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Genomic newborn screening: BabyScreen+ v2.2 MAX Zornitza Stark Gene: max has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v2.1 MAX Zornitza Stark Tag TRAIL study tag was added to gene: MAX.
Genomic newborn screening: BabyScreen+ v2.1 MAX Zornitza Stark reviewed gene: MAX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cancer Predisposition_Paediatric v1.2 MAX Zornitza Stark Phenotypes for gene: MAX were changed from {Pheochromocytoma, susceptibility to}, MIM# 171300 to Multiple endocrine neoplasia, type V, MIM# 621678
Cancer Predisposition_Paediatric v1.1 MAX Zornitza Stark Classified gene: MAX as Red List (low evidence)
Cancer Predisposition_Paediatric v1.1 MAX Zornitza Stark Gene: max has been classified as Red List (Low Evidence).
Cancer Predisposition_Paediatric v1.0 MAX Zornitza Stark edited their review of gene: MAX: Changed phenotypes: Multiple endocrine neoplasia, type V, MIM# 621678
Mendeliome v2.527 MAX Zornitza Stark Phenotypes for gene: MAX were changed from {Pheochromocytoma, susceptibility to}, MIM# 171300; Polydactyly-macrocephaly syndrome, MIM# 620712 to Multiple endocrine neoplasia, type V, MIM# 621678; Polydactyly-macrocephaly syndrome, MIM# 620712
Mendeliome v2.526 MAX Zornitza Stark edited their review of gene: MAX: Changed phenotypes: Multiple endocrine neoplasia, type V, MIM# 621678
Fetal anomalies v2.68 CDK20 Zornitza Stark Phenotypes for gene: CDK20 were changed from Ciliopathy, MONDO:0005308, CDK20-related to Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Fetal anomalies v2.67 CDK20 Zornitza Stark edited their review of gene: CDK20: Changed phenotypes: Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Clefting disorders v1.24 CDK20 Zornitza Stark Phenotypes for gene: CDK20 were changed from Ciliopathy, MONDO:0005308, CDK20-related to Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Clefting disorders v1.23 CDK20 Zornitza Stark edited their review of gene: CDK20: Changed phenotypes: Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Polydactyly v1.19 CDK20 Zornitza Stark Phenotypes for gene: CDK20 were changed from Ciliopathy, MONDO:0005308, CDK20-related to Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Polydactyly v1.18 CDK20 Zornitza Stark edited their review of gene: CDK20: Changed phenotypes: Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Mendeliome v2.526 CDK20 Zornitza Stark Phenotypes for gene: CDK20 were changed from Ciliopathy, MONDO:0005308, CDK20-related to Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Mendeliome v2.525 CDK20 Zornitza Stark edited their review of gene: CDK20: Changed phenotypes: Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Hydrocephalus_Ventriculomegaly v1.13 CDK20 Zornitza Stark Phenotypes for gene: CDK20 were changed from Ciliopathy, MONDO:0005308, CDK20-related to Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Hydrocephalus_Ventriculomegaly v1.12 CDK20 Zornitza Stark edited their review of gene: CDK20: Changed phenotypes: Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Ciliopathies v2.17 CDK20 Zornitza Stark Phenotypes for gene: CDK20 were changed from Ciliopathy, MONDO:0005308, CDK20-related to Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Ciliopathies v2.16 CDK20 Zornitza Stark edited their review of gene: CDK20: Changed phenotypes: Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Anophthalmia_Microphthalmia_Coloboma v2.7 CDK20 Zornitza Stark Phenotypes for gene: CDK20 were changed from Ciliopathy, MONDO:0005308, CDK20-related to Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Anophthalmia_Microphthalmia_Coloboma v2.6 CDK20 Zornitza Stark edited their review of gene: CDK20: Changed phenotypes: Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Cardiomyopathy_Paediatric v1.171 ETFB Eleanor Ludington reviewed gene: ETFB: Rating: RED; Mode of pathogenicity: None; Publications: 27081516; Phenotypes: multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.171 DNAJC19 Eleanor Ludington reviewed gene: DNAJC19: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34580891, 35611801, 27928778, 38283849; Phenotypes: 3-methylglutaconic aciduria type 5, MONDO:0012435, 3-methylgutaconic aciduria, type V, OMIM:610198; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.171 EMD Lucy Spencer Mode of inheritance for gene: EMD was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cardiomyopathy_Paediatric v1.170 EMD Lucy Spencer Phenotypes for gene: EMD were changed from Emery-Dreifuss muscular dystrophy 1, X-linked, 310300 to Emery-Dreifuss muscular dystrophy 1, X-linked, MIM#310300
Cardiomyopathy_Paediatric v1.169 EMD Lucy Spencer reviewed gene: EMD: Rating: GREEN; Mode of pathogenicity: None; Publications: 42047848, 37639473; Phenotypes: Emery-Dreifuss muscular dystrophy 1, X-linked MIM#310300; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cardiomyopathy_Paediatric v1.169 SGSH Lucy Spencer Phenotypes for gene: SGSH were changed from Mucopolysaccharidosis Type IIIA; Mucopolysaccharidosis Type III; MUCOPOLYSACCHARIDOSIS TYPE 3A; MPS IIIA, Sanfilippo A disease (Mucopolysaccharidoses); Mucopolysaccharidosis, Type III to Mucopolysaccharidosis type IIIA (Sanfilippo A) MIM#252900
Cardiomyopathy_Paediatric v1.168 SGSH Lucy Spencer Publications for gene: SGSH were set to 27604308
Cardiomyopathy_Paediatric v1.167 SGSH Lucy Spencer reviewed gene: SGSH: Rating: AMBER; Mode of pathogenicity: None; Publications: 2789611:40160092; Phenotypes: Mucopolysaccharidosis type IIIA (Sanfilippo A) MIM#252900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy v2.39 NDUFS6 Sangavi Sivagnanasundram Classified gene: NDUFS6 as Green List (high evidence)
Hereditary Neuropathy v2.39 NDUFS6 Sangavi Sivagnanasundram Gene: ndufs6 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.38 NDUFS6 Sangavi Sivagnanasundram gene: NDUFS6 was added
gene: NDUFS6 was added to Hereditary Neuropathy. Sources: Literature
Mode of inheritance for gene: NDUFS6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFS6 were set to 41683799; 38549004; 38459834; 38217609
Phenotypes for gene: NDUFS6 were set to peripheral neuropathy MONDO:0020127
Review for gene: NDUFS6 was set to GREEN
Added comment: >3 unrelated individuals with biallelic variants in NDUFS6 presenting with various neurological phenotypes with peripheral neuropathy as a presenting feature.
Note: 38459834 reports homozygous c.309+5G>A in 5 individuals from 3 families.
Sources: Literature
Hereditary Neuropathy v2.37 NFASC Sangavi Sivagnanasundram Classified gene: NFASC as Amber List (moderate evidence)
Hereditary Neuropathy v2.37 NFASC Sangavi Sivagnanasundram Gene: nfasc has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v2.36 NFASC Sangavi Sivagnanasundram gene: NFASC was added
gene: NFASC was added to Hereditary Neuropathy. Sources: Literature
Mode of inheritance for gene: NFASC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFASC were set to 31501903
Phenotypes for gene: NFASC were set to neurodevelopmental disorder with central and peripheral motor dysfunction, MONDO:0032698
Review for gene: NFASC was set to AMBER
Added comment: 3 individuals from 2 families (one family is consanguineous) reported with neurodevelopmental disorder and peripheral neuropathy as a presenting feature.
Sources: Literature
Hereditary Neuropathy v2.35 SPG7 Sangavi Sivagnanasundram Publications for gene: SPG7 were set to 41062329; 40824590; 38549004; 37983191; 35348942; 32999401
Hereditary Neuropathy v2.34 SPG7 Sangavi Sivagnanasundram gene: SPG7 was added
gene: SPG7 was added to Hereditary Neuropathy. Sources: Literature
Mode of inheritance for gene: SPG7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPG7 were set to 41062329; 40824590; 38549004; 37983191; 35348942; 32999401
Phenotypes for gene: SPG7 were set to hereditary spastic paraplegia 7, MONDO:0011803
Review for gene: SPG7 was set to RED
Added comment: 35348942 - 1/5 individuals with biallelic variant in SPG7 and peripheral neuropathy as a presenting feature

38549004 - reports two individuals with biallelic variants in SPG7. Affected individuals had peripheral neuropathy as a presenting feature

Note, the reported variants in these publications do have a high FAF in gnomAD v4.1. Rated Red given the population frequencies in gnomAD
Sources: Literature
Hereditary Neuropathy v2.33 PIGG Sangavi Sivagnanasundram Classified gene: PIGG as Green List (high evidence)
Hereditary Neuropathy v2.33 PIGG Sangavi Sivagnanasundram Gene: pigg has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.32 PIGG Sangavi Sivagnanasundram gene: PIGG was added
gene: PIGG was added to Hereditary Neuropathy. Sources: Literature
Mode of inheritance for gene: PIGG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGG were set to 41744056; 39444079
Phenotypes for gene: PIGG were set to PIGG-related hereditary neuropathy MONDO:0002316
Review for gene: PIGG was set to GREEN
Added comment: PMID 39444079 reports 7 individuals from 6 families with neurological/neuromuscular phenotype including distal hereditary motor neuropathy, motor conduction block, childhood tremor, febrile seizures and mild cerebellar signs, all harbouring biallelic loss‑of‑function PIGG variants (including the recurrent p.Trp505* and missense Val339Gly, Gly19Glu). The affected individuals were reported to have a milder neuropathy phenotype as per their NCS results.

PMID 41744056 reports a 27‑year‑old woman with adolescent‑onset motor neuropathy, myokymia and gait ataxia carrying a homozygous nonsense PIGG variant (p.Trp505* - this variant has a FAF of 0.1% in gnomADv4.1 however appears to be a recurrent variant reported in multiple individuals in the literature).
Sources: Literature
Congenital Disorders of Glycosylation v2.2 PIGB Zornitza Stark Tag founder tag was added to gene: PIGB.
Defects of intrinsic and innate immunity v2.3 IRAK2 Zornitza Stark Publications for gene: IRAK2 were set to PMID: 39299377
Defects of intrinsic and innate immunity v2.2 IRAK2 Zornitza Stark Mode of inheritance for gene: IRAK2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v2.1 IRAK2 Zornitza Stark Classified gene: IRAK2 as Amber List (moderate evidence)
Defects of intrinsic and innate immunity v2.1 IRAK2 Zornitza Stark Gene: irak2 has been classified as Amber List (Moderate Evidence).
Defects of intrinsic and innate immunity v2.0 IRAK2 Zornitza Stark edited their review of gene: IRAK2: Added comment: PMID 42168171 reports 12 individuals from 11 unrelated Chinese families with a spectrum of complex immunologic disorders who all had the same homozygous variant in the IRAK2 gene identified by whole-exome or whole-genome sequencing. The individuals could be categorized into 3 phenotypic subgroups: immunodeficiency-predominant (P1 and P2), autoimmunity-predominant (P3-P7, P11, and P12), and autoinflammation-predominant (P8-P10). The variant is a homozygous 183-bp deletion (c.95_277del, NM_001570), resulting in an in-frame deletion of exon 2 along with portions of the flanking intronic regions (Ala32_Trp93delinsGly). Variant is relatively common in East Asian individuals, including 2 homozygotes in gnomAD.; Changed rating: AMBER; Changed publications: 42168171; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Autoinflammatory Disorders v3.17 IRAK2 Zornitza Stark Publications for gene: IRAK2 were set to PMID: 39299377
Autoinflammatory Disorders v3.16 IRAK2 Zornitza Stark Mode of inheritance for gene: IRAK2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Autoinflammatory Disorders v3.15 IRAK2 Zornitza Stark Classified gene: IRAK2 as Amber List (moderate evidence)
Autoinflammatory Disorders v3.15 IRAK2 Zornitza Stark Gene: irak2 has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v3.14 IRAK2 Zornitza Stark edited their review of gene: IRAK2: Added comment: PMID 42168171 reports 12 individuals from 11 unrelated Chinese families with a spectrum of complex immunologic disorders who all had the same homozygous variant in the IRAK2 gene identified by whole-exome or whole-genome sequencing. The individuals could be categorized into 3 phenotypic subgroups: immunodeficiency-predominant (P1 and P2), autoimmunity-predominant (P3-P7, P11, and P12), and autoinflammation-predominant (P8-P10). The variant is a homozygous 183-bp deletion (c.95_277del, NM_001570), resulting in an in-frame deletion of exon 2 along with portions of the flanking intronic regions (Ala32_Trp93delinsGly). Variant is relatively common in East Asian individuals, including 2 homozygotes in gnomAD.; Changed rating: AMBER; Changed publications: 42168171; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Imprinting disorders v2.1 Sarah Milton Copied Region ISCA-37447-Loss from panel Intellectual disability syndromic and non-syndromic
Imprinting disorders v2.1 ISCA-37447-Loss Sarah Milton Region: ISCA-37447-Loss was added
Region: ISCA-37447-Loss was added to Imprinting disorders. Sources: ClinGen,Expert Review Green,Expert Review Green,ClinGen
SV/CNV tags were added to Region: ISCA-37447-Loss.
Mode of inheritance for Region: ISCA-37447-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for Region: ISCA-37447-Loss were set to 41926606; 39446997
Phenotypes for Region: ISCA-37447-Loss were set to Temple syndrome MIM#616222; Kagami-Ogata syndrome MIM#608149
Cardiomyopathy_Paediatric v1.167 DMD Richard Lin changed review comment from: Dystrophin gene mutations are associated with X-linked progressive muscular dystrophy, including Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD). Cardiomyopathy is a feature of the disease, and results from dystrophin deficiency in the heart (PMID: 29395990).

The age of onset of cardiomyopathy is reported to be in the mid teens in boys with DMD, with a range of onset from 10-21 years (PMID: 16246949, 27230049). Children with very large deletions or following an episode of viral myocarditis have been reported to develop earlier onset LV dysfunction (PMID: 36252992).

A proportion of female dystrophinopathy carriers are also at risk of cardiomyopathy with or without skeletal muscle disease (PMID: 29395990), though there are limited reports of paediatric onset cardiomyopathy. Dilated cardiomyopathy was diagnosed in 1 out of 24 female carriers of DCM aged between 5 and 15 years. In a cohort study, cardiac hypertrophy was diagnosed in 2 out of 24 female DMD carriers, and 2 out of 9 BMD carriers (PMID: 8614119).; to: Dystrophin gene mutations are associated with X-linked progressive muscular dystrophy, including Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD). Cardiomyopathy is a feature of the disease, and results from dystrophin deficiency in the heart (PMID: 29395990).

The age of onset of cardiomyopathy is reported to be in the mid teens in boys with DMD, with a range of onset from 10-21 years (PMID: 16246949, 27230049). Children with very large deletions or following an episode of viral myocarditis have been reported to develop earlier onset LV dysfunction (PMID: 36252992).

A proportion of female dystrophinopathy carriers are also at risk of cardiomyopathy with or without skeletal muscle disease (PMID: 29395990), though there are limited reports of paediatric onset cardiomyopathy. In a cohort study, dilated cardiomyopathy was diagnosed in 1 out of 24 female carriers of DCM aged between 5 and 15 years. Cardiac hypertrophy was diagnosed in 2 out of 24 female DMD carriers, and 2 out of 9 BMD carriers in the same cohort (PMID: 8614119).
Cardiomyopathy_Paediatric v1.167 TMEM70 Richard Lin changed review comment from: Biallelic pathogenic variants in TMEM70 are associated with mitochondrial disease (ClinGen curation classified as definitive association). Paediatric onset cardiomyopathy, predominantly hypertrophic, and less commonly left ventricular noncompaction is well described.

PMID: 20335238 - Hypertrophic cardiomyopathy found in 76% (19/25 patients from 16 families) of neonatal onset TMEM70 associated ATP synthase deficiency. Twenty-four patients were homozygous for the c.317-2A>G mutation in the TMEM70 gene and one patient was compound heterozygote for c.[317-2A>G];[118_119insGT].
PMID: 26550569 - 4 affected sibs from one family with paediatric onset disease including noncompaction cardiomyopathy, 3 affected were homozygotes for TMEM70:c.317-2A>G, remaining affected child was not genotyped.
PMID: 27649480 - single case report of a male child who was homozygous for c.317-2A>G, diagnosed with neonatal onset hypertrophic cardiomyopathy.
PMID: 30899493 - infantile onset left ventricular noncompaction, compound heterozygous for a frameshift and a splice site variant c.[141delG];[316+1G>A]
PMID: 30950220 - 2 affected siblings who were homozygous for a frameshift variant c.105dupT (p.Val36Cysfs*52). Both were noted to have cardiac hypertrophy during antenatal fetal echocardiography.
PMID: 31729175 - 1 affected child who was homozygous for c.317-2A>G with dilated cardiomyopathy AND non compaction
PMID: 36751706 - 1 affected child with neonatal onset hyerptrophic cardiomyopathy and left ventricular non compaction, aortic dilatation. Homozygous for a missense VUS c.563T>C, p.(Leu188Pro), asserted by authors to be pathogenic based on a consistent metabolomic profile.; to: Biallelic pathogenic variants in TMEM70 are associated with mitochondrial disease (ClinGen curation classified as definitive association). Paediatric onset cardiomyopathy, predominantly hypertrophic, and less commonly left ventricular noncompaction is well described.

