGA Zornitza Stark Gene: naga has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2523 NAGA Zornitza Stark edited their review of gene: NAGA: Changed rating: AMBER
Genetic Epilepsy v0.2523 MTOR Zornitza Stark Marked gene: MTOR as ready
Genetic Epilepsy v0.2523 MTOR Zornitza Stark Gene: mtor has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2523 MTOR Zornitza Stark Phenotypes for gene: MTOR were changed from to Smith-Kingsmore syndrome, MIM# 616638; Focal cortical dysplasia, type II, somatic, MIM# 607341; Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes, MONDO:0100283
Genetic Epilepsy v0.2522 MTOR Zornitza Stark Mode of pathogenicity for gene: MTOR was changed from to Other
Genetic Epilepsy v0.2521 MTOR Zornitza Stark Publications for gene: MTOR were set to
Genetic Epilepsy v0.2520 MTOR Zornitza Stark Mode of inheritance for gene: MTOR was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2519 MTHFR Zornitza Stark Marked gene: MTHFR as ready
Genetic Epilepsy v0.2519 MTHFR Zornitza Stark Gene: mthfr has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2519 MTHFR Zornitza Stark Phenotypes for gene: MTHFR were changed from Homocystinuria due to MTHFR deficiency MIM#236250 to Homocystinuria due to MTHFR deficiency MIM#236250
Genetic Epilepsy v0.2518 MTHFR Zornitza Stark Phenotypes for gene: MTHFR were changed from to Homocystinuria due to MTHFR deficiency MIM#236250
Genetic Epilepsy v0.2517 MTHFR Zornitza Stark Publications for gene: MTHFR were set to
Genetic Epilepsy v0.2516 MTHFR Zornitza Stark Mode of inheritance for gene: MTHFR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2515 MTHFR Zornitza Stark reviewed gene: MTHFR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Homocystinuria due to MTHFR deficiency MIM#236250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2515 MOCS2 Zornitza Stark Mode of inheritance for gene: MOCS2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2514 MOCS2 Zornitza Stark Mode of inheritance for gene: MOCS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2513 MOCS2 Zornitza Stark reviewed gene: MOCS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Molybdenum cofactor deficiency B MIM#252160; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2513 MMADHC Zornitza Stark Marked gene: MMADHC as ready
Genetic Epilepsy v0.2513 MMADHC Zornitza Stark Gene: mmadhc has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2513 MMADHC Zornitza Stark Phenotypes for gene: MMADHC were changed from to Homocystinuria, cblD type, variant 1 MIM#277410; Methylmalonic aciduria and homocystinuria, cblD type MIM#277410; Methylmalonic aciduria, cblD type, variant 2 MIM#277410
Genetic Epilepsy v0.2513 MMADHC Zornitza Stark Publications for gene: MMADHC were set to
Genetic Epilepsy v0.2512 MMADHC Zornitza Stark Mode of inheritance for gene: MMADHC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2511 MMACHC Zornitza Stark Marked gene: MMACHC as ready
Genetic Epilepsy v0.2511 MMACHC Zornitza Stark Gene: mmachc has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2511 MMACHC Zornitza Stark Phenotypes for gene: MMACHC were changed from to Methylmalonic aciduria and homocystinuria, cblC type MIM#277400
Genetic Epilepsy v0.2510 MMACHC Zornitza Stark Publications for gene: MMACHC were set to
Genetic Epilepsy v0.2509 MMACHC Zornitza Stark Mode of inheritance for gene: MMACHC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2508 MLC1 Zornitza Stark Marked gene: MLC1 as ready
Genetic Epilepsy v0.2508 MLC1 Zornitza Stark Gene: mlc1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2508 MLC1 Zornitza Stark Phenotypes for gene: MLC1 were changed from to Megalencephalic leukoencephalopathy with subcortical cysts (MIM#604004)
Genetic Epilepsy v0.2507 MLC1 Zornitza Stark Publications for gene: MLC1 were set to
Genetic Epilepsy v0.2506 MLC1 Zornitza Stark Mode of inheritance for gene: MLC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2505 MFF Zornitza Stark Marked gene: MFF as ready
Genetic Epilepsy v0.2505 MFF Zornitza Stark Gene: mff has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2505 MFF Zornitza Stark Phenotypes for gene: MFF were changed from to Encephalopathy due to defective mitochondrial and peroxisomal fission 2, MIM# 617086
Genetic Epilepsy v0.2504 MFF Zornitza Stark Publications for gene: MFF were set to
Genetic Epilepsy v0.2503 MFF Zornitza Stark Mode of inheritance for gene: MFF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1621 KAT6B Ain Roesley Phenotypes for gene: KAT6B were changed from SBBYSS syndrome MIM#603736; Genitopatellar syndrome MIM#606170 to SBBYSS syndrome MIM#603736; Genitopatellar syndrome MIM#606170; KAT6B-related multiple congenital anomalies syndrome MONDO:0036042
Intellectual disability syndromic and non-syndromic v0.5725 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Neurodevelopmental disorder, MONDO:0700092, SV2A-related to Neurodevelopmental disorder, MONDO:0700092, SV2A-related; Developmental and epileptic encephalopathy 113, MIM# 620772
Intellectual disability syndromic and non-syndromic v0.5724 SV2A Zornitza Stark reviewed gene: SV2A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 113, MIM# 620772; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2502 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Neurodevelopmental disorder, MONDO:0700092, SV2A-related; Developmental and epileptic encephalopathy 113, MIM# 620772 to Neurodevelopmental disorder, MONDO:0700092, SV2A-related; Developmental and epileptic encephalopathy 113, MIM# 620772
Genetic Epilepsy v0.2501 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Neurodevelopmental disorder, MONDO:0700092, SV2A-related to Neurodevelopmental disorder, MONDO:0700092, SV2A-related; Developmental and epileptic encephalopathy 113, MIM# 620772
Genetic Epilepsy v0.2500 SV2A Zornitza Stark reviewed gene: SV2A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 113, MIM# 620772; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.252 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Neurodevelopmental disorder, MONDO:0700092, SV2A-related to Developmental and epileptic encephalopathy 113, MIM# 620772
Microcephaly v1.251 SV2A Zornitza Stark reviewed gene: SV2A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 113, MIM# 620772; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1620 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Neurodevelopmental disorder, MONDO:0700092, SV2A-related to Neurodevelopmental disorder, MONDO:0700092, SV2A-related; Developmental and epileptic encephalopathy 113, MIM# 620772
Mendeliome v1.1619 SV2A Zornitza Stark edited their review of gene: SV2A: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, SV2A-related, Developmental and epileptic encephalopathy 113, MIM# 620772
Fetal anomalies v1.220 PRDM6 Ain Roesley Classified gene: PRDM6 as Amber List (moderate evidence)
Fetal anomalies v1.220 PRDM6 Ain Roesley Gene: prdm6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.219 PRDM6 Ain Roesley edited their review of gene: PRDM6: Changed rating: AMBER; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.219 WASHC5 Ain Roesley Classified gene: WASHC5 as Green List (high evidence)
Fetal anomalies v1.219 WASHC5 Ain Roesley Gene: washc5 has been classified as Green List (High Evidence).
Fetal anomalies v1.218 WASHC5 Ain Roesley reviewed gene: WASHC5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ritscher-Schinzel syndrome 1 MIM#220210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v1.218 SLC37A4 Ain Roesley Classified gene: SLC37A4 as Amber List (moderate evidence)
Fetal anomalies v1.218 SLC37A4 Ain Roesley Gene: slc37a4 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.217 SLC37A4 Ain Roesley reviewed gene: SLC37A4: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v1.217 RBFOX2 Ain Roesley Marked gene: RBFOX2 as ready
Fetal anomalies v1.217 RBFOX2 Ain Roesley Gene: rbfox2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.217 RBFOX2 Ain Roesley Classified gene: RBFOX2 as Amber List (moderate evidence)
Fetal anomalies v1.217 RBFOX2 Ain Roesley Gene: rbfox2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.216 RBFOX2 Ain Roesley gene: RBFOX2 was added
gene: RBFOX2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RBFOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBFOX2 were set to 26785492; 27670201; 27485310; 25205790; 35137168; 26785492; 37165897
Review for gene: RBFOX2 was set to AMBER
gene: RBFOX2 was marked as current diagnostic
Added comment: PMID: 37165897
1x 'splice altering' de novo in in an individual with HLSH + AVSD

- PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (eg. nonsense, frameshift, or canonical splice disruptions). All 3 probands have hypoplastic left heart syndrome (HLHS). No further patient-specific clinical or variant info were available. Same cohort later included in PMID: 32368696, listed 4 de novo variants in this gene, in patients with left ventricular outflow tract obstruction (LVOTO) or conotruncal defects (CTDs).

- PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492.
- PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing.

- PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS.

- PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS.
Sources: Literature
Fetal anomalies v1.215 PRDM6 Ain Roesley reviewed gene: PRDM6: Rating: ; Mode of pathogenicity: None; Publications: 38071433; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Congenital Heart Defect v0.414 RBFOX2 Ain Roesley Publications for gene: RBFOX2 were set to 26785492; 27670201; 27485310; 25205790; 35137168; 26785492
Congenital Heart Defect v0.413 RBFOX2 Ain Roesley commented on gene: RBFOX2
Congenital Heart Defect v0.413 KDR Ain Roesley Classified gene: KDR as Green List (high evidence)
Congenital Heart Defect v0.413 KDR Ain Roesley Gene: kdr has been classified as Green List (High Evidence).
Congenital Heart Defect v0.413 KDR Ain Roesley Classified gene: KDR as Green List (high evidence)
Congenital Heart Defect v0.413 KDR Ain Roesley Gene: kdr has been classified as Green List (High Evidence).
Congenital Heart Defect v0.413 KDR Ain Roesley Classified gene: KDR as Green List (high evidence)
Congenital Heart Defect v0.413 KDR Ain Roesley Gene: kdr has been classified as Green List (High Evidence).
Congenital Heart Defect v0.412 KDR Ain Roesley reviewed gene: KDR: Rating: GREEN; Mode of pathogenicity: None; Publications: 34113005, 30232381, 28991257, 30232381; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Fetal anomalies v1.215 KDR Ain Roesley Classified gene: KDR as Green List (high evidence)
Fetal anomalies v1.215 KDR Ain Roesley Gene: kdr has been classified as Green List (High Evidence).
Fetal anomalies v1.214 KDR Ain Roesley Marked gene: KDR as ready
Fetal anomalies v1.214 KDR Ain Roesley Gene: kdr has been classified as Red List (Low Evidence).
Fetal anomalies v1.214 KDR Ain Roesley Publications for gene: KDR were set to 34113005; 30232381
Fetal anomalies v1.213 KDR Ain Roesley Mode of inheritance for gene: KDR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.212 KDR Ain Roesley edited their review of gene: KDR: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.212 KDR Ain Roesley edited their review of gene: KDR: Changed rating: GREEN; Changed publications: 34113005, 30232381, 28991257, 30232381; Set current diagnostic: yes
Fetal anomalies v1.212 KDR Ain Roesley changed review comment from: PMID:30232381
5x families (6 affecteds) with ToF: 2x PTCs + 2x missense + 1x inframe del
noted that all individuals were adults at time of assessment but known to have ToF and/or other CHD

PMID:34113005;
1x family with 2 affecteds, Chet for 2x missense
Sources: Literature; to: GREEN for AD
RED for AR

PMID:30232381
5x families (6 affecteds) with ToF: 2x PTCs + 2x missense + 1x inframe del
noted that all individuals were adults at time of assessment but known to have ToF and/or other CHD

PMID: 34328347;
cohort of ToF, looking into LoF variants
4x identified + 1x classified as VUS (stop gain in penultimate exon)
1x stop gain citing PMID: 28991257

PMID:34113005;
1x family with 2 affecteds, Chet for 2x missense



Sources: Literature
Fetal anomalies v1.212 KDR Ain Roesley gene: KDR was added
gene: KDR was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KDR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: KDR were set to 34113005; 30232381
Phenotypes for gene: KDR were set to Tetralogy of Fallot
Added comment: PMID:30232381
5x families (6 affecteds) with ToF: 2x PTCs + 2x missense + 1x inframe del
noted that all individuals were adults at time of assessment but known to have ToF and/or other CHD

PMID:34113005;
1x family with 2 affecteds, Chet for 2x missense
Sources: Literature
Fetal anomalies v1.211 IRX4 Ain Roesley Marked gene: IRX4 as ready
Fetal anomalies v1.211 IRX4 Ain Roesley Gene: irx4 has been classified as Red List (Low Evidence).
Fetal anomalies v1.211 IRX4 Ain Roesley gene: IRX4 was added
gene: IRX4 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: IRX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRX4 were set to 21544582
Phenotypes for gene: IRX4 were set to Ventricular septal defect
Review for gene: IRX4 was set to RED
gene: IRX4 was marked as current diagnostic
Added comment: Two individuals with novel missense variants identified in a large cohort in 2011.

nothing new in punned
Sources: Literature
Fetal anomalies v1.210 HEY2 Ain Roesley Marked gene: HEY2 as ready
Fetal anomalies v1.210 HEY2 Ain Roesley Gene: hey2 has been classified as Red List (Low Evidence).
Fetal anomalies v1.210 HEY2 Ain Roesley gene: HEY2 was added
gene: HEY2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: HEY2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: HEY2 were set to 32820247
Phenotypes for gene: HEY2 were set to congenital heart defects and thoracic aortic aneurysms
Review for gene: HEY2 was set to RED
gene: HEY2 was marked as current diagnostic
Added comment: A very large family affected by CHD and familial thoracic aortic aneurysms. Trio genome sequencing was carried out in an index patient with critical CHD, and family members had either exome or Sanger sequencing. Identified homozygous loss-of-function variant (c.318_319delAG, p.G108*) in HEY2 in 3 individuals in family with critical CHD, whereas the 20 heterozygous carriers show a spectrum of CVDs (CHD and FTAA, but varying expressivity and incomplete penetrance).

Other studies show that knockout of HEY2 in mice results in cardiovascular defects (CVDs), including septal defects, cardiomyopathy, a thin-walled aorta, and valve anomalies.
Sources: Literature
Fetal anomalies v1.209 DOHH Ain Roesley Marked gene: DOHH as ready
Fetal anomalies v1.209 DOHH Ain Roesley Gene: dohh has been classified as Green List (High Evidence).
Fetal anomalies v1.209 DOHH Ain Roesley Classified gene: DOHH as Green List (high evidence)
Fetal anomalies v1.209 DOHH Ain Roesley Gene: dohh has been classified as Green List (High Evidence).
Fetal anomalies v1.208 DOHH Ain Roesley changed review comment from: 4 families - 5 affecteds

1x cardiomyopathy at prenatal examination
4/5 presented with CHD post-natally - VSD, ASD, severe cardiomegaly, Shone syndrome with aortic coarctation; bicuspid aortic valve; tricuspid-valve insufficiency etc

microcephaly was post-natal
Sources: Literature; to: 4 families - 5 affecteds

prenatal examination:
1x cardiomyopathy
1x increased nuchal translucency; chylothorax

post-natal:
4/5 presented with CHD - VSD, ASD, severe cardiomegaly, Shone syndrome with aortic coarctation; bicuspid aortic valve; tricuspid-valve insufficiency etc

5/5 microcephaly
Fetal anomalies v1.208 DOHH Ain Roesley gene: DOHH was added
gene: DOHH was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, MIM# 620066
Review for gene: DOHH was set to GREEN
gene: DOHH was marked as current diagnostic
Added comment: 4 families - 5 affecteds

1x cardiomyopathy at prenatal examination
4/5 presented with CHD post-natally - VSD, ASD, severe cardiomegaly, Shone syndrome with aortic coarctation; bicuspid aortic valve; tricuspid-valve insufficiency etc

microcephaly was post-natal
Sources: Literature
Fetal anomalies v1.207 AMOTL1 Ain Roesley Marked gene: AMOTL1 as ready
Fetal anomalies v1.207 AMOTL1 Ain Roesley Gene: amotl1 has been classified as Green List (High Evidence).
Fetal anomalies v1.207 AMOTL1 Ain Roesley Classified gene: AMOTL1 as Green List (high evidence)
Fetal anomalies v1.207 AMOTL1 Ain Roesley Gene: amotl1 has been classified as Green List (High Evidence).
Fetal anomalies v1.207 AMOTL1 Ain Roesley Classified gene: AMOTL1 as Green List (high evidence)
Fetal anomalies v1.207 AMOTL1 Ain Roesley Gene: amotl1 has been classified as Green List (High Evidence).
Fetal anomalies v1.206 AMOTL1 Ain Roesley gene: AMOTL1 was added
gene: AMOTL1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: AMOTL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AMOTL1 were set to 36751037
Phenotypes for gene: AMOTL1 were set to Orofacial clefting syndrome, MONDO:0015335, AMOTL1-related
Review for gene: AMOTL1 was set to GREEN
gene: AMOTL1 was marked as current diagnostic
Added comment: PMID: 36751037- 16 individuals from 12 families with orofacial clefting syndrome and het variants in AMOTL1. Many in 1 hotspot: 5 individuals from 3 families have R157C, 6 individuals from another 4 families have R157H, 1 has P160L, and another has Q161R. Out of this hostpaot- 1 with P368A, 1 with E507K, 1 with E579K. 7 are de novo. All but 2 have clefting, 7 are dysmorphic, 5 have hearing loss, 9 have CHD, 7 have tall stature, 6 have dev delay. Other features include liver disease, myopia, scoliosis and immune involvement.

Another 2 families have been previously reported (described in the panelapp review below) with variants in this hotspot 1 has 2 individuals with R157C, the other has 1 individual with P160L. All hotspot are absent from gnomad v2.
Sources: Literature
Fetal anomalies v1.205 AL117258.1 Ain Roesley Marked gene: AL117258.1 as ready
Fetal anomalies v1.205 AL117258.1 Ain Roesley Gene: al117258.1 has been classified as Green List (High Evidence).
Fetal anomalies v1.205 AL117258.1 Ain Roesley Classified gene: AL117258.1 as Green List (high evidence)
Fetal anomalies v1.205 AL117258.1 Ain Roesley Gene: al117258.1 has been classified as Green List (High Evidence).
Fetal anomalies v1.204 AL117258.1 Ain Roesley gene: AL117258.1 was added
gene: AL117258.1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: AL117258.1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AL117258.1 were set to 34903892
Phenotypes for gene: AL117258.1 were set to Heterotaxy; congenital heart defects
Review for gene: AL117258.1 was set to GREEN
gene: AL117258.1 was marked as current diagnostic
Added comment: Gene also known as CIROP and LMLN2

Homozygous or compound heterozygous CIROP variants identified in 12 families with congenital heart defects associated with heterotaxy.

Functional tests performed on Xenopus and zebrafish embryos showed that CIROP was essential for left side symmetry and is expressed in ciliated left–right organisers.
Sources: Literature
Sources: Literature
Genetic Epilepsy v0.2500 MED12 Zornitza Stark Marked gene: MED12 as ready
Genetic Epilepsy v0.2500 MED12 Zornitza Stark Gene: med12 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2500 MED12 Zornitza Stark Mode of inheritance for gene: MED12 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, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2499 MED12 Zornitza Stark Phenotypes for gene: MED12 were changed from to Ohdo syndrome, X-linked MIM#300895; Lujan-Fryns syndrome MIM#309520; Opitz-Kaveggia syndrome MIM#305450
Genetic Epilepsy v0.2498 MED12 Zornitza Stark Publications for gene: MED12 were set to 33244166; 32174975; 30006928; 27312080; 33244166
Genetic Epilepsy v0.2497 MED12 Zornitza Stark Publications for gene: MED12 were set to
Genetic Epilepsy v0.2497 MED12 Zornitza Stark Mode of inheritance for gene: MED12 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)
Genetic Epilepsy v0.2496 MECP2 Zornitza Stark Marked gene: MECP2 as ready
Genetic Epilepsy v0.2496 MECP2 Zornitza Stark Gene: mecp2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2496 MECP2 Zornitza Stark Phenotypes for gene: MECP2 were changed from to Rett syndrome, MIM# 312750; Intellectual developmental disorder, X-linked, syndromic 13, MIM# 300055; Encephalopathy, neonatal severe, MIM# 300673
Genetic Epilepsy v0.2495 MECP2 Zornitza Stark Publications for gene: MECP2 were set to
Genetic Epilepsy v0.2494 MECP2 Zornitza Stark Mode of inheritance for gene: MECP2 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)
Genetic Epilepsy v0.2493 MBOAT7 Zornitza Stark Marked gene: MBOAT7 as ready
Genetic Epilepsy v0.2493 MBOAT7 Zornitza Stark Gene: mboat7 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2493 MBOAT7 Zornitza Stark Phenotypes for gene: MBOAT7 were changed from to intellectual disability MIM#617188
Genetic Epilepsy v0.2492 MBOAT7 Zornitza Stark Publications for gene: MBOAT7 were set to
Genetic Epilepsy v0.2491 MBOAT7 Zornitza Stark Mode of inheritance for gene: MBOAT7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2490 KCNJ11 Zornitza Stark Marked gene: KCNJ11 as ready
Genetic Epilepsy v0.2490 KCNJ11 Zornitza Stark Gene: kcnj11 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2490 KCNJ11 Zornitza Stark Phenotypes for gene: KCNJ11 were changed from to Diabetes mellitus, transient neonatal, 3 610582; Diabetes, permanent neonatal, with or without neurologic features 606176; Hyperinsulinemic hypoglycemia, familial, 2 601820
Genetic Epilepsy v0.2489 KCNJ11 Zornitza Stark Publications for gene: KCNJ11 were set to
Genetic Epilepsy v0.2488 KCNJ11 Zornitza Stark Mode of inheritance for gene: KCNJ11 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2487 DYNC1H1 Zornitza Stark Marked gene: DYNC1H1 as ready
Genetic Epilepsy v0.2487 DYNC1H1 Zornitza Stark Gene: dync1h1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2487 DYNC1H1 Zornitza Stark Phenotypes for gene: DYNC1H1 were changed from to Cortical dysplasia, complex, with other brain malformations 13, MIM# 614563
Genetic Epilepsy v0.2486 DYNC1H1 Zornitza Stark Publications for gene: DYNC1H1 were set to
Genetic Epilepsy v0.2485 DYNC1H1 Zornitza Stark Mode of inheritance for gene: DYNC1H1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2484 DYNC1H1 Zornitza Stark edited their review of gene: DYNC1H1: Changed phenotypes: Cortical dysplasia, complex, with other brain malformations 13, MIM# 614563
Prepair 1000+ v1.6 ADPRHL2 Zornitza Stark Classified gene: ADPRHL2 as Amber List (moderate evidence)
Prepair 1000+ v1.6 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark changed review comment from: Fourteen unrelated families reported with stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS), an autosomal recessive neurodegenerative disorder with onset in the first years of life following normal early development. The disorder is characterised by cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some individuals develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy.

New HGNC approved name is ADPRS.; to: Fourteen unrelated families reported with stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS), an autosomal recessive neurodegenerative disorder with onset in the first years of life following normal early development. The disorder is characterised by cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some individuals develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy.

New HGNC approved name is ADPRS.

To be upgraded to GREEN in next version of panel.
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark edited their review of gene: ADPRHL2: Changed rating: AMBER
Genetic Epilepsy v0.2484 MAP2K2 Zornitza Stark Marked gene: MAP2K2 as ready
Genetic Epilepsy v0.2484 MAP2K2 Zornitza Stark Gene: map2k2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2484 MAP2K2 Zornitza Stark Phenotypes for gene: MAP2K2 were changed from to Cardiofaciocutaneous syndrome 4, MIM# 615280
Genetic Epilepsy v0.2483 MAP2K2 Zornitza Stark Publications for gene: MAP2K2 were set to
Genetic Epilepsy v0.2482 MAP2K2 Zornitza Stark Mode of pathogenicity for gene: MAP2K2 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
Genetic Epilepsy v0.2481 MAP2K2 Zornitza Stark Mode of inheritance for gene: MAP2K2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2480 MAP2K1 Zornitza Stark Marked gene: MAP2K1 as ready
Genetic Epilepsy v0.2480 MAP2K1 Zornitza Stark Gene: map2k1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2480 MAP2K1 Zornitza Stark Phenotypes for gene: MAP2K1 were changed from to Cardiofaciocutaneous syndrome 3, MIM# 615279
Genetic Epilepsy v0.2479 MAP2K1 Zornitza Stark Publications for gene: MAP2K1 were set to
Genetic Epilepsy v0.2478 MAP2K1 Zornitza Stark Mode of pathogenicity for gene: MAP2K1 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
Genetic Epilepsy v0.2477 MAP2K1 Zornitza Stark Mode of inheritance for gene: MAP2K1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2476 MAF Zornitza Stark Marked gene: MAF as ready
Genetic Epilepsy v0.2476 MAF Zornitza Stark Gene: maf has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2476 MAF Zornitza Stark Phenotypes for gene: MAF were changed from to Ayme-Gripp syndrome (MIM#601088)
Genetic Epilepsy v0.2475 MAF Zornitza Stark Publications for gene: MAF were set to
Genetic Epilepsy v0.2474 MAF Zornitza Stark Mode of inheritance for gene: MAF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2473 KIF1A Zornitza Stark Marked gene: KIF1A as ready
Genetic Epilepsy v0.2473 KIF1A Zornitza Stark Gene: kif1a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2473 KIF1A Zornitza Stark Phenotypes for gene: KIF1A were changed from to NESCAV syndrome, MIM# 614255
Genetic Epilepsy v0.2472 KIF1A Zornitza Stark Publications for gene: KIF1A were set to
Genetic Epilepsy v0.2471 KIF1A Zornitza Stark Mode of inheritance for gene: KIF1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2470 KIF1A Zornitza Stark changed review comment from: HSN2C is an autosomal recessive disorder characterized by onset in the first decade of progressive distal sensory loss leading to ulceration and amputation of the fingers and toes. Affected individuals also develop distal muscle weakness, primarily affecting the lower limbs. At least 4 families reported, although 3 shared same founder variant.

De novo variants in this gene are also more commonly associated with spastic paraplegia, and a complex neurodevelopmental disorder, NESCAV syndrome.; to: De novo variants in this gene are also more commonly associated with spastic paraplegia, and a complex neurodevelopmental disorder, NESCAV syndrome, which can include seizures.
Genetic Epilepsy v0.2470 KIF1A Zornitza Stark edited their review of gene: KIF1A: Changed phenotypes: NESCAV syndrome, MIM# 614255; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2470 KIAA1109 Zornitza Stark Marked gene: KIAA1109 as ready
Genetic Epilepsy v0.2470 KIAA1109 Zornitza Stark Gene: kiaa1109 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2470 KIAA1109 Zornitza Stark Phenotypes for gene: KIAA1109 were changed from to lkuraya-Kucinskas syndrome, MIM# 617822
Genetic Epilepsy v0.2469 KIAA1109 Zornitza Stark Publications for gene: KIAA1109 were set to
Genetic Epilepsy v0.2468 KIAA1109 Zornitza Stark Mode of inheritance for gene: KIAA1109 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2467 KCTD7 Zornitza Stark Marked gene: KCTD7 as ready
Genetic Epilepsy v0.2467 KCTD7 Zornitza Stark Gene: kctd7 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2467 KCTD7 Zornitza Stark Phenotypes for gene: KCTD7 were changed from to Epilepsy, progressive myoclonic 3, with or without intracellular inclusions (MIM#611726), AR
Genetic Epilepsy v0.2466 KCTD7 Zornitza Stark Publications for gene: KCTD7 were set to
Genetic Epilepsy v0.2465 KCTD7 Zornitza Stark Mode of inheritance for gene: KCTD7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2464 ITPA Zornitza Stark Marked gene: ITPA as ready
Genetic Epilepsy v0.2464 ITPA Zornitza Stark Gene: itpa has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2464 ITPA Zornitza Stark Phenotypes for gene: ITPA were changed from to Developmental and epileptic encephalopathy 35, MIM# 616647
Genetic Epilepsy v0.2463 ITPA Zornitza Stark Publications for gene: ITPA were set to
Genetic Epilepsy v0.2462 ITPA Zornitza Stark Mode of inheritance for gene: ITPA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2461 IKBKG Zornitza Stark Marked gene: IKBKG as ready
Genetic Epilepsy v0.2461 IKBKG Zornitza Stark Gene: ikbkg has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2461 IKBKG Zornitza Stark Phenotypes for gene: IKBKG were changed from to Incontinentia pigmenti, MIM# 308300
Genetic Epilepsy v0.2460 IKBKG Zornitza Stark Publications for gene: IKBKG were set to
Genetic Epilepsy v0.2459 IKBKG Zornitza Stark Mode of inheritance for gene: IKBKG 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)
Genetic Epilepsy v0.2458 IKBKG Zornitza Stark changed review comment from: X-linked systemic autoinflammatory disease (SAIDX) is characterized by the onset of systemic autoinflammation in the first months of life. Features include lymphadenopathy, hepatosplenomegaly, fever, panniculitis, and nodular skin rash. Additional manifestations may include inflammation of the optic nerve, intracranial hemorrhage, and lipodystrophy. Laboratory studies show hypogammaglobulinemia, increased or decreased white blood cell count, autoimmune cytopenias, elevated serum inflammatory markers, and a type I interferon signature. 6 unrelated boys and a girl reported. All variants resulted in absence of the domain encoded by exon 5 (NEMOdelEx5).

Note variants in this gene are associated with immunodeficiency +/- ectodermal features and with IP.; to: X-linked systemic autoinflammatory disease (SAIDX) is characterized by the onset of systemic autoinflammation in the first months of life. Features include lymphadenopathy, hepatosplenomegaly, fever, panniculitis, and nodular skin rash. Additional manifestations may include inflammation of the optic nerve, intracranial hemorrhage, and lipodystrophy. Laboratory studies show hypogammaglobulinemia, increased or decreased white blood cell count, autoimmune cytopenias, elevated serum inflammatory markers, and a type I interferon signature. 6 unrelated boys and a girl reported. All variants resulted in absence of the domain encoded by exon 5 (NEMOdelEx5).

Note variants in this gene are associated with immunodeficiency +/- ectodermal features and with IP.

Seizures reported in the IP phenotype.
Genetic Epilepsy v0.2458 IFIH1 Zornitza Stark Marked gene: IFIH1 as ready
Genetic Epilepsy v0.2458 IFIH1 Zornitza Stark Gene: ifih1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2458 IFIH1 Zornitza Stark Phenotypes for gene: IFIH1 were changed from to Aicardi-Goutieres syndrome 7, MIM#615846
Genetic Epilepsy v0.2457 IFIH1 Zornitza Stark Publications for gene: IFIH1 were set to
Genetic Epilepsy v0.2456 IFIH1 Zornitza Stark Mode of pathogenicity for gene: IFIH1 was changed from to Other
Genetic Epilepsy v0.2455 IFIH1 Zornitza Stark Mode of inheritance for gene: IFIH1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2454 IDH2 Zornitza Stark Marked gene: IDH2 as ready
Genetic Epilepsy v0.2454 IDH2 Zornitza Stark Gene: idh2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2454 IDH2 Zornitza Stark Phenotypes for gene: IDH2 were changed from to D-2-hydroxyglutaric aciduria 2, MIM# 613657
Genetic Epilepsy v0.2453 IDH2 Zornitza Stark Publications for gene: IDH2 were set to
Genetic Epilepsy v0.2452 IDH2 Zornitza Stark Mode of inheritance for gene: IDH2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2451 HTRA2 Zornitza Stark Marked gene: HTRA2 as ready
Genetic Epilepsy v0.2451 HTRA2 Zornitza Stark Gene: htra2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2451 HTRA2 Zornitza Stark Phenotypes for gene: HTRA2 were changed from to 3-methylglutaconic aciduria, type VIII, MIM# 617248
Genetic Epilepsy v0.2450 HTRA2 Zornitza Stark Publications for gene: HTRA2 were set to
Genetic Epilepsy v0.2449 HTRA2 Zornitza Stark Mode of inheritance for gene: HTRA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2448 HSPD1 Zornitza Stark changed review comment from: Multiple families reported with bi-allelic variants in HSPD1 and hypomyelinating leukodystrophy. Supportive mouse model. In addition, two unrelated individuals reported with same de novo missense p.Leu47Val and leukodystrophy.