PMID: 20335238 - Hypertrophic cardiomyopathy found in 76% (19/25 patients from 16 families) of neonatal onset TMEM70 associated ATP synthase deficiency. All except one patient were homozygous for the c.317-2A>G mutation in the TMEM70 gene, with the remaining patient being compound heterozygote for c.[317-2A>G];[118_119insGT].
PMID: 26550569 - 4 affected sibs from one family with paediatric onset disease including noncompaction cardiomyopathy, 3 affected were homozygotes for TMEM70:c.317-2A>G, remaining affected child was not genotyped.
PMID: 27649480 - single case report of a male child who was homozygous for c.317-2A>G, diagnosed with neonatal onset hypertrophic cardiomyopathy.
PMID: 30899493 - infantile onset left ventricular noncompaction, compound heterozygous for a frameshift and a splice site variant c.[141delG];[316+1G>A]
PMID: 30950220 - 2 affected siblings who were homozygous for a frameshift variant c.105dupT (p.Val36Cysfs*52). Both were noted to have cardiac hypertrophy during antenatal fetal echocardiography.
PMID: 31729175 - 1 affected child who was homozygous for c.317-2A>G with dilated cardiomyopathy AND non compaction
PMID: 36751706 - 1 affected child with neonatal onset hyerptrophic cardiomyopathy and left ventricular non compaction, aortic dilatation. Homozygous for a missense VUS c.563T>C, p.(Leu188Pro), asserted by authors to be pathogenic based on a consistent metabolomic profile.
Mendeliome v2.525 IRAK2 Zornitza Stark Phenotypes for gene: IRAK2 were changed from Immune dysregulation, MONDO:0957790, IRAK2-related to Immune dysregulation with autoimmunity, autoinflammation, and immunodeficiency, MIM# 621671
Mendeliome v2.524 IRAK2 Zornitza Stark edited their review of gene: IRAK2: Changed phenotypes: Immune dysregulation with autoimmunity, autoinflammation, and immunodeficiency, MIM# 621671
Mendeliome v2.524 IRAK2 Zornitza Stark Publications for gene: IRAK2 were set to PMID: 39299377
Mendeliome v2.523 IRAK2 Zornitza Stark Mode of inheritance for gene: IRAK2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.522 IRAK2 Zornitza Stark Classified gene: IRAK2 as Amber List (moderate evidence)
Mendeliome v2.522 IRAK2 Zornitza Stark Gene: irak2 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.521 IRAK2 Zornitza Stark Tag founder tag was added to gene: IRAK2.
Mendeliome v2.521 IRAK2 Zornitza Stark edited their review of gene: IRAK2: Added comment: PMID 42168171 reports 12 individuals from 11 unrelated Chinese families with a spectrum of complex immunologic disorders who all had the same homozygous variant in the IRAK2 gene identified by whole-exome or whole-genome sequencing. The individuals could be categorized into 3 phenotypic subgroups: immunodeficiency-predominant (P1 and P2), autoimmunity-predominant (P3-P7, P11, and P12), and autoinflammation-predominant (P8-P10). The variant is a homozygous 183-bp deletion (c.95_277del, NM_001570), resulting in an in-frame deletion of exon 2 along with portions of the flanking intronic regions (Ala32_Trp93delinsGly). Variant is relatively common in East Asian individuals, including 2 homozygotes in gnomAD.; Changed rating: AMBER; Changed publications: 42168171; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.521 Sarah Milton Copied Region ISCA-37447-Loss from panel Common deletion and duplication syndromes
Mendeliome v2.521 ISCA-37447-Loss Sarah Milton Region: ISCA-37447-Loss was added
Region: ISCA-37447-Loss was added to Mendeliome. Sources: Expert Review Green,ClinGen
SV/CNV tags were added to Region: ISCA-37447-Loss.
Mode of inheritance for Region: ISCA-37447-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for Region: ISCA-37447-Loss were set to 41926606; 39446997
Phenotypes for Region: ISCA-37447-Loss were set to Temple syndrome MIM#616222; Kagami-Ogata syndrome MIM#608149
Intellectual disability syndromic and non-syndromic v2.133 Sarah Milton Copied Region ISCA-37447-Loss from panel Common deletion and duplication syndromes
Intellectual disability syndromic and non-syndromic v2.133 ISCA-37447-Loss Sarah Milton Region: ISCA-37447-Loss was added
Region: ISCA-37447-Loss was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,ClinGen
SV/CNV tags were added to Region: ISCA-37447-Loss.
Mode of inheritance for Region: ISCA-37447-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for Region: ISCA-37447-Loss were set to 41926606; 39446997
Phenotypes for Region: ISCA-37447-Loss were set to Temple syndrome MIM#616222; Kagami-Ogata syndrome MIM#608149
Growth failure v2.24 Sarah Milton Copied Region ISCA-37447-Loss from panel Common deletion and duplication syndromes
Growth failure v2.24 ISCA-37447-Loss Sarah Milton Region: ISCA-37447-Loss was added
Region: ISCA-37447-Loss was added to Growth failure. Sources: Expert Review Green,ClinGen
SV/CNV tags were added to Region: ISCA-37447-Loss.
Mode of inheritance for Region: ISCA-37447-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for Region: ISCA-37447-Loss were set to 41926606; 39446997
Phenotypes for Region: ISCA-37447-Loss were set to Temple syndrome MIM#616222; Kagami-Ogata syndrome MIM#608149
Fetal anomalies v2.67 Sarah Milton Copied Region ISCA-37447-Loss from panel Common deletion and duplication syndromes
Fetal anomalies v2.67 ISCA-37447-Loss Sarah Milton Region: ISCA-37447-Loss was added
Region: ISCA-37447-Loss was added to Fetal anomalies. Sources: Expert Review Green,ClinGen
SV/CNV tags were added to Region: ISCA-37447-Loss.
Mode of inheritance for Region: ISCA-37447-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for Region: ISCA-37447-Loss were set to 41926606; 39446997
Phenotypes for Region: ISCA-37447-Loss were set to Temple syndrome MIM#616222; Kagami-Ogata syndrome MIM#608149
Common deletion and duplication syndromes v1.7 ISCA-37447-Loss Sarah Milton Marked Region: ISCA-37447-Loss as ready
Common deletion and duplication syndromes v1.7 ISCA-37447-Loss Sarah Milton Region: isca-37447-loss has been classified as Green List (High Evidence).
Common deletion and duplication syndromes v1.7 ISCA-37447-Loss Sarah Milton Classified Region: ISCA-37447-Loss as Green List (high evidence)
Common deletion and duplication syndromes v1.7 ISCA-37447-Loss Sarah Milton Region: isca-37447-loss has been classified as Green List (High Evidence).
Common deletion and duplication syndromes v1.6 ISCA-37447-Loss Sarah Milton Region: ISCA-37447-Loss was added
Region: ISCA-37447-Loss was added to Common deletion and duplication syndromes. Sources: ClinGen
SV/CNV tags were added to Region: ISCA-37447-Loss.
Mode of inheritance for Region: ISCA-37447-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for Region: ISCA-37447-Loss were set to 41926606; 39446997
Phenotypes for Region: ISCA-37447-Loss were set to Temple syndrome MIM#616222; Kagami-Ogata syndrome MIM#608149
Review for Region: ISCA-37447-Loss was set to GREEN
Added comment: This entry defines a region on chromosome 14 associated with Temple syndrome and Kagami Ogata syndrome.
This syndromes are typically caused by maternal UPD or paternal UPD of chromosome 14 respectively.

The defined region in this entry contains MEG3 - long non coding RNA, maternally expressed.
DLK1 - paternally expressed protein coding gene which is an epidermal growth factor

This region is imprinted with maternal deletions resulting in Kagami Ogata syndrome and paternal deletions resulting in Temple syndrome.

Other causes of these syndromes include abnormal methylation of MEG3/DLK1 DMR or MEG3::TSS-DMR.
Sources: ClinGen
Hereditary Neuropathy v2.31 GNE Sangavi Sivagnanasundram Classified gene: GNE as Amber List (moderate evidence)
Hereditary Neuropathy v2.31 GNE Sangavi Sivagnanasundram Gene: gne has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v2.30 GNE Sangavi Sivagnanasundram gene: GNE was added
gene: GNE was added to Hereditary Neuropathy. Sources: Literature
Mode of inheritance for gene: GNE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNE were set to 33094863
Phenotypes for gene: GNE were set to GNE-related motor neuropathy MONDO:0100546
Review for gene: GNE was set to AMBER
Added comment: PMID 33094863 reports two unrelated individuals from two unrelated families (one consanguineous) with adult‑onset progressive motor axonal neuropathy carrying rare biallelic GNE missense variants.
Sources: Literature
Cardiomyopathy_Paediatric v1.167 AGL Sarah Milton reviewed gene: AGL: Rating: GREEN; Mode of pathogenicity: None; Publications: 27106217; Phenotypes: Glycogen storage disease IIIa and IIIb, MIM#232400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.167 ACADVL Sarah Milton reviewed gene: ACADVL: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301763; Phenotypes: VLCAD deficiency, MIM#201475; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.167 DMD Richard Lin reviewed gene: DMD: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 8614119, 16246949, 27230049, 29395990, 36252992; Phenotypes: Becker muscular dystrophy, MIM:300376, Cardiomyopathy, dilated, 3B, MIM:302045, Duchenne muscular dystrophy, MIM: 310200; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cardiomyopathy_Paediatric v1.167 TMEM43 Sarah Milton reviewed gene: TMEM43: Rating: GREEN; Mode of pathogenicity: None; Publications: 18313022, 26840987; Phenotypes: Arrhythmogenic right ventricular dysplasia 5, MIM#604400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hand and foot malformations v1.10 FAT1 Zornitza Stark reviewed gene: FAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v2.520 AFF3 Zornitza Stark Publications for gene: AFF3 were set to 31388108; 33961779
Intellectual disability syndromic and non-syndromic v2.132 AFF3 Zornitza Stark Publications for gene: AFF3 were set to 31388108; 33961779
Mendeliome v2.519 GLYR1 Zornitza Stark Marked gene: GLYR1 as ready
Mendeliome v2.519 GLYR1 Zornitza Stark Gene: glyr1 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v1.35 GLYR1 Zornitza Stark Marked gene: GLYR1 as ready
Congenital Heart Defect v1.35 GLYR1 Zornitza Stark Gene: glyr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.519 ATP5ME Zornitza Stark Marked gene: ATP5ME as ready
Mendeliome v2.519 ATP5ME Zornitza Stark Gene: atp5me has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v2.7 ATP5ME Zornitza Stark Marked gene: ATP5ME as ready
Mitochondrial disease v2.7 ATP5ME Zornitza Stark Gene: atp5me has been classified as Amber List (Moderate Evidence).
Mendeliome v2.519 PREX1 Zornitza Stark Marked gene: PREX1 as ready
Mendeliome v2.519 PREX1 Zornitza Stark Gene: prex1 has been classified as Red List (Low Evidence).
Autism v1.18 PREX1 Zornitza Stark Marked gene: PREX1 as ready
Autism v1.18 PREX1 Zornitza Stark Gene: prex1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v2.131 PREX1 Zornitza Stark Marked gene: PREX1 as ready
Intellectual disability syndromic and non-syndromic v2.131 PREX1 Zornitza Stark Gene: prex1 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.167 FASTKD2 Zornitza Stark Marked gene: FASTKD2 as ready
Cardiomyopathy_Paediatric v1.167 FASTKD2 Zornitza Stark Gene: fastkd2 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.167 FASTKD2 Zornitza Stark Phenotypes for gene: FASTKD2 were changed from ?Mitochondrial complex IV deficiency, 220110 to FASTKD2-related infantile mitochondrial encephalomyopathy, MONDO:0015632
Cardiomyopathy_Paediatric v1.166 FASTKD2 Zornitza Stark Publications for gene: FASTKD2 were set to 28499982
Cardiomyopathy_Paediatric v1.165 FASTKD2 Zornitza Stark Classified gene: FASTKD2 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.165 FASTKD2 Zornitza Stark Gene: fastkd2 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.164 MMACHC Zornitza Stark Marked gene: MMACHC as ready
Cardiomyopathy_Paediatric v1.164 MMACHC Zornitza Stark Gene: mmachc has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.164 MMACHC Zornitza Stark Phenotypes for gene: MMACHC were changed from Dehydration, hepatomegaly, lethargy, coma, acidosis, high anion gap; Methylmalonic aciduria; DCM; Methylmalonic aciduria and homocystinuria, cblC type, 277400; Hypertrophic-hypocontractile cardiomyopathy to methylmalonic aciduria and homocystinuria type cblC, MONDO:0010184
Cardiomyopathy_Paediatric v1.163 MMACHC Zornitza Stark Publications for gene: MMACHC were set to 27604308
Cardiomyopathy_Paediatric v1.162 MMACHC Zornitza Stark Classified gene: MMACHC as Green List (high evidence)
Cardiomyopathy_Paediatric v1.162 MMACHC Zornitza Stark Gene: mmachc has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.161 TSFM Zornitza Stark Marked gene: TSFM as ready
Cardiomyopathy_Paediatric v1.161 TSFM Zornitza Stark Gene: tsfm has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.161 TSFM Zornitza Stark Phenotypes for gene: TSFM were changed from Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Combined oxidative phosphorylation deficiency 3, 610505; Combined oxidative phosphorylation deficiency 3 610505 to Combined oxidative phosphorylation deficiency 3, MIM# 610505
Cardiomyopathy_Paediatric v1.160 TSFM Zornitza Stark Publications for gene: TSFM were set to 27604308
Cardiomyopathy_Paediatric v1.159 TSFM Zornitza Stark reviewed gene: TSFM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 3, MIM# 610505; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.159 DSC2 Zornitza Stark Marked gene: DSC2 as ready
Cardiomyopathy_Paediatric v1.159 DSC2 Zornitza Stark Gene: dsc2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.159 SDHD Sarah Milton Marked gene: SDHD as ready
Cardiomyopathy_Paediatric v1.159 SDHD Sarah Milton Gene: sdhd has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.159 DSC2 Zornitza Stark Phenotypes for gene: DSC2 were changed from Arrhythmogenic right ventricular dysplasia 11; Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair to familial isolated arrhythmogenic right ventricular dysplasia, MONDO:0016342
Cardiomyopathy_Paediatric v1.158 SDHD Sarah Milton Classified gene: SDHD as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.158 SDHD Sarah Milton Gene: sdhd has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.157 SDHD Sarah Milton reviewed gene: SDHD: Rating: AMBER; Mode of pathogenicity: None; Publications: 34012134, 26008905; Phenotypes: Mitochondrial complex II deficiency, Nuclear type 3 MIM#619167; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.157 DSC2 Zornitza Stark Publications for gene: DSC2 were set to
Cardiomyopathy_Paediatric v1.156 DSC2 Zornitza Stark Mode of inheritance for gene: DSC2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.155 DSC2 Zornitza Stark Classified gene: DSC2 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.155 DSC2 Zornitza Stark Gene: dsc2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.154 FKTN Zornitza Stark Marked gene: FKTN as ready
Cardiomyopathy_Paediatric v1.154 FKTN Zornitza Stark Gene: fktn has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.154 FKTN Zornitza Stark Phenotypes for gene: FKTN were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type; Dilated Cardiomyopathy, Recessive; Fukuyama Congenital Muscular Dystrophy; Fukuyama congenital muscular dystrophy; Muscular dystrophy-dystroglycanopathy (congenital without mental retardation), type B, 4 613152; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 253800; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4 611588; Cardiomyopathy, dilated, 1X; Fukutin deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies) to dilated cardiomyopathy 1X, MONDO:0012704; muscular dystrophy-dystroglycanopathy, type A, MONDO:0000171
Cardiomyopathy_Paediatric v1.153 FKTN Zornitza Stark Publications for gene: FKTN were set to 27604308
Cardiomyopathy_Paediatric v1.152 NDUFV2 Zornitza Stark Marked gene: NDUFV2 as ready
Cardiomyopathy_Paediatric v1.152 NDUFV2 Zornitza Stark Gene: ndufv2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.152 NDUFV2 Zornitza Stark Phenotypes for gene: NDUFV2 were changed from Mitochondrial complex I deficiency, nuclear type 7, 618229 to Mitochondrial complex I deficiency, nuclear type 7, MIM#618229
Cardiomyopathy_Paediatric v1.151 NDUFV2 Zornitza Stark Publications for gene: NDUFV2 were set to
Cardiomyopathy_Paediatric v1.150 GATA6 Zornitza Stark Marked gene: GATA6 as ready
Cardiomyopathy_Paediatric v1.150 GATA6 Zornitza Stark Gene: gata6 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.150 GATA6 Zornitza Stark Phenotypes for gene: GATA6 were changed from to dilated cardiomyopathy, MONDO:0005021, GATA6-related
Cardiomyopathy_Paediatric v1.149 GATA6 Zornitza Stark Publications for gene: GATA6 were set to
Cardiomyopathy_Paediatric v1.148 GATA6 Zornitza Stark Classified gene: GATA6 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.148 GATA6 Zornitza Stark Gene: gata6 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.147 GATA6 Zornitza Stark reviewed gene: GATA6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: dilated cardiomyopathy, MONDO:0005021, GATA6-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.147 GATA6 Sarah Milton reviewed gene: GATA6: Rating: AMBER; Mode of pathogenicity: None; Publications: 35962153; Phenotypes: dilated cardiomyopathy, MONDO:0005021, GATA6-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.147 NDUFV2 Richard Lin reviewed gene: NDUFV2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMIDs: 12754703, 19167255, 26008862; Phenotypes: Leigh syndrome, MONDO:0009723, Mitochondrial complex I deficiency, nuclear type 7, MIM: 618229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.147 FKTN Richard Lin reviewed gene: FKTN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 17036286, 23746544, 24144914, 27521547, 35743126; Phenotypes: dilated cardiomyopathy 1X, MONDO:0012704, muscular dystrophy-dystroglycanopathy, type A, MONDO:0000171; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.147 DSC2 Richard Lin changed review comment from: Two studies report 3 unrelated patients with biallelic DSC2 variants and paediatric onset arrhythmogenic (right ventricular) cardiomyopathy (PMIDs: 24793512, 26310507). Reported variants in DSC2 are likely VUS.

PMID: 24793512 - 10 year old F with sudden cardiac arrest and typical/advanced features of ARVC, found to be homozygous for an inframe deletion in DSC2:c.712_714delGAT, p.(Asp238del). 2 male sibs and both parents heterozygous for the same variant, clinically unaffected.
PMID: 26310507 - cohort study which found a homozygous missense variant DSC2: c.536A>G, p.(Asp179Gly) in 5 patients from 4 families, including 2 unrelated paediatric patients aged 14 and 11 with arrhythmogenic cardiomyopathy
PMID: 20197793 - functional study which shown that the DSC2 p.Asp179Gly variant protein correctly colocalizes at the cell membrane with endogenous desmoglein in a transfected desmosome-forming cell line, indicating this variant has no impact on desmosome assembly; to: Association between heterozygous variants and arrhythmogenic right ventricular dysplasia classified as definitive by ClinGen. Reported cases are adult-onset disease.

Two studies report 3 unrelated patients with biallelic DSC2 variants and paediatric onset arrhythmogenic (right ventricular) cardiomyopathy (PMIDs: 24793512, 26310507), though reported variants are likely VUS.

PMID: 24793512 - 10 year old F with sudden cardiac arrest and typical/advanced features of ARVC, found to be homozygous for an inframe deletion in DSC2:c.712_714delGAT, p.(Asp238del). 2 male sibs and both parents heterozygous for the same variant, clinically unaffected.
PMID: 26310507 - cohort study which found a homozygous missense variant DSC2: c.536A>G, p.(Asp179Gly) in 5 patients from 4 families, including 2 unrelated paediatric patients aged 14 and 11 with arrhythmogenic cardiomyopathy
PMID: 20197793 - functional study which shown that the DSC2 p.Asp179Gly variant protein correctly colocalises at the cell membrane with endogenous desmoglein in a transfected desmosome-forming cell line, indicating this variant has no impact on desmosome assembly
Cardiomyopathy_Paediatric v1.147 DSC2 Richard Lin changed review comment from: Two studies report 3 unrelated patients with paediatric onset arrhythmogenic (right ventricular) cardiomyopathy (PMIDs: 24793512, 26310507). Reported variants are likely VUS.

PMID: 24793512 - 10 year old F with sudden cardiac arrest and typical/advanced features of ARVC, found to be homozygous for an inframe deletion in DSC2:c.712_714delGAT, p.(Asp238del). 2 male sibs and both parents heterozygous for the same variant, clinically unaffected.
PMID: 26310507 - cohort study which found a homozygous missense variant DSC2: c.536A>G, p.(Asp179Gly) in 5 patients from 4 families, including 2 unrelated paediatric patients aged 14 and 11 with arrhythmogenic cardiomyopathy
PMID: 20197793 - functional study which shown that the DSC2 p.Asp179Gly variant protein correctly colocalizes at the cell membrane with endogenous desmoglein in a transfected desmosome-forming cell line, indicating this variant has no impact on desmosome assembly; to: Two studies report 3 unrelated patients with biallelic DSC2 variants and paediatric onset arrhythmogenic (right ventricular) cardiomyopathy (PMIDs: 24793512, 26310507). Reported variants in DSC2 are likely VUS.

PMID: 24793512 - 10 year old F with sudden cardiac arrest and typical/advanced features of ARVC, found to be homozygous for an inframe deletion in DSC2:c.712_714delGAT, p.(Asp238del). 2 male sibs and both parents heterozygous for the same variant, clinically unaffected.
PMID: 26310507 - cohort study which found a homozygous missense variant DSC2: c.536A>G, p.(Asp179Gly) in 5 patients from 4 families, including 2 unrelated paediatric patients aged 14 and 11 with arrhythmogenic cardiomyopathy
PMID: 20197793 - functional study which shown that the DSC2 p.Asp179Gly variant protein correctly colocalizes at the cell membrane with endogenous desmoglein in a transfected desmosome-forming cell line, indicating this variant has no impact on desmosome assembly
Cardiomyopathy_Paediatric v1.147 DSC2 Richard Lin changed review comment from: Two studies report 3 unrelated patients with paediatric onset arrhythmogenic (right ventricular) cardiomyopathy (PMIDs: 24793512, 26310507). Reported variants are likely VUS.

PMID: 24793512 - 10 year old F with sudden cardiac arrest and typical/advanced features of ARVC, found to be homozygous for an inframe deletion in DSC2:c.712_714delGAT, p.(Asp238del). 2 male sibs and both parents heterozygous for the same variant, clinically unaffected.
PMID: 26310507 - cohort study which found a homozygous missense variant DSC2: c.536A>G, p.(Asp179Gly) in 5 patients from 4 families, including 2 unrelated paediatric patients aged 14 and 11 with arrhythmogenic cardiomyopathy
PMID: 20197793 - functional study which shown that the DSC2 p.Asp179Gly variant protein correctly colocalizes at the cell membrane with endogenous desmoglein in a transfected desmosome-forming cell line, indicating this variant has no impact on desmosome assembly; to: Two studies report 3 unrelated patients with paediatric onset arrhythmogenic (right ventricular) cardiomyopathy (PMIDs: 24793512, 26310507). Reported variants are likely VUS.

PMID: 24793512 - 10 year old F with sudden cardiac arrest and typical/advanced features of ARVC, found to be homozygous for an inframe deletion in DSC2:c.712_714delGAT, p.(Asp238del). 2 male sibs and both parents heterozygous for the same variant, clinically unaffected.
PMID: 26310507 - cohort study which found a homozygous missense variant DSC2: c.536A>G, p.(Asp179Gly) in 5 patients from 4 families, including 2 unrelated paediatric patients aged 14 and 11 with arrhythmogenic cardiomyopathy
PMID: 20197793 - functional study which shown that the DSC2 p.Asp179Gly variant protein correctly colocalizes at the cell membrane with endogenous desmoglein in a transfected desmosome-forming cell line, indicating this variant has no impact on desmosome assembly
Cardiomyopathy_Paediatric v1.147 DSC2 Richard Lin reviewed gene: DSC2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMIDs: 20197793, 24793512, 26310507; Phenotypes: Syndromic disease, MONDO:0002254, familial isolated arrhythmogenic right ventricular dysplasia, MONDO:0016342; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v2.1 MAX TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"

Rationale: Clinician supported inclusion, childhood cancer predisposition causing (Pheochromocytomas and paragangliomas)
Sources: Expert Review; to: Please tag as "TRAIL Study"

Clinician supported inclusion, childhood cancer predisposition causing pheochromocytomas and paragangliomas, monitoring for early intervention

Sources: Expert Review
Genomic newborn screening: BabyScreen+ v2.1 TMEM127 TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"

Rationale: Clinician supported inclusion, childhood cancer predisposition causing (Pheochromocytomas and paragangliomas)
Sources: Expert Review; to: Please tag as "TRAIL Study"

Clinician supported inclusion, childhood cancer predisposition causing pheochromocytomas and paragangliomas, monitoring for early intervention

Sources: Expert Review
Common deletion and duplication syndromes v1.5 ISCA-37446-Loss Sarah Milton Chromosome 22q11.2 deletion syndrome, distal was changed to Chromosome 22q11.2 deletion syndrome, DiGeorge syndrome
Source Expert list was removed from Region: ISCA-37446-Loss.
Source ClinGen was added to Region: ISCA-37446-Loss.
Clefting disorders v1.23 ISCA-37446-Loss Sarah Milton Chromosome 22q11.2 deletion syndrome, distal was changed to Chromosome 22q11.2 deletion syndrome, DiGeorge syndrome
Source Expert list was removed from Region: ISCA-37446-Loss.
Source Expert list was removed from Region: ISCA-37446-Loss.
Source ClinGen was added to Region: ISCA-37446-Loss.
Intellectual disability syndromic and non-syndromic v2.131 ISCA-37446-Loss Sarah Milton Chromosome 22q11.2 deletion syndrome, distal was changed to Chromosome 22q11.2 deletion syndrome, DiGeorge syndrome
Source Expert list was removed from Region: ISCA-37446-Loss.
Source Expert list was removed from Region: ISCA-37446-Loss.
Source ClinGen was added to Region: ISCA-37446-Loss.
Severe Combined Immunodeficiency v2.5 ISCA-37446-Loss Sarah Milton Chromosome 22q11.2 deletion syndrome, distal was changed to Chromosome 22q11.2 deletion syndrome, DiGeorge syndrome
Source Expert list was removed from Region: ISCA-37446-Loss.
Source Expert list was removed from Region: ISCA-37446-Loss.
Source ClinGen was added to Region: ISCA-37446-Loss.
Genetic Epilepsy v2.39 ISCA-37446-Loss Sarah Milton Chromosome 22q11.2 deletion syndrome, distal was changed to Chromosome 22q11.2 deletion syndrome, DiGeorge syndrome
Source Expert list was removed from Region: ISCA-37446-Loss.
Source Expert list was removed from Region: ISCA-37446-Loss.
Source ClinGen was added to Region: ISCA-37446-Loss.
Congenital Heart Defect v1.35 ISCA-37446-Loss Sarah Milton Chromosome 22q11.2 deletion syndrome, distal was changed to Chromosome 22q11.2 deletion syndrome, DiGeorge syndrome
Source Expert list was removed from Region: ISCA-37446-Loss.
Source Expert list was removed from Region: ISCA-37446-Loss.
Source ClinGen was added to Region: ISCA-37446-Loss.
Cardiomyopathy_Paediatric v1.147 TSFM Richard Lin reviewed gene: TSFM: Rating: GREEN; Mode of pathogenicity: None; Publications: PMIDs: 35071363, 31451716, 31267352, 27677415, 25037205, 21741925, 17033963; Phenotypes: Mitochondrial disease, MONDO:0044970; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v2.1 MAX TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"

Rationale: Clinician supported inclusion, childhood cancer predisposition causing (Pheochromocytomas and paragangliomas)
Sources: Expert Review; to: Please tag as "TRAIL Study"

Rationale: Clinician supported inclusion, childhood cancer predisposition causing (Pheochromocytomas and paragangliomas)
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v2.1 MAX TRAIL SCHN gene: MAX was added
gene: MAX was added to Genomic newborn screening: BabyScreen+. Sources: Expert Review
Mode of inheritance for gene: MAX was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: MAX was set to RED
Added comment: Please tag as "TRAIL Study"

Rationale: Clinician supported inclusion, childhood cancer predisposition causing (Pheochromocytomas and paragangliomas)
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v2.1 TMEM127 TRAIL SCHN reviewed gene: TMEM127: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v2.1 TMEM127 TRAIL SCHN Deleted their review
Genomic newborn screening: BabyScreen+ v2.1 TMEM127 TRAIL SCHN gene: TMEM127 was added
gene: TMEM127 was added to Genomic newborn screening: BabyScreen+. Sources: Expert Review
Mode of inheritance for gene: TMEM127 was set to BIALLELIC, autosomal or pseudoautosomal
Added comment: Please tag as "TRAIL Study"

Rationale: Clinician supported inclusion, childhood cancer predisposition causing (Pheochromocytomas and paragangliomas)
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v2.1 IFNAR1 TRAIL SCHN gene: IFNAR1 was added
gene: IFNAR1 was added to Genomic newborn screening: BabyScreen+. Sources: Expert Review
Mode of inheritance for gene: IFNAR1 was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: IFNAR1 was set to RED
Added comment: Please tag as "TRAIL Study"

Contributed by one of the immunologists (for TRAIL only). Predicts adverse outcome to MMR vaccine.
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v2.1 LPIN1 TRAIL SCHN gene: LPIN1 was added
gene: LPIN1 was added to Genomic newborn screening: BabyScreen+. Sources: Expert Review
Mode of inheritance for gene: LPIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: LPIN1 was set to RED
Added comment: Please tag as "TRAIL Study"

Suggested by metabolic clinician. Known cause of severe rhabdomyolysis, early monitoring and treatment can improve outcomes.
Sources: Expert Review
Growth failure v2.22 ISCA-37397-Loss Sarah Milton GRCh38 position for ISCA-37397-Loss was changed from 21443089-23306926 to 21562828-22620608.
Source Expert list was removed from Region: ISCA-37397-Loss.
Source Expert list was removed from Region: ISCA-37397-Loss.
Source ClinGen was added to Region: ISCA-37397-Loss.
Common deletion and duplication syndromes v1.4 ISCA-37397-Loss Sarah Milton GRCh38 position for ISCA-37397-Loss was changed from 21443089-23306926 to 21562828-22620608.
Source Expert list was removed from Region: ISCA-37397-Loss.
Source ClinGen was added to Region: ISCA-37397-Loss.
Intellectual disability syndromic and non-syndromic v2.130 ISCA-37397-Loss Sarah Milton GRCh38 position for ISCA-37397-Loss was changed from 21443089-23306926 to 21562828-22620608.
Source Expert list was removed from Region: ISCA-37397-Loss.
Source Expert list was removed from Region: ISCA-37397-Loss.
Source ClinGen was added to Region: ISCA-37397-Loss.
Congenital Heart Defect v1.34 ISCA-37397-Loss Sarah Milton GRCh38 position for ISCA-37397-Loss was changed from 21443089-23306926 to 21562828-22620608.
Source Expert list was removed from Region: ISCA-37397-Loss.
Source Expert list was removed from Region: ISCA-37397-Loss.
Source ClinGen was added to Region: ISCA-37397-Loss.
Intellectual disability syndromic and non-syndromic v2.129 ISCA-37397-Gain Sarah Milton GRCh38 position for ISCA-37397-Gain was changed from 21443089-23306926 to 21562828-22620608.
Source Expert list was removed from Region: ISCA-37397-Gain.
Source Expert list was removed from Region: ISCA-37397-Gain.
Source ClinGen was added to Region: ISCA-37397-Gain.
Cardiomyopathy_Paediatric v1.147 TMEM70 Richard Lin reviewed gene: TMEM70: Rating: GREEN; Mode of pathogenicity: None; Publications: PMIDs: 20335238, 26550569, 27649480, 30899493, 30950220, 31729175, 36751706; Phenotypes: mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, MONDO:0013546; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.147 MMACHC Richard Lin changed review comment from: Biallelic variants in MMACHC are associated with Cobalamin C deficiency (cblC deficiency), a multisystemic condition.

Cardiomyopathy is described to occur in 10-25% of patients with early onset (below the age of 1 year) MMACHC-associated cblC deficiency in the 2026 Remethylation Disorders guidelines (PMID: 42231716). The predominant cardiomyopathy phenotype is left ventricular non compaction cardiomyopathy (PMIDs: 19767224, 20632110, 23430797, 24599607, 40830795, 42231716). Paediatric onset dilated cardiomyopathy has also been rarely reported (PMID: 19248038, 33562640, 38745823); to: Biallelic variants in MMACHC are associated with Cobalamin C deficiency (cblC deficiency), a multisystemic condition.