In addition, mono-allelic variants found in families with SPG.; to: Multiple families reported with bi-allelic variants in HSPD1 and hypomyelinating leukodystrophy. Supportive mouse model. In addition, two unrelated individuals reported with same de novo missense p.Leu47Val and leukodystrophy.

In addition, mono-allelic variants found in families with SPG, not relevant to this panel.
Genetic Epilepsy v0.2448 HSPD1 Zornitza Stark edited their review of gene: HSPD1: Changed phenotypes: Leukodystrophy, hypomyelinating, 4, MIM# 612233; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2448 HSPD1 Zornitza Stark Marked gene: HSPD1 as ready
Genetic Epilepsy v0.2448 HSPD1 Zornitza Stark Gene: hspd1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2448 HSPD1 Zornitza Stark Phenotypes for gene: HSPD1 were changed from to Leukodystrophy, hypomyelinating, 4, MIM# 612233
Genetic Epilepsy v0.2447 HSPD1 Zornitza Stark Mode of inheritance for gene: HSPD1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2446 HSPD1 Zornitza Stark Publications for gene: HSPD1 were set to
Genetic Epilepsy v0.2445 HSPD1 Zornitza Stark Mode of inheritance for gene: HSPD1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2444 HSD17B4 Zornitza Stark Marked gene: HSD17B4 as ready
Genetic Epilepsy v0.2444 HSD17B4 Zornitza Stark Gene: hsd17b4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2444 HSD17B4 Zornitza Stark Phenotypes for gene: HSD17B4 were changed from to D-bifunctional protein deficiency, AR (MIM#261515); Perrault syndrome 1, AR (MIM#233400)
Genetic Epilepsy v0.2443 HSD17B4 Zornitza Stark Publications for gene: HSD17B4 were set to
Genetic Epilepsy v0.2442 HSD17B4 Zornitza Stark Mode of inheritance for gene: HSD17B4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2441 HRAS Zornitza Stark Marked gene: HRAS as ready
Genetic Epilepsy v0.2441 HRAS Zornitza Stark Gene: hras has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2441 HRAS Zornitza Stark Phenotypes for gene: HRAS were changed from Costello syndrome, MIM# 218040 to Costello syndrome, MIM# 218040
Genetic Epilepsy v0.2440 HRAS Zornitza Stark Phenotypes for gene: HRAS were changed from to Costello syndrome, MIM# 218040
Genetic Epilepsy v0.2439 HRAS Zornitza Stark Publications for gene: HRAS were set to
Genetic Epilepsy v0.2438 HRAS Zornitza Stark Mode of pathogenicity for gene: HRAS 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
Genetic Epilepsy v0.2437 HRAS Zornitza Stark Mode of inheritance for gene: HRAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2436 HMGCL Zornitza Stark Marked gene: HMGCL as ready
Genetic Epilepsy v0.2436 HMGCL Zornitza Stark Gene: hmgcl has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2436 HMGCL Zornitza Stark Phenotypes for gene: HMGCL were changed from to HMG-CoA lyase deficiency, MIM# 246450
Genetic Epilepsy v0.2435 HMGCL Zornitza Stark Publications for gene: HMGCL were set to
Genetic Epilepsy v0.2434 HMGCL Zornitza Stark Mode of inheritance for gene: HMGCL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2433 HLCS Zornitza Stark Marked gene: HLCS as ready
Genetic Epilepsy v0.2433 HLCS Zornitza Stark Gene: hlcs has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2433 HLCS Zornitza Stark Phenotypes for gene: HLCS were changed from to Holocarboxylase synthetase deficiency, MIM# 253270
Genetic Epilepsy v0.2432 HLCS Zornitza Stark Publications for gene: HLCS were set to
Genetic Epilepsy v0.2431 HLCS Zornitza Stark Mode of inheritance for gene: HLCS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2430 HEXB Zornitza Stark Marked gene: HEXB as ready
Genetic Epilepsy v0.2430 HEXB Zornitza Stark Gene: hexb has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2430 HEXB Zornitza Stark Phenotypes for gene: HEXB were changed from to Sandhoff disease, infantile, juvenile, and adult forms, MIM# 268800; MONDO:0010006
Genetic Epilepsy v0.2429 HEXB Zornitza Stark Mode of inheritance for gene: HEXB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2428 HEXA Zornitza Stark Marked gene: HEXA as ready
Genetic Epilepsy v0.2428 HEXA Zornitza Stark Gene: hexa has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2428 HEXA Zornitza Stark Phenotypes for gene: HEXA were changed from to GM2-gangliosidosis, several forms 272800; Tay-Sachs disease 272800
Genetic Epilepsy v0.2427 HEXA Zornitza Stark Publications for gene: HEXA were set to
Genetic Epilepsy v0.2426 HEXA Zornitza Stark Mode of inheritance for gene: HEXA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2425 HEPACAM Zornitza Stark Marked gene: HEPACAM as ready
Genetic Epilepsy v0.2425 HEPACAM Zornitza Stark Gene: hepacam has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2425 HEPACAM Zornitza Stark Phenotypes for gene: HEPACAM were changed from to Megalencephalic leukoencephalopathy with subcortical cysts 2A, MIM# 613925; Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without mental retardation, MIM# 613926
Genetic Epilepsy v0.2424 HEPACAM Zornitza Stark Publications for gene: HEPACAM were set to
Genetic Epilepsy v0.2423 HEPACAM Zornitza Stark Mode of inheritance for gene: HEPACAM was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genetic Epilepsy v0.2422 HAX1 Zornitza Stark Marked gene: HAX1 as ready
Genetic Epilepsy v0.2422 HAX1 Zornitza Stark Gene: hax1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2422 HAX1 Zornitza Stark Phenotypes for gene: HAX1 were changed from to Neutropaenia, severe congenital 3, autosomal recessive, MIM# 610738; Kostmann syndrome MONDO:0012548
Genetic Epilepsy v0.2421 HAX1 Zornitza Stark Publications for gene: HAX1 were set to
Genetic Epilepsy v0.2420 HAX1 Zornitza Stark Mode of inheritance for gene: HAX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2419 GOSR2 Zornitza Stark Marked gene: GOSR2 as ready
Genetic Epilepsy v0.2419 GOSR2 Zornitza Stark Gene: gosr2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2419 GOSR2 Zornitza Stark Phenotypes for gene: GOSR2 were changed from to Epilepsy, progressive myoclonic 6 , MIM#614018
Genetic Epilepsy v0.2418 GOSR2 Zornitza Stark Publications for gene: GOSR2 were set to
Genetic Epilepsy v0.2417 GOSR2 Zornitza Stark Mode of inheritance for gene: GOSR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2416 GNAQ Zornitza Stark Marked gene: GNAQ as ready
Genetic Epilepsy v0.2416 GNAQ Zornitza Stark Gene: gnaq has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2416 GNAQ Zornitza Stark Phenotypes for gene: GNAQ were changed from to Sturge-Weber syndrome, somatic, mosaic 185300
Genetic Epilepsy v0.2415 GNAQ Zornitza Stark Publications for gene: GNAQ were set to
Genetic Epilepsy v0.2414 GNAQ Zornitza Stark Mode of pathogenicity for gene: GNAQ was changed from to Other
Genetic Epilepsy v0.2413 GNAQ Zornitza Stark Mode of inheritance for gene: GNAQ was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2412 GNAQ Zornitza Stark Tag somatic tag was added to gene: GNAQ.
Genetic Epilepsy v0.2412 GM2A Zornitza Stark Marked gene: GM2A as ready
Genetic Epilepsy v0.2412 GM2A Zornitza Stark Gene: gm2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2412 GM2A Zornitza Stark Phenotypes for gene: GM2A were changed from to GM2-gangliosidosis, AB variant MIM#272750
Genetic Epilepsy v0.2411 GM2A Zornitza Stark Publications for gene: GM2A were set to
Genetic Epilepsy v0.2410 GM2A Zornitza Stark Mode of inheritance for gene: GM2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2409 GLUL Zornitza Stark Marked gene: GLUL as ready
Genetic Epilepsy v0.2409 GLUL Zornitza Stark Gene: glul has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2409 GLUL Zornitza Stark Phenotypes for gene: GLUL were changed from to Glutamine deficiency, congenital MIM#610015
Genetic Epilepsy v0.2408 GLUL Zornitza Stark Publications for gene: GLUL were set to
Genetic Epilepsy v0.2407 GLUL Zornitza Stark Mode of inheritance for gene: GLUL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2406 GLUL Zornitza Stark reviewed gene: GLUL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glutamine deficiency, congenital MIM#610015; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2406 GLUD1 Zornitza Stark Marked gene: GLUD1 as ready
Genetic Epilepsy v0.2406 GLUD1 Zornitza Stark Gene: glud1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2406 GLUD1 Zornitza Stark Phenotypes for gene: GLUD1 were changed from to Hyperinsulinism-hyperammonemia syndrome, MIM# 606762
Genetic Epilepsy v0.2405 GLUD1 Zornitza Stark Publications for gene: GLUD1 were set to
Genetic Epilepsy v0.2404 GLUD1 Zornitza Stark Mode of inheritance for gene: GLUD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2403 GLUD1 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association. Hypoglycaemic seizures.
Genetic Epilepsy v0.2403 GLDC Zornitza Stark Marked gene: GLDC as ready
Genetic Epilepsy v0.2403 GLDC Zornitza Stark Gene: gldc has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2403 GLDC Zornitza Stark Phenotypes for gene: GLDC were changed from to Glycine encephalopathy (MIM#605899)
Genetic Epilepsy v0.2402 GLDC Zornitza Stark Publications for gene: GLDC were set to
Genetic Epilepsy v0.2401 GLDC Zornitza Stark Mode of inheritance for gene: GLDC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2400 GLB1 Zornitza Stark Marked gene: GLB1 as ready
Genetic Epilepsy v0.2400 GLB1 Zornitza Stark Gene: glb1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2400 GLB1 Zornitza Stark Phenotypes for gene: GLB1 were changed from to GM1-gangliosidosis, type I MIM#230500; GM1-gangliosidosis, type II MIM# 230600
Genetic Epilepsy v0.2399 GLB1 Zornitza Stark Publications for gene: GLB1 were set to
Genetic Epilepsy v0.2398 GLB1 Zornitza Stark Mode of inheritance for gene: GLB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2397 GFM1 Zornitza Stark Marked gene: GFM1 as ready
Genetic Epilepsy v0.2397 GFM1 Zornitza Stark Gene: gfm1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2397 GFM1 Zornitza Stark Phenotypes for gene: GFM1 were changed from to Combined oxidative phosphorylation deficiency 1 MIM#609060
Genetic Epilepsy v0.2396 GFM1 Zornitza Stark Publications for gene: GFM1 were set to
Genetic Epilepsy v0.2395 GFM1 Zornitza Stark Mode of inheritance for gene: GFM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2394 GFAP Zornitza Stark Marked gene: GFAP as ready
Genetic Epilepsy v0.2394 GFAP Zornitza Stark Gene: gfap has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2394 GFAP Zornitza Stark Phenotypes for gene: GFAP were changed from to Alexander disease, MIM# 203450
Genetic Epilepsy v0.2393 GFAP Zornitza Stark Publications for gene: GFAP were set to
Genetic Epilepsy v0.2392 GFAP Zornitza Stark Mode of inheritance for gene: GFAP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2391 GCH1 Zornitza Stark Marked gene: GCH1 as ready
Genetic Epilepsy v0.2391 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2391 GCH1 Zornitza Stark Phenotypes for gene: GCH1 were changed from to Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910
Genetic Epilepsy v0.2390 GCH1 Zornitza Stark Publications for gene: GCH1 were set to
Genetic Epilepsy v0.2389 GCH1 Zornitza Stark Mode of inheritance for gene: GCH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2388 GCH1 Zornitza Stark Deleted their comment
Genetic Epilepsy v0.2388 GCH1 Zornitza Stark edited their review of gene: GCH1: Added comment: Well established gene-disease association, seizures are part of the phenotype.; Changed publications: 7730309; Changed phenotypes: Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2388 GALC Zornitza Stark Marked gene: GALC as ready
Genetic Epilepsy v0.2388 GALC Zornitza Stark Gene: galc has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2388 GALC Zornitza Stark Phenotypes for gene: GALC were changed from to Krabbe disease, MIM# 245200; MONDO:0009499
Genetic Epilepsy v0.2387 GALC Zornitza Stark Publications for gene: GALC were set to
Genetic Epilepsy v0.2386 GALC Zornitza Stark Mode of inheritance for gene: GALC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2385 GALC Zornitza Stark changed review comment from: Krabbe disease is an autosomal recessive lysosomal disorder affecting the white matter of the central and peripheral nervous systems. Most patients present within the first 6 months of life with 'infantile' or 'classic' disease manifest as extreme irritability, spasticity, and developmental delay. There is severe motor and mental deterioration, leading to decerebration and death by age 2 years. Approximately 10 to 15% of patients have a later onset, commonly differentiated as late-infantile (6 months to 3 years), juvenile (3 to 8 years), and even adult-onset forms. Multiple families reported.; to: Krabbe disease is an autosomal recessive lysosomal disorder affecting the white matter of the central and peripheral nervous systems. Most patients present within the first 6 months of life with 'infantile' or 'classic' disease manifest as extreme irritability, spasticity, and developmental delay. There is severe motor and mental deterioration, leading to decerebration and death by age 2 years. Approximately 10 to 15% of patients have a later onset, commonly differentiated as late-infantile (6 months to 3 years), juvenile (3 to 8 years), and even adult-onset forms. Multiple families reported.

Seizures are part of the phenotype.
Genetic Epilepsy v0.2385 FUCA1 Zornitza Stark Marked gene: FUCA1 as ready
Genetic Epilepsy v0.2385 FUCA1 Zornitza Stark Gene: fuca1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2385 FUCA1 Zornitza Stark Phenotypes for gene: FUCA1 were changed from to Fucosidosis, MIM# 230000; MONDO:0009254
Genetic Epilepsy v0.2384 FUCA1 Zornitza Stark Publications for gene: FUCA1 were set to
Genetic Epilepsy v0.2383 FUCA1 Zornitza Stark Mode of inheritance for gene: FUCA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2382 FUCA1 Zornitza Stark changed review comment from: Fucosidosis is an autosomal recessive lysosomal storage disease caused by defective alpha-L-fucosidase with accumulation of fucose in the tissues. Clinical features include angiokeratoma, progressive psychomotor retardation, neurologic signs, coarse facial features, and dysostosis multiplex. Well established gene-disease association, multiple families reported.; to: Fucosidosis is an autosomal recessive lysosomal storage disease caused by defective alpha-L-fucosidase with accumulation of fucose in the tissues. Clinical features include angiokeratoma, progressive psychomotor retardation, neurologic signs, coarse facial features, and dysostosis multiplex. Well established gene-disease association, multiple families reported.

Seizures are part of the phenotype.
Genetic Epilepsy v0.2382 FRRS1L Zornitza Stark Marked gene: FRRS1L as ready
Genetic Epilepsy v0.2382 FRRS1L Zornitza Stark Gene: frrs1l has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2382 FRRS1L Zornitza Stark Phenotypes for gene: FRRS1L were changed from to Developmental and epileptic encephalopathy, 37 MONDO:0014859
Genetic Epilepsy v0.2381 FRRS1L Zornitza Stark Publications for gene: FRRS1L were set to
Genetic Epilepsy v0.2380 FRRS1L Zornitza Stark Mode of inheritance for gene: FRRS1L was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2379 DPM1 Zornitza Stark Marked gene: DPM1 as ready
Genetic Epilepsy v0.2379 DPM1 Zornitza Stark Gene: dpm1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2379 DPM1 Zornitza Stark Publications for gene: DPM1 were set to 23856421
Genetic Epilepsy v0.2378 DPM1 Zornitza Stark Phenotypes for gene: DPM1 were changed from to Congenital disorder of glycosylation, type Ie, 608799
Genetic Epilepsy v0.2377 DPM1 Zornitza Stark Publications for gene: DPM1 were set to
Genetic Epilepsy v0.2376 DPM1 Zornitza Stark Mode of inheritance for gene: DPM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2375 DPM1 Zornitza Stark reviewed gene: DPM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type Ie, 608799; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2375 DNM1L Zornitza Stark Marked gene: DNM1L as ready
Genetic Epilepsy v0.2375 DNM1L Zornitza Stark Gene: dnm1l has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2375 DNM1L Zornitza Stark Phenotypes for gene: DNM1L were changed from Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 - MIM#614388 (AD, AR) to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 - MIM#614388 (AD, AR)
Genetic Epilepsy v0.2374 DNM1L Zornitza Stark Phenotypes for gene: DNM1L were changed from to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 - MIM#614388 (AD, AR)
Genetic Epilepsy v0.2374 DNM1L Zornitza Stark Mode of inheritance for gene: DNM1L was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2373 DNM1L Zornitza Stark Mode of inheritance for gene: DNM1L was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark Tag new gene name tag was added to gene: ADPRHL2.
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark Marked gene: ADPRHL2 as ready
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark Classified gene: ADPRHL2 as Green List (high evidence)
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.4 ADPRHL2 Zornitza Stark reviewed gene: ADPRHL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, MIM#618170; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1619 GNE Zornitza Stark Phenotypes for gene: GNE were changed from Nonaka myopathy 605820; Sialuria MIM#269921; ADUDP-GlcNAc epimerase/kinase deficiency (Disorders of multiple glycosylation and other glycosylation pathways) to Thrombocytopenia 12 with or without myopathy, MIM#620757; Nonaka myopathy 605820; Sialuria MIM#269921; ADUDP-GlcNAc epimerase/kinase deficiency (Disorders of multiple glycosylation and other glycosylation pathways)
Mendeliome v1.1618 GNE Zornitza Stark edited their review of gene: GNE: Changed phenotypes: Thrombocytopenia 12 with or without myopathy, MIM#620757, Nonaka myopathy 605820, Sialuria MIM#269921, ADUDP-GlcNAc epimerase/kinase deficiency (Disorders of multiple glycosylation and other glycosylation pathways)
Bleeding and Platelet Disorders v1.29 GNE Zornitza Stark Phenotypes for gene: GNE were changed from Thrombocytopaenia; Myopathy to Thrombocytopenia 12 with or without myopathy, MIM#620757
Bleeding and Platelet Disorders v1.28 GNE Zornitza Stark edited their review of gene: GNE: Changed phenotypes: Thrombocytopenia 12 with or without myopathy, MIM#620757
Cardiomyopathy_Paediatric v0.184 ANK2 Elena Savva Marked gene: ANK2 as ready
Cardiomyopathy_Paediatric v0.184 ANK2 Elena Savva Gene: ank2 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v0.184 ANK2 Elena Savva Added comment: Comment on phenotypes: Association is disputed, gene associated to a neurodevelopmental disorder
Cardiomyopathy_Paediatric v0.184 ANK2 Elena Savva Phenotypes for gene: ANK2 were changed from to Cardiac arrhythmia, ankyrin-B-related MIM#600919; Long QT syndrome 4 MIM#600919
Cardiomyopathy_Paediatric v0.183 ANK2 Elena Savva Classified gene: ANK2 as Red List (low evidence)
Cardiomyopathy_Paediatric v0.183 ANK2 Elena Savva Gene: ank2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2372 FOXG1 Zornitza Stark Marked gene: FOXG1 as ready
Genetic Epilepsy v0.2372 FOXG1 Zornitza Stark Gene: foxg1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2372 FOXG1 Zornitza Stark Phenotypes for gene: FOXG1 were changed from to Rett syndrome, congenital variant, MIM# 613454
Genetic Epilepsy v0.2371 FOXG1 Zornitza Stark Publications for gene: FOXG1 were set to
Genetic Epilepsy v0.2370 FOXG1 Zornitza Stark Mode of inheritance for gene: FOXG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2369 FOXG1 Zornitza Stark reviewed gene: FOXG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Rett syndrome, congenital variant, MIM# 613454; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2369 EXOSC3 Zornitza Stark Marked gene: EXOSC3 as ready
Genetic Epilepsy v0.2369 EXOSC3 Zornitza Stark Gene: exosc3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2369 EXOSC3 Zornitza Stark Phenotypes for gene: EXOSC3 were changed from to Pontocerebellar hypoplasia, type 1B, MIM# 614678
Genetic Epilepsy v0.2368 EXOSC3 Zornitza Stark Publications for gene: EXOSC3 were set to
Genetic Epilepsy v0.2367 EXOSC3 Zornitza Stark Mode of inheritance for gene: EXOSC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2366 EXOSC3 Zornitza Stark changed review comment from: Pontocerebellar hypoplasia type 1B is a severe autosomal recessive neurologic disorder characterized by a combination of cerebellar and spinal motor neuron degeneration beginning at birth. There is diffuse muscle weakness, progressive microcephaly, global developmental delay, and brainstem involvement. PCH1B can be divided into mild, moderate, and severe subgroups that vary in age at onset, progression, clinical and neuroradiologic severity, and survival. Multiple families reported.; to: Pontocerebellar hypoplasia type 1B is a severe autosomal recessive neurologic disorder characterized by a combination of cerebellar and spinal motor neuron degeneration beginning at birth. There is diffuse muscle weakness, progressive microcephaly, global developmental delay, and brainstem involvement. PCH1B can be divided into mild, moderate, and severe subgroups that vary in age at onset, progression, clinical and neuroradiologic severity, and survival. Multiple families reported.

Seizures are part of the phenotype.
Genetic Epilepsy v0.2366 EPM2A Zornitza Stark Marked gene: EPM2A as ready
Genetic Epilepsy v0.2366 EPM2A Zornitza Stark Gene: epm2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2366 EPM2A Zornitza Stark Phenotypes for gene: EPM2A were changed from Lafora disease MONDO:0009697 to Lafora disease MONDO:0009697
Genetic Epilepsy v0.2365 EPM2A Zornitza Stark Phenotypes for gene: EPM2A were changed from to Lafora disease MONDO:0009697
Genetic Epilepsy v0.2364 EPM2A Zornitza Stark Publications for gene: EPM2A were set to
Genetic Epilepsy v0.2363 EPM2A Zornitza Stark Mode of inheritance for gene: EPM2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1618 SAMD7 Zornitza Stark Phenotypes for gene: SAMD7 were changed from Macular dystrophy, retinal, SAMD7-related MONDO:0031166 to Macular dystrophy with or without cone dysfunction, MIM# 620762
Mendeliome v1.1617 SAMD7 Zornitza Stark reviewed gene: SAMD7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Macular dystrophy with or without cone dysfunction, MIM# 620762; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Macular Dystrophy/Stargardt Disease v0.45 SAMD7 Zornitza Stark Phenotypes for gene: SAMD7 were changed from Macular dystrophy, retinal, SAMD7-related MONDO:0031166 to Macular dystrophy with or without cone dysfunction, MIM# 620762
Macular Dystrophy/Stargardt Disease v0.44 SAMD7 Zornitza Stark reviewed gene: SAMD7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Macular dystrophy with or without cone dysfunction, MIM# 620762; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1617 FHL2 Zornitza Stark Marked gene: FHL2 as ready
Mendeliome v1.1617 FHL2 Zornitza Stark Gene: fhl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1617 FHL2 Zornitza Stark Classified gene: FHL2 as Amber List (moderate evidence)
Mendeliome v1.1617 FHL2 Zornitza Stark Gene: fhl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1616 FHL2 Zornitza Stark gene: FHL2 was added
gene: FHL2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: FHL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FHL2 were set to 36854411; 25358972
Phenotypes for gene: FHL2 were set to Cardiomyopathy, MONDO:0004994, FHL2-related
Review for gene: FHL2 was set to AMBER
Added comment: Emerging evidence that variants in this gene may be associated with cardiomyopathy.

Reports of HCM and DCM.

c.391C>T (p.Arg131Cys) may be recurrent in early-onset DCM.
Sources: Expert Review
Cardiomyopathy_Paediatric v0.182 FHL2 Zornitza Stark Marked gene: FHL2 as ready
Cardiomyopathy_Paediatric v0.182 FHL2 Zornitza Stark Gene: fhl2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.182 FHL2 Zornitza Stark Classified gene: FHL2 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v0.182 FHL2 Zornitza Stark Gene: fhl2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.181 FHL2 Zornitza Stark gene: FHL2 was added
gene: FHL2 was added to Cardiomyopathy_Paediatric. Sources: Expert Review
Mode of inheritance for gene: FHL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FHL2 were set to 36854411; 25358972
Phenotypes for gene: FHL2 were set to Cardiomyopathy, MONDO:0004994, FHL2-related
Review for gene: FHL2 was set to AMBER
Added comment: Emerging evidence that variants in this gene may be associated with cardiomyopathy.

Reports of HCM and DCM.

c.391C>T (p.Arg131Cys) may be recurrent in early-onset DCM.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5724 ZFHX3 Zornitza Stark Publications for gene: ZFHX3 were set to 37292950
Intellectual disability syndromic and non-syndromic v0.5723 ZFHX3 Zornitza Stark edited their review of gene: ZFHX3: Added comment: Now published PMID 38412861; Changed publications: 38412861
Mendeliome v1.1615 ZFHX3 Zornitza Stark Publications for gene: ZFHX3 were set to
Mendeliome v1.1614 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Mendeliome v1.1614 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Mendeliome v1.1614 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Mendeliome v1.1614 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Mendeliome v1.1613 ZRSR2 Zornitza Stark gene: ZRSR2 was added
gene: ZRSR2 was added to Mendeliome. Sources: Expert Review
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
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: Expert Review
Intellectual disability syndromic and non-syndromic v0.5723 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from developmental and epileptic encephalopathy MONDO:0100062, SLC32A1-related to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755
Genetic Epilepsy v0.2362 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from Genetic epilepsy with febrile seizures plus; Developmental and epileptic encephalopathy MONDO:0100062, SLC32A1-related to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755
Genetic Epilepsy v0.2361 SLC32A1 Zornitza Stark edited their review of gene: SLC32A1: Changed phenotypes: Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755
Mendeliome v1.1612 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from Genetic epilepsy with febrile seizures plus; Developmental and epileptic encephalopathy MONDO:0100062, SLC32A1-related to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755
Mendeliome v1.1611 SLC32A1 Zornitza Stark edited their review of gene: SLC32A1: Changed phenotypes: Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755
Intellectual disability syndromic and non-syndromic v0.5722 PTRHD1 Zornitza Stark Phenotypes for gene: PTRHD1 were changed from Parkinsonism; Intellectual disability to Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747
Intellectual disability syndromic and non-syndromic v0.5721 PTRHD1 Zornitza Stark edited their review of gene: PTRHD1: Changed phenotypes: Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747
Mendeliome v1.1611 PTRHD1 Zornitza Stark Phenotypes for gene: PTRHD1 were changed from Parkinsonism; Intellectual disability to Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747
Early-onset Parkinson disease v0.295 PTRHD1 Zornitza Stark Phenotypes for gene: PTRHD1 were changed from early-onset parkinsonism; intellectual disability to Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747
Early-onset Parkinson disease v0.294 PTRHD1 Zornitza Stark reviewed gene: PTRHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v0.34 DMP1 Zornitza Stark Marked gene: DMP1 as ready
Osteopetrosis v0.34 DMP1 Zornitza Stark Gene: dmp1 has been classified as Green List (High Evidence).
Osteopetrosis v0.34 DMP1 Zornitza Stark Classified gene: DMP1 as Green List (high evidence)
Osteopetrosis v0.34 DMP1 Zornitza Stark Gene: dmp1 has been classified as Green List (High Evidence).
Osteopetrosis v0.33 DMP1 Zornitza Stark gene: DMP1 was added
gene: DMP1 was added to Osteopetrosis. Sources: Expert Review
Mode of inheritance for gene: DMP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DMP1 were set to 17033625
Phenotypes for gene: DMP1 were set to Hypophosphataemic rickets, MIM#600980
Review for gene: DMP1 was set to GREEN
Added comment: Included due to phenotypic overlap: osteosclerotic changes on X-rays, severe in some individuals.
Sources: Expert Review
Mendeliome v1.1610 BBS4 Bryony Thompson reviewed gene: BBS4: Rating: RED; Mode of pathogenicity: None; Publications: 37588201; Phenotypes: autosomal dominant polycystic liver disease MONDO:0000447; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1610 BBS4 Bryony Thompson Deleted their review
Mendeliome v1.1610 ZFHX3 Lucy Spencer reviewed gene: ZFHX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38412861; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), ZFHX3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1610 EFEMP1 Zornitza Stark Phenotypes for gene: EFEMP1 were changed from Glaucoma 1, open angle, H, MIM# 611276; Doyne honeycomb degeneration of retina, MIM# 126600; EFEMP1-related connective tissue disorder to Glaucoma 1, open angle, H, MIM# 611276; Doyne honeycomb degeneration of retina, MIM# 126600; EFEMP1-related connective tissue disorder
Mendeliome v1.1609 EFEMP1 Zornitza Stark Phenotypes for gene: EFEMP1 were changed from Doyne honeycomb degeneration of retina, MIM# 126600; EFEMP1-related connective tissue disorder to Glaucoma 1, open angle, H, MIM# 611276; Doyne honeycomb degeneration of retina, MIM# 126600; EFEMP1-related connective tissue disorder
Mendeliome v1.1608 EFEMP1 Zornitza Stark edited their review of gene: EFEMP1: Changed phenotypes: Doyne honeycomb degeneration of retina, MIM# 126600, EFEMP1-related connective tissue disorder, Glaucoma 1, open angle, H, MIM# 611276
Glaucoma congenital v1.9 EFEMP1 Zornitza Stark Phenotypes for gene: EFEMP1 were changed from Juvenile-onset open angle glaucoma, MONDO:0020367, EFEMP1-related to Glaucoma 1, open angle, H, MIM# 611276
Glaucoma congenital v1.8 EFEMP1 Zornitza Stark reviewed gene: EFEMP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glaucoma 1, open angle, H, MIM# 611276; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2361 DIAPH1 Zornitza Stark Marked gene: DIAPH1 as ready
Genetic Epilepsy v0.2361 DIAPH1 Zornitza Stark Gene: diaph1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2361 DIAPH1 Zornitza Stark Phenotypes for gene: DIAPH1 were changed from to Seizures, cortical blindness, microcephaly syndrome, MIM# 616632
Genetic Epilepsy v0.2360 DIAPH1 Zornitza Stark Publications for gene: DIAPH1 were set to
Genetic Epilepsy v0.2359 DIAPH1 Zornitza Stark Mode of inheritance for gene: DIAPH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2358 DIAPH1 Zornitza Stark reviewed gene: DIAPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Seizures, cortical blindness, microcephaly syndrome, MIM# 616632; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2358 DHCR24 Zornitza Stark Marked gene: DHCR24 as ready
Genetic Epilepsy v0.2358 DHCR24 Zornitza Stark Gene: dhcr24 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2358 DHCR24 Zornitza Stark Phenotypes for gene: DHCR24 were changed from to Desmosterolosis, MIM# 602398
Genetic Epilepsy v0.2357 DHCR24 Zornitza Stark Publications for gene: DHCR24 were set to
Genetic Epilepsy v0.2356 DHCR24 Zornitza Stark Mode of inheritance for gene: DHCR24 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2355 DHCR24 Zornitza Stark changed review comment from: Clinical features include multiple congenital anomalies, including contractures and brain anomalies; intellectual disability; and elevated levels of the cholesterol precursor desmosterol in plasma, tissue, and cultured cells.

At least 10 unrelated families reported, mouse model.; to: Clinical features include multiple congenital anomalies, including contractures and brain anomalies; intellectual disability; and elevated levels of the cholesterol precursor desmosterol in plasma, tissue, and cultured cells.