Cardiomyopathy is described to occur in 10-25% of patients with early onset (below the age of 1 year) MMACHC-associated cblC deficiency in the 2026 Remethylation Disorders guidelines (PMID: 42231716). The predominant cardiomyopathy phenotype is left ventricular non compaction cardiomyopathy (PMIDs: 19767224, 20632110, 23430797, 24599607, 40830795, 42231716). Paediatric onset dilated cardiomyopathy has also been rarely reported (PMID: 19248038, 33562640, 38745823)
Cardiomyopathy_Paediatric v1.147 PCCB Zornitza Stark Marked gene: PCCB as ready
Cardiomyopathy_Paediatric v1.147 PCCB Zornitza Stark Gene: pccb has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.147 PCCB Zornitza Stark Phenotypes for gene: PCCB were changed from as PCCA (metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections); Propionic acidemia; Propionicacidemia 606054; Propionic aciduria; Dehydration, hepatomegaly, lethargy, coma, acidosis, high anion gap; DCM; Propionic aciduria (Organic acidurias); Hypertrophic-hypocontractile cardiomyopathy; Propionicacidemia to propionic acidemia, MONDO:0011628
Cardiomyopathy_Paediatric v1.146 PCCB Zornitza Stark Publications for gene: PCCB were set to 27604308
Cardiomyopathy_Paediatric v1.145 PCCB Zornitza Stark reviewed gene: PCCB: Rating: GREEN; Mode of pathogenicity: None; Publications: 37529955, 36768524, 36393899, 34203287; Phenotypes: propionic acidemia, MONDO:0011628; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.145 HADHB Zornitza Stark Marked gene: HADHB as ready
Cardiomyopathy_Paediatric v1.145 HADHB Zornitza Stark Gene: hadhb has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.145 HADHB Zornitza Stark Phenotypes for gene: HADHB were changed from Trifunctional protein deficiency 609015; Mitochondrial trifunctional protein deficiency (Disorders of mitochondrial fatty acid oxidation); Mitochondrial Trifunctional Protein deficiency; Liver disease, hypotonia, hypoketotic hypoglycaemia, neuropathy, lactic acidosis, retinopathy, hypoparathyroidism; HCM; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) to mitochondrial trifunctional protein deficiency, MONDO:0012172
Cardiomyopathy_Paediatric v1.144 HADHB Zornitza Stark Publications for gene: HADHB were set to 27604308
Cardiomyopathy_Paediatric v1.143 HADHB Zornitza Stark reviewed gene: HADHB: Rating: GREEN; Mode of pathogenicity: None; Publications: 39088276, 28515471; Phenotypes: mitochondrial trifunctional protein deficiency, MONDO:0012172; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.143 HADHA Zornitza Stark Marked gene: HADHA as ready
Cardiomyopathy_Paediatric v1.143 HADHA Zornitza Stark Gene: hadha has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.143 HADHA Zornitza Stark Phenotypes for gene: HADHA were changed from Trifunctional protein deficiency 609015; Mitochondrial trifunctional protein deficiency (Disorders of mitochondrial fatty acid oxidation); Mitochondrial Trifunctional Protein deficiency; Liver disease, hypotonia, hypoketotic hypoglycaemia, neuropathy, lactic acidosis, retinopathy, hypoparathyroidism; HCM; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) to mitochondrial trifunctional protein deficiency, MONDO:0012172
Cardiomyopathy_Paediatric v1.142 HADHA Zornitza Stark Publications for gene: HADHA were set to 27604308
Cardiomyopathy_Paediatric v1.141 HADHA Zornitza Stark reviewed gene: HADHA: Rating: GREEN; Mode of pathogenicity: None; Publications: 39088276, 37754774, 35677112, 32999401, 28515471; Phenotypes: mitochondrial trifunctional protein deficiency, MONDO:0012172; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v2.128 TXNIP Zornitza Stark Marked gene: TXNIP as ready
Intellectual disability syndromic and non-syndromic v2.128 TXNIP Zornitza Stark Gene: txnip has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.128 TXNIP Zornitza Stark Publications for gene: TXNIP were set to 41116060; 30755400
Intellectual disability syndromic and non-syndromic v2.127 TXNIP Zornitza Stark Classified gene: TXNIP as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.127 TXNIP Zornitza Stark Gene: txnip has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.126 TXNIP Zornitza Stark edited their review of gene: TXNIP: Added comment: ID is not a consistent feature.; Changed rating: AMBER
Mitochondrial disease v2.7 TXNIP Zornitza Stark Marked gene: TXNIP as ready
Mitochondrial disease v2.7 TXNIP Zornitza Stark Gene: txnip has been classified as Green List (High Evidence).
Mitochondrial disease v2.7 TXNIP Zornitza Stark Publications for gene: TXNIP were set to 41116060; 30755400
Mitochondrial disease v2.6 TXNIP Zornitza Stark commented on gene: TXNIP: Included as lactic acidosis is a consistent feature of the condition.
Mitochondrial disease v2.6 Zornitza Stark Copied gene TXNIP from panel Miscellaneous Metabolic Disorders
Mitochondrial disease v2.6 TXNIP Zornitza Stark gene: TXNIP was added
gene: TXNIP was added to Mitochondrial disease. Sources: Expert Review Green,Literature,Literature
Mode of inheritance for gene: TXNIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TXNIP were set to 41116060; 30755400
Phenotypes for gene: TXNIP were set to Metabolic disease MONDO:0005066, TXNIP-related
Intellectual disability syndromic and non-syndromic v2.126 Zornitza Stark Copied gene TXNIP from panel Miscellaneous Metabolic Disorders
Intellectual disability syndromic and non-syndromic v2.126 TXNIP Zornitza Stark gene: TXNIP was added
gene: TXNIP was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature,Literature
Mode of inheritance for gene: TXNIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TXNIP were set to 41116060; 30755400
Phenotypes for gene: TXNIP were set to Metabolic disease MONDO:0005066, TXNIP-related
Miscellaneous Metabolic Disorders v2.3 TXNIP Zornitza Stark Classified gene: TXNIP as Green List (high evidence)
Miscellaneous Metabolic Disorders v2.3 TXNIP Zornitza Stark Gene: txnip has been classified as Green List (High Evidence).
Miscellaneous Metabolic Disorders v2.2 Zornitza Stark Added reviews for gene TXNIP from panel Mendeliome
Mendeliome v2.519 TXNIP Zornitza Stark Publications for gene: TXNIP were set to 41116060; 30755400
Mendeliome v2.518 TXNIP Zornitza Stark Classified gene: TXNIP as Green List (high evidence)
Mendeliome v2.518 TXNIP Zornitza Stark Gene: txnip has been classified as Green List (High Evidence).
Mendeliome v2.517 TXNIP Zornitza Stark reviewed gene: TXNIP: Rating: GREEN; Mode of pathogenicity: None; Publications: 42448226, 41116060, 30755400; Phenotypes: Metabolic disease MONDO:0005066, TXNIP-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v2.11 PALM3 Zornitza Stark Marked gene: PALM3 as ready
Deafness_IsolatedAndComplex v2.11 PALM3 Zornitza Stark Gene: palm3 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v2.11 Zornitza Stark Copied gene PALM3 from panel Mendeliome
Deafness_IsolatedAndComplex v2.11 PALM3 Zornitza Stark gene: PALM3 was added
gene: PALM3 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Literature
Mode of inheritance for gene: PALM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PALM3 were set to 42527583; 10.64898/2026.04.20.26351093
Phenotypes for gene: PALM3 were set to Non-syndromic genetic hearing loss, MONDO:0019497, PALM3-related
Mendeliome v2.517 PALM3 Zornitza Stark Marked gene: PALM3 as ready
Mendeliome v2.517 PALM3 Zornitza Stark Gene: palm3 has been classified as Red List (Low Evidence).
Mendeliome v2.517 PALM3 Zornitza Stark gene: PALM3 was added
gene: PALM3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PALM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PALM3 were set to 42527583; 10.64898/2026.04.20.26351093
Phenotypes for gene: PALM3 were set to Non-syndromic genetic hearing loss, MONDO:0019497, PALM3-related
Review for gene: PALM3 was set to RED
Added comment: PMID 42527583 reports one individual from a consanguineous family with a homozygous canonical splice‑site PALM3 variant (c.314+1G>A) presenting with autosomal recessive non‑syndromic sensorineural hearing loss. Minigene splice assay shows exon skipping and Palm3 knockout mice display auditory dysfunction, supporting a loss‑of‑function mechanism.
Sources: Literature
Cardiomyopathy_Paediatric v1.141 MMACHC Richard Lin reviewed gene: MMACHC: Rating: GREEN; Mode of pathogenicity: None; Publications: 19248038, 19767224, 20632110, 23430797, 24599607, 33562640, 38745823, 40830795, 42231716; Phenotypes: methylmalonic aciduria and homocystinuria type cblC, MONDO:0010184; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.141 FASTKD2 Richard Lin changed review comment from: PMID 31944455 reports 3 unrelated families with biallelic loss-of-function FASTKD2 variants causing mitochondrial disease; one family presented with childhood‑onset hypertrophic cardiomyopathy. A zebrafish knockdown model showed a decreased heart rate, structural cardiac morphology was not specifically commented by the authors.

PMID: 39094958 reports an adult diagnosed with hypertrophic cardiomyopathy diagnosed at age 37, with CKD, found to be homozygous for a FASTDK2 missense variant c.29G>C p.(Ser10Thr).

PMID: 38111113 reports a 39 year old patient with cardiomyopathy and nephropathy and a FASTKD2: c.29G>C (zygosity unknown), with the same authors as PMID: 39094958. Presumed to be the same patient.

Current evidence is insufficient for diagnostic grade classification for paediatric cardiomyopathy because only a single family with paediatric cardiomyopathy is reported.; to: PMID 31944455 reports 3 unrelated families with biallelic loss-of-function FASTKD2 variants causing mitochondrial disease; one family presented with childhood‑onset hypertrophic cardiomyopathy. A zebrafish knockdown model showed a decreased heart rate, structural cardiac morphology was not specifically commented by the authors.

PMID: 39094958 reports an adult diagnosed with hypertrophic cardiomyopathy diagnosed at age 37, with CKD, found to be homozygous for a FASTDK2 missense variant c.29G>C p.(Ser10Thr).

PMID: 38111113 reports a 39 year old patient with cardiomyopathy and nephropathy and a FASTKD2: c.29G>C variant (zygosity unknown), with the same authors as PMID: 39094958. Presumed to be the same patient.

Current evidence is insufficient for diagnostic grade classification for paediatric cardiomyopathy because only a single family with paediatric cardiomyopathy is reported.
Cardiomyopathy_Paediatric v1.141 FASTKD2 Richard Lin changed review comment from: PMID 31944455 reports 3 unrelated families with biallelic loss-of-function FASTKD2 variants causing mitochondrial disease; one family presented with childhood‑onset hypertrophic cardiomyopathy. A zebrafish knockdown model showed a decreased heart rate, cardiac morphology was not specifically commented by the authors.

PMID: 39094958 reports an adult diagnosed with hypertrophic cardiomyopathy diagnosed at age 37, with CKD, found to be homozygous for a FASTDK2 missense variant c.29G>C p.(Ser10Thr).

PMID: 38111113 reports a 39 year old patient with cardiomyopathy and nephropathy and a FASTKD2: c.29G>C (zygosity unknown), with the same authors as PMID: 39094958. Presumed to be the same patient.

Current evidence is insufficient for diagnostic grade classification for paediatric cardiomyopathy because only a single family with paediatric cardiomyopathy is reported.; to: PMID 31944455 reports 3 unrelated families with biallelic loss-of-function FASTKD2 variants causing mitochondrial disease; one family presented with childhood‑onset hypertrophic cardiomyopathy. A zebrafish knockdown model showed a decreased heart rate, structural cardiac morphology was not specifically commented by the authors.

PMID: 39094958 reports an adult diagnosed with hypertrophic cardiomyopathy diagnosed at age 37, with CKD, found to be homozygous for a FASTDK2 missense variant c.29G>C p.(Ser10Thr).

PMID: 38111113 reports a 39 year old patient with cardiomyopathy and nephropathy and a FASTKD2: c.29G>C (zygosity unknown), with the same authors as PMID: 39094958. Presumed to be the same patient.

Current evidence is insufficient for diagnostic grade classification for paediatric cardiomyopathy because only a single family with paediatric cardiomyopathy is reported.
Cardiomyopathy_Paediatric v1.141 FASTKD2 Richard Lin reviewed gene: FASTKD2: Rating: RED; Mode of pathogenicity: None; Publications: 31944455; Phenotypes: FASTKD2-related infantile mitochondrial encephalomyopathy, MONDO:0015632; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v2.66 CDC6 Lucy Spencer Publications for gene: CDC6 were set to 21358632
Fetal anomalies v2.65 CDC6 Lucy Spencer Classified gene: CDC6 as Green List (high evidence)
Fetal anomalies v2.65 CDC6 Lucy Spencer Gene: cdc6 has been classified as Green List (High Evidence).
Growth failure v2.21 CDC6 Lucy Spencer Publications for gene: CDC6 were set to 21358632
Growth failure v2.20 CDC6 Lucy Spencer Classified gene: CDC6 as Green List (high evidence)
Growth failure v2.20 CDC6 Lucy Spencer Gene: cdc6 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.122 CDC6 Lucy Spencer Publications for gene: CDC6 were set to
Skeletal dysplasia v1.121 CDC6 Lucy Spencer Classified gene: CDC6 as Green List (high evidence)
Skeletal dysplasia v1.121 CDC6 Lucy Spencer Gene: cdc6 has been classified as Green List (High Evidence).
Microcephaly v2.27 CDC6 Lucy Spencer Publications for gene: CDC6 were set to 21358632
Microcephaly v2.26 CDC6 Lucy Spencer Classified gene: CDC6 as Green List (high evidence)
Microcephaly v2.26 CDC6 Lucy Spencer Gene: cdc6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.125 CDC6 Lucy Spencer reviewed gene: CDC6: Rating: RED; Mode of pathogenicity: None; Publications: 35023948, 42496035; Phenotypes: Meier-Gorlin syndrome 5 (MIM#613805); Mode of inheritance: None
Skeletal dysplasia v1.120 Lucy Spencer Added reviews for gene CDC6 from panel Mendeliome
Microcephaly v2.25 Lucy Spencer Added reviews for gene CDC6 from panel Mendeliome
Growth failure v2.19 Lucy Spencer Added reviews for gene CDC6 from panel Mendeliome
Fetal anomalies v2.64 Lucy Spencer Added reviews for gene CDC6 from panel Mendeliome
Mendeliome v2.516 CDC6 Lucy Spencer Publications for gene: CDC6 were set to 21358632
Mendeliome v2.515 CDC6 Lucy Spencer Classified gene: CDC6 as Green List (high evidence)
Mendeliome v2.515 CDC6 Lucy Spencer Gene: cdc6 has been classified as Green List (High Evidence).
Mendeliome v2.514 CDC6 Lucy Spencer reviewed gene: CDC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 21358632, 42496035, 35023948; Phenotypes: Meier-Gorlin syndrome 5 MIM#613805; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.141 IDUA Zornitza Stark Marked gene: IDUA as ready
Cardiomyopathy_Paediatric v1.141 IDUA Zornitza Stark Gene: idua has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.141 IDUA Zornitza Stark Phenotypes for gene: IDUA were changed from Scheie syndrome; Hurler-Scheie syndrome; Mucopolysaccharidosis type 1H; Mucopolysaccharidosis Ih/s, 607015; Mucopolysaccharidosis Ih, 607014; Mucopolysaccharidosis type 1S; Hurler syndrome; MPS I, Hurler, Scheie disease (Mucopolysaccharidoses); Mucopolysaccharidosis, Type I; Mucopolysaccharidosis type 1H/S; Mucopolysaccharidosis Is, 607016 to mucopolysaccharidosis type 1, MONDO:0001586
Cardiomyopathy_Paediatric v1.140 IDUA Zornitza Stark Publications for gene: IDUA were set to 27604308
Cardiomyopathy_Paediatric v1.139 IDUA Zornitza Stark reviewed gene: IDUA: Rating: GREEN; Mode of pathogenicity: None; Publications: 41582445, 35893030, 27146977; Phenotypes: mucopolysaccharidosis type 1, MONDO:0001586; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.139 IDS Zornitza Stark Marked gene: IDS as ready
Cardiomyopathy_Paediatric v1.139 IDS Zornitza Stark Gene: ids has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.139 IDS Zornitza Stark Phenotypes for gene: IDS were changed from MPS II, Hunter disease (Mucopolysaccharidoses); MUCOPOLYSACCHARIDOSIS TYPE 2; Mucopolysaccharidosis Type II; Mucopolysaccharidosis II, 309900 to mucopolysaccharidosis type 2, MONDO:0010674
Cardiomyopathy_Paediatric v1.138 IDS Zornitza Stark Publications for gene: IDS were set to 27604308
Cardiomyopathy_Paediatric v1.137 IDS Zornitza Stark reviewed gene: IDS: Rating: GREEN; Mode of pathogenicity: None; Publications: 35882106, 34193122, 32256517, 27146977; Phenotypes: mucopolysaccharidosis type 2, MONDO:0010674; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cardiomyopathy_Paediatric v1.137 HRAS Zornitza Stark Marked gene: HRAS as ready
Cardiomyopathy_Paediatric v1.137 HRAS Zornitza Stark Gene: hras has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.137 HRAS Zornitza Stark reviewed gene: HRAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 34964243, 34618388, 31712860, 30732632, 27554254, 25914166; Phenotypes: Costello syndrome, MONDO:0009026; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v1.33 EHMT2 Zornitza Stark Marked gene: EHMT2 as ready
Congenital Heart Defect v1.33 EHMT2 Zornitza Stark Gene: ehmt2 has been classified as Green List (High Evidence).
Congenital Heart Defect v1.33 EHMT2 Zornitza Stark Classified gene: EHMT2 as Green List (high evidence)
Congenital Heart Defect v1.33 EHMT2 Zornitza Stark Gene: ehmt2 has been classified as Green List (High Evidence).
Mendeliome v2.514 EHMT2 Zornitza Stark Marked gene: EHMT2 as ready
Mendeliome v2.514 EHMT2 Zornitza Stark Gene: ehmt2 has been classified as Green List (High Evidence).
Mendeliome v2.514 EHMT2 Zornitza Stark Classified gene: EHMT2 as Green List (high evidence)
Mendeliome v2.514 EHMT2 Zornitza Stark Gene: ehmt2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.125 EHMT2 Zornitza Stark Marked gene: EHMT2 as ready
Intellectual disability syndromic and non-syndromic v2.125 EHMT2 Zornitza Stark Gene: ehmt2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.125 EHMT2 Zornitza Stark Classified gene: EHMT2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v2.125 EHMT2 Zornitza Stark Gene: ehmt2 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v1.2 XXYLT1 Zornitza Stark Marked gene: XXYLT1 as ready
Macular Dystrophy/Stargardt Disease v1.2 XXYLT1 Zornitza Stark Gene: xxylt1 has been classified as Amber List (Moderate Evidence).
Macular Dystrophy/Stargardt Disease v1.2 Zornitza Stark Copied gene XXYLT1 from panel Mendeliome
Macular Dystrophy/Stargardt Disease v1.2 XXYLT1 Zornitza Stark gene: XXYLT1 was added
gene: XXYLT1 was added to Macular Dystrophy/Stargardt Disease. Sources: Expert Review Amber,Literature
founder tags were added to gene: XXYLT1.
Mode of inheritance for gene: XXYLT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XXYLT1 were set to 42530953
Phenotypes for gene: XXYLT1 were set to Inherited retinal dystrophy, MONDO:0019118, XXYLT1-related
Mendeliome v2.513 XXYLT1 Zornitza Stark Marked gene: XXYLT1 as ready
Mendeliome v2.513 XXYLT1 Zornitza Stark Gene: xxylt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.513 XXYLT1 Zornitza Stark Classified gene: XXYLT1 as Amber List (moderate evidence)
Mendeliome v2.513 XXYLT1 Zornitza Stark Gene: xxylt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.512 XXYLT1 Zornitza Stark gene: XXYLT1 was added
gene: XXYLT1 was added to Mendeliome. Sources: Literature
founder tags were added to gene: XXYLT1.
Mode of inheritance for gene: XXYLT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XXYLT1 were set to 42530953
Phenotypes for gene: XXYLT1 were set to Inherited retinal dystrophy, MONDO:0019118, XXYLT1-related
Review for gene: XXYLT1 was set to AMBER
Added comment: PMID 42530953 reports 7 individuals from 5 families with biallelic loss-of-function and missense variants in XXYLT1 presenting with inherited retinal dystrophy (cone‑rod or macular dystrophy). Homozygous c.505‑1G>C splice‑site variant found in four Finnish families (founder allele) and homozygous c.766G>A missense variant in a consanguineous UK family. Phenotypes included visual deterioration, cystoid macular oedema and schisis‑like macular changes; RNA splicing assays show exon 2 skipping for the recurrent c.505‑1G>C founder variant and Xylt1 knockout mice recapitulated retinal abnormalities.
Sources: Literature
Retinitis pigmentosa v1.12 DNAJC17 Zornitza Stark Marked gene: DNAJC17 as ready
Retinitis pigmentosa v1.12 DNAJC17 Zornitza Stark Gene: dnajc17 has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa v1.12 Zornitza Stark Copied gene DNAJC17 from panel Autoinflammatory Disorders
Retinitis pigmentosa v1.12 DNAJC17 Zornitza Stark gene: DNAJC17 was added
gene: DNAJC17 was added to Retinitis pigmentosa. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: DNAJC17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC17 were set to PMID: 42495638
Phenotypes for gene: DNAJC17 were set to Inborn error of immunity, MONDO:0003778, DNAJC17-related
Disorders of immune dysregulation v2.10 GPR174 Zornitza Stark Marked gene: GPR174 as ready
Disorders of immune dysregulation v2.10 GPR174 Zornitza Stark Gene: gpr174 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v2.10 Zornitza Stark Copied gene GPR174 from panel Mendeliome
Disorders of immune dysregulation v2.10 GPR174 Zornitza Stark gene: GPR174 was added
gene: GPR174 was added to Disorders of immune dysregulation. Sources: Expert Review Green,Literature
preprint tags were added to gene: GPR174.
Mode of inheritance for gene: GPR174 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GPR174 were set to 42528559
Phenotypes for gene: GPR174 were set to Inborn error of immunity, MONDO:0003778, GPR174-related
Mendeliome v2.511 GPR174 Zornitza Stark edited their review of gene: GPR174: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v2.511 GPR174 Zornitza Stark Marked gene: GPR174 as ready
Mendeliome v2.511 GPR174 Zornitza Stark Gene: gpr174 has been classified as Green List (High Evidence).
Mendeliome v2.511 GPR174 Zornitza Stark Mode of inheritance for gene: GPR174 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v2.510 GPR174 Zornitza Stark Classified gene: GPR174 as Green List (high evidence)
Mendeliome v2.510 GPR174 Zornitza Stark Gene: gpr174 has been classified as Green List (High Evidence).
Mendeliome v2.509 GPR174 Zornitza Stark gene: GPR174 was added
gene: GPR174 was added to Mendeliome. Sources: Literature
preprint tags were added to gene: GPR174.
Mode of inheritance for gene: GPR174 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: GPR174 were set to 42528559
Phenotypes for gene: GPR174 were set to Inborn error of immunity, MONDO:0003778, GPR174-related
Review for gene: GPR174 was set to GREEN
Added comment: PMID 42528559 reports six hemizygous males from five families with X-linked loss-of-function GPR174 variants presenting with childhood-onset lymphadenopathy, splenomegaly, histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease) and autoimmune cytopenias. Cell‑based cAMP reporter assays and protein‑level analyses demonstrate reduced receptor abundance and signalling, and CD8 T‑cell hyper‑proliferation.
Sources: Literature
Intellectual disability syndromic and non-syndromic v2.124 Lucy Spencer Copied gene PREX1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.124 PREX1 Lucy Spencer gene: PREX1 was added
gene: PREX1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PREX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PREX1 were set to 42399407; 26621702
Phenotypes for gene: PREX1 were set to Neurodevelopmental disorder (MONDO:0700092), PREX1-related
Genetic Epilepsy v2.38 Lucy Spencer Copied gene PREX1 from panel Mendeliome
Genetic Epilepsy v2.38 PREX1 Lucy Spencer gene: PREX1 was added
gene: PREX1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PREX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PREX1 were set to 42399407; 26621702
Phenotypes for gene: PREX1 were set to Neurodevelopmental disorder (MONDO:0700092), PREX1-related
Autism v1.18 Lucy Spencer Copied gene PREX1 from panel Mendeliome
Autism v1.18 PREX1 Lucy Spencer gene: PREX1 was added
gene: PREX1 was added to Autism. Sources: Literature
Mode of inheritance for gene: PREX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PREX1 were set to 42399407; 26621702
Phenotypes for gene: PREX1 were set to Neurodevelopmental disorder (MONDO:0700092), PREX1-related
Mendeliome v2.508 PREX1 Lucy Spencer gene: PREX1 was added
gene: PREX1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PREX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PREX1 were set to 42399407; 26621702
Phenotypes for gene: PREX1 were set to Neurodevelopmental disorder (MONDO:0700092), PREX1-related
Review for gene: PREX1 was set to RED
Added comment: PMID 42399407 reports 1 individual with a de novo heterozygous missense p.Y191C PREX1 variant which has 1 heterozygote in gnomad. The proband had onset of epilepsy at 9yo which remitted at 13yo, she had no intellectual disability or abnormal MRI findings. Her mother also has several seizures and her maternal grandfather had one seizure as a child, however the PREX1 variant identified in the proband was de novo. Functional analysis of the variant showed that it reduced the GDP/GTP exchange activity of PREX1 towards RAC1 and attenuated downstream signaling.

PMID 26621702 reports four probands with a heterozygous ~1.4 kb deletion over the promoter and exon 1 of PREX1 presenting. All presented with childhood‑onset autism spectrum disorder.
Sources: Literature
Mitochondrial disease v2.5 Lucy Spencer Copied gene ATP5ME from panel Mendeliome
Mitochondrial disease v2.5 ATP5ME Lucy Spencer gene: ATP5ME was added
gene: ATP5ME was added to Mitochondrial disease. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: ATP5ME was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP5ME were set to 42403019
Phenotypes for gene: ATP5ME were set to Mitochondrial disease (MONDO:0044970), ATP5ME-related
Mendeliome v2.507 ATP5ME Lucy Spencer Classified gene: ATP5ME as Amber List (moderate evidence)
Mendeliome v2.507 ATP5ME Lucy Spencer Gene: atp5me has been classified as Amber List (Moderate Evidence).
Mendeliome v2.506 ATP5ME Lucy Spencer gene: ATP5ME was added
gene: ATP5ME was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP5ME was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP5ME were set to 42403019
Phenotypes for gene: ATP5ME were set to Mitochondrial disease (MONDO:0044970), ATP5ME-related
Review for gene: ATP5ME was set to AMBER
Added comment: PMID 42403019 reports one individual from one consanguineous family with a homozygous 62‑bp deletion (NC_000004.12: g.674234_674295del, c.-48_14del) in ATP5ME. The proband had neuroregression, encephalopathy, spasticity, sensorineural hearing loss and optic atrophy. Patient fibroblasts show markedly reduced ATP5ME transcript and protein levels and reduced expression and activity of OXPHOS complexes I, IV and V. A zebrafish atp5me (orthologue) knockout model recapitulated the developmental and locomotor defects in the proband, and these defects were rescued by complementation with human ATP5ME mRNA.
Sources: Literature
Congenital Heart Defect v1.32 Lucy Spencer Copied gene GLYR1 from panel Mendeliome
Congenital Heart Defect v1.32 GLYR1 Lucy Spencer gene: GLYR1 was added
gene: GLYR1 was added to Congenital Heart Defect. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: GLYR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GLYR1 were set to 35182466; 38070486
Phenotypes for gene: GLYR1 were set to Congenital heart disease (MONDO:0005453), GLYR1-related
Mendeliome v2.505 GLYR1 Lucy Spencer Classified gene: GLYR1 as Amber List (moderate evidence)
Mendeliome v2.505 GLYR1 Lucy Spencer Gene: glyr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.504 GLYR1 Lucy Spencer gene: GLYR1 was added
gene: GLYR1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GLYR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GLYR1 were set to 35182466; 38070486
Phenotypes for gene: GLYR1 were set to Congenital heart disease (MONDO:0005453), GLYR1-related
Review for gene: GLYR1 was set to AMBER
Added comment: PMID 35182466 reports 1 individual with a de novo heterozygous missense GLYR1 p.P496L variant causing congenital heart disease with atrioventricular septal defects, left‑ventricular outflow tract obstruction and pulmonary stenosis. Functional assays including co‑immunoprecipitation, and a luciferase reporter assay demonstrated loss‑of‑function effects. In a mouse knock‑in model 54% of homozygous P496L mice and 15.5% of heterozygous mice had postnatal lethality between days 0-1, while for WT mice it was only 4.4, and VSD was seen in 15% of homozygous mice.

PMID 38070486 reports 4 individuals from 1 family harbouring a heterozygous frameshift GLYR1 c.1132delA p.R378Gfs*23 variant presenting with atrial and ventricular septal defects, arrhythmia and pulmonary hypertension. The variant segregated with disease in 4 affected individuals and was not present in 1 unaffected family member. However this variant has 74 heterozygotes in gnomad v4 and while it is predicted to undergo NMD a western blot in this paper suggests it creates a truncated protein.
Sources: Literature
Cardiomyopathy_Paediatric v1.137 COA6 Zornitza Stark Marked gene: COA6 as ready
Cardiomyopathy_Paediatric v1.137 COA6 Zornitza Stark Gene: coa6 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.137 COA6 Zornitza Stark Phenotypes for gene: COA6 were changed from Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4 616501 to Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4, MONDO:0014668
Cardiomyopathy_Paediatric v1.136 COA6 Zornitza Stark Publications for gene: COA6 were set to 25339201; 22277967; 25959673; 24549041
Cardiomyopathy_Paediatric v1.135 COA6 Zornitza Stark reviewed gene: COA6: Rating: GREEN; Mode of pathogenicity: None; Publications: 26160915, 25959673; Phenotypes: cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4, MONDO:0014668; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.135 BRAF Zornitza Stark Phenotypes for gene: BRAF were changed from Noonan syndrome 7 613706; Cardiofaciocutaneous syndrome 115150; syndromic HCM to Noonan syndrome, MONDO:0018997; cardiofaciocutaneous syndrome 1, MONDO:0007265
Cardiomyopathy_Paediatric v1.134 BRAF Zornitza Stark Publications for gene: BRAF were set to 19206169; 21396583
Cardiomyopathy_Paediatric v1.133 BRAF Zornitza Stark reviewed gene: BRAF: Rating: GREEN; Mode of pathogenicity: None; Publications: 37697378, 35770001, 35024745, 33274568, 30732632, 29704308, 29696744, 27569062; Phenotypes: Noonan syndrome, MONDO:0018997, cardiofaciocutaneous syndrome 1, MONDO:0007265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.133 MLYCD Zornitza Stark Marked gene: MLYCD as ready
Cardiomyopathy_Paediatric v1.133 MLYCD Zornitza Stark Gene: mlycd has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.133 MLYCD Zornitza Stark Phenotypes for gene: MLYCD were changed from malonic aciduria; 3.5.1. Malonyl CoA decarboxylase deficiency Other disorders of fatty acid and ketone body metabolism); Malonic aciduria; Malonyl-CoA decarboxylase deficiency (Organic acidurias); Mild clinical features. Developmental delay, epilepsy; Malonyl-CoA decarboxylase deficiency; HCM; Hypertrophic-hypocontractile cardiomyopathy to malonic aciduria, MONDO:0009556
Cardiomyopathy_Paediatric v1.132 MLYCD Zornitza Stark Publications for gene: MLYCD were set to 27604308; 12955715; 7609455; 9177981
Cardiomyopathy_Paediatric v1.131 MLYCD Zornitza Stark reviewed gene: MLYCD: Rating: GREEN; Mode of pathogenicity: None; Publications: 39069445, 37206471, 37144154, 34884438, 32602666, 31395333, 28781843; Phenotypes: malonic aciduria, MONDO:0009556; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.131 MAP2K1 Zornitza Stark Marked gene: MAP2K1 as ready
Cardiomyopathy_Paediatric v1.131 MAP2K1 Zornitza Stark Gene: map2k1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.131 MAP2K1 Zornitza Stark Phenotypes for gene: MAP2K1 were changed from ?Noonan syndrome; Cardiofaciocutaneous Syndrome; Cardio-Facio-Cutaneous syndrome; Cardiofaciocutaneous syndrome 3; syndromic HCM; CFC syndrome; LEOPARD syndrome to cardiofaciocutaneous syndrome, MONDO:0015280
Cardiomyopathy_Paediatric v1.130 MAP2K1 Zornitza Stark Publications for gene: MAP2K1 were set to 23321623 (publication referring to Noonan syndrome association).; PMID: 21396583
Cardiomyopathy_Paediatric v1.129 MAP2K1 Zornitza Stark reviewed gene: MAP2K1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37697378, 36777711; Phenotypes: cardiofaciocutaneous syndrome, MONDO:0015280; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.129 LZTR1 Zornitza Stark Marked gene: LZTR1 as ready
Cardiomyopathy_Paediatric v1.129 LZTR1 Zornitza Stark Gene: lztr1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.129 LZTR1 Zornitza Stark Phenotypes for gene: LZTR1 were changed from Schwannomatosis-2, susceptibility to 615670; Noonan syndrome 10 616564 to Noonan syndrome 10, MIM# 616564
Cardiomyopathy_Paediatric v1.128 LZTR1 Zornitza Stark Publications for gene: LZTR1 were set to 25795793; 29469822
Cardiomyopathy_Paediatric v1.127 LZTR1 Zornitza Stark reviewed gene: LZTR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36357925, 35770001, 30872527, 30732632, 30368668, 29469822; Phenotypes: Noonan syndrome 10, MONDO:0014693; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.127 KRAS Zornitza Stark Publications for gene: KRAS were set to PMID: 21396583
Cardiomyopathy_Paediatric v1.126 KRAS Zornitza Stark reviewed gene: KRAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 32078254, 30732632, 30430033; Phenotypes: Noonan syndrome 3, MONDO:0012371; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.126 SCN5A Zornitza Stark Marked gene: SCN5A as ready
Cardiomyopathy_Paediatric v1.126 SCN5A Zornitza Stark Gene: scn5a has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.126 SCN5A Zornitza Stark Phenotypes for gene: SCN5A were changed from Dilated cardiomyopathy; Arrhythmogenic right ventricular cardiomyopathy; Brugada syndrome; Cardiomyopathy, dilated, 1E; Long QT syndrome to dilated cardiomyopathy 1E MONDO:0011003; arrhythmogenic right ventricular cardiomyopathy, MONDO:0016587
Cardiomyopathy_Paediatric v1.125 SCN5A Zornitza Stark Publications for gene: SCN5A were set to doi:10. 1007/ s12265-016-9673-5; 24317018
Cardiomyopathy_Paediatric v1.124 SCN5A Zornitza Stark reviewed gene: SCN5A: Rating: GREEN; Mode of pathogenicity: None; Publications: 39133258, 38731905, 38352122, 36166435, 34884792, 31930659, 31024045; Phenotypes: dilated cardiomyopathy 1E MONDO:0011003, arrhythmogenic right ventricular cardiomyopathy, MONDO:0016587; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.124 RIT1 Zornitza Stark Marked gene: RIT1 as ready
Cardiomyopathy_Paediatric v1.124 RIT1 Zornitza Stark Gene: rit1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.124 RIT1 Zornitza Stark Phenotypes for gene: RIT1 were changed from Noonan syndrome 8; Noonan syndrome type 8; Noonan syndrome 8 615355 to Noonan syndrome 8, MONDO:0014143
Cardiomyopathy_Paediatric v1.123 RIT1 Zornitza Stark Publications for gene: RIT1 were set to 23791108; 24939608; 25124994
Cardiomyopathy_Paediatric v1.122 RIT1 Zornitza Stark reviewed gene: RIT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34887308, 33686258, 30732632, 26757980, 26714497; Phenotypes: Noonan syndrome 8, MONDO:0014143; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.122 RBM20 Zornitza Stark Marked gene: RBM20 as ready
Cardiomyopathy_Paediatric v1.122 RBM20 Zornitza Stark Gene: rbm20 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.122 RBM20 Zornitza Stark Phenotypes for gene: RBM20 were changed from Cardiomyopathy, dilated, 1DD to Cardiomyopathy, dilated, 1DD, MIM#613172
Cardiomyopathy_Paediatric v1.121 RBM20 Zornitza Stark Publications for gene: RBM20 were set to
Cardiomyopathy_Paediatric v1.120 RBM20 Zornitza Stark reviewed gene: RBM20: Rating: GREEN; Mode of pathogenicity: None; Publications: 41175027, 40399739, 40339755, 37593875, 35893073, 34540771, 34011823, 33302605, 32969603, 29367541, 26458567; Phenotypes: Cardiomyopathy, dilated, 1DD, MIM#613172; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.120 NKX2-5 Zornitza Stark Marked gene: NKX2-5 as ready
Cardiomyopathy_Paediatric v1.120 NKX2-5 Zornitza Stark Gene: nkx2-5 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.120 NKX2-5 Zornitza Stark Phenotypes for gene: NKX2-5 were changed from Atrialseptaldefect7,withorwithoutAVconductiondefects,108900 to NKX2.5-related congenital, conduction and myopathic heart disease, MONDO:0800441
Cardiomyopathy_Paediatric v1.119 NKX2-5 Zornitza Stark Publications for gene: NKX2-5 were set to
Cardiomyopathy_Paediatric v1.118 NKX2-5 Zornitza Stark reviewed gene: NKX2-5: Rating: GREEN; Mode of pathogenicity: None; Publications: 36357925, 35683556, 34277740, 33082984, 27855642, 27855642, 26913919; Phenotypes: NKX2.5-related congenital, conduction and myopathic heart disease, MONDO:0800441; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Macular Dystrophy/Stargardt Disease v1.1 KATNA1 Zornitza Stark Marked gene: KATNA1 as ready
Macular Dystrophy/Stargardt Disease v1.1 KATNA1 Zornitza Stark Gene: katna1 has been classified as Amber List (Moderate Evidence).
Macular Dystrophy/Stargardt Disease v1.1 Zornitza Stark Copied gene KATNA1 from panel Mendeliome
Macular Dystrophy/Stargardt Disease v1.1 KATNA1 Zornitza Stark gene: KATNA1 was added
gene: KATNA1 was added to Macular Dystrophy/Stargardt Disease. Sources: Expert Review Amber,Literature
preprint tags were added to gene: KATNA1.
Mode of inheritance for gene: KATNA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KATNA1 were set to 42466416
Phenotypes for gene: KATNA1 were set to Macular dystrophy, non-syndromic MONDO:0020242
Mendeliome v2.503 KATNA1 Zornitza Stark Marked gene: KATNA1 as ready
Mendeliome v2.503 KATNA1 Zornitza Stark Gene: katna1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.503 KATNA1 Zornitza Stark Tag preprint tag was added to gene: KATNA1.
Bone Marrow Failure v2.9 MYB Zornitza Stark Marked gene: MYB as ready
Bone Marrow Failure v2.9 MYB Zornitza Stark Gene: myb has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v2.10 MYB Zornitza Stark Classified gene: MYB as Amber List (moderate evidence)
Combined Immunodeficiency v2.10 MYB Zornitza Stark Gene: myb has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v2.9 Zornitza Stark Added reviews for gene MYB from panel Mendeliome
Bone Marrow Failure v2.9 Zornitza Stark Copied gene MYB from panel Mendeliome
Bone Marrow Failure v2.9 MYB Zornitza Stark gene: MYB was added
gene: MYB was added to Bone Marrow Failure. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: MYB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYB were set to 20130238; 27577878; 29654210; 36168523
Phenotypes for gene: MYB were set to combined immunodeficiency, MONDO:0015131
Mendeliome v2.503 MYB Zornitza Stark Classified gene: MYB as Amber List (moderate evidence)
Mendeliome v2.503 MYB Zornitza Stark Gene: myb has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.118 FKRP Zornitza Stark Marked gene: FKRP as ready
Cardiomyopathy_Paediatric v1.118 FKRP Zornitza Stark Gene: fkrp has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.118 FKRP Zornitza Stark Phenotypes for gene: FKRP were changed from to autosomal recessive limb-girdle muscular dystrophy type 2I, MONDO:0011787
Cardiomyopathy_Paediatric v1.117 FKRP Zornitza Stark Publications for gene: FKRP were set to
Cardiomyopathy_Paediatric v1.116 FKRP Zornitza Stark Classified gene: FKRP as Red List (low evidence)
Cardiomyopathy_Paediatric v1.116 FKRP Zornitza Stark Gene: fkrp has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.115 FKRP Zornitza Stark reviewed gene: FKRP: Rating: RED; Mode of pathogenicity: None; Publications: 31671740; Phenotypes: autosomal recessive limb-girdle muscular dystrophy type 2I, MONDO:0011787; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.115 BCS1L Zornitza Stark Marked gene: BCS1L as ready
Cardiomyopathy_Paediatric v1.115 BCS1L Zornitza Stark Gene: bcs1l has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.115 BCS1L Zornitza Stark Phenotypes for gene: BCS1L were changed from Leigh syndrome, 256000; Mitochondrial complex III deficiency, nuclear type 1, 124000 to mitochondrial complex III deficiency nuclear type 1, MONDO:0007415
Cardiomyopathy_Paediatric v1.114 BCS1L Zornitza Stark Publications for gene: BCS1L were set to
Cardiomyopathy_Paediatric v1.113 BCS1L Zornitza Stark reviewed gene: BCS1L: Rating: RED; Mode of pathogenicity: None; Publications: 37001142; Phenotypes: mitochondrial complex III deficiency nuclear type 1, MONDO:0007415; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.113 MYH6 Zornitza Stark Phenotypes for gene: MYH6 were changed from Cardiomyopathy, familial hypertrophic, 14; Cardiomyopathy, dilated, 1EE to dilated cardiomyopathy 1EE MONDO:0013198; hypertrophic cardiomyopathy MONDO:0005045
Cardiomyopathy_Paediatric v1.112 MYH6 Zornitza Stark Publications for gene: MYH6 were set to
Cardiomyopathy_Paediatric v1.111 MYH6 Zornitza Stark reviewed gene: MYH6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: dilated cardiomyopathy 1EE MONDO:0013198, hypertrophic cardiomyopathy MONDO:0005045; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.111 ETFDH Zornitza Stark Marked gene: ETFDH as ready
Cardiomyopathy_Paediatric v1.111 ETFDH Zornitza Stark Gene: etfdh has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.111 ETFDH Zornitza Stark Phenotypes for gene: ETFDH were changed from Multiple acyl-CoA dehydrogenase deficiency (MADD) (glutaric aciduria type II); Glutaric acidemia IIC; Secondary CoQ10 deficiency (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); HCM; ETF-ubiquinone oxidoreductase deficiency (Disorders of mitochondrial fatty acid oxidation); Facial and cerebral malformations, cystic renal disease, liver disease, hypoketotic hypoglycaemia; Disorders of ubiquinone metabolism and biosynthesis; GLUTARIC ACIDURIA TYPE 2C to multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Cardiomyopathy_Paediatric v1.110 ETFDH Zornitza Stark Publications for gene: ETFDH were set to 24816252; 27604308
Cardiomyopathy_Paediatric v1.109 ETFDH Zornitza Stark Classified gene: ETFDH as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.109 ETFDH Zornitza Stark Gene: etfdh has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.108 ETFDH Zornitza Stark reviewed gene: ETFDH: Rating: AMBER; Mode of pathogenicity: None; Publications: 30027710; Phenotypes: multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dilated Cardiomyopathy v2.9 MYLK3 Zornitza Stark Marked gene: MYLK3 as ready
Dilated Cardiomyopathy v2.9 MYLK3 Zornitza Stark Gene: mylk3 has been classified as Amber List (Moderate Evidence).
Dilated Cardiomyopathy v2.9 MYLK3 Zornitza Stark Publications for gene: MYLK3 were set to 29235529; 31244672; 32213617; 32870709
Dilated Cardiomyopathy v2.8 MYLK3 Zornitza Stark changed review comment from: 4 monoallelic families reported – PMID 30690923, PMID 29235529 (2 families), PMID 37128901 and 3 biallelic families – PMID 32870709. A mouse knock‑in model and patient‑derived iPSC‑cardiomyocyte rescue (PMID 37128901) provide functional validation.