At least 10 unrelated families reported, mouse model. Seizures are a feature.
Genetic Epilepsy v0.2355 DDX3X Zornitza Stark Marked gene: DDX3X as ready
Genetic Epilepsy v0.2355 DDX3X Zornitza Stark Gene: ddx3x has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2355 DDX3X Zornitza Stark Phenotypes for gene: DDX3X were changed from to Intellectual developmental disorder, X-linked, syndrome, Snijders Blok type MIM# 300958
Genetic Epilepsy v0.2354 DDX3X Zornitza Stark Publications for gene: DDX3X were set to
Genetic Epilepsy v0.2353 DDX3X Zornitza Stark Mode of inheritance for gene: DDX3X 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)
Genetic Epilepsy v0.2352 DDX3X Zornitza Stark changed review comment from: Syndromic X-linked mental retardation of the Snijders Blok type (MRXSSB), which occurs predominantly in females, is characterised by mildly to severely impaired intellectual development with variable other features including brain abnormalities, microcephaly, hypotonia, movement disorder and/or spasticity, ventricular enlargement, hypoplasia, and behavioural problems. Affected girls have de novo heterozygous mutations consistent with X-linked dominant inheritance. No consistent dysmorphic facial phenotype and onset in infancy.

Multiple unrelated families reported.; to: Syndromic X-linked mental retardation of the Snijders Blok type (MRXSSB), which occurs predominantly in females, is characterised by mildly to severely impaired intellectual development with variable other features including brain abnormalities, microcephaly, hypotonia, movement disorder and/or spasticity, ventricular enlargement, hypoplasia, and behavioural problems. Affected girls have de novo heterozygous mutations consistent with X-linked dominant inheritance. No consistent dysmorphic facial phenotype and onset in infancy.

Multiple unrelated families reported. Seizures are a feature.
Genetic Epilepsy v0.2352 DCX Zornitza Stark Marked gene: DCX as ready
Genetic Epilepsy v0.2352 DCX Zornitza Stark Gene: dcx has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2352 DCX Zornitza Stark Phenotypes for gene: DCX were changed from to Lissencephaly, X-linked, MIM# 300067; Subcortical laminal heterotopia, X-linked 300067
Genetic Epilepsy v0.2351 DCX Zornitza Stark Publications for gene: DCX were set to
Genetic Epilepsy v0.2350 DCX Zornitza Stark Mode of inheritance for gene: DCX 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)
Genetic Epilepsy v0.2349 DCX Zornitza Stark changed review comment from: DCX mutations cause classic lissencephaly with mental retardation in hemizygous males and a milder phenotype known as subcortical band heterotopia in females, sometimes in the same family. The subcortical lamina heterotopia found in heterozygous females is also referred to as 'double cortex' (DC) syndrome. Multiple affected families reported.; to: DCX mutations cause classic lissencephaly with mental retardation in hemizygous males and a milder phenotype known as subcortical band heterotopia in females, sometimes in the same family. The subcortical lamina heterotopia found in heterozygous females is also referred to as 'double cortex' (DC) syndrome. Multiple affected families reported. Seizures are a feature of the condition.
Genetic Epilepsy v0.2349 D2HGDH Zornitza Stark Marked gene: D2HGDH as ready
Genetic Epilepsy v0.2349 D2HGDH Zornitza Stark Gene: d2hgdh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2349 D2HGDH Zornitza Stark Phenotypes for gene: D2HGDH were changed from to D-2-hydroxyglutaric aciduria MIM#600721
Genetic Epilepsy v0.2348 D2HGDH Zornitza Stark Publications for gene: D2HGDH were set to
Genetic Epilepsy v0.2347 D2HGDH Zornitza Stark Mode of inheritance for gene: D2HGDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2346 D2HGDH Zornitza Stark changed review comment from: More than 3 families reported.; to: More than 3 families reported, early onset encephalopathy is a key feature.
Genetic Epilepsy v0.2346 CTSD Zornitza Stark Marked gene: CTSD as ready
Genetic Epilepsy v0.2346 CTSD Zornitza Stark Gene: ctsd has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2346 CTSD Zornitza Stark Phenotypes for gene: CTSD were changed from to Ceroid lipofuscinosis, neuronal, 10, MIM# 610127; MONDO:0012414
Genetic Epilepsy v0.2345 CTSD Zornitza Stark Publications for gene: CTSD were set to
Genetic Epilepsy v0.2344 CTSD Zornitza Stark Mode of inheritance for gene: CTSD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2343 CTSD Zornitza Stark changed review comment from: Neurodegenerative disorder though severe congenital forms also reported.; to: Neurodegenerative disorder though severe congenital forms also reported, seizures are a key feature.
Genetic Epilepsy v0.2343 COQ9 Zornitza Stark Marked gene: COQ9 as ready
Genetic Epilepsy v0.2343 COQ9 Zornitza Stark Gene: coq9 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2343 COQ9 Zornitza Stark Phenotypes for gene: COQ9 were changed from to Coenzyme Q10 deficiency, primary, 5, MIM#614654
Genetic Epilepsy v0.2342 COQ9 Zornitza Stark Publications for gene: COQ9 were set to
Genetic Epilepsy v0.2341 COQ9 Zornitza Stark Mode of inheritance for gene: COQ9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2340 COQ9 Zornitza Stark reviewed gene: COQ9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coenzyme Q10 deficiency, primary, 5, MIM#614654; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2340 COQ4 Zornitza Stark Marked gene: COQ4 as ready
Genetic Epilepsy v0.2340 COQ4 Zornitza Stark Gene: coq4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2340 COQ4 Zornitza Stark Phenotypes for gene: COQ4 were changed from to Coenzyme Q10 deficiency, primary, 7, MIM# 616276
Genetic Epilepsy v0.2339 COQ4 Zornitza Stark Publications for gene: COQ4 were set to
Genetic Epilepsy v0.2338 COQ4 Zornitza Stark Mode of inheritance for gene: COQ4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2337 COQ2 Zornitza Stark Marked gene: COQ2 as ready
Genetic Epilepsy v0.2337 COQ2 Zornitza Stark Gene: coq2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2337 COQ2 Zornitza Stark Phenotypes for gene: COQ2 were changed from to Coenzyme Q10 deficiency, primary, 1, MIM# 607426; MONDO:0011829
Genetic Epilepsy v0.2336 COQ2 Zornitza Stark Publications for gene: COQ2 were set to
Genetic Epilepsy v0.2335 COQ2 Zornitza Stark Mode of inheritance for gene: COQ2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.203 MYCN Zornitza Stark Phenotypes for gene: MYCN were changed from Feingold syndrome 1 (MIM#164280); Neurodevelopmental disorder (MONDO:0700092), MYCN-related to Feingold syndrome 1 (MIM#164280); Megalencephaly-polydactyly syndrome, MIM# 620748
Fetal anomalies v1.202 MYCN Zornitza Stark edited their review of gene: MYCN: Changed phenotypes: Feingold syndrome 1, MIM# 164280, Megalencephaly-polydactyly syndrome, MIM# 620748
Hand and foot malformations v0.73 MYCN Zornitza Stark Marked gene: MYCN as ready
Hand and foot malformations v0.73 MYCN Zornitza Stark Gene: mycn has been classified as Green List (High Evidence).
Hand and foot malformations v0.73 MYCN Zornitza Stark Phenotypes for gene: MYCN were changed from Feingold syndrome (Microcephaly-oculo-digito-esophageal-duodenal) 164280 to Megalencephaly-polydactyly syndrome, MIM# 620748; Feingold syndrome (Microcephaly-oculo-digito-esophageal-duodenal) 164280
Hand and foot malformations v0.72 MYCN Zornitza Stark reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Megalencephaly-polydactyly syndrome, MIM# 620748; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.276 MYCN Zornitza Stark Phenotypes for gene: MYCN were changed from Neurodevelopmental disorder (MONDO:0700092), MYCN-related to Megalencephaly-polydactyly syndrome, MIM# 620748
Polydactyly v0.275 MYCN Zornitza Stark reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Megalencephaly-polydactyly syndrome, MIM# 620748; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Macrocephaly_Megalencephaly v0.140 MYCN Zornitza Stark Phenotypes for gene: MYCN were changed from Neurodevelopmental disorder (MONDO:0700092), MYCN-related to Megalencephaly-polydactyly syndrome, MIM# 620748
Macrocephaly_Megalencephaly v0.139 MYCN Zornitza Stark reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Megalencephaly-polydactyly syndrome, MIM# 620748; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5721 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Intellectual disability syndromic and non-syndromic v0.5720 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.519 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Callosome v0.518 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v1.21 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Muscular dystrophy and myopathy_Paediatric v1.20 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.251 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Microcephaly v1.250 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1608 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Mendeliome v1.1607 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Autism v0.197 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Autism v0.196 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1607 RREB1 Zornitza Stark Phenotypes for gene: RREB1 were changed from Noonan syndrome-like disorder to Rasopathy, MONDO:0021060, RREB1-related
Microcephaly v1.250 RGS6 Zornitza Stark Phenotypes for gene: RGS6 were changed from Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149 to Neurodevelopmental disorder, MONDO:0700092, RGS6-related
Mendeliome v1.1606 RGS6 Zornitza Stark Phenotypes for gene: RGS6 were changed from Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149 to Neurodevelopmental disorder, MONDO:0700092, RGS6-related
Cataract v0.364 RGS6 Zornitza Stark Phenotypes for gene: RGS6 were changed from Neurodevelopmental disorder, MONDO:0700092, RGS6-related to Neurodevelopmental disorder, MONDO:0700092, RGS6-related
Cataract v0.363 RGS6 Zornitza Stark Phenotypes for gene: RGS6 were changed from Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149 to Neurodevelopmental disorder, MONDO:0700092, RGS6-related
Mendeliome v1.1605 ZSCAN10 Zornitza Stark Marked gene: ZSCAN10 as ready
Mendeliome v1.1605 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Mendeliome v1.1605 ZSCAN10 Zornitza Stark Classified gene: ZSCAN10 as Green List (high evidence)
Mendeliome v1.1605 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.173 ZSCAN10 Zornitza Stark Marked gene: ZSCAN10 as ready
Deafness_IsolatedAndComplex v1.173 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.173 ZSCAN10 Zornitza Stark Classified gene: ZSCAN10 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.173 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5720 ZSCAN10 Zornitza Stark Marked gene: ZSCAN10 as ready
Intellectual disability syndromic and non-syndromic v0.5720 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5720 ZSCAN10 Zornitza Stark Classified gene: ZSCAN10 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5720 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.20 SNUPN Zornitza Stark Phenotypes for gene: SNUPN were changed from autosomal recessive limb-girdle muscular dystrophy MONDO:0015152 to autosomal recessive limb-girdle muscular dystrophy MONDO:0015152, SNUPN-related
Mendeliome v1.1604 CORIN Zornitza Stark Phenotypes for gene: CORIN were changed from Preeclampsia/eclampsia 5 MIM#614595; ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734) to Preeclampsia/eclampsia 5 MIM#614595; Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734)
Mendeliome v1.1603 CORIN Zornitza Stark Publications for gene: CORIN were set to 22437503
Mendeliome v1.1602 CORIN Zornitza Stark Phenotypes for gene: CORIN were changed from Preeclampsia/eclampsia 5 MIM#614595 to Preeclampsia/eclampsia 5 MIM#614595; ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734)
Genetic Epilepsy v0.2334 DIP2C Zornitza Stark Classified gene: DIP2C as Green List (high evidence)
Genetic Epilepsy v0.2334 DIP2C Zornitza Stark Gene: dip2c has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2333 DIP2C Zornitza Stark reviewed gene: DIP2C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), DIP2C-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.202 CELSR3 Zornitza Stark Marked gene: CELSR3 as ready
Fetal anomalies v1.202 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Fetal anomalies v1.202 CELSR3 Zornitza Stark Classified gene: CELSR3 as Green List (high evidence)
Fetal anomalies v1.202 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Fetal anomalies v1.201 CELSR3 Zornitza Stark edited their review of gene: CELSR3: Changed rating: GREEN
Fetal anomalies v1.201 CELSR3 Zornitza Stark gene: CELSR3 was added
gene: CELSR3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CELSR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CELSR3 were set to 38429302
Phenotypes for gene: CELSR3 were set to Neurodevelopmental disorder (MONDO#0700092), CELSR3-related
Added comment: PMID: 38429302:12 affected individuals from 11 families reported with bi-allelic variants. Phenotype ranged from CNS anomalies (7/12), CNS and CAKUT (3/12) and CAKUT only (2/12). 8/12 has ID/DD. Only missense variants reported and 1 inframe variant. Functional studies done in zebrafish demonstrate similar structural anomalies of the developing pronephros and neuronal abnormalities to affected individuals
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.138 CELSR3 Zornitza Stark Marked gene: CELSR3 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.138 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.138 CELSR3 Zornitza Stark Classified gene: CELSR3 as Green List (high evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.138 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.137 CELSR3 Zornitza Stark gene: CELSR3 was added
gene: CELSR3 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic. Sources: Literature
Mode of inheritance for gene: CELSR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CELSR3 were set to 38429302
Phenotypes for gene: CELSR3 were set to Neurodevelopmental disorder (MONDO#0700092), CELSR3-related
Review for gene: CELSR3 was set to GREEN
Added comment: PMID: 38429302:12 affected individuals from 11 families reported with bi-allelic variants. Phenotype ranged from CNS anomalies (7/12), CNS and CAKUT (3/12) and CAKUT only (2/12). 8/12 has ID/DD. Only missense variants reported and 1 inframe variant. Functional studies done in zebrafish demonstrate similar structural anomalies of the developing pronephros and neuronal abnormalities to affected individuals.
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.136 CHD7 Zornitza Stark Marked gene: CHD7 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.136 CHD7 Zornitza Stark Gene: chd7 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.136 CHD7 Zornitza Stark Phenotypes for gene: CHD7 were changed from to CHARGE syndrome MIM#214800
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.135 CHD7 Zornitza Stark Mode of inheritance for gene: CHD7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.134 CHD7 Zornitza Stark reviewed gene: CHD7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: CHARGE syndrome MIM#214800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.134 ACE Zornitza Stark Marked gene: ACE as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.134 ACE Zornitza Stark Gene: ace has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.134 ACE Zornitza Stark Deleted their review
Intellectual disability syndromic and non-syndromic v0.5719 CELSR3 Zornitza Stark Marked gene: CELSR3 as ready
Intellectual disability syndromic and non-syndromic v0.5719 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5719 CELSR3 Zornitza Stark Classified gene: CELSR3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5719 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Mendeliome v1.1601 CELSR3 Zornitza Stark Marked gene: CELSR3 as ready
Mendeliome v1.1601 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Mendeliome v1.1601 CELSR3 Zornitza Stark Classified gene: CELSR3 as Green List (high evidence)
Mendeliome v1.1601 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Regression v0.547 CIAO1 Zornitza Stark Marked gene: CIAO1 as ready
Regression v0.547 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Regression v0.547 CIAO1 Zornitza Stark Classified gene: CIAO1 as Green List (high evidence)
Regression v0.547 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Regression v0.546 CIAO1 Zornitza Stark gene: CIAO1 was added
gene: CIAO1 was added to Regression. Sources: Literature
Mode of inheritance for gene: CIAO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CIAO1 were set to 38411040; 38196629
Phenotypes for gene: CIAO1 were set to Neurodegenerative disease, MONDO:0005559, CIAO1-related
Review for gene: CIAO1 was set to GREEN
Added comment: PMID:38196629 (note pre-print) describes 4 unrelated patients with core features of progressive muscle weakness, respiratory insufficiency, joint hyperlaxity, ankle tightness, calf pseudohypertrophy, elevated CK, and larning disabilities/difficulties. 2 patients presented with increased iron deposition in the brain. Age of recognition of myopathic symptoms varied from early childhood to adolescence. Muscle biopsy showed variation in fiber size and an increase in internalized nuclei, as well as scattered degenerating/regenerating fibers and a mild to minimal increase in endomysial fibrosis. Electron microscopy revealed morphologically abnormal mitochondria.

PMID: 38411040 reports 2 unrelated patients. Patient 1 was born with microcephaly and borderline hypertonia, and died at 18 months of respiratory failure from bronchiolitis. Patient 2 presented with failure to thrive, a hyperkinetic movement disorder, and autism before deteriorating in late teens with muscle weakness, recurrent pneuomonia with respiratory insufficiency, and eventually death due to multi-organ failure with carnificating pneumonia, septic cardiomyopathy, and intracranial hemorrhages. Immune deficiency was ruled out.

All variants reported were homozygous or compound heterozygous missense variants, with the exception of one large in-frame deletion of exon 7. Cell line studies showed the variants resulted in reduced protein stability and downstream cellular defects which could be rescued by wild-type CIAO1.
Sources: Literature
Mendeliome v1.1600 CIAO1 Zornitza Stark Marked gene: CIAO1 as ready
Mendeliome v1.1600 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Mendeliome v1.1600 CIAO1 Zornitza Stark Phenotypes for gene: CIAO1 were changed from Neuromuscular disease, CIAO1-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, CIAO1-related
Mendeliome v1.1599 CIAO1 Zornitza Stark Classified gene: CIAO1 as Green List (high evidence)
Mendeliome v1.1599 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.19 CIAO1 Zornitza Stark Phenotypes for gene: CIAO1 were changed from Neuromuscular disease, CIAO1-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, CIAO1-related
Muscular dystrophy and myopathy_Paediatric v1.18 CIAO1 Zornitza Stark Phenotypes for gene: CIAO1 were changed from Neurodegenerative disease, MONDO:0005559, CIAO1-related to Neuromuscular disease, CIAO1-related (MONDO:0019056)
Muscular dystrophy and myopathy_Paediatric v1.17 CIAO1 Zornitza Stark Marked gene: CIAO1 as ready
Muscular dystrophy and myopathy_Paediatric v1.17 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.17 CIAO1 Zornitza Stark Phenotypes for gene: CIAO1 were changed from Neuromuscular disease, CIAO1-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, CIAO1-related
Muscular dystrophy and myopathy_Paediatric v1.16 CIAO1 Zornitza Stark Classified gene: CIAO1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.16 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Regression v0.545 MMS19 Zornitza Stark Marked gene: MMS19 as ready
Regression v0.545 MMS19 Zornitza Stark Gene: mms19 has been classified as Red List (Low Evidence).
Regression v0.545 MMS19 Zornitza Stark gene: MMS19 was added
gene: MMS19 was added to Regression. Sources: Literature
Mode of inheritance for gene: MMS19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMS19 were set to 38411040
Phenotypes for gene: MMS19 were set to Neurodegenerative disease, MONDO:0005559, MMS19-related
Review for gene: MMS19 was set to RED
Added comment: Single patient reported with postnatal microcephaly, bilateral cataracts, failure to thrive, progressive spastic tetraparesis, scoliosis, myoclonic epilepsy and precocious puberty. Cerebral MRI at age 4 years showed pontocerebellar atrophy and white matter abnormalities. Patient died age 13 after recurrent respiratory tract infections. A homozygous in-frame deletion p.(Glu213del) was identified. Cell line studies supported pathogenicity of the variant. A zebrafish knockout model showed Mms19 deficiency had detrimental effects on development.
Sources: Literature
Genetic Epilepsy v0.2333 MMS19 Zornitza Stark Marked gene: MMS19 as ready
Genetic Epilepsy v0.2333 MMS19 Zornitza Stark Gene: mms19 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2333 MMS19 Zornitza Stark Phenotypes for gene: MMS19 were changed from Neuromuscular disease, MMS19-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, MMS19-related
Genetic Epilepsy v0.2332 MMS19 Zornitza Stark Classified gene: MMS19 as Red List (low evidence)
Genetic Epilepsy v0.2332 MMS19 Zornitza Stark Gene: mms19 has been classified as Red List (Low Evidence).
Mendeliome v1.1598 MMS19 Zornitza Stark Marked gene: MMS19 as ready
Mendeliome v1.1598 MMS19 Zornitza Stark Gene: mms19 has been classified as Red List (Low Evidence).
Mendeliome v1.1598 MMS19 Zornitza Stark Phenotypes for gene: MMS19 were changed from Neuromuscular disease, MMS19-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, MMS19-related
Mendeliome v1.1597 MMS19 Zornitza Stark Classified gene: MMS19 as Red List (low evidence)
Mendeliome v1.1597 MMS19 Zornitza Stark Gene: mms19 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.15 MMS19 Zornitza Stark Classified gene: MMS19 as Red List (low evidence)
Muscular dystrophy and myopathy_Paediatric v1.15 MMS19 Zornitza Stark Gene: mms19 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.14 MMS19 Zornitza Stark Marked gene: MMS19 as ready
Muscular dystrophy and myopathy_Paediatric v1.14 MMS19 Zornitza Stark Gene: mms19 has been removed from the panel.
Muscular dystrophy and myopathy_Paediatric v1.14 MMS19 Zornitza Stark Phenotypes for gene: MMS19 were changed from Neuromuscular disease, MMS19-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, MMS19-related
Hereditary Neuropathy v1.10 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Intellectual disability syndromic and non-syndromic v0.5718 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Genetic Epilepsy v0.2331 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Microcephaly v1.249 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Microcephaly v1.249 NARS Zornitza Stark edited their review of gene: NARS: Changed rating: GREEN
Mendeliome v1.1596 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Fetal anomalies v1.200 NARS Zornitza Stark edited their review of gene: NARS: Changed rating: GREEN
Fetal anomalies v1.200 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Muscular dystrophy and myopathy_Paediatric v1.13 MMS19 Paul De Fazio gene: MMS19 was added
gene: MMS19 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: MMS19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMS19 were set to 38411040
Phenotypes for gene: MMS19 were set to Neuromuscular disease, MMS19-related (MONDO:0019056)
Review for gene: MMS19 was set to RED
gene: MMS19 was marked as current diagnostic
Added comment: Single patient reported with postnatal microcephaly, bilateral cataracts, failure to thrive, progressive spastic tetraparesis, scoliosis, myoclonic epilepsy and precocious puberty. Cerebral MRI at age 4 years showed pontocerebellar atrophy and white matter abnormalities. Patient died age 13 after recurrent respiratory tract infections. A homozygous in-frame deletion p.(Glu213del) was identified. Cell line studies supported pathogenicity of the variant. A zebrafish knockout model showed Mms19 deficiency had detrimental effects on development.
Sources: Literature
Genetic Epilepsy v0.2331 MMS19 Paul De Fazio gene: MMS19 was added
gene: MMS19 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: MMS19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMS19 were set to 38411040
Phenotypes for gene: MMS19 were set to Neuromuscular disease, MMS19-related (MONDO:0019056)
Review for gene: MMS19 was set to RED
gene: MMS19 was marked as current diagnostic
Added comment: Single patient reported with postnatal microcephaly, bilateral cataracts, failure to thrive, progressive spastic tetraparesis, scoliosis, myoclonic epilepsy and precocious puberty. Cerebral MRI at age 4 years showed pontocerebellar atrophy and white matter abnormalities. Patient died age 13 after recurrent respiratory tract infections. A homozygous in-frame deletion p.(Glu213del) was identified. Cell line studies supported pathogenicity of the variant. A zebrafish knockout model showed Mms19 deficiency had detrimental effects on development.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.13 CIAO1 Paul De Fazio gene: CIAO1 was added
gene: CIAO1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CIAO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CIAO1 were set to 38411040; 38196629
Phenotypes for gene: CIAO1 were set to Neuromuscular disease, CIAO1-related (MONDO:0019056)
Penetrance for gene: CIAO1 were set to unknown
Review for gene: CIAO1 was set to GREEN
gene: CIAO1 was marked as current diagnostic
Added comment: PMID:38196629 (note pre-print) describes 4 unrelated patients with core features of progressive muscle weakness, respiratory insufficiency, joint hyperlaxity, ankle tightness, calf pseudohypertrophy, elevated CK, and larning disabilities/difficulties. 2 patients presented with increased iron deposition in the brain. Age of recognition of myopathic symptoms varied from early childhood to adolescence. Muscle biopsy showed variation in fiber size and an increase in internalized nuclei, as well as scattered degenerating/regenerating fibers and a mild to minimal increase in endomysial fibrosis. Electron microscopy revealed morphologically abnormal mitochondria.

PMID: 38411040 reports 2 unrelated patients. Patient 1 was born with microcephaly and borderline hypertonia, and died at 18 months of respiratory failure from bronchiolitis. Patient 2 presented with failure to thrive, a hyperkinetic movement disorder, and autism before deteriorating in late teens with muscle weakness, recurrent pneuomonia with respiratory insufficiency, and eventually death due to multi-organ failure with carnificating pneumonia, septic cardiomyopathy, and intracranial hemorrhages. Immune deficiency was ruled out.

All variants reported were homozygous or compound heterozygous missense variants, with the exception of one large in-frame deletion of exon 7. Cell line studies showed the variants resulted in reduced protein stability and downstream cellular defects which could be rescued by wild-type CIAO1.
Sources: Literature
Mendeliome v1.1596 CIAO1 Paul De Fazio changed review comment from: PMID:38196629 (note pre-print) describes 4 unrelated patients with core features of progressive muscle weakness, respiratory insufficiency, joint hyperlaxity, ankle tightness, calf pseudohypertrophy, elevated CK, and larning disabilities/difficulties. 2 patients presented with increased iron deposition in the brain. Age of recognition of myopathic symptoms varied from early childhood to adolescence.

PMID: 38411040 reports 2 unrelated patients. Patient 1 was born with microcephaly and borderline hypertonia, and died at 18 months of respiratory failure from bronchiolitis. Patient 2 presented with failure to thrive, a hyperkinetic movement disorder, and autism before deteriorating in late teens with muscle weakness, recurrent pneuomonia with respiratory insufficiency, and eventually death due to multi-organ failure with carnificating pneumonia, septic cardiomyopathy, and intracranial hemorrhages. Immune deficiency was ruled out.

All variants reported were homozygous or compound heterozygous missense variants, with the exception of one large in-frame deletion of exon 7. Cell line studies showed the variants resulted in reduced protein stability and downstream cellular defects which could be rescued by wild-type CIAO1.
Sources: Literature; to: PMID:38196629 (note pre-print) describes 4 unrelated patients with core features of progressive muscle weakness, respiratory insufficiency, joint hyperlaxity, ankle tightness, calf pseudohypertrophy, elevated CK, and larning disabilities/difficulties. 2 patients presented with increased iron deposition in the brain. Age of recognition of myopathic symptoms varied from early childhood to adolescence. Muscle biopsy showed variation in fiber size and an increase in internalized nuclei, as well as scattered degenerating/regenerating fibers and a mild to minimal increase in endomysial fibrosis. Electron microscopy revealed morphologically abnormal mitochondria.

PMID: 38411040 reports 2 unrelated patients. Patient 1 was born with microcephaly and borderline hypertonia, and died at 18 months of respiratory failure from bronchiolitis. Patient 2 presented with failure to thrive, a hyperkinetic movement disorder, and autism before deteriorating in late teens with muscle weakness, recurrent pneuomonia with respiratory insufficiency, and eventually death due to multi-organ failure with carnificating pneumonia, septic cardiomyopathy, and intracranial hemorrhages. Immune deficiency was ruled out.

All variants reported were homozygous or compound heterozygous missense variants, with the exception of one large in-frame deletion of exon 7. Cell line studies showed the variants resulted in reduced protein stability and downstream cellular defects which could be rescued by wild-type CIAO1.
Mendeliome v1.1596 MMS19 Paul De Fazio gene: MMS19 was added
gene: MMS19 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MMS19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMS19 were set to 38411040
Phenotypes for gene: MMS19 were set to Neuromuscular disease, MMS19-related (MONDO:0019056)
Penetrance for gene: MMS19 were set to unknown
Review for gene: MMS19 was set to RED
gene: MMS19 was marked as current diagnostic
Added comment: Single patient reported with postnatal microcephaly, bilateral cataracts, failure to thrive, progressive spastic tetraparesis, scoliosis, myoclonic epilepsy and precocious puberty. Cerebral MRI at age 4 years showed pontocerebellar atrophy and white matter abnormalities. Patient died age 13 after recurrent respiratory tract infections. A homozygous in-frame deletion p.(Glu213del) was identified. Cell line studies supported pathogenicity of the variant. A zebrafish knockout model also showed a detrimental effect of Mms19 deficincy.
Sources: Literature
Mendeliome v1.1596 CIAO1 Paul De Fazio gene: CIAO1 was added
gene: CIAO1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CIAO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CIAO1 were set to 38411040; 38196629
Phenotypes for gene: CIAO1 were set to Neuromuscular disease, CIAO1-related (MONDO:0019056)
Penetrance for gene: CIAO1 were set to unknown
Review for gene: CIAO1 was set to GREEN
gene: CIAO1 was marked as current diagnostic
Added comment: PMID:38196629 (note pre-print) describes 4 unrelated patients with core features of progressive muscle weakness, respiratory insufficiency, joint hyperlaxity, ankle tightness, calf pseudohypertrophy, elevated CK, and larning disabilities/difficulties. 2 patients presented with increased iron deposition in the brain. Age of recognition of myopathic symptoms varied from early childhood to adolescence.

PMID: 38411040 reports 2 unrelated patients. Patient 1 was born with microcephaly and borderline hypertonia, and died at 18 months of respiratory failure from bronchiolitis. Patient 2 presented with failure to thrive, a hyperkinetic movement disorder, and autism before deteriorating in late teens with muscle weakness, recurrent pneuomonia with respiratory insufficiency, and eventually death due to multi-organ failure with carnificating pneumonia, septic cardiomyopathy, and intracranial hemorrhages. Immune deficiency was ruled out.