Monoallelic association is Moderate by ClinGen.

However, the biallelic association is the one that is pertinent to this panel.; to: 4 monoallelic families reported – PMID 30690923, PMID 29235529 (2 families), PMID 37128901 and 3 biallelic families – PMID 32870709. A mouse knock‑in model and patient‑derived iPSC‑cardiomyocyte rescue (PMID 37128901) provide functional validation.

Monoallelic association is Moderate by ClinGen.

Biallelic association is paediatric onset.
Dilated Cardiomyopathy v2.8 Zornitza Stark Copied gene MYLK3 from panel Cardiomyopathy_Paediatric
Dilated Cardiomyopathy v2.8 MYLK3 Zornitza Stark gene: MYLK3 was added
gene: MYLK3 was added to Dilated Cardiomyopathy. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: MYLK3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYLK3 were set to 29235529; 31244672; 32213617; 32870709
Phenotypes for gene: MYLK3 were set to dilated cardiomyopathy, MONDO:0005021, MYLK3-related
Cardiomyopathy_Paediatric v1.108 MYLK3 Zornitza Stark Phenotypes for gene: MYLK3 were changed from Dilated cardiomyopathy to dilated cardiomyopathy, MONDO:0005021, MYLK3-related
Cardiomyopathy_Paediatric v1.107 MYLK3 Zornitza Stark edited their review of gene: MYLK3: Added comment: 4 monoallelic families reported – PMID 30690923, PMID 29235529 (2 families), PMID 37128901 and 3 biallelic families – PMID 32870709. A mouse knock‑in model and patient‑derived iPSC‑cardiomyocyte rescue (PMID 37128901) provide functional validation.

Monoallelic association is Moderate by ClinGen.

However, the biallelic association is the one that is pertinent to this panel.; Changed publications: 37128901, 32870709, 30690923, 29235529; Changed phenotypes: dilated cardiomyopathy, MONDO:0005021
Cardiomyopathy_Paediatric v1.107 LAMA4 Zornitza Stark Marked gene: LAMA4 as ready
Cardiomyopathy_Paediatric v1.107 LAMA4 Zornitza Stark Gene: lama4 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.107 LAMA4 Zornitza Stark Phenotypes for gene: LAMA4 were changed from to dilated cardiomyopathy 1JJ, MONDO:0014095
Cardiomyopathy_Paediatric v1.106 LAMA4 Zornitza Stark Publications for gene: LAMA4 were set to
Cardiomyopathy_Paediatric v1.105 LAMA4 Zornitza Stark reviewed gene: LAMA4: Rating: RED; Mode of pathogenicity: None; Publications: 39686469, 39272661, 36270459, 35893073, 35526016, 31024045; Phenotypes: dilated cardiomyopathy 1JJ, MONDO:0014095; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v2.123 DCTN4 Rylee Peters Marked gene: DCTN4 as ready
Intellectual disability syndromic and non-syndromic v2.123 DCTN4 Rylee Peters Gene: dctn4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.123 Rylee Peters Copied gene DCTN4 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.123 DCTN4 Rylee Peters gene: DCTN4 was added
gene: DCTN4 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: DCTN4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DCTN4 were set to 42378292
Phenotypes for gene: DCTN4 were set to Neurodevelopmental disorder, MONDO:0700092, DCTN4-related
Mendeliome v2.502 DCTN4 Rylee Peters Marked gene: DCTN4 as ready
Mendeliome v2.502 DCTN4 Rylee Peters Gene: dctn4 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.502 DCTN4 Rylee Peters Classified gene: DCTN4 as Amber List (moderate evidence)
Mendeliome v2.502 DCTN4 Rylee Peters Gene: dctn4 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.501 DCTN4 Rylee Peters gene: DCTN4 was added
gene: DCTN4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DCTN4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DCTN4 were set to 42378292
Phenotypes for gene: DCTN4 were set to Neurodevelopmental disorder, MONDO:0700092, DCTN4-related
Review for gene: DCTN4 was set to AMBER
Added comment: PMID:42378292 describes two unrelated families with ID, language impairment and cognitive dysfunction. One individual harboured a de novo nonsense variant, p.Tyr240*, absent from gnomAD. A second had an inherited p.Gln268Arg missense variant (affected parent), also absent from gnomAD; brain MRI in the proband and parent showed brain anomalies.
Two additional unrelated individuals with developmental delay carried de novo missense variants, p.Arg115His (34 heterozygotes in gnomAD) and p.Arg238Cys (absent from gnomAD).

Functional evidence: A Y240X mouse model showed embryonic lethality in homozygotes, while heterozygotes had ~50% reduction in DCN4 mRNA, impaired synaptic development and significantly reduced learning ability.
Sources: Literature
Intellectual disability syndromic and non-syndromic v2.122 AFF3 Rylee Peters Phenotypes for gene: AFF3 were changed from KINSSHIP syndrome, MIM# 619297 to KINSSHIP syndrome, MIM# 619297; Neurodevelopmental disorder, MONDO:0700092, AFF3-related
Intellectual disability syndromic and non-syndromic v2.121 AFF3 Rylee Peters Mode of inheritance for gene: AFF3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v2.120 Rylee Peters Added reviews for gene AFF3 from panel Mendeliome
Mendeliome v2.500 AFF3 Rylee Peters Phenotypes for gene: AFF3 were changed from KINSSHIP syndrome, MIM# 619297 to KINSSHIP syndrome, MIM# 619297; Neurodevelopmental disorder, MONDO:0700092, AFF3-related
Mendeliome v2.499 AFF3 Rylee Peters Mode of inheritance for gene: AFF3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v2.498 AFF3 Rylee Peters reviewed gene: AFF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38811945; Phenotypes: KINSSHIP syndrome, MIM# 619297, Neurodevelopmental disorder, MONDO:0700092, AFF3-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hand and foot malformations v1.10 FAT1 Lucy Spencer Phenotypes for gene: FAT1 were changed from facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy to Focal segmental glomerulosclerosis (MONDO:0100313), FAT1-related
Hand and foot malformations v1.9 Lucy Spencer Added reviews for gene FAT1 from panel Proteinuria
Anophthalmia_Microphthalmia_Coloboma v2.6 Lucy Spencer Added reviews for gene FAT1 from panel Proteinuria
Proteinuria v1.3 FAT1 Lucy Spencer reviewed gene: FAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Focal segmental glomerulosclerosis (MONDO:0100313), FAT1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuria v1.3 FAT1 Lucy Spencer Phenotypes for gene: FAT1 were changed from facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy to Focal segmental glomerulosclerosis (MONDO:0100313), FAT1-related
Anophthalmia_Microphthalmia_Coloboma v2.5 FAT1 Lucy Spencer Phenotypes for gene: FAT1 were changed from facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy to Focal segmental glomerulosclerosis (MONDO:0100313), FAT1-related
Mendeliome v2.498 FAT1 Lucy Spencer Publications for gene: FAT1 were set to 30862798
Mendeliome v2.497 FAT1 Lucy Spencer Phenotypes for gene: FAT1 were changed from syndromic disease MONDO:0002254, FAT1-related; facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy to Focal segmental glomerulosclerosis (MONDO:0100313), FAT1-related; Facioscapulohumeral muscular dystrophy (MONDO:0001347), FAT1-related
Mendeliome v2.496 FAT1 Lucy Spencer edited their review of gene: FAT1: Added comment: Clingen: Strong for Focal segmental glomerulosclerosis (MONDO:0100313), FAT1-related

describe the condition as "syndromic, characterized by renal failure and podocyte foot process effacement, as well as cancer, vision anomalies, and brain structural issues". All the reported phenotypes likely represent 1 spectrum of disease (with the exception of the proposed AD Facioscapulohumeral (FSHG) Dystrophy-Like Phenotype which is currently red- clingen have not reviews the AD association); Changed rating: GREEN; Changed phenotypes: Focal segmental glomerulosclerosis (MONDO:0100313), FAT1-related, Facioscapulohumeral muscular dystrophy (MONDO:0001347), FAT1-related; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.5 FAT1 Lucy Spencer Phenotypes for gene: FAT1 were changed from syndromic disease MONDO:0002254, FAT1-related; facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy to Facioscapulohumeral muscular dystrophy (MONDO:0001347), FAT1-related
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.4 FAT1 Lucy Spencer Publications for gene: FAT1 were set to 30862798
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.3 FAT1 Lucy Spencer Mode of inheritance for gene: FAT1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.2 FAT1 Lucy Spencer Classified gene: FAT1 as Red List (low evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.2 FAT1 Lucy Spencer Gene: fat1 has been classified as Red List (Low Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.1 Lucy Spencer Copied gene FAT1 from panel Mendeliome
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.1 FAT1 Lucy Spencer gene: FAT1 was added
gene: FAT1 was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAT1 were set to 30862798
Phenotypes for gene: FAT1 were set to syndromic disease MONDO:0002254, FAT1-related; facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy
Mendeliome v2.496 FAT1 Lucy Spencer reviewed gene: FAT1: Rating: RED; Mode of pathogenicity: None; Publications: 25615407; Phenotypes: Facioscapulohumeral muscular dystrophy (MONDO:0001347), FAT1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Common deletion and duplication syndromes v1.3 ISCA-37397-Gain Sarah Milton GRCh38 position for ISCA-37397-Gain was changed from 21443089-23306926 to 21562828-22620608.
Source Expert list was removed from Region: ISCA-37397-Gain.
Source ClinGen was added to Region: ISCA-37397-Gain.
Skeletal dysplasia v1.119 Sarah Milton Copied Region MSX2 upstream regulatory region from panel Mendeliome
Skeletal dysplasia v1.119 MSX2 upstream regulatory region Sarah Milton Region: MSX2 upstream regulatory region was added
Region: MSX2 upstream regulatory region was added to Skeletal dysplasia. Sources: Expert Review Amber,Literature
regulatory region tags were added to Region: MSX2 upstream regulatory region.
Mode of inheritance for Region: MSX2 upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: MSX2 upstream regulatory region were set to 22717651; 42609732
Phenotypes for Region: MSX2 upstream regulatory region were set to Parietal foramina 1 MIM#168500; Parietal foramina with cleidocranial dysplasia MIM#168550
Fetal anomalies v2.63 Sarah Milton Copied Region MSX2 upstream regulatory region from panel Mendeliome
Fetal anomalies v2.63 MSX2 upstream regulatory region Sarah Milton Region: MSX2 upstream regulatory region was added
Region: MSX2 upstream regulatory region was added to Fetal anomalies. Sources: Expert Review Amber,Literature
regulatory region tags were added to Region: MSX2 upstream regulatory region.
Mode of inheritance for Region: MSX2 upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: MSX2 upstream regulatory region were set to 22717651; 42609732
Phenotypes for Region: MSX2 upstream regulatory region were set to Parietal foramina 1 MIM#168500; Parietal foramina with cleidocranial dysplasia MIM#168550
Mendeliome v2.496 MSX2 upstream regulatory region Sarah Milton Marked Region: MSX2 upstream regulatory region as ready
Mendeliome v2.496 MSX2 upstream regulatory region Sarah Milton Region: msx2 upstream regulatory region has been classified as Amber List (Moderate Evidence).
Mendeliome v2.496 MSX2 upstream regulatory region Sarah Milton Classified Region: MSX2 upstream regulatory region as Amber List (moderate evidence)
Mendeliome v2.496 MSX2 upstream regulatory region Sarah Milton Region: msx2 upstream regulatory region has been classified as Amber List (Moderate Evidence).
Mendeliome v2.495 MSX2 upstream regulatory region Sarah Milton Region: MSX2 upstream regulatory region was added
Region: MSX2 upstream regulatory region was added to Mendeliome. Sources: Literature
regulatory region tags were added to Region: MSX2 upstream regulatory region.
Mode of inheritance for Region: MSX2 upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: MSX2 upstream regulatory region were set to 22717651; 42609732
Phenotypes for Region: MSX2 upstream regulatory region were set to Parietal foramina 1 MIM#168500; Parietal foramina with cleidocranial dysplasia MIM#168550
Review for Region: MSX2 upstream regulatory region was set to AMBER
Added comment: MSX2 encodes a homeobox transcription factor that is known to have a role in osteogenic growth.