All variants reported were homozygous or compound heterozygous missense variants, with the exception of one large in-frame deletion of exon 7. Cell line studies showed the variants resulted in reduced protein stability and downstream cellular defects which could be rescued by wild-type CIAO1.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5718 SLC12A9 Zornitza Stark Marked gene: SLC12A9 as ready
Intellectual disability syndromic and non-syndromic v0.5718 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5718 SLC12A9 Zornitza Stark Classified gene: SLC12A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5718 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5717 CELSR3 Crystle Lee gene: CELSR3 was added
gene: CELSR3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CELSR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CELSR3 were set to PMID: 38429302
Phenotypes for gene: CELSR3 were set to Neurodevelopmental disorder (MONDO#0700092), CELSR3-related
Review for gene: CELSR3 was set to GREEN
Added comment: PMID: 38429302:12 affected individuals from 11 families reported with bi-allelic variants. Phenotype ranged from CNS anomalies (7/12), CNS and CAKUT (3/12) and CAKUT only (2/12). 8/12 has ID/DD. Only missense variants reported and 1 inframe variant. Functional studies done in zebrafish demonstrate similar structural anomalies of the developing pronephros and neuronal abnormalities to affected individuals
Sources: Literature
Genetic Epilepsy v0.2331 DIP2C Elena Savva Marked gene: DIP2C as ready
Genetic Epilepsy v0.2331 DIP2C Elena Savva Gene: dip2c has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2331 DIP2C Elena Savva Classified gene: DIP2C as Amber List (moderate evidence)
Genetic Epilepsy v0.2331 DIP2C Elena Savva Gene: dip2c has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1596 THBS2 Ain Roesley Phenotypes for gene: THBS2 were changed from {Lumbar disc herniation, susceptibility to} 603932 to {Lumbar disc herniation, susceptibility to} 603932; connective tissue disorder MONDO:0003900, THBS2-related
Mendeliome v1.1595 THBS2 Ain Roesley Publications for gene: THBS2 were set to
Mendeliome v1.1594 THBS2 Ain Roesley Mode of inheritance for gene: THBS2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1594 THBS2 Ain Roesley Classified gene: THBS2 as Amber List (moderate evidence)
Mendeliome v1.1594 THBS2 Ain Roesley Gene: thbs2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1593 THBS2 Chris Ciotta reviewed gene: THBS2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38433265; Phenotypes: connective tissue disorder MONDO:0003900, THBS2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Chris Ciotta Deleted their comment
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Chris Ciotta Deleted their comment
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Chris Ciotta Deleted their comment
Genetic Epilepsy v0.2330 DIP2C Melanie Marty reviewed gene: DIP2C: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38421105; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), DIP2C-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Chris Ciotta Deleted their comment
Genetic Epilepsy v0.2330 DIP2C Melanie Marty Deleted their review
Genetic Epilepsy v0.2330 DIP2C Melanie Marty gene: DIP2C was added
gene: DIP2C was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: DIP2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DIP2C were set to PMID: 38421105
Phenotypes for gene: DIP2C were set to Neurodevelopmental disorder (MONDO#0700092), DIP2C-related
Review for gene: DIP2C was set to GREEN
Added comment: PMID: 38421105 - Twenty three patients with het DIP2C variants (10 de novo).
All patients had developmental delays affecting expressive language and speech, most had mild dev delay and ID. Four patients had seizures. Additional phenotypic findings were non-specific but recurrent anomalies did include a high anterior hair-line, prominent forehead, and a broad nasal tip. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects,and bicuspid aortic valve)
Sources: Literature
Mendeliome v1.1593 UBAP1L Seb Lunke Marked gene: UBAP1L as ready
Mendeliome v1.1593 UBAP1L Seb Lunke Gene: ubap1l has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Ain Roesley Phenotypes for gene: THBS2 were changed from connective tissue disorder MONDO:0003900, THBS2-related to connective tissue disorder MONDO:0003900, THBS2-related
Mendeliome v1.1593 UBAP1L Seb Lunke Classified gene: UBAP1L as Green List (high evidence)
Mendeliome v1.1593 UBAP1L Seb Lunke Gene: ubap1l has been classified as Green List (High Evidence).
Mendeliome v1.1592 UBAP1L Seb Lunke Classified gene: UBAP1L as Green List (high evidence)
Mendeliome v1.1592 UBAP1L Seb Lunke Gene: ubap1l has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Ain Roesley Marked gene: THBS2 as ready
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Ain Roesley Gene: thbs2 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Ain Roesley Phenotypes for gene: THBS2 were changed from connective tissue disorder MONDO:0003900, THBS2-related to connective tissue disorder MONDO:0003900, THBS2-related
Aortopathy_Connective Tissue Disorders v1.82 THBS2 Ain Roesley Phenotypes for gene: THBS2 were changed from Ehlers-Danlos syndrome to connective tissue disorder MONDO:0003900, THBS2-related
Mendeliome v1.1591 DIP2C Elena Savva Marked gene: DIP2C as ready
Mendeliome v1.1591 DIP2C Elena Savva Gene: dip2c has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.82 THBS2 Chris Ciotta edited their review of gene: THBS2: Added comment: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes were identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.; Changed phenotypes: connective tissue disorder MONDO:0003900, THBS2-related
Intellectual disability syndromic and non-syndromic v0.5717 DIP2C Elena Savva Marked gene: DIP2C as ready
Intellectual disability syndromic and non-syndromic v0.5717 DIP2C Elena Savva Gene: dip2c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5717 SLC12A9 Zornitza Stark Classified gene: SLC12A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5717 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Mendeliome v1.1591 APOLD1 Seb Lunke Marked gene: APOLD1 as ready
Mendeliome v1.1591 APOLD1 Seb Lunke Gene: apold1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.82 THBS2 Ain Roesley Classified gene: THBS2 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v1.82 THBS2 Ain Roesley Gene: thbs2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5717 DIP2C Elena Savva Classified gene: DIP2C as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5717 DIP2C Elena Savva Gene: dip2c has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.82 THBS2 Ain Roesley Classified gene: THBS2 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v1.82 THBS2 Ain Roesley Gene: thbs2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1591 TOGARAM2 Zornitza Stark Marked gene: TOGARAM2 as ready
Mendeliome v1.1591 TOGARAM2 Zornitza Stark Gene: togaram2 has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Chris Ciotta commented on gene: THBS2: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes were identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.
Intellectual disability syndromic and non-syndromic v0.5716 SLC12A9 Zornitza Stark Classified gene: SLC12A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5716 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Mendeliome v1.1591 APOLD1 Seb Lunke Classified gene: APOLD1 as Amber List (moderate evidence)
Mendeliome v1.1591 APOLD1 Seb Lunke Gene: apold1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Chris Ciotta commented on gene: THBS2: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes were identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.
Mendeliome v1.1590 DIP2C Elena Savva Classified gene: DIP2C as Green List (high evidence)
Mendeliome v1.1590 DIP2C Elena Savva Gene: dip2c has been classified as Green List (High Evidence).
Mendeliome v1.1590 TOGARAM2 Zornitza Stark Classified gene: TOGARAM2 as Red List (low evidence)
Mendeliome v1.1590 TOGARAM2 Zornitza Stark Gene: togaram2 has been classified as Red List (Low Evidence).
Mendeliome v1.1589 UBAP1L Ee Ming Wong changed review comment from: - Twelve unrelated families with Hungary, the United States, Israel, Tunisia and the Netherlands with members presenting with autosomal recessive rod-cone or cone-rod dystrophy
- Reported variants included splice, nonsense, frameshift and in-frame del variants
- Age of disease onset was very variable, with some patients experiencing first symptoms during their fourth decade of life or later.
Sources: Literature; to: - Twelve unrelated families with Hungary, the United States, Israel, Tunisia and the Netherlands with members presenting with autosomal recessive rod-cone or cone-rod dystrophy
- Reported variants included splice, nonsense, frameshift and in-frame del variants
- Age of disease onset was very variable, with some patients experiencing first symptoms during their fourth decade of life or later.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5716 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Chris Ciotta edited their review of gene: THBS2: Added comment: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes were identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.; Changed phenotypes: connective tissue disorder MONDO:0003900
Mendeliome v1.1589 CORIN Daniel Flanagan reviewed gene: CORIN: Rating: RED; Mode of pathogenicity: None; Publications: 37913506, 15637153; Phenotypes: ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v1.13 SNUPN Seb Lunke Marked gene: SNUPN as ready
Muscular dystrophy and myopathy_Paediatric v1.13 SNUPN Seb Lunke Gene: snupn has been classified as Green List (High Evidence).
Mendeliome v1.1589 SNUPN Seb Lunke Marked gene: SNUPN as ready
Mendeliome v1.1589 SNUPN Seb Lunke Gene: snupn has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Ain Roesley Classified gene: THBS2 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Ain Roesley Gene: thbs2 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.27 SNUPN Seb Lunke Marked gene: SNUPN as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.27 SNUPN Seb Lunke Gene: snupn has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.28 APOLD1 Seb Lunke Marked gene: APOLD1 as ready
Bleeding and Platelet Disorders v1.28 APOLD1 Seb Lunke Gene: apold1 has been classified as Amber List (Moderate Evidence).
Atrial Fibrillation v1.2 CORIN Seb Lunke Marked gene: CORIN as ready
Atrial Fibrillation v1.2 CORIN Seb Lunke Gene: corin has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5716 SLC12A9 Zornitza Stark Classified gene: SLC12A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5716 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Mendeliome v1.1589 TOGARAM2 Zornitza Stark Classified gene: TOGARAM2 as Red List (low evidence)
Mendeliome v1.1589 TOGARAM2 Zornitza Stark Gene: togaram2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5715 ZSCAN10 Rylee Peters gene: ZSCAN10 was added
gene: ZSCAN10 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZSCAN10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZSCAN10 were set to PMID: 38386308
Phenotypes for gene: ZSCAN10 were set to Syndromic disease MONDO:0002254
Review for gene: ZSCAN10 was set to GREEN
Added comment: Bi-allelic ZSCAN10 loss-of-function variants were identified in seven affected individuals from five unrelated families with syndromic neurodevelopmental disorder.

Highly consistent phenotypic features include global developmental delay, behavioural abnormalities, and variable facial asymmetry with outer and inner ear malformations leading to profound SNHL.

Facial asymmetry was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations.
Sources: Literature
Atrial Fibrillation v1.2 CORIN Seb Lunke Classified gene: CORIN as Red List (low evidence)
Atrial Fibrillation v1.2 CORIN Seb Lunke Gene: corin has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.13 SNUPN Seb Lunke Classified gene: SNUPN as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.13 SNUPN Seb Lunke Gene: snupn has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.27 SNUPN Seb Lunke Classified gene: SNUPN as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.27 SNUPN Seb Lunke Gene: snupn has been classified as Green List (High Evidence).
Mendeliome v1.1588 UBAP1L Ee Ming Wong gene: UBAP1L was added
gene: UBAP1L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UBAP1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBAP1L were set to PMID: 38293907; 38420906
Phenotypes for gene: UBAP1L were set to Cone-rod dystrophy (MONDO:0015993), UBAP1L-related
Review for gene: UBAP1L was set to GREEN
gene: UBAP1L was marked as current diagnostic
Added comment: - Twelve unrelated families with Hungary, the United States, Israel, Tunisia and the Netherlands with members presenting with autosomal recessive rod-cone or cone-rod dystrophy
- Reported variants included splice, nonsense, frameshift and in-frame del variants
- Age of disease onset was very variable, with some patients experiencing first symptoms during their fourth decade of life or later.
Sources: Literature
Bleeding and Platelet Disorders v1.28 APOLD1 Seb Lunke Classified gene: APOLD1 as Amber List (moderate evidence)
Bleeding and Platelet Disorders v1.28 APOLD1 Seb Lunke Gene: apold1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Ain Roesley Classified gene: THBS2 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Ain Roesley Gene: thbs2 has been classified as Amber List (Moderate Evidence).
Atrial Fibrillation v1.1 CORIN Daniel Flanagan gene: CORIN was added
gene: CORIN was added to Atrial Fibrillation. Sources: Expert list
Mode of inheritance for gene: CORIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CORIN were set to 37913506; 15637153
Phenotypes for gene: CORIN were set to ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734)
Review for gene: CORIN was set to RED
Added comment: Two siblings with a homozygous loss-of-function variant in CORIN. Both presented with left atrial hypertrophic cardiomyopathy, hypertension, fibrosis, and arrhythmia isolated to the left atrium. A plasma sample obtained from one of the siblings had no detectable levels of corin.

One sibling also had a het variant, p.(Ser571Thr), in PKP2 (associated with AD ARVC). The PKP2 variant is LP/VUS in ClinVar.

Cor-/- mice exhibit cardiac hypertrophy resulting in a mild decline in cardiac function later in life. Cor-/- mice also have spontaneous hypertension.
Sources: Expert list
Mendeliome v1.1588 SNUPN Seb Lunke Classified gene: SNUPN as Green List (high evidence)
Mendeliome v1.1588 SNUPN Seb Lunke Gene: snupn has been classified as Green List (High Evidence).
Mendeliome v1.1587 CELSR3 Crystle Lee gene: CELSR3 was added
gene: CELSR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CELSR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CELSR3 were set to PMID: 38429302
Phenotypes for gene: CELSR3 were set to Neurodevelopmental disorder (MONDO#0700092), CELSR3-related
Review for gene: CELSR3 was set to GREEN
Added comment: PMID: 38429302:12 affected individuals from 11 families reported with bi-allelic variants. Phenotype ranged from CNS anomalies (7/12), CNS and CAKUT (3/12) and CAKUT only (2/12). Only missense variants reported and 1 inframe variant. Functional studies done in zebrafish demonstrate similar structural anomalies of the developing pronephros and neuronal abnormalities to affected individuals

PMID: 34951123: 5 het missense variants reported in patients with febrile seizures (FS)/epilepsy. Arg3141Gln present in gnomAD (7 hets). No functional studies. Summarised as potentially associated with febrile seizures (FS)/epilepsy
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5715 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Deafness_IsolatedAndComplex v1.172 ZSCAN10 Rylee Peters gene: ZSCAN10 was added
gene: ZSCAN10 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: ZSCAN10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZSCAN10 were set to PMID: 38386308
Phenotypes for gene: ZSCAN10 were set to Syndromic disease MONDO:0002254
Review for gene: ZSCAN10 was set to GREEN
Added comment: Bi-allelic ZSCAN10 loss-of-function variants were identified in seven affected individuals from five unrelated families with syndromic neurodevelopmental disorder.

Highly consistent phenotypic features include global developmental delay, behavioural abnormalities, and variable facial asymmetry with outer and inner ear malformations leading to profound SNHL.

Facial asymmetry was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations.
Sources: Literature
Cone-rod Dystrophy v0.54 UBAP1L Zornitza Stark Marked gene: UBAP1L as ready
Cone-rod Dystrophy v0.54 UBAP1L Zornitza Stark Gene: ubap1l has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.54 UBAP1L Zornitza Stark Classified gene: UBAP1L as Green List (high evidence)
Cone-rod Dystrophy v0.54 UBAP1L Zornitza Stark Gene: ubap1l has been classified as Green List (High Evidence).
Mendeliome v1.1587 APOLD1 Lucy Spencer changed review comment from: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.
Sources: Literature; to: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.

SiRNA silencing of APOLD1 in HBDEC cells resulted in altered cell shape and size, and were associated with endothelial cell junction dismantling. These cells were also almost devoid of VWF.
Sources: Literature
Bleeding and Platelet Disorders v1.27 APOLD1 Lucy Spencer changed review comment from: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.
Sources: Literature; to: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.

SiRNA silencing of APOLD1 in HBDEC cells resulted in altered cell shape and size, and were associated with endothelial cell junction dismantling. These cells were also almost devoid of VWF.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5715 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Mendeliome v1.1587 ZSCAN10 Rylee Peters gene: ZSCAN10 was added
gene: ZSCAN10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZSCAN10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZSCAN10 were set to PMID: 38386308
Phenotypes for gene: ZSCAN10 were set to syndromic disease MONDO:0002254
Review for gene: ZSCAN10 was set to GREEN
Added comment: Bi-allelic ZSCAN10 loss-of-function variants were identified in seven affected individuals from five unrelated families with syndromic neurodevelopmental disorder.

Highly consistent phenotypic features include global developmental delay, behavioural abnormalities, and variable facial asymmetry with outer and inner ear malformations leading to profound SNHL.

Facial asymmetry was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations.
Sources: Literature
Cone-rod Dystrophy v0.53 UBAP1L Ee Ming Wong gene: UBAP1L was added
gene: UBAP1L was added to Cone-rod Dystrophy. Sources: Literature
Mode of inheritance for gene: UBAP1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBAP1L were set to PMID: 38293907; 38420906
Phenotypes for gene: UBAP1L were set to Cone-rod dystrophy (MONDO:0015993), UBAP1L-related
Review for gene: UBAP1L was set to GREEN
gene: UBAP1L was marked as current diagnostic
Added comment: - Twelve unrelated families with Hungary, the United States, Israel, Tunisia and the Netherlands with members presenting with autosomal recessive rod-cone or cone-rod dystrophy
- Reported variants included splice, nonsense, frameshift and in-frame del variants
- Age of disease onset was very variable, with some patients experiencing first symptoms during their fourth decade of life or later.
Sources: Literature
Mendeliome v1.1587 SLC12A9 Zornitza Stark Marked gene: SLC12A9 as ready
Mendeliome v1.1587 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Mendeliome v1.1587 SLC12A9 Zornitza Stark Classified gene: SLC12A9 as Green List (high evidence)
Mendeliome v1.1587 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5715 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Severe developmental delay, epileptic encephalopathy, brain MRI abnormality; intellectual disability, childhood-onset optic atrophy, ataxia to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Genetic Epilepsy v0.2330 SNF8 Elena Savva Classified gene: SNF8 as Amber List (moderate evidence)
Genetic Epilepsy v0.2330 SNF8 Elena Savva Gene: snf8 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5715 POP1 Ain Roesley Publications for gene: POP1 were set to
Hypertrophic cardiomyopathy v0.177 CORIN Seb Lunke Marked gene: CORIN as ready
Hypertrophic cardiomyopathy v0.177 CORIN Seb Lunke Gene: corin has been classified as Red List (Low Evidence).
Mendeliome v1.1586 SNF8 Elena Savva Marked gene: SNF8 as ready
Mendeliome v1.1586 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Mendeliome v1.1586 SLC12A9 Zornitza Stark gene: SLC12A9 was added
gene: SLC12A9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC12A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC12A9 were set to 38334070
Phenotypes for gene: SLC12A9 were set to Neurodevelopmental disorder, MONDO:0700092, SLC12A9-related
Review for gene: SLC12A9 was set to GREEN
Added comment: Three individuals from unrelated families with bi-allelic LoF variants and a neurodevelopment phenotype, skeletal and brain abnormalities, hypopigmentation, dysmorphic features.
Sources: Literature
Callosome v0.518 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Mendeliome v1.1586 SNF8 Elena Savva Classified gene: SNF8 as Green List (high evidence)
Mendeliome v1.1586 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy v0.177 CORIN Seb Lunke Classified gene: CORIN as Red List (low evidence)
Hypertrophic cardiomyopathy v0.177 CORIN Seb Lunke Gene: corin has been classified as Red List (Low Evidence).
Callosome v0.517 SNF8 Elena Savva Classified gene: SNF8 as Green List (high evidence)
Callosome v0.517 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Callosome v0.517 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Severe developmental delay, epileptic encephalopathy, brain MRI abnormality; intellectual disability, childhood-onset optic atrophy, ataxia to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Muscular dystrophy and myopathy_Paediatric v1.12 TUBA4A Seb Lunke Classified gene: TUBA4A as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.12 TUBA4A Seb Lunke Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5714 SLC12A9 Zornitza Stark gene: SLC12A9 was added
gene: SLC12A9 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SLC12A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC12A9 were set to 38334070
Phenotypes for gene: SLC12A9 were set to Neurodevelopmental disorder, MONDO:0700092, SLC12A9-related
Review for gene: SLC12A9 was set to GREEN
Added comment: Three individuals from unrelated families with bi-allelic LoF variants and a neurodevelopmental phenotype, skeletal abnormalities, brain abnormalities, hypopigmentation, dysmorphic features.
Sources: Literature
Genetic Epilepsy v0.2329 SNF8 Elena Savva Classified gene: SNF8 as Amber List (moderate evidence)
Genetic Epilepsy v0.2329 SNF8 Elena Savva Gene: snf8 has been classified as Amber List (Moderate Evidence).
Callosome v0.517 SNF8 Elena Savva Classified gene: SNF8 as Green List (high evidence)
Callosome v0.517 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.12 TUBA4A Seb Lunke Marked gene: TUBA4A as ready
Muscular dystrophy and myopathy_Paediatric v1.12 TUBA4A Seb Lunke Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.12 TUBA4A Seb Lunke Classified gene: TUBA4A as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.12 TUBA4A Seb Lunke Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Callosome v0.516 SNF8 Elena Savva Marked gene: SNF8 as ready
Callosome v0.516 SNF8 Elena Savva Gene: snf8 has been removed from the panel.
Intellectual disability syndromic and non-syndromic v0.5714 SNF8 Elena Savva Marked gene: SNF8 as ready
Intellectual disability syndromic and non-syndromic v0.5714 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5714 SNF8 Elena Savva Classified gene: SNF8 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5714 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2329 SNF8 Elena Savva Classified gene: SNF8 as Amber List (moderate evidence)
Genetic Epilepsy v0.2329 SNF8 Elena Savva Gene: snf8 has been classified as Amber List (Moderate Evidence).
Optic Atrophy v1.30 SNF8 Elena Savva Marked gene: SNF8 as ready
Optic Atrophy v1.30 SNF8 Elena Savva Gene: snf8 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1585 SNF8 Chern Lim gene: SNF8 was added
gene: SNF8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Review for gene: SNF8 was set to GREEN
gene: SNF8 was marked as current diagnostic
Added comment: PMID: 38423010
- Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.
- The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.
- Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech.
Sources: Literature
Aortopathy_Connective Tissue Disorders v1.80 THBS2 Chris Ciotta changed review comment from: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes was identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.
Sources: Literature; to: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes were identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.
Sources: Literature
Optic Atrophy v1.30 SNF8 Elena Savva Classified gene: SNF8 as Amber List (moderate evidence)
Optic Atrophy v1.30 SNF8 Elena Savva Gene: snf8 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.80 THBS2 Chris Ciotta gene: THBS2 was added
gene: THBS2 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: THBS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THBS2 were set to PMID: 38433265
Phenotypes for gene: THBS2 were set to Ehlers-Danlos syndrome
Penetrance for gene: THBS2 were set to Complete
Review for gene: THBS2 was set to AMBER
Added comment: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes was identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.
Sources: Literature
Genetic Epilepsy v0.2328 SNF8 Elena Savva Marked gene: SNF8 as ready
Genetic Epilepsy v0.2328 SNF8 Elena Savva Gene: snf8 has been removed from the panel.
Fetal anomalies v1.200 HSPG2 Ain Roesley Phenotypes for gene: HSPG2 were changed from Schwartz-Jampel syndrome, MONDO:0009717; Silverman-Handmaker type dyssegmental dysplasia, MONDO:0009140; Schwartz-Jampel syndrome, type 1, OMIM:255800; Dyssegmental dysplasia, Silverman-Handmaker type, OMIM:224410 to Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Schwartz-Jampel syndrome, MONDO:0009717; Silverman-Handmaker type dyssegmental dysplasia, MONDO:0009140; Schwartz-Jampel syndrome, type 1, OMIM:255800; Dyssegmental dysplasia, Silverman-Handmaker type, OMIM:224410
Skeletal dysplasia v0.272 HSPG2 Ain Roesley Phenotypes for gene: HSPG2 were changed from Dyssegmental dysplasia, Silverman-Handmaker type 224410; Schwartz-Jampel syndrome, type 1 255800 to Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Dyssegmental dysplasia, Silverman-Handmaker type 224410; Schwartz-Jampel syndrome, type 1 255800
Mendeliome v1.1585 TUBA4A Seb Lunke Marked gene: TUBA4A as ready
Mendeliome v1.1585 TUBA4A Seb Lunke Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.199 HSPG2 Ain Roesley Publications for gene: HSPG2 were set to
Mendeliome v1.1585 TUBA4A Seb Lunke Classified gene: TUBA4A as Amber List (moderate evidence)
Mendeliome v1.1585 TUBA4A Seb Lunke Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.272 HSPG2 Ain Roesley Publications for gene: HSPG2 were set to
Skeletal Dysplasia_Fetal v0.219 HSPG2 Ain Roesley Publications for gene: HSPG2 were set to
Fetal anomalies v1.198 HSPG2 Dean Phelan reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38424183; Phenotypes: Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic Atrophy v1.29 SNF8 Chern Lim gene: SNF8 was added
gene: SNF8 was added to Optic Atrophy. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Review for gene: SNF8 was set to AMBER
gene: SNF8 was marked as current diagnostic
Added comment: PMID: 38423010
- Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.
- The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.
- Three of the patients (from two families) with the milder phenotype also have optic atrophy.

- Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech.
Sources: Literature
Skeletal dysplasia v0.271 HSPG2 Dean Phelan reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38424183; Phenotypes: Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.218 HSPG2 Ain Roesley Phenotypes for gene: HSPG2 were changed from to Schwartz-Jampel syndrome, type 1, MIM#255800; Dyssegmental dysplasia, Silverman-Handmaker type, MIM# 224410; Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139)
Genetic Epilepsy v0.2328 SNF8 Chern Lim gene: SNF8 was added
gene: SNF8 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Review for gene: SNF8 was set to AMBER
gene: SNF8 was marked as current diagnostic
Added comment: PMID: 38423010
- Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.
- The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.
- Two of the patients also had seizures.

- Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech.
Sources: Literature
Mendeliome v1.1584 HSPG2 Dean Phelan reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38424183; Phenotypes: Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy v0.176 CORIN Daniel Flanagan gene: CORIN was added
gene: CORIN was added to Hypertrophic cardiomyopathy_HCM. Sources: Expert list
Mode of inheritance for gene: CORIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CORIN were set to 37913506; 15637153
Phenotypes for gene: CORIN were set to ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734)
Review for gene: CORIN was set to RED
Added comment: Two siblings with a homozygous loss-of-function variant in CORIN. Both presented with left atrial hypertrophic cardiomyopathy, hypertension, fibrosis, and arrhythmia isolated to the left atrium. A plasma sample obtained from one of the siblings had no detectable levels of corin.

One sibling also had a het variant, p.(Ser571Thr), in PKP2 (associated with AD ARVC). The PKP2 variant is LP/VUS in ClinVar.

Cor-/- mice exhibit cardiac hypertrophy resulting in a mild decline in cardiac function later in life. Cor-/- mice also have spontaneous hypertension.
Sources: Expert list
Mendeliome v1.1584 SNUPN Suliman Khan gene: SNUPN was added
gene: SNUPN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SNUPN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNUPN were set to PMID: 38413582; PMID: 38366623
Phenotypes for gene: SNUPN were set to autosomal recessive limb-girdle muscular dystrophy MONDO:0015152
Review for gene: SNUPN was set to GREEN
Added comment: PMID: 38413582: reported 18 children from 15 unrelated families with muscular phenotypes, including proximal upper limb weakness, distal upper and lower limb weakness, and myopathy (EMG) with elevated serum creatinine kinase level. Exome sequencing revealed nine hypomorphic biallelic variants in the SNUPN gene, predominantly clustered in the last coding exon. Functional studies showed that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients’ primary fibroblasts.

PMID: 38366623: reported five individuals from two unrelated families with limb-girdle muscular dystrophy.
Sources: Literature
Mendeliome v1.1584 APOLD1 Lucy Spencer gene: APOLD1 was added
gene: APOLD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: APOLD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APOLD1 were set to 35638551
Phenotypes for gene: APOLD1 were set to Bleeding disorder, vascular-type (MIM#620715)
Review for gene: APOLD1 was set to AMBER
Added comment: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.
Sources: Literature
Callosome v0.516 SNF8 Chern Lim edited their review of gene: SNF8: Changed phenotypes: Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Intellectual disability syndromic and non-syndromic v0.5713 SNF8 Chern Lim edited their review of gene: SNF8: Changed phenotypes: Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Mendeliome v1.1584 RGS6 Seb Lunke Marked gene: RGS6 as ready
Mendeliome v1.1584 RGS6 Seb Lunke Gene: rgs6 has been classified as Red List (Low Evidence).
Mendeliome v1.1584 RGS6 Seb Lunke gene: RGS6 was added
gene: RGS6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RGS6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RGS6 were set to 38332109; 25525169
Phenotypes for gene: RGS6 were set to Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149
Review for gene: RGS6 was set to RED
Added comment: Original paper from 2015 describes single consanguineous with two siblings affected by cataract, developmental delay, and microcephaly >3SD. A homozygous canonical splice variant predicted to lead to NMD in RGS6 was identified by WGS and linkage (rather than full WGS analysis). The 2024 paper speculates that the phenotype is driven by a change in RGS6 isoform balance rather than LoF using a knock-out mouse model. It is noted that the mice did not have microcephaly, and ID was assessed using social interaction. No mention of cataract in the mice.
Sources: Literature
Bleeding and Platelet Disorders v1.27 APOLD1 Lucy Spencer gene: APOLD1 was added
gene: APOLD1 was added to Bleeding and Platelet Disorders. Sources: Literature
Mode of inheritance for gene: APOLD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APOLD1 were set to 35638551
Phenotypes for gene: APOLD1 were set to Bleeding disorder, vascular-type (MIM#620715)
Review for gene: APOLD1 was set to AMBER
Added comment: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.
Sources: Literature
Skeletal Dysplasia_Fetal v0.217 HSPG2 Ain Roesley Marked gene: HSPG2 as ready
Skeletal Dysplasia_Fetal v0.217 HSPG2 Ain Roesley Gene: hspg2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5713 DIP2C Melanie Marty gene: DIP2C was added
gene: DIP2C was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DIP2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DIP2C were set to PMID: 38421105
Phenotypes for gene: DIP2C were set to Neurodevelopmental disorder (MONDO#0700092), DIP2C-related
Review for gene: DIP2C was set to GREEN
Added comment: PMID: 38421105 - Twenty three patients with het DIP2C variants (10 de novo).
All patients had developmental delays affecting expressive language and speech, most had mild dev delay and ID. Four patients had seizures. Additional phenotypic findings were non-specific but recurrent anomalies did include a high anterior hair-line, prominent forehead, and a broad nasal tip. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects,and bicuspid aortic valve)
Sources: Literature
Cataract v0.362 RGS6 Seb Lunke Marked gene: RGS6 as ready
Cataract v0.362 RGS6 Seb Lunke Gene: rgs6 has been classified as Red List (Low Evidence).
Mendeliome v1.1583 TOGARAM2 Naomi Baker gene: TOGARAM2 was added
gene: TOGARAM2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TOGARAM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOGARAM2 were set to PMID:38374469
Phenotypes for gene: TOGARAM2 were set to Nonsyndromic genetic hearing loss (MONDO:0019497), TOGARAM2-related
Review for gene: TOGARAM2 was set to RED
Added comment: Paper reports one individual with bilateral profound hearing loss with a homozygous TOGARAM2 nonsense variant and demonstrated reduced mRNA expression in transfected cells.
Sources: Literature
Cataract v0.362 RGS6 Seb Lunke gene: RGS6 was added
gene: RGS6 was added to Cataract. Sources: Literature
Mode of inheritance for gene: RGS6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RGS6 were set to 38332109; 25525169
Phenotypes for gene: RGS6 were set to Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149
Review for gene: RGS6 was set to RED
Added comment: Original paper from 2015 describes single consanguineous with two siblings affected by cataract, developmental delay, and microcephaly >3SD. A homozygous canonical splice variant predicted to lead to NMD in RGS6 was identified by WGS and linkage (rather than full WGS analysis). The 2024 paper speculates that the phenotype is driven by a change in RGS6 isoform balance rather than LoF using a knock-out mouse model. It is noted that the mice did not have microcephaly, and ID was assessed using social interaction. No mention of cataract in the mice.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.11 SNUPN Suliman Khan gene: SNUPN was added
gene: SNUPN was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: SNUPN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNUPN were set to PMID: 38413582; PMID: 38366623
Phenotypes for gene: SNUPN were set to autosomal recessive limb-girdle muscular dystrophy MONDO:0015152
Penetrance for gene: SNUPN were set to unknown
Added comment: PMID: 38413582: reported 18 children from 15 unrelated families with muscular phenotypes, including proximal upper limb weakness, distal upper and lower limb weakness, and myopathy (EMG) with elevated serum creatinine kinase level. Exome sequencing revealed nine hypomorphic biallelic variants in the SNUPN gene, predominantly clustered in the last coding exon. Functional studies showed that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients’ primary fibroblasts.

PMID: 38366623: reported five individuals from two unrelated families with limb-girdle muscular dystrophy.
Sources: Literature
Mendeliome v1.1583 DIP2C Melanie Marty gene: DIP2C was added
gene: DIP2C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DIP2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DIP2C were set to PMID: 38421105
Phenotypes for gene: DIP2C were set to Neurodevelopmental disorder (MONDO#0700092), DIP2C-related
Review for gene: DIP2C was set to GREEN
Added comment: PMID: 38421105 - Twenty three patients with het DIP2C variants (10 de novo).
All patients had developmental delays affecting expressive language and speech, most had mild dev delay and ID. Four patients had seizures. Additional phenotypic findings were non-specific but recurrent anomalies did include a high anterior hair-line, prominent forehead, and a broad nasal tip. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects,and bicuspid aortic valve)
Sources: Literature
Microcephaly v1.249 RGS6 Seb Lunke Marked gene: RGS6 as ready
Microcephaly v1.249 RGS6 Seb Lunke Gene: rgs6 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5713 DENND5B Elena Savva Publications for gene: DENND5B were set to
Microcephaly v1.249 RGS6 Seb Lunke gene: RGS6 was added
gene: RGS6 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: RGS6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RGS6 were set to 38332109; 25525169
Phenotypes for gene: RGS6 were set to Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149
Review for gene: RGS6 was set to RED
Added comment: Original paper from 2015 describes single consanguineous with two siblings affected by cataract, developmental delay, and microcephaly >3SD. A homozygous canonical splice variant predicted to lead to NMD in RGS6 was identified by WGS and linkage (rather than full WGS analysis). The 2024 paper speculates that the phenotype is driven by a change in RGS6 isoform balance rather than LoF using a knock-out mouse model. It is noted that the mice did not have microcephaly, and ID was assessed using social interaction. No mention of cataract in the mice.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5713 DENND5B Elena Savva Mode of pathogenicity for gene: DENND5B was changed from None to None
Leukodystrophy v0.306 DENND5B Elena Savva Publications for gene: DENND5B were set to
Mendeliome v1.1583 NIT1 Ain Roesley Marked gene: NIT1 as ready
Mendeliome v1.1583 NIT1 Ain Roesley Gene: nit1 has been classified as Green List (High Evidence).
Mendeliome v1.1583 NIT1 Zornitza Stark Marked gene: NIT1 as ready
Mendeliome v1.1583 NIT1 Zornitza Stark Gene: nit1 has been classified as Green List (High Evidence).
Mendeliome v1.1583 NIT1 Ain Roesley Classified gene: NIT1 as Green List (high evidence)
Mendeliome v1.1583 NIT1 Ain Roesley Gene: nit1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.26 SNUPN Suliman Khan gene: SNUPN was added
gene: SNUPN was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for gene: SNUPN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNUPN were set to PMID: 38413582; PMID: 38366623
Phenotypes for gene: SNUPN were set to autosomal recessive limb-girdle muscular dystrophy MONDO:0015152
Penetrance for gene: SNUPN were set to unknown
Review for gene: SNUPN was set to GREEN
Added comment: PMID: 38413582: reported 18 children from 15 unrelated families with muscular phenotypes, including proximal upper limb weakness, distal upper and lower limb weakness, and myopathy (EMG) with elevated serum creatinine kinase level. Exome sequencing revealed nine hypomorphic biallelic variants in the SNUPN gene, predominantly clustered in the last coding exon. Functional studies showed that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients’ primary fibroblasts.