Sequence variants in MSX2 result in Craniosynostosis 2, MIM#604757, Parietal foramina 1 MIM#168500.

PMID: 22717651 summarises 2 unrelated individuals with duplications approx 10-70kb upstream of MSX2 presenting with cleidocranial dysplasia. Mechanism of disease postulated to be overexpression of MSX2, authors report enhancers were underlying some of the duplicated region.

PMID: 42609732 summarised 3 individuals from 2 unrelated families with parietal foramina with microduplications upstream of MSX2.

Mechanism remains somewhat undefined with rare reports.

Note: minimum duplicated region has been used for this entry
Sources: Literature
Skeletal dysplasia v1.118 Sarah Milton Copied Region 8q13 deletion Mesomelia-Synostoses Syndrome from panel Mendeliome
Skeletal dysplasia v1.118 8q13 deletion Mesomelia-Synostoses Syndrome Sarah Milton Region: 8q13 deletion Mesomelia-Synostoses Syndrome was added
Region: 8q13 deletion Mesomelia-Synostoses Syndrome was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
regulatory region tags were added to Region: 8q13 deletion Mesomelia-Synostoses Syndrome.
Mode of inheritance for Region: 8q13 deletion Mesomelia-Synostoses Syndrome was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: 8q13 deletion Mesomelia-Synostoses Syndrome were set to 20602915; 38992676; 30450550; 28328141
Phenotypes for Region: 8q13 deletion Mesomelia-Synostoses Syndrome were set to Mesomelia-synostoses syndrome, MIM#600383
Fetal anomalies v2.62 Sarah Milton Copied Region 8q13 deletion Mesomelia-Synostoses Syndrome from panel Mendeliome
Fetal anomalies v2.62 8q13 deletion Mesomelia-Synostoses Syndrome Sarah Milton Region: 8q13 deletion Mesomelia-Synostoses Syndrome was added
Region: 8q13 deletion Mesomelia-Synostoses Syndrome was added to Fetal anomalies. Sources: Expert Review Green,Literature
regulatory region tags were added to Region: 8q13 deletion Mesomelia-Synostoses Syndrome.
Mode of inheritance for Region: 8q13 deletion Mesomelia-Synostoses Syndrome was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: 8q13 deletion Mesomelia-Synostoses Syndrome were set to 20602915; 38992676; 30450550; 28328141
Phenotypes for Region: 8q13 deletion Mesomelia-Synostoses Syndrome were set to Mesomelia-synostoses syndrome, MIM#600383
Mendeliome v2.494 8q13 deletion Mesomelia-Synostoses Syndrome Sarah Milton Marked Region: 8q13 deletion Mesomelia-Synostoses Syndrome as ready
Mendeliome v2.494 8q13 deletion Mesomelia-Synostoses Syndrome Sarah Milton Region: 8q13 deletion mesomelia-synostoses syndrome has been classified as Green List (High Evidence).
Mendeliome v2.494 8q13 deletion Mesomelia-Synostoses Syndrome Sarah Milton Classified Region: 8q13 deletion Mesomelia-Synostoses Syndrome as Green List (high evidence)
Mendeliome v2.494 8q13 deletion Mesomelia-Synostoses Syndrome Sarah Milton Region: 8q13 deletion mesomelia-synostoses syndrome has been classified as Green List (High Evidence).
Mendeliome v2.493 8q13 deletion Mesomelia-Synostoses Syndrome Sarah Milton Region: 8q13 deletion Mesomelia-Synostoses Syndrome was added
Region: 8q13 deletion Mesomelia-Synostoses Syndrome was added to Mendeliome. Sources: Literature
regulatory region tags were added to Region: 8q13 deletion Mesomelia-Synostoses Syndrome.
Mode of inheritance for Region: 8q13 deletion Mesomelia-Synostoses Syndrome was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: 8q13 deletion Mesomelia-Synostoses Syndrome were set to 20602915; 38992676; 30450550; 28328141
Phenotypes for Region: 8q13 deletion Mesomelia-Synostoses Syndrome were set to Mesomelia-synostoses syndrome, MIM#600383
Review for Region: 8q13 deletion Mesomelia-Synostoses Syndrome was set to GREEN
Added comment: Heterozygous deletions involving SULF1 and SLCO5A1 have been reported in 6 affected individuals from 5 unrelated families with Mesomelia-synostoses syndrome.

Clinical presentation included: Mesomelic limb shortening, acral synostosis, multiple congenital malformations

Deletions ranged from 582-738kb in size with as of yet an unclear mechanism of disease.

Both SULF1 and SLCO5A1 are expressed in skeletal tissues however neither gene is constrained for loss of function in population databases.

Functional studies in mice with homozygous knockout revealed milder defects with reduced bone length, early ossification vertebrae, fusion vertebrae.
The 2 genes are in separate TADs with predicted chondrogenic enhancers in the deleted region as such alteration a regulatory effect is suspected.

Note: minimum coordinates used for this entry
Sources: Literature
Skeletal dysplasia v1.117 Sarah Milton Copied Region 10q24 duplication syndrome Split hand foot malformation 3 from panel Mendeliome
Skeletal dysplasia v1.117 10q24 duplication syndrome Split hand foot malformation 3 Sarah Milton Region: 10q24 duplication syndrome Split hand foot malformation 3 was added
Region: 10q24 duplication syndrome Split hand foot malformation 3 was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for Region: 10q24 duplication syndrome Split hand foot malformation 3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to 30622331; 27600068; 38168117; 35908152; 23596994
Phenotypes for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to Split-hand/foot malformation 3, gene duplication syndrome, MIM#246560
Penetrance for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to Incomplete
Hand and foot malformations v1.8 Sarah Milton Copied Region 10q24 duplication syndrome Split hand foot malformation 3 from panel Mendeliome
Hand and foot malformations v1.8 10q24 duplication syndrome Split hand foot malformation 3 Sarah Milton Region: 10q24 duplication syndrome Split hand foot malformation 3 was added
Region: 10q24 duplication syndrome Split hand foot malformation 3 was added to Hand and foot malformations. Sources: Expert Review Green,Literature
Mode of inheritance for Region: 10q24 duplication syndrome Split hand foot malformation 3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to 30622331; 27600068; 38168117; 35908152; 23596994
Phenotypes for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to Split-hand/foot malformation 3, gene duplication syndrome, MIM#246560
Penetrance for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to Incomplete
Fetal anomalies v2.61 Sarah Milton Copied Region 10q24 duplication syndrome Split hand foot malformation 3 from panel Mendeliome
Fetal anomalies v2.61 10q24 duplication syndrome Split hand foot malformation 3 Sarah Milton Region: 10q24 duplication syndrome Split hand foot malformation 3 was added
Region: 10q24 duplication syndrome Split hand foot malformation 3 was added to Fetal anomalies. Sources: Expert Review Green,Literature
Mode of inheritance for Region: 10q24 duplication syndrome Split hand foot malformation 3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to 30622331; 27600068; 38168117; 35908152; 23596994
Phenotypes for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to Split-hand/foot malformation 3, gene duplication syndrome, MIM#246560
Penetrance for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to Incomplete
Fetal anomalies v2.60 TTN Sarah Milton Source Expert list was removed from TTN.
Phenotypes for gene: TTN were changed from Salih myopathy; Muscular dystrophy, limb-girdle, autosomal recessive 10 to TTN-related myopathy MONDO:0100175
Cardiomyopathy_Paediatric v1.105 TTN Sarah Milton Source South West GLH was removed from TTN.
Source NHS GMS was removed from TTN.
Source ClinGen was added to TTN.
Phenotypes for gene: TTN were changed from Cardiomyopathy, familial hypertrophic, 9,; Cardiomyopathy, dilated, 1G to Dilated cardiomyopathy 1G, MONDO:0011400; Hypertrophic cardiomyopathy, MONDO:0005045
Incidentalome v1.11 TTN Sarah Milton Source Victorian Clinical Genetics Services was removed from TTN.
Source Victorian Clinical Genetics Services was removed from TTN.
Source ClinGen was added to TTN.
Phenotypes for gene: TTN were changed from to Dilated cardiomyopathy 1G, MONDO:0011400; TTN-related myopathy, MONDO:0100175; Myopathy, myofibrillar, 9, with early respiratory failure, MONDO:0011362; Tibial muscular dystrophy, MONDO:0010870; TTN-related myopathy, dominant-negative TTNsv, MONDO:1060225
Hypertrophic cardiomyopathy v2.1 TTN Sarah Milton Source Victorian Clinical Genetics Services was removed from TTN.
Source ClinGen was added to TTN.
Phenotypes for gene: TTN were changed from Hypertrophic cardiomyopathy to Hypertrophic cardiomyopathy MONDO:0005045
Arthrogryposis v2.3 TTN Sarah Milton Source Expert list was removed from TTN.
Source ClinGen was added to TTN.
Mode of inheritance for gene TTN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: TTN were changed from Salih myopathy; Muscular dystrophy, limb-girdle, autosomal recessive 10 to TTN-related myopathy, MONDO:0100175; TTN-related myopathy, dominant-negative TTNsv, MONDO:1060225
Incidentalome v1.10 TTN Sarah Milton changed review comment from: Summary of phenotypes as per Clingen:

Dilated cardiomyopathy 1G, MONDO:0011400
- Definitive association
- AD
- Molecular mechanism - truncating variants in exon with sufficiently high PSI, exact mechanism remains unclear - haploinsufficiency on it's own unlikely to be the only contributing factor, some papers postulate accumulation of truncated poison peptides contribute.

TTN-related myopathy, MONDO:0100175
- Definitive association
- AR
- Lumped: limb-girdle muscular dystrophy, (MIM #608807), centronuclear myopathy, Salih myopathy (MIM #611705), Emery-Dreifuss-like muscular dystrophy (not an OMIM entity), titinopathy with congenital contractures (not an OMIM entity), minicore myopathy (not an OMIM entity), distal titinopathy
- Presumably loss of function molecular mechanism, frameshift, deletion, missense, splice site variants have been called LP/P for this phenotype, PSI less relevant

Myopathy, myofibrillar, 9, with early respiratory failure MONDO:0011362
- Definitive association
- AD
- Missense variants in exon 344 A band

Tibial muscular dystrophy, MONDO:0010870
- Moderate association
- AD
- Variants in M line – missense and truncating exon 363

TTN-related myopathy, dominant-negative TTNsv, MONDO:1060225
- Moderate association
- AD
- Multiexon in frame deletion/CNV escape NMD, expressed
- Located in Z disk, A,I or A/M band deletions
- Phenotype ranges from arthrogryposis to adult onset distal myopathy

Hypertrophic cardiomyopathy, MONDO:0005045, AD
- Limited association
- AD

Arrhythmogenic right ventricular cardiomyopathy, MONDO:0016587
- Disputed association
- AD; to: Summary of phenotypes as per Clingen:

Dilated cardiomyopathy 1G, MONDO:0011400
- Definitive association
- AD
- Molecular mechanism - truncating variants in exon with sufficiently high PSI, exact mechanism remains unclear - haploinsufficiency on it's own unlikely to be the only contributing factor, some papers postulate accumulation of truncated poison peptides contribute.


TTN-related myopathy, MONDO:0100175
- Definitive association
- AR
- Lumped: limb-girdle muscular dystrophy, (MIM #608807), centronuclear myopathy, Salih myopathy (MIM #611705), Emery-Dreifuss-like muscular dystrophy (not an OMIM entity), titinopathy with congenital contractures (not an OMIM entity), minicore myopathy (not an OMIM entity), distal titinopathy
- Presumably loss of function molecular mechanism, frameshift, deletion, missense, splice site variants have been called LP/P for this phenotype, PSI less relevant


Myopathy, myofibrillar, 9, with early respiratory failure MONDO:0011362
- Definitive association
- AD
- Missense variants in exon 344 A band

Tibial muscular dystrophy, MONDO:0010870
- Moderate association
- AD
- Variants in M line – missense and truncating exon 363


TTN-related myopathy, dominant-negative TTNsv, MONDO:1060225
- Moderate association
- AD
- Multiexon in frame deletion/CNV escape NMD, expressed
- Located in Z disk, A,I or A/M band deletions
- Phenotype ranges from arthrogryposis to adult onset distal myopathy