PMID: 38366623: reported five individuals from two unrelated families with limb-girdle muscular dystrophy.
Sources: Literature
Mendeliome v1.1582 NIT1 Zornitza Stark Classified gene: NIT1 as Green List (high evidence)
Mendeliome v1.1582 NIT1 Zornitza Stark Gene: nit1 has been classified as Green List (High Evidence).
Callosome v0.516 SNF8 Chern Lim gene: SNF8 was added
gene: SNF8 was added to Callosome. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to Severe developmental delay, epileptic encephalopathy, brain MRI abnormality; intellectual disability, childhood-onset optic atrophy, ataxia
Review for gene: SNF8 was set to GREEN
gene: SNF8 was marked as current diagnostic
Added comment: PMID: 38423010
- Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.
- The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.
- Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech.
Sources: Literature
Mendeliome v1.1581 NIT1 Paul De Fazio edited their review of gene: NIT1: Changed rating: GREEN
Mendeliome v1.1581 TUBA4A Sarah Pantaleo gene: TUBA4A was added
gene: TUBA4A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to PMID: 38413182
Phenotypes for gene: TUBA4A were set to Congenital myopathy MONDO:0019952
Review for gene: TUBA4A was set to AMBER
Added comment: One novel TUBA4A variant in two unrelated Chinese patients with sporadic congenital myopathy.

Identified candidate genes using laser capture micro dissection, proteomics, WES, clinical data, myopathological changes, electrophysiological exams and thigh muscle MRIs.

The variant is de novo in both patients, c.679C>T, p.(Leu227Phe). The prominent myopathological changes in both patients were muscle fibres with focal myofibrillar disorganisation and rimmed vacuoles. Immunofluorescence showed ubiqution-positive TUBA4A protein aggregates in the muscle fibres with rimmed vacuoles. Overexpression of Leu227Phe resulted in cytoplasmic aggregates which colocalised with ubiquitin in cellular model.

Patient 1 is 14yo and had delayed motor development milestones since infancy. Myopathic face, high-arched palate, waddling gait, winged scapula and muscle weakness in four limbs with lower extremities and proximal muscle more severely affected. Follow up at 14yo showed slight improvement in motor function compared with 3yo.

Patient 2 is 6yo and presented with motor retardation since birth. At 3yo, presented with mild ptosis and ophthalmoparesis, high-arched palate and muscle weakness involving both proximal and distal in all limbs.

No likely pathogenic variants in 116 other protein-encoding genes. Variants confirmed by Sanger sequencing and absent from gnomAD. ACMG predicts likely pathogenic classification.
Sources: Literature
Mendeliome v1.1581 DENND5B Elena Savva Publications for gene: DENND5B were set to
Intellectual disability syndromic and non-syndromic v0.5712 SNF8 Chern Lim gene: SNF8 was added
gene: SNF8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to Severe developmental delay, epileptic encephalopathy, brain MRI abnormality; intellectual disability, childhood-onset optic atrophy, ataxia
Review for gene: SNF8 was set to GREEN
gene: SNF8 was marked as current diagnostic
Added comment: PMID: 38423010
- Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.
- The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.
- Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech.
Sources: Literature
Mendeliome v1.1580 NIT1 Paul De Fazio gene: NIT1 was added
gene: NIT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NIT1 were set to 38430071
Phenotypes for gene: NIT1 were set to Cerebrovascular disorder, NIT1-related (MONDO:0011057)
Penetrance for gene: NIT1 were set to unknown
gene: NIT1 was marked as current diagnostic
Added comment: 5 unrelated families reported with recessively inherited cerebral small vessel disease had compound hetereozygous or homozygous variants in NIT1. 1 family (3 siblings) had p.(Ala68*) in trans with p.(Arg243Trp), the remaining 4 families (1 individual each) were all homozygous for p.(Arg243Trp).

Patients presented in mid-adulthood with progressive movement disorders (e.g. dystonia, chorea, bradykinesia and tremor, gait disturbance, dysarthria) and had abnormal brain MRI findings (honeycomb appearance of the basal ganglia-thalamus complex, due to numerous strongly dilated PVS). 3 patients had non-lobar intracerebral hemorrhage. Slowly progressive cognitive decline was also a key feature.

Metabolic analysis in urine confirmed loss of NIT1 enzymatic function.

Note p.(Arg243Trp) has 1 homozygote in gnomAD v4, but permitted due to later presentation in reported patients.
Sources: Literature
Mendeliome v1.1580 DENND5B Elena Savva reviewed gene: DENND5B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38387458; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), DENND5B-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Muscular dystrophy and myopathy_Paediatric v1.11 TUBA4A Sarah Pantaleo gene: TUBA4A was added
gene: TUBA4A was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to PMID: 38413182
Phenotypes for gene: TUBA4A were set to Congenital myopathy MONDO:0019952
Review for gene: TUBA4A was set to AMBER
Added comment: One novel TUBA4A variant in two unrelated Chinese patients with sporadic congenital myopathy.

Identified candidate genes using laser capture micro dissection, proteomics, WES, clinical data, myopathological changes, electrophysiological exams and thigh muscle MRIs.

The variant is de novo in both patients, c.679C>T, p.(Leu227Phe). The prominent myopathological changes in both patients were muscle fibres with focal myofibrillar disorganisation and rimmed vacuoles. Immunofluorescence showed ubiqution-positive TUBA4A protein aggregates in the muscle fibres with rimmed vacuoles. Overexpression of Leu227Phe resulted in cytoplasmic aggregates which colocalised with ubiquitin in cellular model.

Patient 1 is 14yo and had delayed motor development milestones since infancy. Myopathic face, high-arched palate, waddling gait, winged scapula and muscle weakness in four limbs with lower extremities and proximal muscle more severely affected. Follow up at 14yo showed slight improvement in motor function compared with 3yo.

Patient 2 is 6yo and presented with motor retardation since birth. At 3yo, presented with mild ptosis and ophthalmoparesis, high-arched palate and muscle weakness involving both proximal and distal in all limbs.

No likely pathogenic variants in 116 other protein-encoding genes. Variants confirmed by Sanger sequencing and absent from gnomAD. ACMG predicts likely pathogenic classification.
Sources: Literature
Stroke v1.16 NIT1 Ain Roesley Marked gene: NIT1 as ready
Stroke v1.16 NIT1 Ain Roesley Gene: nit1 has been classified as Green List (High Evidence).
Stroke v1.16 NIT1 Ain Roesley Classified gene: NIT1 as Green List (high evidence)
Stroke v1.16 NIT1 Ain Roesley Gene: nit1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5712 RREB1 Zornitza Stark Marked gene: RREB1 as ready
Intellectual disability syndromic and non-syndromic v0.5712 RREB1 Zornitza Stark Gene: rreb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5712 RREB1 Zornitza Stark Classified gene: RREB1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5712 RREB1 Zornitza Stark Gene: rreb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5711 POP1 Belinda Chong reviewed gene: POP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 38351533; Phenotypes: Anauxetic dysplasia 2, MIM#617396; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal Dysplasia_Fetal v0.217 HSPG2 Dean Phelan reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38424183; Phenotypes: Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5711 RREB1 Zornitza Stark gene: RREB1 was added
gene: RREB1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RREB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RREB1 were set to 32938917; 38332451
Phenotypes for gene: RREB1 were set to Rasopathy, MONDO:0021060, RREB1-related
Review for gene: RREB1 was set to AMBER
Added comment: PMID 32938917: Single individual reported with Noonan syndrome-like features and a deletion encompassing RREB1. Overlapping deletions in publicly reported databases examined, and RREB1 postulated to be the key gene. Rreb1 hemizygous mice display orbital hypertelorism and age dependent cardiac hypertrophy. RREB1 recruits SIN3A and KDM1A to an RRE in target promoters in human and murine cells to control histone H3K4 methylation of MAPK pathway genes. In summary, single well phenotyped individual with a CNV and experimental data to support gene-disease association.

PMID 38332451: de novo LoF variant in an individual with phenotype consistent with the previous reports.
Sources: Literature
Stroke v1.15 NIT1 Paul De Fazio gene: NIT1 was added
gene: NIT1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: NIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NIT1 were set to 38430071
Phenotypes for gene: NIT1 were set to Cerebrovascular disorder, NIT1-related (MONDO:0011057)
Penetrance for gene: NIT1 were set to unknown
Review for gene: NIT1 was set to GREEN
gene: NIT1 was marked as current diagnostic
Added comment: 5 unrelated families reported with recessively inherited cerebral small vessel disease had compound hetereozygous or homozygous variants in NIT1. 1 family (3 siblings) had p.(Ala68*) in trans with p.(Arg243Trp), the remaining 4 families (1 individual each) were all homozygous for p.(Arg243Trp).

Patients presented in mid-adulthood with progressive movement disorders (e.g. dystonia, chorea, bradykinesia and tremor, gait disturbance, dysarthria) and had abnormal brain MRI findings. 3 patients had non-lobar intracerebral hemorrhage. Metabolic analysis in urine confirmed loss of NIT1 enzymatic function.

Note p.(Arg243Trp) has 1 homozygote in gnomAD v4, but permitted due to later presentation in reported patients.
Sources: Literature
Rasopathy v0.102 RREB1 Zornitza Stark Phenotypes for gene: RREB1 were changed from Noonan syndrome-like disorder to Rasopathy, MONDO:0021060, RREB1-related
Rasopathy v0.101 RREB1 Zornitza Stark Publications for gene: RREB1 were set to 32938917
Intellectual disability syndromic and non-syndromic v0.5710 FEZF2 Ain Roesley Marked gene: FEZF2 as ready
Intellectual disability syndromic and non-syndromic v0.5710 FEZF2 Ain Roesley Gene: fezf2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5710 FEZF2 Ain Roesley Classified gene: FEZF2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5710 FEZF2 Ain Roesley Gene: fezf2 has been classified as Green List (High Evidence).
Rasopathy v0.100 RREB1 Zornitza Stark Classified gene: RREB1 as Amber List (moderate evidence)
Rasopathy v0.100 RREB1 Zornitza Stark Gene: rreb1 has been classified as Amber List (Moderate Evidence).
Rasopathy v0.99 RREB1 Zornitza Stark edited their review of gene: RREB1: Added comment: PMID 38332451: de novo LoF variant in an individual with phenotype consistent with the previous reports.; Changed rating: AMBER; Changed publications: 32938917, 38332451; Changed phenotypes: Rasopathy, MONDO:0021060, RREB1-related
Intellectual disability syndromic and non-syndromic v0.5709 FEZF2 Ain Roesley gene: FEZF2 was added
gene: FEZF2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FEZF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FEZF2 were set to 38425142
Phenotypes for gene: FEZF2 were set to neurodevelopmental disorder MONDO:0700092, FEZF2-related
Review for gene: FEZF2 was set to GREEN
gene: FEZF2 was marked as current diagnostic
Added comment: - 7 indiv but 1 has whole gene deletion and 6x SNV (4x PTCs and 2x same missense Arg344Cys)
- of the 6x SNV, 4x de novo + 1x from affected father
- all have ID/ASD
- 1x seizures
- 1x hypotonia
- 1x motor coordination disorder
- 2x enuresis after 7yo
Sources: Literature
Mendeliome v1.1580 FEZF2 Ain Roesley Marked gene: FEZF2 as ready
Mendeliome v1.1580 FEZF2 Ain Roesley Gene: fezf2 has been classified as Green List (High Evidence).
Mendeliome v1.1580 RREB1 Zornitza Stark Publications for gene: RREB1 were set to 32938917
Mendeliome v1.1580 FEZF2 Ain Roesley Classified gene: FEZF2 as Green List (high evidence)
Mendeliome v1.1580 FEZF2 Ain Roesley Gene: fezf2 has been classified as Green List (High Evidence).
Mendeliome v1.1579 RREB1 Zornitza Stark Classified gene: RREB1 as Amber List (moderate evidence)
Mendeliome v1.1579 RREB1 Zornitza Stark Gene: rreb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1578 RREB1 Zornitza Stark edited their review of gene: RREB1: Added comment: PMID 38332451: de novo LoF variant in an individual with phenotype consistent with the previous reports.; Changed rating: AMBER; Changed publications: 32938917, 38332451; Changed phenotypes: Rasopathy, MONDO:0021060, RREB1-related
Mendeliome v1.1578 FEZF2 Ain Roesley gene: FEZF2 was added
gene: FEZF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FEZF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FEZF2 were set to 38425142
Phenotypes for gene: FEZF2 were set to neurodevelopmental disorder MONDO:0700092, FEZF2-related
Review for gene: FEZF2 was set to GREEN
gene: FEZF2 was marked as current diagnostic
Added comment: - 7 indiv but 1 has whole gene deletion and 6x SNV (4x PTCs and 2x same missense Arg344Cys)
- of the 6x SNV, 4x de novo + 1x from affected father
- all have ID/ASD
- 1x seizures
- 1x hypotonia
- 1x motor coordination disorder
- 2x enuresis after 7yo
Sources: Literature
Mendeliome v1.1577 ZFX Zornitza Stark Marked gene: ZFX as ready
Mendeliome v1.1577 ZFX Zornitza Stark Gene: zfx has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5708 ZFX Zornitza Stark Phenotypes for gene: ZFX were changed from X-linked neurodevelopmental disorder with recurrent facial gestalt to Neurodevelopmental disorder, MONDO:0700092, ZFX-related
Mendeliome v1.1577 ZFX Zornitza Stark Classified gene: ZFX as Green List (high evidence)
Mendeliome v1.1577 ZFX Zornitza Stark Gene: zfx has been classified as Green List (High Evidence).
Mendeliome v1.1576 ZFX Zornitza Stark gene: ZFX was added
gene: ZFX was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZFX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZFX were set to 26350204; 26740508; 38325380
Phenotypes for gene: ZFX were set to Neurodevelopmental disorder, MONDO:0700092, ZFX-related
Review for gene: ZFX was set to GREEN
Added comment: A single ZFX variant has been associated with a neurodevelopmental disorder, that has a Rett syndrome-like phenotype disorder, in a 14 year old male. The ZFX variant was allelic with another X-linked variant in SHROOM4. These variants were inherited from the mother, who had random X inactivation pattern (PMID: 26740508).
PMID: 38325380 reports 11 ZFX variants in 18 subjects from 16 unrelated families (14 males and 4 females) with an X-linked neurodevelopmental disorder with recurrent facial gestalt. Seven variants were truncating and the remaining were missense variants within the Zinc finger array. In the pedigree of family 6 (figure 3, PMID: 38325380), it was apparent that there were female carriers of the ZFX variant (GRCh38 chrX: 24229396A>G, c.2438A>G, p.Tyr774Cys) with hyperparathyroidism and two affected males and one affected female, with the neurodevelopmental disorder. It appeared that skewed X-inactivation in the female carriers was responsible for the different phenotypic features. The association between ZFX variants and a novel neurodevelopmental disorder, was further supported by functional studies showing altered transcriptional activity in missense variants and altered behavior in a zebrafish loss-of-function model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5707 ZFX Zornitza Stark Marked gene: ZFX as ready
Intellectual disability syndromic and non-syndromic v0.5707 ZFX Zornitza Stark Gene: zfx has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5707 ZFX Zornitza Stark Classified gene: ZFX as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5707 ZFX Zornitza Stark Gene: zfx has been classified as Green List (High Evidence).
Fetal anomalies v1.198 NARS Zornitza Stark reviewed gene: NARS: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive, MIM# 619091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy v1.10 NARS Zornitza Stark commented on gene: NARS: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).
Intellectual disability syndromic and non-syndromic v0.5706 NARS Zornitza Stark commented on gene: NARS: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).
Genetic Epilepsy v0.2328 NARS Zornitza Stark commented on gene: NARS: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).
Microcephaly v1.248 NARS Zornitza Stark reviewed gene: NARS: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive, MIM# 619091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1575 NARS Zornitza Stark commented on gene: NARS: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).
Mendeliome v1.1575 STX4 Zornitza Stark Phenotypes for gene: STX4 were changed from Non-syndromic genetic hearing loss, MONDO:0019497, STX4-related. to Deafness, autosomal recessive 123, MIM# 620745
Mendeliome v1.1574 DES Zornitza Stark Mode of inheritance for gene: DES was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Dystonia and Chorea v0.234 PAH Natalie Lim gene: PAH was added
gene: PAH was added to Dystonia - complex. Sources: Expert Review
Mode of inheritance for gene: PAH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAH were set to PMID: 25614310, PMID: 15390012, PMID: 30369906
Phenotypes for gene: PAH were set to Phenylketonuria MIM#261600
Review for gene: PAH was set to GREEN
Added comment: Reports of parkinsonism and dystonia have been documented as delayed manifestations amongst PKU patients although rare.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5706 ZFX Sarah Leigh gene: ZFX was added
gene: ZFX was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZFX 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: ZFX were set to 26350204; 26740508; 38325380
Phenotypes for gene: ZFX were set to X-linked neurodevelopmental disorder with recurrent facial gestalt
Review for gene: ZFX was set to GREEN
Added comment: To date, germline variants in ZFX have not been associated with a phenotype in OMIM or Gen2Phen.
A single ZFX variant has been associated with a neurodevelopmental disorder, that has a Rett syndrome-like phenotype disorder, in a 14 year old male. The ZFX variant was allelic with another X-linked variant in SHROOM4. These variants were inherited from the mother, who had random X inactivation pattern (PMID: 26740508).
PMID: 38325380 reports 11 ZFX variants in 18 subjects from 16 unrelated families (14 males and 4 females) with an X-linked neurodevelopmental disorder with recurrent facial gestalt. Seven variants were truncating and the remaining were missense variants within the Zinc finger array. In the pedigree of family 6 (figure 3, PMID: 38325380), it was apparent that there were female carriers of the ZFX variant (GRCh38 chrX: 24229396A>G, c.2438A>G, p.Tyr774Cys) with hyperparathyroidism and two affected males and one affected female, with the neurodevelopmental disorder. It appeared that skewed X-inactivation in the female carriers was responsible for the different phenotypic features. The association between ZFX variants and a novel neurodevelopmental disorder, was further supported by functional studies showing altered transcriptional activity in missense variants and altered behavior in a zebrafish loss-of-function model.
Sources: Literature
Inflammatory bowel disease v0.118 ELF4 Peter McNaughton gene: ELF4 was added
gene: ELF4 was added to Inflammatory bowel disease. Sources: Literature
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 PMID: 38231408
Phenotypes for gene: ELF4 were set to Inflammatory bowel disease
Review for gene: ELF4 was set to GREEN
Added comment: Cohort of 14 patients from 13 families with many presenting with gastrointestinal inflammation and ulceration. Frequently patients had been labelled with IBD prior to diagnosis of ELF4.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5706 PI4K2A Zornitza Stark Phenotypes for gene: PI4K2A were changed from complex neurodevelopmental disorder with motor features, PI4K2A-related, MONDO:0100516 to Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, MIM# 620732
Genetic Epilepsy v0.2328 PI4K2A Zornitza Stark Phenotypes for gene: PI4K2A were changed from complex neurodevelopmental disorder with motor features, PI4K2A-related, MONDO:0100516 to Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, MIM# 620732
Mendeliome v1.1573 PI4K2A Zornitza Stark Phenotypes for gene: PI4K2A were changed from complex neurodevelopmental disorder with motor features, PI4K2A-related, MONDO:0100516; Cutis laxa, intellectual disability, movement disorder to Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, MIM# 620732; Cutis laxa, intellectual disability, movement disorder
Genetic Epilepsy v0.2327 ALDH3A2 Zornitza Stark Mode of inheritance for gene: ALDH3A2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1572 KLF14 Bryony Thompson Marked gene: KLF14 as ready
Mendeliome v1.1572 KLF14 Bryony Thompson Gene: klf14 has been classified as Red List (Low Evidence).
Mendeliome v1.1572 KLF14 Bryony Thompson Classified gene: KLF14 as Red List (low evidence)
Mendeliome v1.1572 KLF14 Bryony Thompson Gene: klf14 has been classified as Red List (Low Evidence).
Mendeliome v1.1571 NOTCH2NL Bryony Thompson Tag STR tag was added to gene: NOTCH2NL.
Mendeliome v1.1571 NLRP12 Bryony Thompson Publications for gene: NLRP12 were set to 18230725; 21360512; 24064030; 27633793
Fetal anomalies v1.198 THSD1 Zornitza Stark Marked gene: THSD1 as ready
Fetal anomalies v1.198 THSD1 Zornitza Stark Gene: thsd1 has been classified as Green List (High Evidence).
Fetal anomalies v1.198 THSD1 Zornitza Stark Classified gene: THSD1 as Green List (high evidence)
Fetal anomalies v1.198 THSD1 Zornitza Stark Gene: thsd1 has been classified as Green List (High Evidence).
Fetal anomalies v1.197 THSD1 Zornitza Stark gene: THSD1 was added
gene: THSD1 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: THSD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: THSD1 were set to 33569873; 27895300
Phenotypes for gene: THSD1 were set to Lymphatic malformation 13, MIM# 620244
Review for gene: THSD1 was set to GREEN
Added comment: PMID: 33569873 - 1 fetus with a homozygous PTC and nonimmune hydrops fetalis (NIHF), congenital heart disease and hemangiomas. FHx of 1/3 triplets with severe hydrops fetalis, not sequenced.
- Paper reviews previous NIHF cases and reports another homozygous PTC in two families ( and a recurring homozygous missense (p.Cys206Tyr) in three families.


PMID: 27895300- Mouse model has hydrocephaly with poor perfusion.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5705 CBL Hali Van Niel reviewed gene: CBL: Rating: GREEN; Mode of pathogenicity: None; Publications: 20694012, 20543203, 11315197; Phenotypes: CBL-related disorder MONDO:0013308; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 CACNA1A Hali Van Niel reviewed gene: CACNA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27476654, 33985586; Phenotypes: developmental and epileptic encephalopathy, 42 MONDO:0014917; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 C12orf65 Hali Van Niel reviewed gene: C12orf65: Rating: GREEN; Mode of pathogenicity: None; Publications: 24284555, 20598281, 23188110, 24080142, PMID: 3479531; Phenotypes: hereditary spastic paraplegia 55 MONDO:0014020; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BTD Hali Van Niel reviewed gene: BTD: Rating: GREEN; Mode of pathogenicity: None; Publications: 7550325, 9375914, 37751899, 32741581; Phenotypes: biotinidase deficiency MONDO:0009665; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BSCL2 Hali Van Niel reviewed gene: BSCL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 12362029, 26072926, 28916377; Phenotypes: congenital generalized lipodystrophy type 2 MONDO:0010020; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1570 PCSK2 Bryony Thompson Classified gene: PCSK2 as Red List (low evidence)
Mendeliome v1.1570 PCSK2 Bryony Thompson Gene: pcsk2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5705 BCS1L Hali Van Niel reviewed gene: BCS1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 9777342, 17314340, 11528392, 30582773, 30582773, 25914718; Phenotypes: Bjornstad syndrome MONDO:0009872; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BCKDHB Hali Van Niel reviewed gene: BCKDHB: Rating: GREEN; Mode of pathogenicity: None; Publications: 7672509, 11509994, 14742428; Phenotypes: maple syrup urine disease type 1B MONDO:0023692; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BCKDHA Hali Van Niel reviewed gene: BCKDHA: Rating: GREEN; Mode of pathogenicity: None; Publications: 7883996, 7672509, 34288399; Phenotypes: maple syrup urine disease type 1A MONDO:0023691; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BBS2 Hali Van Niel reviewed gene: BBS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11285252, 11567139; Phenotypes: Bardet-Biedl syndrome 2 MONDO:0014432; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BBS12 Hali Van Niel reviewed gene: BBS12: Rating: GREEN; Mode of pathogenicity: None; Publications: 17160889, 20827784; Phenotypes: Bardet-Biedl syndrome 12 MONDO:0014440; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BBS10 Hali Van Niel reviewed gene: BBS10: Rating: GREEN; Mode of pathogenicity: None; Publications: 16582908, 20805367, 27245532; Phenotypes: Phenotype: Bardet-Biedl syndrome 10 MONDO:0014438; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BBS1 Hali Van Niel reviewed gene: BBS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12118255, 12677556, 12567324; Phenotypes: Bardet-Biedl syndrome 1 MONDO:0008854; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1569 RFX6 Bryony Thompson Added comment: Comment on mode of inheritance: Mitchell-Riley syndrome is AR and MODY is AD
Mendeliome v1.1569 RFX6 Bryony Thompson Mode of inheritance for gene: RFX6 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
Mendeliome v1.1568 PPP2R2B Bryony Thompson Tag STR tag was added to gene: PPP2R2B.
Mendeliome v1.1568 SAMD12 Bryony Thompson Tag STR tag was added to gene: SAMD12.
Monogenic Diabetes v0.50 APPL1 Bryony Thompson Publications for gene: APPL1 were set to 26073777
Monogenic Diabetes v0.49 APPL1 Bryony Thompson Classified gene: APPL1 as Red List (low evidence)
Monogenic Diabetes v0.49 APPL1 Bryony Thompson Gene: appl1 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.48 APPL1 Bryony Thompson Deleted their comment
Monogenic Diabetes v0.48 APPL1 Bryony Thompson edited their review of gene: APPL1: Added comment: PMID: 36208030 - a study using the UK Biobank comparing individuals with and without diabetes found LoF variants in APPL1 were ‘Inconsistent’ with being high penetrant for diabetes (failed both statistical criteria - enrichment & comparison to maximum credible allele frequency). Refutes previous study.; Changed rating: RED; Changed publications: 26073777, 36208030
Mendeliome v1.1568 APPL1 Bryony Thompson Publications for gene: APPL1 were set to 26073777
Mendeliome v1.1567 APPL1 Bryony Thompson Classified gene: APPL1 as Red List (low evidence)
Mendeliome v1.1567 APPL1 Bryony Thompson Gene: appl1 has been classified as Red List (Low Evidence).
Mendeliome v1.1566 APPL1 Bryony Thompson Deleted their comment
Mendeliome v1.1566 APPL1 Bryony Thompson edited their review of gene: APPL1: Added comment: PMID: 36208030 - a study using the UK Biobank comparing individuals with and without diabetes found LoF variants in APPL1 were ‘Inconsistent’ with being high penetrant for diabetes (failed both statistical criteria - enrichment & comparison to maximum credible allele frequency). Refutes previous study.; Changed rating: RED; Changed publications: 26073777, 36208030
Monogenic Diabetes v0.48 KLF11 Bryony Thompson Marked gene: KLF11 as ready
Monogenic Diabetes v0.48 KLF11 Bryony Thompson Gene: klf11 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.48 KLF11 Bryony Thompson Publications for gene: KLF11 were set to 15774581; 26248217; 23589285; 31124255
Monogenic Diabetes v0.47 KLF11 Bryony Thompson Classified gene: KLF11 as Red List (low evidence)
Monogenic Diabetes v0.47 KLF11 Bryony Thompson Added comment: Comment on list classification: Association with monogenic diabetes now Refuted Classification - 02/08/2023. ClinGen Monogenic Diabetes GCEP - https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_b1e38a49-7c12-4514-a2a1-109e04da146f-2023-02-08T170000.000Z?page=1&size=25&search=
Monogenic Diabetes v0.47 KLF11 Bryony Thompson Gene: klf11 has been classified as Red List (Low Evidence).
Mendeliome v1.1566 KLF11 Bryony Thompson Publications for gene: KLF11 were set to 15774581; 26248217; 23589285; 31124255
Mendeliome v1.1565 KLF11 Bryony Thompson Classified gene: KLF11 as Red List (low evidence)
Mendeliome v1.1565 KLF11 Bryony Thompson Added comment: Comment on list classification: Association with monogenic diabetes now Refuted
Classification - 02/08/2023. ClinGen Monogenic Diabetes GCEP - https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_b1e38a49-7c12-4514-a2a1-109e04da146f-2023-02-08T170000.000Z?page=1&size=25&search=
Mendeliome v1.1565 KLF11 Bryony Thompson Gene: klf11 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.46 PPARG Hali Van Niel reviewed gene: PPARG: Rating: RED; Mode of pathogenicity: None; Publications: 30207237, 34900790; Phenotypes: diabetes mellitus MONDO:0005015; Mode of inheritance: Unknown
Mendeliome v1.1564 KLF14 Hali Van Niel changed review comment from: PMID: 33389382
Case-sibling study of 92 healthy individuals and 92 type 2 diabetes patients found KLF14 SNPs associated with susceptibility to type 2 diabetes

PMID: 35081256
Large scale association analysis found type 2 susceptibility of KLF14 SNPS appearing to be driven by reduced insulin sensitivity

PMID: 24486580
Global Meta-analysis found risk allele SNP associated with increased risk of type 2 diabetes (in global population)
Sources: Other; to: Cannot find any evidence of association with mendelian disease

PMID: 33389382
Case-sibling study of 92 healthy individuals and 92 type 2 diabetes patients found KLF14 SNPs associated with susceptibility to type 2 diabetes

PMID: 35081256
Large scale association analysis found type 2 susceptibility of KLF14 SNPS appearing to be driven by reduced insulin sensitivity

PMID: 24486580
Global Meta-analysis found risk allele SNP associated with increased risk of type 2 diabetes (in global population)
Sources: Other
Mendeliome v1.1564 KLF14 Hali Van Niel gene: KLF14 was added
gene: KLF14 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: KLF14 was set to Unknown
Publications for gene: KLF14 were set to 33389382; 35081256; 24486580
Phenotypes for gene: KLF14 were set to diabetes mellitus MONDO:0005015
Review for gene: KLF14 was set to RED
Added comment: PMID: 33389382
Case-sibling study of 92 healthy individuals and 92 type 2 diabetes patients found KLF14 SNPs associated with susceptibility to type 2 diabetes

PMID: 35081256
Large scale association analysis found type 2 susceptibility of KLF14 SNPS appearing to be driven by reduced insulin sensitivity

PMID: 24486580
Global Meta-analysis found risk allele SNP associated with increased risk of type 2 diabetes (in global population)
Sources: Other
Mendeliome v1.1564 PCSK2 Hali Van Niel gene: PCSK2 was added
gene: PCSK2 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: PCSK2 was set to Unknown
Publications for gene: PCSK2 were set to 26607656; 7698505; 17618154
Phenotypes for gene: PCSK2 were set to diabetes mellitus MONDO:0005015
Review for gene: PCSK2 was set to RED
Added comment: Cannot find any evidence of association with mendelian disease

PMID: 26607656

10 SNPs genotyped, genetic polymorphisms responsible for glucose homeostasis and incidental diabetes

PMID: 7698505
DNA polymorphism found in 11% of non insulin dependent diabetes patients (out of 152 japanese patients) vs 4% in health population (out of 102 japanese patients).

PMID: 17618154
29 SNPS analysed across PCSK2, 4 SNPS associated type 2 diabetes in african american population
Sources: Other
Mendeliome v1.1564 ACO2 Zornitza Stark Publications for gene: ACO2 were set to 22405087; 25351951; 30689204; 32519519; 25351951
Mendeliome v1.1563 ACO2 Zornitza Stark Mode of inheritance for gene: ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Optic Atrophy v1.29 ACO2 Zornitza Stark Publications for gene: ACO2 were set to 25351951; 22405087
Optic Atrophy v1.28 ACO2 Zornitza Stark Mode of inheritance for gene: ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mitochondrial disease v0.918 ACO2 Zornitza Stark Publications for gene: ACO2 were set to 22405087; 25351951; 30689204; 32519519; 25351951
Mitochondrial disease v0.917 ACO2 Zornitza Stark Mode of inheritance for gene: ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genetic Epilepsy v0.2326 TSEN34 Zornitza Stark Marked gene: TSEN34 as ready
Genetic Epilepsy v0.2326 TSEN34 Zornitza Stark Added comment: Comment when marking as ready: No publications specifically reporting seizures identified.
Genetic Epilepsy v0.2326 TSEN34 Zornitza Stark Gene: tsen34 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2326 TSEN34 Zornitza Stark Marked gene: TSEN34 as ready
Genetic Epilepsy v0.2326 TSEN34 Zornitza Stark Gene: tsen34 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2326 WDFY3 Zornitza Stark Phenotypes for gene: WDFY3 were changed from ?Microcephaly 18, primary, autosomal dominant MIM#617520 to Microcephaly 18, primary, autosomal dominant MIM#617520
Mendeliome v1.1562 YEATS2 Zornitza Stark Tag STR tag was added to gene: YEATS2.
Genetic Epilepsy v0.2325 YEATS2 Zornitza Stark Tag STR tag was added to gene: YEATS2.
Genetic Epilepsy v0.2325 ZMIZ1 Zornitza Stark Classified gene: ZMIZ1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2325 ZMIZ1 Zornitza Stark Gene: zmiz1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2324 ZMIZ1 Zornitza Stark reviewed gene: ZMIZ1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies MIM#618659; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2324 ZSWIM6 Elena Savva Marked gene: ZSWIM6 as ready
Genetic Epilepsy v0.2324 ZSWIM6 Elena Savva Gene: zswim6 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2324 ZSWIM6 Elena Savva Classified gene: ZSWIM6 as Green List (high evidence)
Genetic Epilepsy v0.2324 ZSWIM6 Elena Savva Gene: zswim6 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2323 ZSWIM6 Elena Savva gene: ZSWIM6 was added
gene: ZSWIM6 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ZSWIM6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZSWIM6 were set to PMID: 29198722; 33958584
Phenotypes for gene: ZSWIM6 were set to Acromelic frontonasal dysostosis MIM#603671; Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features MIM#617865
Review for gene: ZSWIM6 was set to GREEN
Added comment: Seizures listed in OMIM as a feature of both conditions.

PMID: 29198722 - seven unrelated individuals with a recurrent de novo nonsense variant p.Arg913* in the penultimate exon. 4/7 confirmed to have seizures or possible seizures.

PMID: 33958584 - Japanese male patient with severe neurodevelopmental delay, epilepsy, distinctive facial features, microcephaly, growth deficiency, abnormal behavior, and frequent vomiting but without frontonasal or limb malformations. Proband had the same de novo p.Arg913* variant
Sources: Literature
Genetic Epilepsy v0.2322 ZMIZ1 Elena Savva Marked gene: ZMIZ1 as ready
Genetic Epilepsy v0.2322 ZMIZ1 Elena Savva Gene: zmiz1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2322 ZMIZ1 Elena Savva gene: ZMIZ1 was added
gene: ZMIZ1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ZMIZ1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZMIZ1 were set to PMID: 30639322
Phenotypes for gene: ZMIZ1 were set to Neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies MIM#618659
Review for gene: ZMIZ1 was set to RED
Added comment: Seizures (rare) listed in OMIM

PMID: 30639322 - gene-disease establishing paper. Cohort of 19 probands (16 unrelated), where 3 were reported with seizures.
Sources: Literature
Genetic Epilepsy v0.2321 ZIC2 Elena Savva Marked gene: ZIC2 as ready
Genetic Epilepsy v0.2321 ZIC2 Elena Savva Gene: zic2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2321 ZIC2 Elena Savva gene: ZIC2 was added
gene: ZIC2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ZIC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ZIC2 were set to Holoprosencephaly 5 MIM#609637
Review for gene: ZIC2 was set to RED
Added comment: No evidence of SNVs in this gene causing epilepsy/seizures.

This gene was listed in the Oliver list.
Sources: Literature
Genetic Epilepsy v0.2320 YEATS2 Elena Savva Marked gene: YEATS2 as ready
Genetic Epilepsy v0.2320 YEATS2 Elena Savva Gene: yeats2 has been classified as Red List (Low Evidence).
Mendeliome v1.1562 YEATS2 Elena Savva Marked gene: YEATS2 as ready
Mendeliome v1.1562 YEATS2 Elena Savva Gene: yeats2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2320 YEATS2 Elena Savva gene: YEATS2 was added
gene: YEATS2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: YEATS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: YEATS2 were set to PMID: 22713812; 31539032
Phenotypes for gene: YEATS2 were set to ?Epilepsy, myoclonic, familial adult, 4 MIM#615127
Review for gene: YEATS2 was set to RED
Added comment: PMID: 22713812 - 13 members of a single family with Benign Adult Familial Myoclonic Epilepsy (BAFME). The average age of onset was 19.5 (range 10–33) years for tremor and 25 (range 19–33) years for seizures.
PMID: 31539032 - Expansions of TTTTA and insertions of TTTCA repeats in intron 1 of YEATS2 segregated in the same family ^.
Sources: Literature
Mendeliome v1.1562 YEATS2 Elena Savva gene: YEATS2 was added
gene: YEATS2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: YEATS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: YEATS2 were set to PMID: 22713812; 31539032
Phenotypes for gene: YEATS2 were set to ?Epilepsy, myoclonic, familial adult, 4 MIM#615127
Review for gene: YEATS2 was set to RED
Added comment: PMID: 22713812 - 13 members of a single family with Benign Adult Familial Myoclonic Epilepsy (BAFME). The average age of onset was 19.5 (range 10–33) years for tremor and 25 (range 19–33) years for seizures.
PMID: 31539032 - Expansions of TTTTA and insertions of TTTCA repeats in intron 1 of YEATS2 segregated in the same family ^.
Sources: Literature
Genetic Epilepsy v0.2319 XPR1 Elena Savva Marked gene: XPR1 as ready
Genetic Epilepsy v0.2319 XPR1 Elena Savva Gene: xpr1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2319 XPR1 Elena Savva Classified gene: XPR1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2319 XPR1 Elena Savva Gene: xpr1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2318 XPR1 Elena Savva gene: XPR1 was added
gene: XPR1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: XPR1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: XPR1 were set to PMID: 33433330
Phenotypes for gene: XPR1 were set to Basal ganglia calcification, idiopathic, 6 MIM#616413
Review for gene: XPR1 was set to AMBER
Added comment: Seizures (in some patients) listed in OMIM

PMID: 33433330
- chet proband (PTC, missense) with paroxysmal kinesigenic dyskinesia with infantile convulsions, and generalized tonic-clonic seizures (GTCS) at the age of 2 years. Both parents were unaffected.
- Only missense in AD disease had been reported.
- Reviews literature, notes seizures 2/12 unrelated individuals, where an additional proband was ?seizures?
Sources: Literature
Genetic Epilepsy v0.2317 WDFY3 Elena Savva Marked gene: WDFY3 as ready
Genetic Epilepsy v0.2317 WDFY3 Elena Savva Gene: wdfy3 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2317 WDFY3 Elena Savva gene: WDFY3 was added
gene: WDFY3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: WDFY3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WDFY3 were set to PMID: 31327001
Phenotypes for gene: WDFY3 were set to ?Microcephaly 18, primary, autosomal dominant MIM#617520
Review for gene: WDFY3 was set to RED
Added comment: PMID: 31327001 - cohort of 13 probands and mouse model, NONE had reported to have epilepsy/seizures.

Gene was listed as part of the Oliver review for genes associated with epilepsy
Sources: Literature
Genetic Epilepsy v0.2316 WASHC4 Elena Savva Marked gene: WASHC4 as ready
Genetic Epilepsy v0.2316 WASHC4 Elena Savva Gene: washc4 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2316 WASHC4 Elena Savva gene: WASHC4 was added
gene: WASHC4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: WASHC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WASHC4 were set to PMID: 34599609
Phenotypes for gene: WASHC4 were set to Intellectual developmental disorder, autosomal recessive 43 MIM#615817
Review for gene: WASHC4 was set to RED
Added comment: PMID: 34599609 - two siblings, only 1 sibling presented with epilepsy with generalized tonic–clonic seizures and received oxcarbazepine (seizure-free on therapy). They were homozygous for a missense, some functional studies supporting pathogenicity.
Review of previous reports did NOT describe any other reports of seizures.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5705 WASHC4 Elena Savva Phenotypes for gene: WASHC4 were changed from ?Mental retardation, autosomal recessive 43; OMIM #615817 to Intellectual developmental disorder, autosomal recessive 43 MIM#615817
Mendeliome v1.1561 WASHC4 Elena Savva Phenotypes for gene: WASHC4 were changed from Mental retardation, autosomal recessive 43, MIM #615817 to Intellectual developmental disorder, autosomal recessive 43 MIM#615817
Genetic Epilepsy v0.2315 WAC Elena Savva Marked gene: WAC as ready
Genetic Epilepsy v0.2315 WAC Elena Savva Gene: wac has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2315 WAC Elena Savva Classified gene: WAC as Green List (high evidence)
Genetic Epilepsy v0.2315 WAC Elena Savva Gene: wac has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2314 WAC Elena Savva gene: WAC was added
gene: WAC was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: WAC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WAC were set to PMID: 36420948
Phenotypes for gene: WAC were set to Desanto-Shinawi syndrome MIM#616708
Review for gene: WAC was set to GREEN
Added comment: Seizures (in some patients) listed in OMIM

PMID: 36420948 - reviews literature, describes seizures in 10/33 probands
Sources: Literature
Mendeliome v1.1560 UGGT1 Elena Savva Marked gene: UGGT1 as ready
Mendeliome v1.1560 UGGT1 Elena Savva Gene: uggt1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2313 UGGT1 Elena Savva Marked gene: UGGT1 as ready
Genetic Epilepsy v0.2313 UGGT1 Elena Savva Gene: uggt1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2313 UGGT1 Elena Savva gene: UGGT1 was added
gene: UGGT1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: UGGT1 was set to Unknown
Review for gene: UGGT1 was set to RED
Added comment: Gene was on the Oliver list for epilepsy genes.

No gene-disease association paper has been published.

GnomAD NOT constrained for LOF variants.
Sources: Literature
Mendeliome v1.1560 UGGT1 Elena Savva gene: UGGT1 was added
gene: UGGT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UGGT1 was set to Unknown
Review for gene: UGGT1 was set to RED
Added comment: Gene was on the Oliver list for epilepsy genes.

No gene-disease association paper has been published.

GnomAD NOT constrained for LOF variants.
Sources: Literature
Genetic Epilepsy v0.2312 UBTF Elena Savva Classified gene: UBTF as Amber List (moderate evidence)
Genetic Epilepsy v0.2312 UBTF Elena Savva Gene: ubtf has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2312 UBTF Elena Savva Classified gene: UBTF as Amber List (moderate evidence)
Genetic Epilepsy v0.2312 UBTF Elena Savva Gene: ubtf has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2311 UBTF Elena Savva Marked gene: UBTF as ready
Genetic Epilepsy v0.2311 UBTF Elena Savva Gene: ubtf has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2311 UBTF Elena Savva gene: UBTF was added
gene: UBTF was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: UBTF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: UBTF were set to PMID: 30517966
Phenotypes for gene: UBTF were set to Neurodegeneration, childhood-onset, with brain atrophy MIM#617672
Review for gene: UBTF was set to AMBER
Added comment: PMID: 30517966 - recurring de novo missense p.Glu210Lys, observed in 11 probands with neurodegeneration. 3/11 had seizures. Paper had an additional proband with this variant and drug-resistant epilepsy.
Sources: Literature
Fetal anomalies v1.196 FZD5 Zornitza Stark Phenotypes for gene: FZD5 were changed from Autosomal Dominant Coloboma to Microphthalmia/coloboma 11, MIM# 620731
Fetal anomalies v1.195 FZD5 Zornitza Stark Classified gene: FZD5 as Amber List (moderate evidence)
Fetal anomalies v1.195 FZD5 Zornitza Stark Gene: fzd5 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.194 FZD5 Zornitza Stark edited their review of gene: FZD5: Changed rating: AMBER
Fetal anomalies v1.194 FZD5 Zornitza Stark edited their review of gene: FZD5: Changed phenotypes: Microphthalmia/coloboma 11, MIM# 620731
Mendeliome v1.1559 FZD5 Zornitza Stark Phenotypes for gene: FZD5 were changed from Coloboma MONDO:0001476 to Microphthalmia/coloboma 11, MIM# 620731
Mendeliome v1.1558 FZD5 Zornitza Stark edited their review of gene: FZD5: Changed phenotypes: Microphthalmia/coloboma 11, MIM# 620731
Anophthalmia_Microphthalmia_Coloboma v1.39 FZD5 Zornitza Stark Phenotypes for gene: FZD5 were changed from Coloboma (MONDO:0001476), FZD5-related to Microphthalmia/coloboma 11, MIM# 620731
Anophthalmia_Microphthalmia_Coloboma v1.38 FZD5 Zornitza Stark edited their review of gene: FZD5: Changed phenotypes: Microphthalmia/coloboma 11, MIM# 620731
Metal Metabolism Disorders v0.37 STAB1 Zornitza Stark Phenotypes for gene: STAB1 were changed from Iron metabolism metabolism, MONDO:0002279, STAB1-related; Hyperferritinaemia without iron overload to Hyperferritinemia, MIM# 620729
Metal Metabolism Disorders v0.36 STAB1 Zornitza Stark reviewed gene: STAB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperferritinemia, MIM# 620729; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1558 STAB1 Zornitza Stark Phenotypes for gene: STAB1 were changed from Iron metabolism disease (MONDO:0002279), STAB1-related to Hyperferritinemia, MIM# 620729
Mendeliome v1.1557 STAB1 Zornitza Stark reviewed gene: STAB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperferritinemia, MIM# 620729; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia and Chorea v0.234 NAA15 Shekeeb Mohammad gene: NAA15 was added
gene: NAA15 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: NAA15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NAA15 were set to 38380600
Phenotypes for gene: NAA15 were set to dystonia; neurodevelopmental delay
Penetrance for gene: NAA15 were set to unknown
Review for gene: NAA15 was set to GREEN
Added comment: previous 3 cases in literature referenced in 38380600
Sources: Literature
Genetic Epilepsy v0.2310 PUM1 Zornitza Stark Phenotypes for gene: PUM1 were changed from Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719; Spinocerebellar ataxia 47, MIM# 617931 to Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Intellectual disability syndromic and non-syndromic v0.5704 PUM1 Zornitza Stark Phenotypes for gene: PUM1 were changed from Spinocerebellar ataxia 47, MIM#617931; intellectual disability; epilepsy to Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Intellectual disability syndromic and non-syndromic v0.5703 PUM1 Zornitza Stark edited their review of gene: PUM1: Changed phenotypes: Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Intellectual disability syndromic and non-syndromic v0.5703 PUM1 Zornitza Stark edited their review of gene: PUM1: Changed phenotypes: Spinocerebellar ataxia 47, MIM#617931, Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Genetic Epilepsy v0.2309 PUM1 Zornitza Stark Phenotypes for gene: PUM1 were changed from intellectual disability; epilepsy; Spinocerebellar ataxia 47, MIM# 617931 to Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719; Spinocerebellar ataxia 47, MIM# 617931
Genetic Epilepsy v0.2308 PUM1 Zornitza Stark edited their review of gene: PUM1: Changed phenotypes: Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Mendeliome v1.1557 PUM1 Zornitza Stark Phenotypes for gene: PUM1 were changed from Spinocerebellar ataxia 47, MIM# 617931; Neurodevelopmental disorder, MONDO:0700092, PUM1-related to Spinocerebellar ataxia 47, MIM# 617931; Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Mendeliome v1.1556 PUM1 Zornitza Stark Publications for gene: PUM1 were set to 29474920; 25768905; 30903679; 31859446
Mendeliome v1.1555 PUM1 Zornitza Stark edited their review of gene: PUM1: Changed phenotypes: Spinocerebellar ataxia 47, MIM# 617931, Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Genetic Epilepsy v0.2308 TWNK Elena Savva Classified gene: TWNK as Green List (high evidence)
Genetic Epilepsy v0.2308 TWNK Elena Savva Gene: twnk has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2307 TWNK Elena Savva Marked gene: TWNK as ready
Genetic Epilepsy v0.2307 TWNK Elena Savva Gene: twnk has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2307 TWNK Elena Savva gene: TWNK was added
gene: TWNK was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TWNK was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TWNK were set to PMID: 19304794
Phenotypes for gene: TWNK were set to Mitochondrial DNA depletion syndrome 7 (hepatocerebral type) MIM#271245; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 MIM#609286
Review for gene: TWNK was set to GREEN
Added comment: PMID: 19304794 - reviews, notes epilepsia partialis continua occurred in 15 patients leading to generalized epileptic statuses in 13/15. Probands had biallelic variants

OMIM lists Seizures (uncommon) as a phenotype for AD disease
Sources: Literature
Genetic Epilepsy v0.2306 TSEN34 Elena Savva gene: TSEN34 was added
gene: TSEN34 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TSEN34 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TSEN34 were set to Pontocerebellar hypoplasia type 2C, MIM#612390
Review for gene: TSEN34 was set to RED
Added comment: Gene was part of the Oliver list, no new publications
Sources: Literature
Genetic Epilepsy v0.2305 TSEN15 Elena Savva Marked gene: TSEN15 as ready
Genetic Epilepsy v0.2305 TSEN15 Elena Savva Gene: tsen15 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2305 TSEN15 Elena Savva Classified gene: TSEN15 as Amber List (moderate evidence)
Genetic Epilepsy v0.2305 TSEN15 Elena Savva Gene: tsen15 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2304 TSEN15 Elena Savva gene: TSEN15 was added
gene: TSEN15 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TSEN15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSEN15 were set to PMID: 27392077
Phenotypes for gene: TSEN15 were set to Pontocerebellar hypoplasia, type 2F MIM#617026
Review for gene: TSEN15 was set to AMBER
Added comment: Few patients reported with disease for this gene

PMID: 27392077 - 2/4 probands had seizures, onset <1 year old. Probands had homozygous missense, none had homs in v4 gnomAD. Functional studies support missense pathogenicity.
Sources: Literature
Mitochondrial disease v0.916 ACO2 Rylee Peters reviewed gene: ACO2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34056600; Phenotypes: Optic atrophy 9, MIM# 616289; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Optic Atrophy v1.27 ACO2 Rylee Peters reviewed gene: ACO2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34056600; Phenotypes: Optic atrophy 9, MIM# 616289; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.1555 ACO2 Rylee Peters reviewed gene: ACO2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34056600; Phenotypes: Optic atrophy 9, MIM# 616289; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genetic Epilepsy v0.2303 TRMT1 Elena Savva Classified gene: TRMT1 as Green List (high evidence)
Genetic Epilepsy v0.2303 TRMT1 Elena Savva Gene: trmt1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2302 TRMT1 Elena Savva Classified gene: TRMT1 as Green List (high evidence)
Genetic Epilepsy v0.2302 TRMT1 Elena Savva Gene: trmt1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2301 TRMT1 Elena Savva Marked gene: TRMT1 as ready
Genetic Epilepsy v0.2301 TRMT1 Elena Savva Gene: trmt1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2301 TRMT1 Elena Savva gene: TRMT1 was added
gene: TRMT1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TRMT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRMT1 were set to PMID: 31898845; 26308914; 30289604
Phenotypes for gene: TRMT1 were set to Intellectual developmental disorder, autosomal recessive 68 MIM#618302
Review for gene: TRMT1 was set to GREEN
Added comment: Rarely reported gene

Seizures (in some patients) described in OMIM.

PMID: 31898845 - homozygous missense in a proband with developmental delay, ID, and epilepsy. Functional studies support pathogenicity of the missense.

PMID: 26308914 - family with a homozygous PTC. The patients did not manifest any other neurological problems, ie. NO seizures.

PMID: 30289604 - two families (total 4 affected) with hom PTC and canonical splice. All had seizures.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5703 TRMT1 Elena Savva Phenotypes for gene: TRMT1 were changed from Mental retardation, autosomal recessive 68; OMIM #618302 to Intellectual developmental disorder, autosomal recessive 68 MIM#618302
Mendeliome v1.1555 TRMT1 Elena Savva Phenotypes for gene: TRMT1 were changed from Mental retardation, autosomal recessive 68; OMIM #618302 to Intellectual developmental disorder, autosomal recessive 68 MIM#618302
Genetic Epilepsy v0.2300 TRIT1 Elena Savva Marked gene: TRIT1 as ready
Genetic Epilepsy v0.2300 TRIT1 Elena Savva Gene: trit1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2300 TRIT1 Elena Savva Classified gene: TRIT1 as Green List (high evidence)
Genetic Epilepsy v0.2300 TRIT1 Elena Savva Gene: trit1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2299 TRIT1 Elena Savva gene: TRIT1 was added
gene: TRIT1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TRIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIT1 were set to PMID: 36047296; 36049610
Phenotypes for gene: TRIT1 were set to Combined oxidative phosphorylation deficiency 35 MIM#617873
Review for gene: TRIT1 was set to GREEN
Added comment: PMID: 36047296 - two probands with tonic–clonic seizures, as well as myoclonic seizures in patient 1. Both probands had chet PTC/missense.

PMID: 36049610 - two probands with seizures. Both probands had chet PTC/missense. Reviews, seizures reported in 100% (20/20) patients, including myoclonic epilepsy and febrile convulsions
Sources: Literature
Genetic Epilepsy v0.2298 TRIP12 Elena Savva Marked gene: TRIP12 as ready
Genetic Epilepsy v0.2298 TRIP12 Elena Savva Gene: trip12 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2298 TRIP12 Elena Savva Classified gene: TRIP12 as Amber List (moderate evidence)
Genetic Epilepsy v0.2298 TRIP12 Elena Savva Gene: trip12 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2297 TRIP12 Elena Savva gene: TRIP12 was added
gene: TRIP12 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TRIP12 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRIP12 were set to PMID: 36275919; 32424948
Phenotypes for gene: TRIP12 were set to Intellectual developmental disorder, autosomal dominant 49 MIM#617752
Review for gene: TRIP12 was set to AMBER
Added comment: Seizures described as a rare feature in OMIM

PMID: 36275919 - patient with GDD, hypotonia and intermittent seizures. De novo synonymous variant with proven splice outcome found.

PMID: 32424948 - reviews, epilepsy observed in 21% (5/24) patients
Sources: Literature
Genetic Epilepsy v0.2296 TRIO Elena Savva Classified gene: TRIO as Green List (high evidence)
Genetic Epilepsy v0.2296 TRIO Elena Savva Gene: trio has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2295 TRIO Elena Savva Marked gene: TRIO as ready
Genetic Epilepsy v0.2295 TRIO Elena Savva Gene: trio has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2295 TRIO Elena Savva gene: TRIO was added
gene: TRIO was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TRIO was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: TRIO were set to Intellectual developmental disorder, autosomal dominant 44, with microcephaly MIM#617061; Intellectual developmental disorder, autosomal dominant 63, with macrocephaly MIM#618825
Review for gene: TRIO was set to GREEN
Added comment: Seizures described in OMIM as a rare feature of both AR and AD disease

GeneReviews: seizures described in 7/19 probands with GOF variants, and 7/29 in individuals with LOF variants. Only one in ten individuals with a TRIO missense variant in the GEFD1 domain had seizures
Sources: Literature
Genetic Epilepsy v0.2294 TREM2 Elena Savva Classified gene: TREM2 as Green List (high evidence)
Genetic Epilepsy v0.2294 TREM2 Elena Savva Gene: trem2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2294 TREM2 Elena Savva Classified gene: TREM2 as Green List (high evidence)
Genetic Epilepsy v0.2294 TREM2 Elena Savva Gene: trem2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2293 TREM2 Elena Savva Marked gene: TREM2 as ready
Genetic Epilepsy v0.2293 TREM2 Elena Savva Gene: trem2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2293 TREM2 Elena Savva gene: TREM2 was added
gene: TREM2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TREM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TREM2 were set to PMID: 36820836; 24910390
Phenotypes for gene: TREM2 were set to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 MIM#618193
Review for gene: TREM2 was set to GREEN
Added comment: PMID: 36820836 - adult with repetitive seizures with a homozygous missense variant. Sibling also affected. No functional studies.

PMID: 24910390 - two siblings with a hom missense, no seizures reported. Summary of literature notes epilepsy in 75% of probands.

Seizures listed in OMIM
Sources: Literature
Genetic Epilepsy v0.2292 TPK1 Elena Savva Marked gene: TPK1 as ready
Genetic Epilepsy v0.2292 TPK1 Elena Savva Gene: tpk1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2292 TPK1 Elena Savva Classified gene: TPK1 as Green List (high evidence)
Genetic Epilepsy v0.2292 TPK1 Elena Savva Gene: tpk1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2291 TPK1 Elena Savva gene: TPK1 was added
gene: TPK1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TPK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPK1 were set to PMID: 37622082
Phenotypes for gene: TPK1 were set to Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type) MIM#614458
Review for gene: TPK1 was set to GREEN
Added comment: PMID: 37622082
- proband 1 had a single convulsive seizure after fever, rashes. Diagnosed with leigh syndrome. Was chet for a PTC and missense.
- proband 2 had frequent tonic seizures, Was chet for a PTC and missense.
Review of literature found seizure (10/28, 35.71%) of reported cases
Sources: Literature
Neurodegeneration with brain iron accumulation v0.32 Bryony Thompson Panel name changed from Neuroferritinopathies to Neurodegeneration with brain iron accumulation
Early-onset Parkinson disease v0.294 FTL Bryony Thompson Publications for gene: FTL were set to 23447832; 20301320
Early-onset Parkinson disease v0.293 FTL Bryony Thompson Publications for gene: FTL were set to
Early-onset Parkinson disease v0.292 FTL Bryony Thompson Mode of inheritance for gene: FTL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Classified gene: FTL as Green List (high evidence)
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Added comment: Comment on list classification: Parkinsonism can be a presenting feature of the condition
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Gene: ftl has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Classified gene: FTL as Green List (high evidence)
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Added comment: Comment on list classification: Parkinsonism can be a presenting feature of the condition
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Gene: ftl has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.290 TAF1 Bryony Thompson Tag STR tag was added to gene: TAF1.
Early-onset Parkinson disease v0.290 FBXO7 Bryony Thompson Marked gene: FBXO7 as ready
Early-onset Parkinson disease v0.290 FBXO7 Bryony Thompson Gene: fbxo7 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.290 FBXO7 Bryony Thompson Publications for gene: FBXO7 were set to
Early-onset Parkinson disease v0.289 FBXO7 Bryony Thompson Phenotypes for gene: FBXO7 were changed from to parkinsonian-pyramidal syndrome MONDO:0009830
Early-onset Parkinson disease v0.288 FBXO7 Bryony Thompson Mode of inheritance for gene: FBXO7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.287 DNAJC6 Bryony Thompson Marked gene: DNAJC6 as ready
Early-onset Parkinson disease v0.287 DNAJC6 Bryony Thompson Gene: dnajc6 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.287 DNAJC6 Bryony Thompson Phenotypes for gene: DNAJC6 were changed from to juvenile onset Parkinson disease 19A MONDO:0014231
Early-onset Parkinson disease v0.286 DNAJC6 Bryony Thompson Publications for gene: DNAJC6 were set to
Early-onset Parkinson disease v0.285 DNAJC6 Bryony Thompson Mode of inheritance for gene: DNAJC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.284 DCTN1 Bryony Thompson Marked gene: DCTN1 as ready
Early-onset Parkinson disease v0.284 DCTN1 Bryony Thompson Gene: dctn1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.284 DCTN1 Bryony Thompson Phenotypes for gene: DCTN1 were changed from Perry syndrome MONDO:0008201 to Perry syndrome MONDO:0008201
Early-onset Parkinson disease v0.283 DCTN1 Bryony Thompson Phenotypes for gene: DCTN1 were changed from to Perry syndrome MONDO:0008201
Early-onset Parkinson disease v0.282 DCTN1 Bryony Thompson Publications for gene: DCTN1 were set to 20945553
Early-onset Parkinson disease v0.282 DCTN1 Bryony Thompson Publications for gene: DCTN1 were set to
Early-onset Parkinson disease v0.281 DCTN1 Bryony Thompson Mode of inheritance for gene: DCTN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.281 DCTN1 Bryony Thompson Mode of inheritance for gene: DCTN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.280 DCTN1 Bryony Thompson Mode of inheritance for gene: DCTN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.280 DCTN1 Bryony Thompson Classified gene: DCTN1 as Green List (high evidence)
Early-onset Parkinson disease v0.280 DCTN1 Bryony Thompson Added comment: Comment on list classification: Parkinsonism is a characteristic feature of Perry syndrome
Early-onset Parkinson disease v0.280 DCTN1 Bryony Thompson Gene: dctn1 has been classified as Green List (High Evidence).
Fetal anomalies v1.194 NEK1 Zornitza Stark Phenotypes for gene: NEK1 were changed from Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520 to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Orofaciodigital syndrome II , MIM# 252100
Fetal anomalies v1.193 NEK1 Zornitza Stark Publications for gene: NEK1 were set to 21211617; 22499340; 25492405; 28123176
Fetal anomalies v1.192 NEK1 Zornitza Stark edited their review of gene: NEK1: Added comment: Single family with OFD phenotype.; Changed publications: 21211617, 22499340, 25492405, 28123176, 27530628; Changed phenotypes: Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520, Orofaciodigital syndrome II , MIM# 252100
Clefting disorders v0.252 NEK1 Zornitza Stark Marked gene: NEK1 as ready
Clefting disorders v0.252 NEK1 Zornitza Stark Gene: nek1 has been classified as Green List (High Evidence).
Clefting disorders v0.252 NEK1 Zornitza Stark Phenotypes for gene: NEK1 were changed from SHORT-RIB THORACIC DYSPLASIA 6 WITH OR WITHOUT POLYDACTYLY; SRTD6 to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Orofaciodigital syndrome II , MIM# 252100
Clefting disorders v0.251 NEK1 Zornitza Stark Publications for gene: NEK1 were set to
Clefting disorders v0.250 NEK1 Zornitza Stark reviewed gene: NEK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21211617, 22499340, 25492405, 28123176, 27530628; Phenotypes: Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520, Orofaciodigital syndrome II , MIM# 252100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1554 NEK1 Zornitza Stark Phenotypes for gene: NEK1 were changed from Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Amyotrophic lateral sclerosis, susceptibility to, 24, MIM# 617892 to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Orofaciodigital syndrome II , MIM# 252100; Amyotrophic lateral sclerosis, susceptibility to, 24, MIM# 617892
Mendeliome v1.1553 NEK1 Zornitza Stark Publications for gene: NEK1 were set to 21211617; 22499340; 25492405; 28123176; 33445179
Mendeliome v1.1552 NEK1 Zornitza Stark edited their review of gene: NEK1: Added comment: PMID 27530628: two brothers with OFD phenotype.; Changed publications: 21211617, 22499340, 25492405, 28123176, 27530628; Changed phenotypes: Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520, Orofaciodigital syndrome II , MIM# 252100, Amyotrophic lateral sclerosis, susceptibility to, 24, MIM# 617892
Ciliopathies v1.51 NEK1 Zornitza Stark Phenotypes for gene: NEK1 were changed from Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520 to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Orofaciodigital syndrome II , MIM# 252100
Ciliopathies v1.50 NEK1 Zornitza Stark Publications for gene: NEK1 were set to 21211617; 22499340; 25492405; 28123176
Ciliopathies v1.49 NEK1 Zornitza Stark edited their review of gene: NEK1: Added comment: PMID 27530628: two brothers with OFD phenotype.; Changed publications: 21211617, 22499340, 25492405, 28123176, 27530628; Changed phenotypes: Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520, Orofaciodigital syndrome II , MIM# 252100
Mendeliome v1.1552 HMBS Zornitza Stark Phenotypes for gene: HMBS were changed from Porphyria, acute intermittent, MIM#176000; Porphyria, acute intermittent, non-erythroid variant, MIM#176000 to Porphyria, acute intermittent, MIM#176000; Porphyria, acute intermittent, non-erythroid variant, MIM#176000; Encephalopathy, porphyria-related MIM#620704; Leukoencephalopathy, porphyria-related, MIM#620711
Mendeliome v1.1551 HMBS Zornitza Stark edited their review of gene: HMBS: Changed phenotypes: Porphyria, acute intermittent, MIM#176000, Porphyria, acute intermittent, non-erythroid variant, MIM#176000, Encephalopathy, porphyria-related MIM#620704, Leukoencephalopathy, porphyria-related, MIM#620711
Regression v0.544 HMBS Zornitza Stark Marked gene: HMBS as ready
Regression v0.544 HMBS Zornitza Stark Gene: hmbs has been classified as Green List (High Evidence).
Regression v0.544 HMBS Zornitza Stark Phenotypes for gene: HMBS were changed from to Encephalopathy, porphyria-related MIM#620704; Leukoencephalopathy, porphyria-related, MIM#620711
Regression v0.543 HMBS Zornitza Stark Mode of inheritance for gene: HMBS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.542 HMBS Zornitza Stark reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Encephalopathy, porphyria-related MIM#620704, Leukoencephalopathy, porphyria-related, MIM#620711; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5702 HMBS Zornitza Stark Marked gene: HMBS as ready
Intellectual disability syndromic and non-syndromic v0.5702 HMBS Zornitza Stark Gene: hmbs has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5702 HMBS Zornitza Stark Publications for gene: HMBS were set to 15534187
Intellectual disability syndromic and non-syndromic v0.5701 HMBS Zornitza Stark Classified gene: HMBS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5701 HMBS Zornitza Stark Gene: hmbs has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5700 HMBS Zornitza Stark edited their review of gene: HMBS: Changed publications: 15534187, 34089223; Changed phenotypes: Encephalopathy, porphyria-related MIM#620704, Leukoencephalopathy, porphyria-related, MIM#620711
Intellectual disability syndromic and non-syndromic v0.5700 HMBS Zornitza Stark gene: HMBS was added
gene: HMBS was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: HMBS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HMBS were set to 15534187
Phenotypes for gene: HMBS were set to Encephalopathy, porphyria-related MIM#620704; Leukoencephalopathy, porphyria-related, MIM#620711
Review for gene: HMBS was set to GREEN
Added comment: Several families reported with encephalopathy/leukoencephalopathy and ballelic variants in this gene.
Sources: Expert Review
Leukodystrophy v0.305 HMBS Zornitza Stark Phenotypes for gene: HMBS were changed from Porphyria, acute intermittent, MIM#176000; Acute intermittent porphyria-related leukoencephalopathy to Leukoencephalopathy, porphyria-related, MIM# 620711
Leukodystrophy v0.304 HMBS Zornitza Stark edited their review of gene: HMBS: Changed phenotypes: Leukoencephalopathy, porphyria-related, MIM# 620711
Intellectual disability syndromic and non-syndromic v0.5699 DDX3X Abhijit Kulkarni edited their review of gene: DDX3X: Changed publications: PMID: 32135084, 32852922
Intellectual disability syndromic and non-syndromic v0.5699 DDX3X Abhijit Kulkarni changed review comment from: Genotype-Phenotype Correlations

Females. Affected females with a subset of missense variants generally are more severely affected than those with truncating variants [Lennox et al 2020].

Polymicrogyria has been associated with missense or in-frame deletions [Lennox et al 2020].

Males. While all affected males have had missense DDX3X variants (see Table 6), their female relatives who are heterozygous for the same DDX3X variant do not manifest an atypical neurodevelopmental phenotype.; to: Genotype-Phenotype Correlations

Females. Affected females with a subset of missense variants generally are more severely affected than those with truncating variants PMID: 32135084

Polymicrogyria has been associated with missense or in-frame deletions PMID: 32135084

Males. While all affected males have had missense DDX3X variants , their female relatives who are heterozygous for the same DDX3X variant do not manifest an atypical neurodevelopmental phenotype.
Intellectual disability syndromic and non-syndromic v0.5699 DDX3X Abhijit Kulkarni commented on gene: DDX3X
Mendeliome v1.1551 LCP2 Achchuthan Shanmugasundram reviewed gene: LCP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37211057; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.172 MYO3A Zornitza Stark Phenotypes for gene: MYO3A were changed from Deafness, autosomal recessive 30, MIM# 607101; dominant deafness to Deafness, autosomal recessive 30, MIM# 607101; Deafness, autosomal dominant 90, MIM# 620722
Deafness_IsolatedAndComplex v1.171 MYO3A Zornitza Stark edited their review of gene: MYO3A: Changed phenotypes: Deafness, autosomal recessive 30, MIM# 607101, Deafness, autosomal dominant 90, MIM# 620722
Mendeliome v1.1551 MYO3A Zornitza Stark Phenotypes for gene: MYO3A were changed from Deafness, autosomal recessive 30 OMIM:607101; autosomal recessive nonsyndromic deafness 30 MONDO:0011774; dominant deafness to Deafness, autosomal recessive 30, MIM# 607101; Deafness, autosomal dominant 90, MIM# 620722
Mendeliome v1.1550 MYO3A Zornitza Stark edited their review of gene: MYO3A: Changed phenotypes: Deafness, autosomal recessive 30, MIM# 607101, Deafness, autosomal dominant 90, MIM# 620722
Deafness_IsolatedAndComplex v1.171 TMTC2 Zornitza Stark Phenotypes for gene: TMTC2 were changed from Deafness, autosomal dominant to Deafness, autosomal dominant; Deafness, autosomal recessive 122, MIM# 620714
Deafness_IsolatedAndComplex v1.170 TMTC2 Zornitza Stark Publications for gene: TMTC2 were set to
Deafness_IsolatedAndComplex v1.169 TMTC2 Zornitza Stark Mode of inheritance for gene: TMTC2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.168 TMTC2 Zornitza Stark commented on gene: TMTC2: Single family reported with bi-allelic variants. Mouse model.
Deafness_IsolatedAndComplex v1.168 TMTC2 Zornitza Stark edited their review of gene: TMTC2: Changed publications: 29671961, 27311106, 37943620, 30188326; Changed phenotypes: Deafness, autosomal recessive 122, MIM# 620714; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1550 TMTC2 Zornitza Stark Phenotypes for gene: TMTC2 were changed from Deafness to Deafness, autosomal recessive 122, MIM# 620714
Mendeliome v1.1549 TMTC2 Zornitza Stark Publications for gene: TMTC2 were set to 29671961; 27311106
Mendeliome v1.1548 TMTC2 Zornitza Stark Mode of inheritance for gene: TMTC2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1547 TMTC2 Zornitza Stark edited their review of gene: TMTC2: Added comment: Single family reported with bi-allelic variants.

Mouse model.; Changed publications: 29671961, 27311106, 37943620, 30188326; Changed phenotypes: Deafness, autosomal recessive 122, MIM# 620714; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Autism v0.196 TMLHE Bryony Thompson Classified gene: TMLHE as Red List (low evidence)
Autism v0.196 TMLHE Bryony Thompson Added comment: Comment on list classification: ClinGen Disputed gene-disease association Classification - 03/02/2021 by ID & Autism GCEP: https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_7a780ea6-ad4e-417a-a596-27188e327aad-2021-03-02T050000.000Z?page=1&size=25&search=
Autism v0.196 TMLHE Bryony Thompson Gene: tmlhe has been classified as Red List (Low Evidence).
Mendeliome v1.1547 TMLHE Bryony Thompson Classified gene: TMLHE as Red List (low evidence)
Mendeliome v1.1547 TMLHE Bryony Thompson Added comment: Comment on list classification: ClinGen Disputed gene-disease association Classification - 03/02/2021 by ID & Autism GCEP: https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_7a780ea6-ad4e-417a-a596-27188e327aad-2021-03-02T050000.000Z?page=1&size=25&search=
Mendeliome v1.1547 TMLHE Bryony Thompson Gene: tmlhe has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5699 TMLHE Bryony Thompson Classified gene: TMLHE as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5699 TMLHE Bryony Thompson Added comment: Comment on list classification: ClinGen Disputed gene-disease association Classification - 03/02/2021 by ID & Autism GCEP: https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_7a780ea6-ad4e-417a-a596-27188e327aad-2021-03-02T050000.000Z?page=1&size=25&search=
Intellectual disability syndromic and non-syndromic v0.5699 TMLHE Bryony Thompson Gene: tmlhe has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.279 CSF1R Bryony Thompson Marked gene: CSF1R as ready
Early-onset Parkinson disease v0.279 CSF1R Bryony Thompson Gene: csf1r has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.279 CSF1R Bryony Thompson Phenotypes for gene: CSF1R were changed from to leukoencephalopathy, diffuse hereditary, with spheroids 1 MONDO:0800027
Early-onset Parkinson disease v0.278 CSF1R Bryony Thompson Publications for gene: CSF1R were set to
Early-onset Parkinson disease v0.277 CSF1R Bryony Thompson Mode of inheritance for gene: CSF1R was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.276 CSF1R Bryony Thompson Classified gene: CSF1R as Green List (high evidence)
Early-onset Parkinson disease v0.276 CSF1R Bryony Thompson Added comment: Comment on list classification: Parkinsonian signs can be a feature on the condition
Early-onset Parkinson disease v0.276 CSF1R Bryony Thompson Gene: csf1r has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.275 C19orf12 Bryony Thompson Marked gene: C19orf12 as ready
Early-onset Parkinson disease v0.275 C19orf12 Bryony Thompson Gene: c19orf12 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.275 C19orf12 Bryony Thompson Phenotypes for gene: C19orf12 were changed from to neurodegeneration with brain iron accumulation 4 MONDO:0013674
Early-onset Parkinson disease v0.274 C19orf12 Bryony Thompson Publications for gene: C19orf12 were set to
Early-onset Parkinson disease v0.273 C19orf12 Bryony Thompson Mode of inheritance for gene: C19orf12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.272 ATP1A3 Bryony Thompson Marked gene: ATP1A3 as ready
Early-onset Parkinson disease v0.272 ATP1A3 Bryony Thompson Gene: atp1a3 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.272 ATP1A3 Bryony Thompson Phenotypes for gene: ATP1A3 were changed from to ATP1A3-associated neurological disorder MONDO:0700002
Early-onset Parkinson disease v0.271 ATP1A3 Bryony Thompson Publications for gene: ATP1A3 were set to
Early-onset Parkinson disease v0.270 ATP1A3 Bryony Thompson Mode of inheritance for gene: ATP1A3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.269 ATP1A3 Bryony Thompson Classified gene: ATP1A3 as Green List (high evidence)
Early-onset Parkinson disease v0.269 ATP1A3 Bryony Thompson Added comment: Comment on list classification: Parkinsonism is a major feature of the condition
Early-onset Parkinson disease v0.269 ATP1A3 Bryony Thompson Gene: atp1a3 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.268 ATP13A2 Bryony Thompson Marked gene: ATP13A2 as ready
Early-onset Parkinson disease v0.268 ATP13A2 Bryony Thompson Gene: atp13a2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.268 ATP13A2 Bryony Thompson Phenotypes for gene: ATP13A2 were changed from to parkinsonism due to ATP13A2 deficiency MONDO:0017809
Early-onset Parkinson disease v0.267 ATP13A2 Bryony Thompson Publications for gene: ATP13A2 were set to
Early-onset Parkinson disease v0.266 ATP13A2 Bryony Thompson Mode of inheritance for gene: ATP13A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.275 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Skeletal dysplasia v0.271 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Skeletal Dysplasia_Fetal v0.217 LFNG Elena Savva Marked gene: LFNG as ready
Skeletal Dysplasia_Fetal v0.217 LFNG Elena Savva Gene: lfng has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.217 LFNG Elena Savva Phenotypes for gene: LFNG were changed from to Spondylocostal dysostosis 3, autosomal recessive, MIM#609813
Skeletal Dysplasia_Fetal v0.216 LFNG Elena Savva Publications for gene: LFNG were set to
Skeletal Dysplasia_Fetal v0.216 LFNG Elena Savva Mode of inheritance for gene: LFNG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.270 LFNG Elena Savva Marked gene: LFNG as ready
Skeletal dysplasia v0.270 LFNG Elena Savva Gene: lfng has been classified as Green List (High Evidence).
Skeletal dysplasia v0.270 LFNG Elena Savva Publications for gene: LFNG were set to 30196550; 16385447
Skeletal dysplasia v0.270 LFNG Elena Savva Phenotypes for gene: LFNG were changed from Spondylocostal dysostosis 3, autosomal recessive 609813 to Spondylocostal dysostosis 3, autosomal recessive MIM#609813
Skeletal dysplasia v0.269 LFNG Elena Savva Classified gene: LFNG as Green List (high evidence)
Skeletal dysplasia v0.269 LFNG Elena Savva Gene: lfng has been classified as Green List (High Evidence).
Polydactyly v0.274 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Polydactyly v0.274 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Polydactyly v0.273 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Polydactyly v0.273 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Polydactyly v0.272 RAB34 Elena Savva Marked gene: RAB34 as ready
Polydactyly v0.272 RAB34 Elena Savva Gene: rab34 has been classified as Red List (Low Evidence).
Polydactyly v0.272 RAB34 Elena Savva gene: RAB34 was added
gene: RAB34 was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to 37619988; 37384395
Phenotypes for gene: RAB34 were set to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Review for gene: RAB34 was set to GREEN
Added comment: PMID: 37619988
- Compound heterozygous variants identified in a fetus with multiple malformations, including a combination of rarely occurring pre- and postaxial polydactyly.
- Rab34-/- mice displayed polydactyly.

PMID: 37384395
- Biallelic variants in RAB34 were identified in 3 unrelated families. All affected individuals presented a novel form of OFDS accompanied by prexial and central polydactyly/bilateral polysyndactyly
Sources: Literature
Skeletal dysplasia v0.268 RAB34 Elena Savva Marked gene: RAB34 as ready
Skeletal dysplasia v0.268 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.268 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Skeletal dysplasia v0.268 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.267 RAB34 Elena Savva gene: RAB34 was added
gene: RAB34 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to 37619988; 37384395
Phenotypes for gene: RAB34 were set to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Review for gene: RAB34 was set to GREEN
Added comment: PMID: 37619988
- Compound heterozygous variants identified in RAB34 in a fetus with multiple malformations, including posterior neck edema, micrognathia, low-set and small ears, auricular hypoplasia, cleft lip and palate, short extremities, and a combination of rarely occurring pre- and postaxial polydactyly.
- Rab34-/- mice displayed a ciliopathy phenotype with cleft palate and polydactyly.

PMID: 37384395
- Biallelic variants in RAB34 were identified in 3 unrelated families. Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects. Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, and brain malformations), resulting in medical termination for three probands.
Sources: Literature
Skeletal Dysplasia_Fetal v0.215 KIAA0586 Elena Savva Publications for gene: KIAA0586 were set to
Skeletal dysplasia v0.266 KIAA0586 Elena Savva Classified gene: KIAA0586 as Green List (high evidence)
Skeletal dysplasia v0.266 KIAA0586 Elena Savva Gene: kiaa0586 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.214 KIAA0586 Elena Savva Phenotypes for gene: KIAA0586 were changed from to Joubert syndrome 23 MIM#616490; Short-rib thoracic dysplasia 14 with polydactyly MIM#616546
Skeletal dysplasia v0.266 KIAA0586 Elena Savva Classified gene: KIAA0586 as Green List (high evidence)
Skeletal dysplasia v0.266 KIAA0586 Elena Savva Gene: kiaa0586 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.214 KIAA0586 Elena Savva Mode of inheritance for gene: KIAA0586 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.265 KIAA0586 Elena Savva Marked gene: KIAA0586 as ready
Skeletal dysplasia v0.265 KIAA0586 Elena Savva Gene: kiaa0586 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.265 KIAA0586 Elena Savva gene: KIAA0586 was added
gene: KIAA0586 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: KIAA0586 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0586 were set to PMID: 36538006; 26096313; 26166481
Phenotypes for gene: KIAA0586 were set to Joubert syndrome 23 MIM#616490; Short-rib thoracic dysplasia 14 with polydactyly MIM#616546
Review for gene: KIAA0586 was set to GREEN
Added comment: PMID: 36538006 - fetus with post-axial polydactyly, short limbs and persistent left superior vena cava (PLSVC) with a dilated coronary sinus. Chet variants c.3940+1G>A
and c.3303G>A (synonymous) were identified. Functional studies support an impact for both variants.

PMID: 26096313 - 9 unrelated families with Joubert syndrome. MRI shows the molar tooth sign in 3/3 scanned patients. Patients tended to have biallelic PTCs, though missense also reported. p.Arg143Lysfs*4 appears to be a recurring mutation, seen in patients either as a homozygote or in chet with another unique mutation in 7/9 families. Interestingly these 7 families were of different ethnicity

PMID: 26166481 - Four unrelated families reported with a severe neurological/skeletal phenotype. However, note same variant identified in three of the families, indicative of founder effect. Gene is also associated with Joubert syndrome.
Sources: Literature
Skeletal dysplasia v0.264 HYLS1 Elena Savva Marked gene: HYLS1 as ready
Skeletal dysplasia v0.264 HYLS1 Elena Savva Gene: hyls1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.264 HYLS1 Elena Savva Phenotypes for gene: HYLS1 were changed from to Hydrolethalus syndrome MIM#236680
Skeletal dysplasia v0.264 HYLS1 Elena Savva Publications for gene: HYLS1 were set to
Skeletal dysplasia v0.263 HYLS1 Elena Savva Classified gene: HYLS1 as Amber List (moderate evidence)
Skeletal dysplasia v0.263 HYLS1 Elena Savva Gene: hyls1 has been classified as Amber List (Moderate Evidence).
Skeletal Dysplasia_Fetal v0.213 HYLS1 Elena Savva Publications for gene: HYLS1 were set to 15843405; 18648327; 19400947; 19656802; 32509774; 26830932
Skeletal Dysplasia_Fetal v0.212 HYLS1 Elena Savva edited their review of gene: HYLS1: Added comment: PMID: 34212369 - additional two fetuses with a phenotype of HLS with brain abnormalities, limbs malformations with pre and postaxial hexadactyly and abnormal genitalia. Probands were het for the Finnish founder variant (p.Asp211Gly) but each chet with a novel variant (p.(Arg221Pro, p.(Arg205*)). One fetus had occipital meningocele
molar tooth sign, the other craniorachischisis; Changed publications: PMID: 26830932, 34212369, 15843405, 18648327, 19400947, 19656802, 32509774; Changed phenotypes: Hydrolethalus syndrome MIM#236680
Prepair 1000+ v1.4 PIEZO1 Crystle Lee gene: PIEZO1 was added
gene: PIEZO1 was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: PIEZO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIEZO1 were set to PMID: 26333996
Phenotypes for gene: PIEZO1 were set to Lymphatic malformation 6, MIM#616843
Review for gene: PIEZO1 was set to GREEN
Added comment: Biallelic mutations in PIEZO1 reported in 10 patients from 6 families with generalized lymphatic dysplasia (GLD) This is characterized by a uniform, widespread lymphedema affecting all segments of the body, with systemic involvement such as intestinal and/or pulmonary lymphangiectasia, pleural effusions, chylothoraces and/or pericardial effusions.
Sources: Literature
Mendeliome v1.1546 ANKZF1 Zornitza Stark reviewed gene: ANKZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28302725, 36857589; Phenotypes: Infantile-onset inflammatory bowel disease, MONDO:0005265, ANKZF1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Inflammatory bowel disease v0.118 ANKZF1 Zornitza Stark Publications for gene: ANKZF1 were set to 28302725
Inflammatory bowel disease v0.117 ANKZF1 Zornitza Stark Mode of inheritance for gene: ANKZF1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Inflammatory bowel disease v0.116 ANKZF1 Zornitza Stark Classified gene: ANKZF1 as Green List (high evidence)
Inflammatory bowel disease v0.116 ANKZF1 Zornitza Stark Gene: ankzf1 has been classified as Green List (High Evidence).
Mendeliome v1.1546 CARD8 Zornitza Stark Classified gene: CARD8 as Amber List (moderate evidence)
Mendeliome v1.1546 CARD8 Zornitza Stark Gene: card8 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1545 CARD8 Zornitza Stark edited their review of gene: CARD8: Added comment: Additional individual reported with JRA and IBD.; Changed rating: AMBER; Changed publications: 29408806, 37724393
Inflammatory bowel disease v0.115 CARD8 Zornitza Stark Classified gene: CARD8 as Amber List (moderate evidence)
Inflammatory bowel disease v0.115 CARD8 Zornitza Stark Gene: card8 has been classified as Amber List (Moderate Evidence).
Inflammatory bowel disease v0.114 HSPA1L Zornitza Stark Marked gene: HSPA1L as ready
Inflammatory bowel disease v0.114 HSPA1L Zornitza Stark Gene: hspa1l has been classified as Amber List (Moderate Evidence).
Inflammatory bowel disease v0.114 HSPA1L Zornitza Stark Classified gene: HSPA1L as Amber List (moderate evidence)
Inflammatory bowel disease v0.114 HSPA1L Zornitza Stark Gene: hspa1l has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.192 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Clefting disorders v0.250 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Callosome v0.516 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Skeletal Ciliopathies v1.12 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Orofaciodigital syndrome 20, MIM#620718 to Orofaciodigital syndrome 20, MIM#620718
Skeletal Ciliopathies v1.11 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Radial Ray Abnormalities v1.10 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Mendeliome v1.1545 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Ciliopathies v1.49 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Skeletal Dysplasia_Fetal v0.212 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Skeletal Dysplasia_Fetal v0.211 RAB34 Zornitza Stark reviewed gene: RAB34: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Orofaciodigital syndrome 20, MIM#620718; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1544 ONECUT1 Bryony Thompson Marked gene: ONECUT1 as ready
Mendeliome v1.1544 ONECUT1 Bryony Thompson Gene: onecut1 has been classified as Green List (High Evidence).
Mendeliome v1.1544 ONECUT1 Bryony Thompson Classified gene: ONECUT1 as Green List (high evidence)
Mendeliome v1.1544 ONECUT1 Bryony Thompson Gene: onecut1 has been classified as Green List (High Evidence).
Mendeliome v1.1543 ONECUT1 Bryony Thompson gene: ONECUT1 was added
gene: ONECUT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ONECUT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ONECUT1 were set to 37639628; 34663987; 10825208
Phenotypes for gene: ONECUT1 were set to Neonatal diabetes mellitus MONDO:0016391
Review for gene: ONECUT1 was set to GREEN
Added comment: 3 unrelated neonatal diabetes cases with homozygous variants & supporting iPSC/mouse models
PMID: 37639628 - UK biobank study of ONECUT1 variants in neonatal diabetes mellitus (NDM), MODY, and type 2 diabetes. Identified a case with syndromic NDM with a homozygous frameshift (p.Met289Argfs*8). Rare heterozygous variants were not enriched in individuals with suspected MODY (n=484). Heterozygous null variants were significantly associated with type 2 diabetes (p=0.006) as a potential susceptibility gene.

PMID: 34663987 - 2 consanguineous families with homozygous variants (Glu231Ter or Glu231Asp) in cases with syndromic ND. Directed differentiation of human pluripotent stem cells revealed that loss of ONECUT1 impairs pancreatic progenitor formation.

PMID: 10825208 - Hnf6 (old gene name) null mice have diabetes
Sources: Literature
Monogenic Diabetes v0.46 ONECUT1 Bryony Thompson Marked gene: ONECUT1 as ready
Monogenic Diabetes v0.46 ONECUT1 Bryony Thompson Gene: onecut1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.46 ONECUT1 Bryony Thompson Phenotypes for gene: ONECUT1 were changed from Syndromic diabetes to Syndromic diabetes; Neonatal diabetes mellitus MONDO:0016391
Monogenic Diabetes v0.45 ONECUT1 Bryony Thompson Publications for gene: ONECUT1 were set to PMID: 34663987
Monogenic Diabetes v0.44 ONECUT1 Bryony Thompson Classified gene: ONECUT1 as Green List (high evidence)
Monogenic Diabetes v0.44 ONECUT1 Bryony Thompson Gene: onecut1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.43 ONECUT1 Bryony Thompson reviewed gene: ONECUT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37639628, 34663987, 10825208; Phenotypes: Neonatal diabetes mellitus MONDO:0016391; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inflammatory bowel disease v0.113 HSPA1L Zornitza Stark gene: HSPA1L was added
gene: HSPA1L was added to Inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: HSPA1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HSPA1L were set to 28126021
Phenotypes for gene: HSPA1L were set to inflammatory bowel disease, MONDO:0005265, HSPA1L-related
Review for gene: HSPA1L was set to AMBER
Added comment: PMID:28126021 reported the identification of a heterozygous de novo variant (p.Ser277Leu) in HSPA1L in a patient with inflammatory bowel disease. In addition, five additional rare HSPA1L variants (p.Gly77Ser, p.Leu172del, p.Thr267Ile, p.Ala268Thr, p.Glu558Asp) were identified in six patients from a cohort of 136 IBD patients with WES data. Functional studies showed that all six HSPA1L variant proteins showed decreased chaperone activity in vitro. Moreover, three variants demonstrated dominant negative effects on HSPA1L and HSPA1A protein activity.

However, the variants identified are present at relatively high frequencies in gnomad V4, in particular p.Thr267Ile is present in 281 individuals, and the p.Ala268Thr is present in 4,753 individuals.
Sources: Literature
Mendeliome v1.1542 HSPA1L Zornitza Stark Marked gene: HSPA1L as ready
Mendeliome v1.1542 HSPA1L Zornitza Stark Gene: hspa1l has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1542 HSPA1L Zornitza Stark Classified gene: HSPA1L as Amber List (moderate evidence)
Mendeliome v1.1542 HSPA1L Zornitza Stark Gene: hspa1l has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1541 HSPA1L Zornitza Stark reviewed gene: HSPA1L: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: inflammatory bowel disease, MONDO:0005265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autoinflammatory Disorders v1.34 SCGN Zornitza Stark Marked gene: SCGN as ready
Autoinflammatory Disorders v1.34 SCGN Zornitza Stark Gene: scgn has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v1.34 SCGN Zornitza Stark Classified gene: SCGN as Amber List (moderate evidence)
Autoinflammatory Disorders v1.34 SCGN Zornitza Stark Gene: scgn has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v1.33 SCGN Zornitza Stark gene: SCGN was added
gene: SCGN was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: SCGN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCGN were set to 31663849
Phenotypes for gene: SCGN were set to ulcerative colitis, MONDO:0005101
Review for gene: SCGN was set to AMBER
Added comment: PMID:31663849 reported three siblings with homozygous missense SCGN variant and with early-onset ulcerative colitis. Functional studies demonstrated that SCGN variant identified impacted the localisation of the SNARE complex partner, SNAP25, leading to impaired hormone release. In addition, SCGN knockout mouse model recapitulated impaired hormone release and susceptibility to DSS-induced colitis.
Sources: Literature
Mendeliome v1.1541 SCGN Zornitza Stark Marked gene: SCGN as ready
Mendeliome v1.1541 SCGN Zornitza Stark Gene: scgn has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1541 SCGN Zornitza Stark Classified gene: SCGN as Amber List (moderate evidence)
Mendeliome v1.1541 SCGN Zornitza Stark Gene: scgn has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v1.32 SIRT1 Zornitza Stark Marked gene: SIRT1 as ready
Autoinflammatory Disorders v1.32 SIRT1 Zornitza Stark Gene: sirt1 has been classified as Red List (Low Evidence).
Autoinflammatory Disorders v1.32 SIRT1 Zornitza Stark gene: SIRT1 was added
gene: SIRT1 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: SIRT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SIRT1 were set to 23473037
Phenotypes for gene: SIRT1 were set to autoimmune disease, MONDO:0007179, SIRT1-related
Review for gene: SIRT1 was set to RED
Added comment: PMID:23473037 reported the identification of a missense SIRT1 variant (p.Leu107Pro) in five members of a single family and all five of them had autoimmune disorder, four had type I diabetes and one had ulcerative colitis.
Sources: Literature
Mendeliome v1.1540 SIRT1 Zornitza Stark Marked gene: SIRT1 as ready
Mendeliome v1.1540 SIRT1 Zornitza Stark Gene: sirt1 has been classified as Red List (Low Evidence).
Mendeliome v1.1540 SIRT1 Zornitza Stark Classified gene: SIRT1 as Red List (low evidence)
Mendeliome v1.1540 SIRT1 Zornitza Stark Gene: sirt1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2290 TNRC6A Zornitza Stark Marked gene: TNRC6A as ready
Genetic Epilepsy v0.2290 TNRC6A Zornitza Stark Gene: tnrc6a has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2290 TNRC6A Zornitza Stark Phenotypes for gene: TNRC6A were changed from ?Epilepsy, familial adult myoclonic, 6 MIM#618074 to Epilepsy, familial adult myoclonic, 6 MIM#618074
Mendeliome v1.1539 TNRC6A Elena Savva Marked gene: TNRC6A as ready
Mendeliome v1.1539 TNRC6A Elena Savva Gene: tnrc6a has been classified as Red List (Low Evidence).
Mendeliome v1.1539 TNRC6A Elena Savva gene: TNRC6A was added
gene: TNRC6A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TNRC6A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNRC6A were set to PMID: 29507423; 33040085
Phenotypes for gene: TNRC6A were set to ?Epilepsy, familial adult myoclonic, 6 MIM#618074
Review for gene: TNRC6A was set to RED
Added comment: PMID: 29507423;33040085 - intronic expansion in a cohort with familial myoclonic epilepsy, also observed in controls but enriched in the affect cohort.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2289 TNRC6A Elena Savva gene: TNRC6A was added
gene: TNRC6A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TNRC6A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNRC6A were set to PMID: 29507423; 33040085
Phenotypes for gene: TNRC6A were set to ?Epilepsy, familial adult myoclonic, 6 MIM#618074
Review for gene: TNRC6A was set to RED
Added comment: PMID: 29507423;33040085 - intronic expansion in a cohort with familial myoclonic epilepsy, also observed in controls but enriched in the affect cohort.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2289 TNRC6A Elena Savva gene: TNRC6A was added
gene: TNRC6A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TNRC6A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNRC6A were set to PMID: 29507423; 33040085
Phenotypes for gene: TNRC6A were set to ?Epilepsy, familial adult myoclonic, 6 MIM#618074
Review for gene: TNRC6A was set to RED
Added comment: PMID: 29507423;33040085 - intronic expansion in a cohort with familial myoclonic epilepsy, also observed in controls but enriched in the affect cohort.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2288 TLK2 Elena Savva Marked gene: TLK2 as ready
Genetic Epilepsy v0.2288 TLK2 Elena Savva Gene: tlk2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2288 TLK2 Elena Savva Classified gene: TLK2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2288 TLK2 Elena Savva Gene: tlk2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2287 TLK2 Elena Savva gene: TLK2 was added
gene: TLK2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TLK2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TLK2 were set to 37662408; 31558842
Phenotypes for gene: TLK2 were set to Intellectual developmental disorder, autosomal dominant 57 MIM#618050
Review for gene: TLK2 was set to AMBER
Added comment: Seizures (13%) in OMIM

PMID: 37662408 - NOT PEER REVIEWED. Patient presenting with ID, seizures, global developmental delay, hypothyroidism, and primary immunodeficiency. De novo missense found, but also another de novo PTC in MDM1. Functional studies support missense pathogenicity

PMID: 31558842 - HOM missense patient with a severe neurodev disorder, parents are clinically unaffected. She presented with epileptic spasms at the age of 6 months. Her EEG showed hypsarrhythmia suggesting West syndrome. She has been seizure-free since 3 years of age.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5698 FBXO31 Lucy Spencer reviewed gene: FBXO31: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 45 (MIM#615979); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1538 FBXO31 Lucy Spencer reviewed gene: FBXO31: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 45 (MIM#615979); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1538 SIRT1 Achchuthan Shanmugasundram gene: SIRT1 was added
gene: SIRT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SIRT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SIRT1 were set to 23473037
Phenotypes for gene: SIRT1 were set to autoimmune disease, MONDO:0007179
Review for gene: SIRT1 was set to RED
Added comment: PMID:23473037 reported the identification of a missense SIRT1 variant (p.Leu107Pro) in five members of a single family and all five of them had autoimmune disorder, four had type I diabetes and one had ulcerative colitis.
Sources: Literature
Mendeliome v1.1538 SCGN Achchuthan Shanmugasundram gene: SCGN was added
gene: SCGN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SCGN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCGN were set to 31663849
Phenotypes for gene: SCGN were set to ulcerative colitis, MONDO:0005101
Review for gene: SCGN was set to AMBER
Added comment: PMID:31663849 reported three siblings with homozygous missense SCGN variant and with early-onset ulcerative colitis. Functional studies demonstrated that SCGN variant identified impacted the localisation of the SNARE complex partner, SNAP25, leading to impaired hormone release. In addition, SCGN knockout mouse model recapitulated impaired hormone release and susceptibility to DSS-induced colitis.
Sources: Literature
Mendeliome v1.1538 HSPA1L Achchuthan Shanmugasundram gene: HSPA1L was added
gene: HSPA1L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HSPA1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HSPA1L were set to 28126021
Phenotypes for gene: HSPA1L were set to inflammatory bowel disease, MONDO:0005265
Review for gene: HSPA1L was set to GREEN
Added comment: PMID:28126021 reported the identification of a heterozygous de novo variant (p.Ser277Leu) in HSPA1L in a patient with inflammatory bowel disease. In addition, five additional rare HSPA1L variants (p.Gly77Ser, p.Leu172del, p.Thr267Ile, p.Ala268Thr, p.Glu558Asp) were identified in six patients from a cohort of 136 IBD patients with WES data.

Functional studies showed that all six HSPA1L variant proteins showed decreased chaperone activity in vitro. Moreover, three variants demonstrated dominant negative effects on HSPA1L and HSPA1A protein activity.
Sources: Literature
Inflammatory bowel disease v0.112 CARD8 Achchuthan Shanmugasundram reviewed gene: CARD8: Rating: AMBER; Mode of pathogenicity: None; Publications: 37724393; Phenotypes: ?Inflammatory bowel disease (Crohn disease) 30, OMIM:619079; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Inflammatory bowel disease v0.112 ANKZF1 Achchuthan Shanmugasundram reviewed gene: ANKZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28302725, 36857589; Phenotypes: inflammatory bowel disease, MONDO:0005265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Neurodegeneration with brain iron accumulation v0.31 DDHD1 Shekeeb Mohammad gene: DDHD1 was added
gene: DDHD1 was added to Neuroferritinopathies. Sources: Literature
Mode of inheritance for gene: DDHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDHD1 were set to 28818478
Phenotypes for gene: DDHD1 were set to spastic paraplegia; sensory neuropathy
Review for gene: DDHD1 was set to GREEN
gene: DDHD1 was marked as current diagnostic
Added comment: Sources: Literature
Neurodegeneration with brain iron accumulation v0.31 THAP1 Shekeeb Mohammad gene: THAP1 was added
gene: THAP1 was added to Neuroferritinopathies. Sources: Literature
Mode of inheritance for gene: THAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THAP1 were set to 38094642; 33665847
Phenotypes for gene: THAP1 were set to cervical dystonia; dystonia; dystonic tremor
Review for gene: THAP1 was set to GREEN
gene: THAP1 was marked as current diagnostic
Added comment: 3 published cases; 1 under clinical care with a pathogenic THAP1 variant.
Sources: Literature
Neurodegeneration with brain iron accumulation v0.31 SQSTM1 Shekeeb Mohammad gene: SQSTM1 was added
gene: SQSTM1 was added to Neuroferritinopathies. Sources: Literature
Mode of inheritance for gene: SQSTM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SQSTM1 were set to 27545679
Phenotypes for gene: SQSTM1 were set to ataxia; dystonia; gaze palsy; neuroregression; cognitive decline; childhood dementia
Review for gene: SQSTM1 was set to GREEN
gene: SQSTM1 was marked as current diagnostic
Added comment: Sources: Literature
Neurodegeneration with brain iron accumulation v0.31 ATP7B Shekeeb Mohammad reviewed gene: ATP7B: Rating: GREEN; Mode of pathogenicity: None; Publications: 33680437, 28376267, 34289020; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Genetic Epilepsy v0.2286 FLNA Zornitza Stark Marked gene: FLNA as ready
Genetic Epilepsy v0.2286 FLNA Zornitza Stark Gene: flna has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2286 FLNA Zornitza Stark Phenotypes for gene: FLNA were changed from to Heterotopia, periventricular, 1, MIM# 300049
Genetic Epilepsy v0.2285 FLNA Zornitza Stark Publications for gene: FLNA were set to
Genetic Epilepsy v0.2284 FLNA Zornitza Stark Mode of inheritance for gene: FLNA 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)
Genetic Epilepsy v0.2283 FKTN Zornitza Stark Marked gene: FKTN as ready
Genetic Epilepsy v0.2283 FKTN Zornitza Stark Gene: fktn has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2283 FKTN Zornitza Stark Phenotypes for gene: FKTN were changed from to Muscular dystrophy-dystroglycanopathy MONDO:0018276
Genetic Epilepsy v0.2282 FKTN Zornitza Stark Publications for gene: FKTN were set to
Genetic Epilepsy v0.2281 FKTN Zornitza Stark Mode of inheritance for gene: FKTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2280 FKTN Zornitza Stark reviewed gene: FKTN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy MONDO:0018276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2280 FBXL4 Zornitza Stark Marked gene: FBXL4 as ready
Genetic Epilepsy v0.2280 FBXL4 Zornitza Stark Gene: fbxl4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2280 FBXL4 Zornitza Stark Phenotypes for gene: FBXL4 were changed from to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) MIM#615471
Genetic Epilepsy v0.2279 FBXL4 Zornitza Stark Publications for gene: FBXL4 were set to
Genetic Epilepsy v0.2278 FBXL4 Zornitza Stark Mode of inheritance for gene: FBXL4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2277 FBXL4 Zornitza Stark reviewed gene: FBXL4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) MIM#615471; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2277 FARS2 Zornitza Stark Marked gene: FARS2 as ready
Genetic Epilepsy v0.2277 FARS2 Zornitza Stark Gene: fars2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2277 FARS2 Zornitza Stark Phenotypes for gene: FARS2 were changed from to combined oxidative phosphorylation defect type 14 MONDO:0013986
Genetic Epilepsy v0.2276 FARS2 Zornitza Stark Publications for gene: FARS2 were set to
Genetic Epilepsy v0.2275 FARS2 Zornitza Stark Mode of inheritance for gene: FARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2274 TET3 Zornitza Stark Marked gene: TET3 as ready
Genetic Epilepsy v0.2274 TET3 Zornitza Stark Gene: tet3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2274 TET3 Zornitza Stark Classified gene: TET3 as Green List (high evidence)
Genetic Epilepsy v0.2274 TET3 Zornitza Stark Gene: tet3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2273 TET3 Zornitza Stark reviewed gene: TET3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Beck-Fahrner syndrome MIM#618798; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.191 THOC2 Zornitza Stark Phenotypes for gene: THOC2 were changed from Mental retardation, X-linked 12/35 MIM#300957 to Mental retardation, X-linked 12/35 MIM#300957; Arthrogryposis (MONDO:0008779), THOC2-related
Fetal anomalies v1.190 THOC2 Zornitza Stark Publications for gene: THOC2 were set to 26166480; 32116545; 29851191; 32960281
Fetal anomalies v1.189 THOC2 Zornitza Stark edited their review of gene: THOC2: Added comment: PMID: 34976470 - arthrogryposis multiplex congenita phenotype (AMC) in two male fetuses in a family, caused by splice deletion c.2482-1_2484delGTCA which was mat inherited. No splice studies conducted, mother was normal. Postulate that amorphic or severe null pathogenic variants (possible complete loss of function) lead to AMC phenotype

PMID: 37945483 - a proband with AMC and the same splice site mutation ^ above, but de novo. Cytoplasmic bodies also detected in muscle; Changed publications: 29851191, 34976470, 37945483; Changed phenotypes: Mental retardation, X-linked 12/35 MIM#300957, Arthrogryposis (MONDO:0008779), THOC2-related
Genetic Epilepsy v0.2273 TK2 Elena Savva Marked gene: TK2 as ready
Genetic Epilepsy v0.2273 TK2 Elena Savva Gene: tk2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2273 TK2 Elena Savva Classified gene: TK2 as Green List (high evidence)
Genetic Epilepsy v0.2273 TK2 Elena Savva Gene: tk2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2272 TK2 Elena Savva gene: TK2 was added
gene: TK2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TK2 were set to 25446393; 16504786
Phenotypes for gene: TK2 were set to Mitochondrial DNA depletion syndrome 2 (myopathic type), MIM#609560; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3, MIM# 617069
Review for gene: TK2 was set to GREEN
Added comment: GeneReviews: Seizures 11/34 (32%) in infantile onset cases

PMID: 25446393 - two siblings with chet missense, presenting with early onset myopathy with profound loss of muscle mass, axonal neuropathy, respiratory failure as well as severe brain atrophy with status epilepticus.

PMID: 16504786 - five children in two families reported with infantile encephalomyopathy with biallelic missense. Generalised seizures described in 2/3 siblings from one family
Sources: Literature
Genetic Epilepsy v0.2271 THOC2 Elena Savva Marked gene: THOC2 as ready
Genetic Epilepsy v0.2271 THOC2 Elena Savva Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2271 THOC2 Elena Savva Classified gene: THOC2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2271 THOC2 Elena Savva Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2270 THOC2 Elena Savva gene: THOC2 was added
gene: THOC2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: THOC2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: THOC2 were set to PMID: 26166480; 29851191
Phenotypes for gene: THOC2 were set to Intellectual developmental disorder, X-linked 12 MIM#300957
Review for gene: THOC2 was set to AMBER
Added comment: Seizures (in some patients) described in OMIM

PMID: 26166480 - gene-disease establishing paper, epilepsy described in 5/20 individuals where affected individuals were from three families. Only missense reported but all segregated well in families and had backing functional studies.

PMID: 29851191 - overlapping authors with ^, expanded cohort. Only 1/7 probands had epilepsy with an additional proband "suspected"
Sources: Literature
Arthrogryposis v0.405 THOC2 Elena Savva Classified gene: THOC2 as Amber List (moderate evidence)
Arthrogryposis v0.405 THOC2 Elena Savva Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.405 THOC2 Elena Savva Classified gene: THOC2 as Amber List (moderate evidence)
Arthrogryposis v0.405 THOC2 Elena Savva Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.404 THOC2 Elena Savva Classified gene: THOC2 as Amber List (moderate evidence)
Arthrogryposis v0.404 THOC2 Elena Savva Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.403 THOC2 Elena Savva Marked gene: THOC2 as ready
Arthrogryposis v0.403 THOC2 Elena Savva Gene: thoc2 has been classified as Red List (Low Evidence).
Arthrogryposis v0.403 THOC2 Elena Savva gene: THOC2 was added
gene: THOC2 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: THOC2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: THOC2 were set to PMID: 34976470; 37945483
Phenotypes for gene: THOC2 were set to Arthrogryposis (MONDO:0008779), THOC2-related
Review for gene: THOC2 was set to AMBER
Added comment: PMID: 34976470 - arthrogryposis multiplex congenita phenotype (AMC) in two male fetuses in a family, caused by splice deletion c.2482-1_2484delGTCA which was mat inherited. No splice studies conducted, mother was normal.
Postulate that amorphic or severe null pathogenic variants (possible complete loss of function) lead to AMC phenotype

PMID: 37945483 - a proband with AMC and the same splice site mutation ^ above, but de novo. Cytoplasmic bodies also detected in muscle
Sources: Literature
Genetic Epilepsy v0.2269 TGIF1 Elena Savva Marked gene: TGIF1 as ready
Genetic Epilepsy v0.2269 TGIF1 Elena Savva Gene: tgif1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2269 TGIF1 Elena Savva gene: TGIF1 was added
gene: TGIF1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TGIF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TGIF1 were set to Holoprosencephaly 4 MIM#142946
Review for gene: TGIF1 was set to RED
Added comment: Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2268 TET3 Elena Savva gene: TET3 was added
gene: TET3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TET3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TET3 were set to 36192301
Phenotypes for gene: TET3 were set to Beck-Fahrner syndrome MIM#618798
Review for gene: TET3 was set to AMBER
Added comment: Seizures (in some patients) noted in OMIM

GeneReviews: seizure disorder described in 9/24 patients

PMID: 36192301 - de novo PTC, generalized tonic-clonic seizures began at 5yo

Difficulty finding additional literature stating patient phenotypes
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5698 TET3 Elena Savva Phenotypes for gene: TET3 were changed from Intellectual disability; dysmorphic features; abnormal growth; movement disorders to Beck-Fahrner syndrome MIM#618798
Mendeliome v1.1538 TET3 Elena Savva Phenotypes for gene: TET3 were changed from Intellectual disability; dysmorphic features; abnormal growth; movement disorders to Beck-Fahrner syndrome MIM#618798
Genetic Epilepsy v0.2267 TBC1D7 Elena Savva Marked gene: TBC1D7 as ready
Genetic Epilepsy v0.2267 TBC1D7 Elena Savva Gene: tbc1d7 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2267 TBC1D7 Elena Savva gene: TBC1D7 was added
gene: TBC1D7 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TBC1D7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D7 were set to 23687350; 24515783
Phenotypes for gene: TBC1D7 were set to Macrocephaly/megalencephaly syndrome, autosomal recessive MIM#248000
Review for gene: TBC1D7 was set to RED
Added comment: PMID: 23687350 - There is no history of seizures in two siblings, but EEG recording showed some epileptic activity in the right temporal lobe

PMID: 24515783 - There is no history of seizures; EEG and brain SPECT were normal.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2266 EIF2B4 Zornitza Stark Marked gene: EIF2B4 as ready
Genetic Epilepsy v0.2266 EIF2B4 Zornitza Stark Added comment: Comment when marking as ready: Seizures are a feature.
Genetic Epilepsy v0.2266 EIF2B4 Zornitza Stark Gene: eif2b4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2266 EIF2B4 Zornitza Stark Phenotypes for gene: EIF2B4 were changed from to leukoencephalopathy with vanishing white matter MONDO:0011380
Genetic Epilepsy v0.2265 EIF2B4 Zornitza Stark Publications for gene: EIF2B4 were set to
Genetic Epilepsy v0.2264 EIF2B4 Zornitza Stark Mode of inheritance for gene: EIF2B4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2263 EIF2B3 Zornitza Stark Marked gene: EIF2B3 as ready
Genetic Epilepsy v0.2263 EIF2B3 Zornitza Stark Gene: eif2b3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2263 EIF2B3 Zornitza Stark Phenotypes for gene: EIF2B3 were changed from to leukoencephalopathy with vanishing white matter MONDO:0011380
Genetic Epilepsy v0.2262 EIF2B3 Zornitza Stark Publications for gene: EIF2B3 were set to
Genetic Epilepsy v0.2261 EIF2B3 Zornitza Stark Mode of inheritance for gene: EIF2B3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2260 EIF2B2 Zornitza Stark Marked gene: EIF2B2 as ready
Genetic Epilepsy v0.2260 EIF2B2 Zornitza Stark Gene: eif2b2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2260 EIF2B2 Zornitza Stark Phenotypes for gene: EIF2B2 were changed from to Leukoencephalopathy with vanishing white matter, MIM#603896; Ovarioleukodystrophy, MIM# 603896
Genetic Epilepsy v0.2259 EIF2B2 Zornitza Stark Publications for gene: EIF2B2 were set to
Genetic Epilepsy v0.2258 EIF2B2 Zornitza Stark Mode of inheritance for gene: EIF2B2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2257 EIF2B1 Zornitza Stark Marked gene: EIF2B1 as ready
Genetic Epilepsy v0.2257 EIF2B1 Zornitza Stark Gene: eif2b1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2257 EIF2B1 Zornitza Stark Phenotypes for gene: EIF2B1 were changed from to Leukoencephalopathy with vanishing white matter MIM#603896; Neonatal diabetes mellitus, MONDO:0016391, EIF2B1-related
Genetic Epilepsy v0.2256 EIF2B1 Zornitza Stark Publications for gene: EIF2B1 were set to
Genetic Epilepsy v0.2255 EIF2B1 Zornitza Stark Mode of inheritance for gene: EIF2B1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2254 POMK Zornitza Stark Marked gene: POMK as ready
Genetic Epilepsy v0.2254 POMK Zornitza Stark Gene: pomk has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2254 POMK Zornitza Stark Classified gene: POMK as Amber List (moderate evidence)
Genetic Epilepsy v0.2254 POMK Zornitza Stark Gene: pomk has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2253 POMK Zornitza Stark reviewed gene: POMK: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 MIM#615249; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1537 PRDM8 Zornitza Stark Marked gene: PRDM8 as ready
Mendeliome v1.1537 PRDM8 Zornitza Stark Gene: prdm8 has been classified as Red List (Low Evidence).
Mendeliome v1.1537 PRDM8 Zornitza Stark gene: PRDM8 was added
gene: PRDM8 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PRDM8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDM8 were set to 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: Expert list
Genetic Epilepsy v0.2253 PRDM8 Zornitza Stark Marked gene: PRDM8 as ready
Genetic Epilepsy v0.2253 PRDM8 Zornitza Stark Gene: prdm8 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2253 PRDM8 Zornitza Stark Classified gene: PRDM8 as Red List (low evidence)
Genetic Epilepsy v0.2253 PRDM8 Zornitza Stark Gene: prdm8 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2252 PRDM8 Zornitza Stark Classified gene: PRDM8 as Red List (low evidence)
Genetic Epilepsy v0.2252 PRDM8 Zornitza Stark Gene: prdm8 has been classified as Red List (Low Evidence).
Mendeliome v1.1536 PRIMA1 Zornitza Stark Marked gene: PRIMA1 as ready
Mendeliome v1.1536 PRIMA1 Zornitza Stark Gene: prima1 has been classified as Red List (Low Evidence).
Mendeliome v1.1536 PRIMA1 Zornitza Stark gene: PRIMA1 was added
gene: PRIMA1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PRIMA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRIMA1 were set to 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: Expert list
Genetic Epilepsy v0.2251 PRIMA1 Zornitza Stark Marked gene: PRIMA1 as ready
Genetic Epilepsy v0.2251 PRIMA1 Zornitza Stark Gene: prima1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2251 PRIMA1 Zornitza Stark Classified gene: PRIMA1 as Red List (low evidence)
Genetic Epilepsy v0.2251 PRIMA1 Zornitza Stark Gene: prima1 has been classified as Red List (Low Evidence).
Fetal anomalies v1.189 MAX Zornitza Stark Phenotypes for gene: MAX were changed from Syndromic disease (MONDO:0002254), MAX-related to Polydactyly-macrocephaly syndrome, MIM# 620712
Fetal anomalies v1.188 MAX Zornitza Stark reviewed gene: MAX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polydactyly-macrocephaly syndrome, MIM# 620712; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5697 MAX Zornitza Stark Phenotypes for gene: MAX were changed from Syndromic disease (MONDO:0002254), MAX-related to Polydactyly-macrocephaly syndrome, MIM# 620712
Polydactyly v0.271 MAX Zornitza Stark Phenotypes for gene: MAX were changed from Syndromic disease (MONDO:0002254), MAX-related to Polydactyly-macrocephaly syndrome, MIM# 620712
Polydactyly v0.270 MAX Zornitza Stark reviewed gene: MAX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polydactyly-macrocephaly syndrome, MIM# 620712; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1535 MAX Zornitza Stark Phenotypes for gene: MAX were changed from {Pheochromocytoma, susceptibility to}, MIM# 171300; Syndromic disease (MONDO:0002254), MAX-related to {Pheochromocytoma, susceptibility to}, MIM# 171300; Polydactyly-macrocephaly syndrome, MIM# 620712
Macrocephaly_Megalencephaly v0.139 MAX Zornitza Stark Phenotypes for gene: MAX were changed from Syndromic disease (MONDO:0002254), MAX-related to Polydactyly-macrocephaly syndrome, MIM# 620712
Macrocephaly_Megalencephaly v0.138 MAX Zornitza Stark reviewed gene: MAX: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Polydactyly-macrocephaly syndrome, MIM# 620712; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2250 PPP2R5D Zornitza Stark Marked gene: PPP2R5D as ready
Genetic Epilepsy v0.2250 PPP2R5D Zornitza Stark Gene: ppp2r5d has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2250 PPP2R5D Zornitza Stark Publications for gene: PPP2R5D were set to
Genetic Epilepsy v0.2249 PPP2R5D Zornitza Stark Classified gene: PPP2R5D as Green List (high evidence)
Genetic Epilepsy v0.2249 PPP2R5D Zornitza Stark Gene: ppp2r5d has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2248 POMGNT2 Zornitza Stark Marked gene: POMGNT2 as ready
Genetic Epilepsy v0.2248 POMGNT2 Zornitza Stark Gene: pomgnt2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2248 POMGNT2 Zornitza Stark Classified gene: POMGNT2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2248 POMGNT2 Zornitza Stark Gene: pomgnt2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2247 POMGNT2 Zornitza Stark reviewed gene: POMGNT2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8 MIM#614830; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2247 POGZ Zornitza Stark Marked gene: POGZ as ready
Genetic Epilepsy v0.2247 POGZ Zornitza Stark Gene: pogz has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2247 POGZ Zornitza Stark Classified gene: POGZ as Green List (high evidence)
Genetic Epilepsy v0.2247 POGZ Zornitza Stark Gene: pogz has been classified as Green List (High Evidence).
Mendeliome v1.1534 PLXNC1 Zornitza Stark Marked gene: PLXNC1 as ready
Mendeliome v1.1534 PLXNC1 Zornitza Stark Gene: plxnc1 has been classified as Red List (Low Evidence).
Mendeliome v1.1534 PLXNC1 Zornitza Stark gene: PLXNC1 was added
gene: PLXNC1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PLXNC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLXNC1 were set to 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: Expert list
Genetic Epilepsy v0.2246 PLXNC1 Zornitza Stark Marked gene: PLXNC1 as ready
Genetic Epilepsy v0.2246 PLXNC1 Zornitza Stark Gene: plxnc1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2246 PLXNC1 Zornitza Stark Classified gene: PLXNC1 as Red List (low evidence)
Genetic Epilepsy v0.2246 PLXNC1 Zornitza Stark Gene: plxnc1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2245 PEX13 Zornitza Stark Marked gene: PEX13 as ready
Genetic Epilepsy v0.2245 PEX13 Zornitza Stark Gene: pex13 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2245 PEX13 Zornitza Stark Classified gene: PEX13 as Green List (high evidence)
Genetic Epilepsy v0.2245 PEX13 Zornitza Stark Gene: pex13 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2244 PEX10 Zornitza Stark Marked gene: PEX10 as ready
Genetic Epilepsy v0.2244 PEX10 Zornitza Stark Gene: pex10 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2244 PEX10 Zornitza Stark Classified gene: PEX10 as Red List (low evidence)
Genetic Epilepsy v0.2244 PEX10 Zornitza Stark Gene: pex10 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2243 PCLO Zornitza Stark Marked gene: PCLO as ready
Genetic Epilepsy v0.2243 PCLO Zornitza Stark Gene: pclo has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2243 PCLO Zornitza Stark Classified gene: PCLO as Red List (low evidence)
Genetic Epilepsy v0.2243 PCLO Zornitza Stark Gene: pclo has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2242 PAX6 Zornitza Stark Marked gene: PAX6 as ready
Genetic Epilepsy v0.2242 PAX6 Zornitza Stark Gene: pax6 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2242 PAX6 Zornitza Stark Classified gene: PAX6 as Amber List (moderate evidence)
Genetic Epilepsy v0.2242 PAX6 Zornitza Stark Gene: pax6 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2241 PAK3 Zornitza Stark Marked gene: PAK3 as ready
Genetic Epilepsy v0.2241 PAK3 Zornitza Stark Gene: pak3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2241 PAK3 Zornitza Stark Classified gene: PAK3 as Amber List (moderate evidence)
Genetic Epilepsy v0.2241 PAK3 Zornitza Stark Gene: pak3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2240 OFD1 Zornitza Stark Marked gene: OFD1 as ready
Genetic Epilepsy v0.2240 OFD1 Zornitza Stark Gene: ofd1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2240 OFD1 Zornitza Stark Classified gene: OFD1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2240 OFD1 Zornitza Stark Gene: ofd1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2239 NR2F1 Zornitza Stark Marked gene: NR2F1 as ready
Genetic Epilepsy v0.2239 NR2F1 Zornitza Stark Gene: nr2f1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2239 NR2F1 Zornitza Stark Classified gene: NR2F1 as Green List (high evidence)
Genetic Epilepsy v0.2239 NR2F1 Zornitza Stark Gene: nr2f1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2238 NF1 Zornitza Stark Marked gene: NF1 as ready
Genetic Epilepsy v0.2238 NF1 Zornitza Stark Gene: nf1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2238 NF1 Zornitza Stark Classified gene: NF1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2238 NF1 Zornitza Stark Gene: nf1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2237 MCM3AP Zornitza Stark Marked gene: MCM3AP as ready
Genetic Epilepsy v0.2237 MCM3AP Zornitza Stark Gene: mcm3ap has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2237 MCM3AP Zornitza Stark Classified gene: MCM3AP as Red List (low evidence)
Genetic Epilepsy v0.2237 MCM3AP Zornitza Stark Gene: mcm3ap has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2236 LRPPRC Zornitza Stark Marked gene: LRPPRC as ready
Genetic Epilepsy v0.2236 LRPPRC Zornitza Stark Gene: lrpprc has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2236 LRPPRC Zornitza Stark Classified gene: LRPPRC as Amber List (moderate evidence)
Genetic Epilepsy v0.2236 LRPPRC Zornitza Stark Gene: lrpprc has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2235 COL3A1 Zornitza Stark Marked gene: COL3A1 as ready
Genetic Epilepsy v0.2235 COL3A1 Zornitza Stark Gene: col3a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2235 COL3A1 Zornitza Stark Classified gene: COL3A1 as Green List (high evidence)
Genetic Epilepsy v0.2235 COL3A1 Zornitza Stark Gene: col3a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2234 CHD1 Zornitza Stark Marked gene: CHD1 as ready
Genetic Epilepsy v0.2234 CHD1 Zornitza Stark Gene: chd1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2234 CHD1 Zornitza Stark Classified gene: CHD1 as Green List (high evidence)
Genetic Epilepsy v0.2234 CHD1 Zornitza Stark Gene: chd1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2233 SERAC1 Zornitza Stark Classified gene: SERAC1 as Green List (high evidence)
Genetic Epilepsy v0.2233 SERAC1 Zornitza Stark Gene: serac1 has been classified as Green List (High Evidence).
Mendeliome v1.1533 CASZ1 Zornitza Stark Marked gene: CASZ1 as ready
Mendeliome v1.1533 CASZ1 Zornitza Stark Gene: casz1 has been classified as Green List (High Evidence).
Mendeliome v1.1533 CASZ1 Zornitza Stark Classified gene: CASZ1 as Green List (high evidence)
Mendeliome v1.1533 CASZ1 Zornitza Stark Gene: casz1 has been classified as Green List (High Evidence).
Mendeliome v1.1532 CASZ1 Zornitza Stark gene: CASZ1 was added
gene: CASZ1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CASZ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CASZ1 were set to 28099117; 36293425; 31268246
Phenotypes for gene: CASZ1 were set to Dilated cardiomyopathy, MONDO:0005021, CASZ1-related; left ventricular non compaction
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: Expert list
Cardiomyopathy_Paediatric v0.180 CASZ1 Zornitza Stark Marked gene: CASZ1 as ready
Cardiomyopathy_Paediatric v0.180 CASZ1 Zornitza Stark Gene: casz1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.180 CASZ1 Zornitza Stark Phenotypes for gene: CASZ1 were changed from dilated cardiomyopathy, left ventricular non compaction to Dilated cardiomyopathy, MONDO:0005021, CASZ1-related; left ventricular non compaction
Cardiomyopathy_Paediatric v0.179 CASZ1 Zornitza Stark Classified gene: CASZ1 as Green List (high evidence)
Cardiomyopathy_Paediatric v0.179 CASZ1 Zornitza Stark Gene: casz1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2232 SRCAP Zornitza Stark Classified gene: SRCAP as Green List (high evidence)
Genetic Epilepsy v0.2232 SRCAP Zornitza Stark Gene: srcap has been classified as Green List (High Evidence).
Mendeliome v1.1531 SMC3 Zornitza Stark Publications for gene: SMC3 were set to 18996922; 25655089; 31334757
Genetic Epilepsy v0.2231 SYNE1 Zornitza Stark Phenotypes for gene: SYNE1 were changed from Arthrogryposis multiplex congenita 3, myogenic type MIM#618484; Emery-Dreifuss muscular dystrophy 4, autosomal dominant MIM#612998; Spinocerebellar ataxia, autosomal recessive 8 MIM#610743 to Neurodevelopmental disorder, MONDO:0700092
Genetic Epilepsy v0.2230 SYNE1 Zornitza Stark Mode of inheritance for gene: SYNE1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5696 TAF1C Zornitza Stark Marked gene: TAF1C as ready
Intellectual disability syndromic and non-syndromic v0.5696 TAF1C Zornitza Stark Gene: taf1c has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2229 TAOK1 Zornitza Stark Marked gene: TAOK1 as ready
Genetic Epilepsy v0.2229 TAOK1 Zornitza Stark Gene: taok1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5696 NDUFB9 Zornitza Stark Publications for gene: NDUFB9 were set to 22200994
Intellectual disability syndromic and non-syndromic v0.5695 NDUFB9 Zornitza Stark edited their review of gene: NDUFB9: Added comment: PMID: 38129218: Thr144Met, listed as ACMG-P, hom in 1x pt with mito complex I deficiency and leukodystrophy, no functional studies, both parents are het. However, this variant has 2 homozygotes in gnomADv4, so unlikely pathogenic.; Changed publications: 22200994, 38129218
Mitochondrial disease v0.916 NDUFB9 Zornitza Stark Publications for gene: NDUFB9 were set to
Mendeliome v1.1530 NDUFB9 Zornitza Stark Publications for gene: NDUFB9 were set to 22200994
Mendeliome v1.1529 NDUFB9 Zornitza Stark edited their review of gene: NDUFB9: Added comment: PMID: 38129218: Thr144Met, listed as ACMG-P, hom in 1x pt with mito complex I deficiency and leukodystrophy, no functional studies, both parents are het.

However, this variant has 2 homozygotes in gnomADv4 so unlikely pathogenic.; Changed publications: 22200994, 38129218
Mitochondrial disease v0.915 NDUFB9 Chern Lim reviewed gene: NDUFB9: Rating: AMBER; Mode of pathogenicity: None; Publications: 38129218; Phenotypes: Mitochondrial complex I deficiency, nuclear type 24, MIM#618245; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal Macrocystic Disease v0.68 NEK8 Elena Savva Classified gene: NEK8 as Green List (high evidence)
Renal Macrocystic Disease v0.68 NEK8 Elena Savva Gene: nek8 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.67 NEK8 Elena Savva Publications for gene: NEK8 were set to Unpublished ESHG presentation
Mendeliome v1.1529 DNM2 Bryony Thompson reviewed gene: DNM2: Rating: RED; Mode of pathogenicity: None; Publications: 23092955; Phenotypes: fetal akinesia-cerebral and retinal hemorrhage syndrome MONDO:0014149; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2229 NALCN Zornitza Stark Marked gene: NALCN as ready
Genetic Epilepsy v0.2229 NALCN Zornitza Stark Gene: nalcn has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2229 NALCN Zornitza Stark Classified gene: NALCN as Green List (high evidence)
Genetic Epilepsy v0.2229 NALCN Zornitza Stark Gene: nalcn has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.66 NEK8 Lauren Rogers reviewed gene: NEK8: Rating: GREEN; Mode of pathogenicity: None; Publications: 37598857; Phenotypes: Familial cystic renal disease MONDO:0019741; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
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).