Hypertrophic cardiomyopathy, MONDO:0005045, AD
- Limited association
- AD


Arrhythmogenic right ventricular cardiomyopathy, MONDO:0016587
- Disputed association
- AD
Cardiomyopathy_Paediatric v1.104 GBE1 Zornitza Stark Marked gene: GBE1 as ready
Cardiomyopathy_Paediatric v1.104 GBE1 Zornitza Stark Gene: gbe1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.104 GBE1 Zornitza Stark Phenotypes for gene: GBE1 were changed from Glycogen Storage Disorders- Liver; Glycogen Storage Disorders- Muscle; Glycogen storage disease type IV, Andersen (Glycogen storage disorders); Glycogen storage disease IV, 232500; hypotonia, exercise intolerance, polyglucosan bodies in affected tissues; Glycogen Storage Disease Type IV; failure to thrive in addition to hepatomegaly van have neuromuscular adult form ( polyglucosan body ideas which presents with neurogenic bladder, gait difficulties; DCM; Polyglucosan body disease, adult form, 263570; Glycogen storage disease type IV (brancher enzyme deficiency), neuromuscular form; Hypertrophic-hypocontractile cardiomyopathy; Glycogen Storage Disease to glycogen storage disease due to glycogen branching enzyme deficiency, MONDO:0009292
Cardiomyopathy_Paediatric v1.103 GBE1 Zornitza Stark Classified gene: GBE1 as Green List (high evidence)
Cardiomyopathy_Paediatric v1.103 GBE1 Zornitza Stark Gene: gbe1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.102 GBE1 Zornitza Stark reviewed gene: GBE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38516405, 38436530, 38012812, 36830903, 29379554; Phenotypes: glycogen storage disease due to glycogen branching enzyme deficiency, MONDO:0009292; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Incidentalome v1.10 TTN Sarah Milton reviewed gene: TTN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.102 SMAD4 Zornitza Stark Marked gene: SMAD4 as ready
Cardiomyopathy_Paediatric v1.102 SMAD4 Zornitza Stark Gene: smad4 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.102 SMAD4 Zornitza Stark Classified gene: SMAD4 as Green List (high evidence)
Cardiomyopathy_Paediatric v1.102 SMAD4 Zornitza Stark Gene: smad4 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.101 SMAD4 Zornitza Stark gene: SMAD4 was added
gene: SMAD4 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: SMAD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMAD4 were set to 37529930; 34236823; 27302097; 26420300
Phenotypes for gene: SMAD4 were set to Myhre syndrome, MONDO:0007688
Review for gene: SMAD4 was set to GREEN
Added comment: Well established gene-disease association, restrictive cardiomyopathy is part of the phenotype.
Sources: Literature
Cardiomyopathy_Paediatric v1.100 MT-ATP6 Zornitza Stark Marked gene: MT-ATP6 as ready
Cardiomyopathy_Paediatric v1.100 MT-ATP6 Zornitza Stark Gene: mt-atp6 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.100 MT-ATP6 Zornitza Stark Classified gene: MT-ATP6 as Green List (high evidence)
Cardiomyopathy_Paediatric v1.100 MT-ATP6 Zornitza Stark Gene: mt-atp6 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.99 MT-ATP6 Zornitza Stark gene: MT-ATP6 was added
gene: MT-ATP6 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene gene: MT-ATP6 was set to MITOCHONDRIAL
Publications for gene: MT-ATP6 were set to 40367733; 40112238; 39119452; 29101127; 27453250
Phenotypes for gene: MT-ATP6 were set to Mitochondrial complex V (ATP synthase) deficiency, MONDO:0014471, MT-ATP6-related
Review for gene: MT-ATP6 was set to GREEN
Added comment: PMIDs 40367733, 29101127, 39119452, 40112238 and 27453250 collectively report 43 families with MT‑ATP6 variants causing mitochondrial disease phenotypes that include cardiomyopathy. 19 families present with Leigh syndrome and hypertrophic cardiomyopathy and 23 families with mitochondrial proton‑transporting ATP synthase complex deficiency and paediatric cardiomyopathy.
Sources: Literature
Cardiomyopathy_Paediatric v1.98 PPP1CB Zornitza Stark Marked gene: PPP1CB as ready
Cardiomyopathy_Paediatric v1.98 PPP1CB Zornitza Stark Gene: ppp1cb has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.98 PPP1CB Zornitza Stark Phenotypes for gene: PPP1CB were changed from Rasopathy with developmental delay, short stature and sparse slow-growing hair; Noonan syndrome-like disorder with loose anagen hair 2, 617506 to Noonan syndrome-like disorder with loose anagen hair 2, MIM#617506
Cardiomyopathy_Paediatric v1.97 PPP1CB Zornitza Stark Publications for gene: PPP1CB were set to 27264673; 28211982; 27681385
Cardiomyopathy_Paediatric v1.96 PPP1CB Zornitza Stark Classified gene: PPP1CB as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.96 PPP1CB Zornitza Stark Gene: ppp1cb has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.95 PPP1CB Zornitza Stark reviewed gene: PPP1CB: Rating: AMBER; Mode of pathogenicity: None; Publications: 30368668; Phenotypes: Noonan syndrome, MONDO:0018997; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.95 COX10 Zornitza Stark Marked gene: COX10 as ready
Cardiomyopathy_Paediatric v1.95 COX10 Zornitza Stark Gene: cox10 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.95 COX10 Zornitza Stark Phenotypes for gene: COX10 were changed from Mitochondrial complex IV deficiency, 220110 to mitochondrial complex IV deficiency, nuclear type 3, MONDO:0033635
Cardiomyopathy_Paediatric v1.94 COX10 Zornitza Stark Publications for gene: COX10 were set to
Cardiomyopathy_Paediatric v1.93 COX10 Zornitza Stark Classified gene: COX10 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.93 COX10 Zornitza Stark Gene: cox10 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.92 COX10 Zornitza Stark reviewed gene: COX10: Rating: AMBER; Mode of pathogenicity: None; Publications: 30588737, 12928484; Phenotypes: mitochondrial complex IV deficiency, nuclear type 3, MONDO:0033635; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.92 NF1 Zornitza Stark Marked gene: NF1 as ready
Cardiomyopathy_Paediatric v1.92 NF1 Zornitza Stark Gene: nf1 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.92 NF1 Zornitza Stark Phenotypes for gene: NF1 were changed from Neurofibromatosis, type 1 162200; Neurofibromatosis Noonan syndrome; Neurofibromatosis syndrome 1; Neurofibromatosis-Noonan syndrome 601321; Neurofibromatosis-Noonan Syndrome; Noonan syndrome to neurofibromatosis type 1, MONDO:0018975
Cardiomyopathy_Paediatric v1.91 NF1 Zornitza Stark Publications for gene: NF1 were set to 16380919; 19845691; 12707950
Cardiomyopathy_Paediatric v1.90 NF1 Zornitza Stark Classified gene: NF1 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.90 NF1 Zornitza Stark Gene: nf1 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.89 NF1 Zornitza Stark reviewed gene: NF1: Rating: RED; Mode of pathogenicity: None; Publications: 30949358, 30919579; Phenotypes: neurofibromatosis type 1, MONDO:0018975; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.89 SHOC2 Zornitza Stark Marked gene: SHOC2 as ready
Cardiomyopathy_Paediatric v1.89 SHOC2 Zornitza Stark Gene: shoc2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.89 SHOC2 Zornitza Stark Phenotypes for gene: SHOC2 were changed from Noonan-like syndrome with loose anagen hair; syndromic HCM to Noonan syndrome-like disorder with loose anagen hair, MONDO:0011899
Cardiomyopathy_Paediatric v1.88 SHOC2 Zornitza Stark reviewed gene: SHOC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32870709, 31059601, 30732632; Phenotypes: Noonan syndrome-like disorder with loose anagen hair, MONDO:0011899; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.88 NDUFAF1 Zornitza Stark Marked gene: NDUFAF1 as ready
Cardiomyopathy_Paediatric v1.88 NDUFAF1 Zornitza Stark Gene: ndufaf1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.88 NDUFAF1 Zornitza Stark Phenotypes for gene: NDUFAF1 were changed from Mitochondrial complex I deficiency, nuclear type 11, 618234 to mitochondrial complex I deficiency, nuclear type 11, MONDO:0032617
Cardiomyopathy_Paediatric v1.87 NDUFAF1 Zornitza Stark Publications for gene: NDUFAF1 were set to
Cardiomyopathy_Paediatric v1.86 NDUFAF1 Zornitza Stark reviewed gene: NDUFAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39821332, 21931170, 17557076; Phenotypes: mitochondrial complex I deficiency, nuclear type 11, MONDO:0032617; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.86 SOS1 Zornitza Stark Marked gene: SOS1 as ready
Cardiomyopathy_Paediatric v1.86 SOS1 Zornitza Stark Gene: sos1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.86 SOS1 Zornitza Stark Phenotypes for gene: SOS1 were changed from Noonan syndrome; Noonan syndrome 4; Noonan syndrome 4 610733; syndromic HCM to Noonan syndrome 4, MIM# 610733
Cardiomyopathy_Paediatric v1.85 SOS1 Zornitza Stark reviewed gene: SOS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31712860, 31368652, 31024045, 30732632, 29696744; Phenotypes: Noonan syndrome, MONDO:0018997; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.85 PNPLA2 Zornitza Stark Marked gene: PNPLA2 as ready
Cardiomyopathy_Paediatric v1.85 PNPLA2 Zornitza Stark Gene: pnpla2 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.85 PNPLA2 Zornitza Stark Phenotypes for gene: PNPLA2 were changed from DCM; Lipid myopathy, muscle weakness Jordans anomaly - neutral lipidcontaining vacuoles in leukocytes; Neutral lipid storage disease with myopathy NLSDM to neutral lipid storage myopathy, MONDO:0012545
Cardiomyopathy_Paediatric v1.84 PNPLA2 Zornitza Stark Publications for gene: PNPLA2 were set to
Cardiomyopathy_Paediatric v1.83 PNPLA2 Zornitza Stark Classified gene: PNPLA2 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.83 PNPLA2 Zornitza Stark Gene: pnpla2 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.82 PNPLA2 Zornitza Stark reviewed gene: PNPLA2: Rating: RED; Mode of pathogenicity: None; Publications: 39119584, 31655616; Phenotypes: neutral lipid storage myopathy, MONDO:0012545; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.82 NONO Zornitza Stark edited their review of gene: NONO: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cardiomyopathy_Paediatric v1.82 NONO Zornitza Stark Marked gene: NONO as ready
Cardiomyopathy_Paediatric v1.82 NONO Zornitza Stark Gene: nono has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.82 NONO Zornitza Stark Phenotypes for gene: NONO were changed from to syndromic X-linked intellectual disability 34, MONDO:0010501
Cardiomyopathy_Paediatric v1.81 NONO Zornitza Stark Publications for gene: NONO were set to
Cardiomyopathy_Paediatric v1.80 NONO Zornitza Stark Mode of inheritance for gene: NONO was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cardiomyopathy_Paediatric v1.79 NONO Zornitza Stark reviewed gene: NONO: Rating: GREEN; Mode of pathogenicity: None; Publications: 41727761, 41705901, 41213470, 39709004, 38469091, 38110236, 37533431, 36653413, 36426740, 34549882, 33304389, 31883306, 30773818, 27550220, 27329731; Phenotypes: syndromic X-linked intellectual disability 34, MONDO:0010501; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cardiomyopathy_Paediatric v1.79 BAG3 Zornitza Stark Marked gene: BAG3 as ready
Cardiomyopathy_Paediatric v1.79 BAG3 Zornitza Stark Gene: bag3 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.79 BAG3 Zornitza Stark Phenotypes for gene: BAG3 were changed from Cardiomyopathy, dilated, 1HH to myofibrillar myopathy 6, MONDO:0013061; dilated cardiomyopathy 1HH, MONDO:0013479
Cardiomyopathy_Paediatric v1.78 BAG3 Zornitza Stark Publications for gene: BAG3 were set to
Cardiomyopathy_Paediatric v1.77 BAG3 Zornitza Stark reviewed gene: BAG3: Rating: GREEN; Mode of pathogenicity: None; Publications: 40757566, 40493734, 39706847, 34011823, 30442290, 30384889, 27443559; Phenotypes: myofibrillar myopathy 6, MONDO:0013061, dilated cardiomyopathy 1HH, MONDO:0013479; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Repeat Disorders v1.4 Bryony Thompson Copied STR BCLAF3_FRAXG_CCG from panel Mendeliome
Repeat Disorders v1.4 BCLAF3_FRAXG_CCG Bryony Thompson STR: BCLAF3_FRAXG_CCG was added
STR: BCLAF3_FRAXG_CCG was added to Repeat Disorders. Sources: Expert Review Green,Literature
Mode of inheritance for STR: BCLAF3_FRAXG_CCG was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for STR: BCLAF3_FRAXG_CCG were set to 42482100
Phenotypes for STR: BCLAF3_FRAXG_CCG were set to Neurodevelopmental disorder, MONDO:0700092
Intellectual disability syndromic and non-syndromic v2.119 Bryony Thompson Copied STR BCLAF3_FRAXG_CCG from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.119 BCLAF3_FRAXG_CCG Bryony Thompson STR: BCLAF3_FRAXG_CCG was added
STR: BCLAF3_FRAXG_CCG was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for STR: BCLAF3_FRAXG_CCG was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for STR: BCLAF3_FRAXG_CCG were set to 42482100
Phenotypes for STR: BCLAF3_FRAXG_CCG were set to Neurodevelopmental disorder, MONDO:0700092
Genetic Epilepsy v2.37 Bryony Thompson Copied STR BCLAF3_FRAXG_CCG from panel Mendeliome
Genetic Epilepsy v2.37 BCLAF3_FRAXG_CCG Bryony Thompson STR: BCLAF3_FRAXG_CCG was added
STR: BCLAF3_FRAXG_CCG was added to Genetic Epilepsy. Sources: Expert Review Green,Literature
Mode of inheritance for STR: BCLAF3_FRAXG_CCG was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for STR: BCLAF3_FRAXG_CCG were set to 42482100
Phenotypes for STR: BCLAF3_FRAXG_CCG were set to Neurodevelopmental disorder, MONDO:0700092
Mendeliome v2.492 BCLAF3_FRAXG_CCG Bryony Thompson Marked STR: BCLAF3_FRAXG_CCG as ready
Mendeliome v2.492 BCLAF3_FRAXG_CCG Bryony Thompson Str: bclaf3_fraxg_ccg has been classified as Green List (High Evidence).
Mendeliome v2.492 BCLAF3_FRAXG_CCG Bryony Thompson Classified STR: BCLAF3_FRAXG_CCG as Green List (high evidence)
Mendeliome v2.492 BCLAF3_FRAXG_CCG Bryony Thompson Str: bclaf3_fraxg_ccg has been classified as Green List (High Evidence).
Mendeliome v2.491 BCLAF3_FRAXG_CCG Bryony Thompson STR: BCLAF3_FRAXG_CCG was added
STR: BCLAF3_FRAXG_CCG was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: BCLAF3_FRAXG_CCG was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for STR: BCLAF3_FRAXG_CCG were set to 42482100
Phenotypes for STR: BCLAF3_FRAXG_CCG were set to Neurodevelopmental disorder, MONDO:0700092
Review for STR: BCLAF3_FRAXG_CCG was set to GREEN
Added comment: PMID 42482100 reports five affected males with X‑linked hypermethylated CCG repeat expansions in the 5′UTR of BCLAF3, causing transcriptional silencing (loss‑of‑function). Affected individuals present with intellectual disability, epilepsy and autism. Patient‑derived fibroblasts show loss of BCLAF3 RNA and protein and DNA‑methylation arrays confirm promoter hypermethylation. One of the individuals had Williams syndrome and one of the individuals had fragile X, but more severe phenotypes than expected.
Based on LRS across all the individuals, the suggested threshold for hypermethylation is somewhere between 117-172 CCG repeats, but a greater number of individuals with intermediate-sized expansions are required to define a more precise cutoff.
Sources: Literature
Mendeliome v2.490 Sarah Milton removed region:Split hand malformation 3, 10q24 duplication syndrome from the panel
Mendeliome v2.489 Split hand malformation 3, 10q24 duplication syndrome Sarah Milton Deleted their review
Mendeliome v2.489 C2 Sarah Milton changed review comment from: This review is for the monoallelic disease assertion - Amber
The recessive C2 deficiency remains green

C2 is part of classical and lectin pathway once activated splits to C2B and C2A.
2 publications assert a link between gain of function variants in C2 and glomerulopathy/atypical haemolytic uraemic syndrome.

3 unrelated patients were found to have 2 different missense variants (S250C, R249C).

Functional studies supported a gain of function effect increasing C3 on target cells with authors speculating the combined action of CRP and the presence of these variants resulting in elevated complement deposition in kidney microvasculature.

Allele frequencies in gnomAD are relatively high, as such this is likely to be a susceptibility similar to AD variants in other complement genes.; to: This review is for the monoallelic disease assertion - Amber
The recessive C2 deficiency remains green

C2 is part of classical and lectin pathway once activated splits to C2B and C2A.
2 publications assert a link between gain of function variants in C2 and glomerulopathy/atypical haemolytic uraemic syndrome.

3 unrelated patients were found to have 2 different missense variants (S250C, R249C).

Functional studies supported a gain of function effect increasing C3 on target cells with authors speculating the combined action of CRP and the presence of these variants resulting in elevated complement deposition in kidney microvasculature.

Allele frequencies in gnomAD are relatively high, as such this is likely to be a susceptibility similar to AD variants in other complement genes.

Given only a few patients are reported in 2020 and 2021 with relatively high frequency variants this association is marked as amber until further literature is published.
Mendeliome v2.489 C2 Sarah Milton reviewed gene: C2: 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: 36591303, 32113979; Phenotypes: complement 3 glomerulopathy, MONDO:0018013, C2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v2.118 PIGB Zornitza Stark Phenotypes for gene: PIGB were changed from Developmental and epileptic encephalopathy 80, MIM# 618580 to Developmental and epileptic encephalopathy 80, MIM# 618580; Acrofrontofacionasal dysplasia 1, MIM# 201180
Intellectual disability syndromic and non-syndromic v2.117 PIGB Zornitza Stark Publications for gene: PIGB were set to PubMed: 31256876
Intellectual disability syndromic and non-syndromic v2.116 PIGB Zornitza Stark edited their review of gene: PIGB: Added comment: Association with AFFND1, PMID 34400385: two individuals from two Brazilian families reported with the same homozygous intronic variant c.795-19T>G and a distinctive phenotype comprising severe DD/ID, and marked dysmorphic features, including hypertelorism, broad nose with notched nasal tip, cleft lip/palate, and wide and protruding central upper incisors. Vision is impaired due to coloboma and other ocular anomalies, and hearing loss in later life has been reported. Skeletal abnormalities include mesomelic shortening of limbs, distal digital hypoplasia, fibular hypoplasia, and clubfeet.

RED for this association as single, likely founder variant in the Brazilian population.; Changed publications: 34400385; Changed phenotypes: Developmental and epileptic encephalopathy 80, MIM# 618580, Acrofrontofacionasal dysplasia 1, MIM# 201180
Congenital Disorders of Glycosylation v2.2 PIGB Zornitza Stark Phenotypes for gene: PIGB were changed from Developmental and epileptic encephalopathy 80 618580 to Developmental and epileptic encephalopathy 80, MIM# 618580; Acrofrontofacionasal dysplasia 1, MIM# 201180
Congenital Disorders of Glycosylation v2.1 PIGB Zornitza Stark Publications for gene: PIGB were set to 31256876
Congenital Disorders of Glycosylation v2.0 PIGB Zornitza Stark edited their review of gene: PIGB: Added comment: Association with AFFND1, PMID 34400385: two individuals from two Brazilian families reported with the same homozygous intronic variant c.795-19T>G and a distinctive phenotype comprising severe DD/ID, and marked dysmorphic features, including hypertelorism, broad nose with notched nasal tip, cleft lip/palate, and wide and protruding central upper incisors. Vision is impaired due to coloboma and other ocular anomalies, and hearing loss in later life has been reported. Skeletal abnormalities include mesomelic shortening of limbs, distal digital hypoplasia, fibular hypoplasia, and clubfeet.

RED for this association as single, likely founder variant in the Brazilian population.; Changed publications: 31256876, 34400385; Changed phenotypes: Developmental and epileptic encephalopathy 80, MIM# 618580, Acrofrontofacionasal dysplasia 1, MIM# 201180
Frontonasal dysplasia v2.2 PIGB Zornitza Stark Marked gene: PIGB as ready
Frontonasal dysplasia v2.2 PIGB Zornitza Stark Gene: pigb has been classified as Red List (Low Evidence).
Frontonasal dysplasia v2.2 PIGB Zornitza Stark Publications for gene: PIGB were set to
Frontonasal dysplasia v2.1 PIGB Zornitza Stark edited their review of gene: PIGB: Changed publications: 34400385
Frontonasal dysplasia v2.1 PIGB Zornitza Stark gene: PIGB was added
gene: PIGB was added to Frontonasal dysplasia. Sources: Literature
founder tags were added to gene: PIGB.
Mode of inheritance for gene: PIGB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PIGB were set to Acrofrontofacionasal dysplasia 1, MIM# 201180
Review for gene: PIGB was set to RED
Added comment: PMID 34400385: two individuals from two Brazilian families reported with the same homozygous intronic variant c.795-19T>G and a distinctive phenotype comprising severe DD/ID, and marked dysmorphic features, including hypertelorism, broad nose with notched nasal tip, cleft lip/palate, and wide and protruding central upper incisors. Vision is impaired due to coloboma and other ocular anomalies, and hearing loss in later life has been reported. Skeletal abnormalities include mesomelic shortening of limbs, distal digital hypoplasia, fibular hypoplasia, and clubfeet.

Likely founder variant.
Sources: Literature
Mendeliome v2.489 PIGB Zornitza Stark Phenotypes for gene: PIGB were changed from Developmental and epileptic encephalopathy 80, MIM# 618580 to Developmental and epileptic encephalopathy 80, MIM# 618580; Acrofrontofacionasal dysplasia 1, MIM# 201180
Mendeliome v2.488 PIGB Zornitza Stark Publications for gene: PIGB were set to 31256876
Mendeliome v2.487 PIGB Zornitza Stark edited their review of gene: PIGB: Added comment: Association with AFFND1, PMID 34400385: two individuals from two Brazilian families reported with the same homozygous intronic variant c.795-19T>G and a distinctive phenotype comprising severe DD/ID, and marked dysmorphic features, including hypertelorism, broad nose with notched nasal tip, cleft lip/palate, and wide and protruding central upper incisors. Vision is impaired due to coloboma and other ocular anomalies, and hearing loss in later life has been reported. Skeletal abnormalities include mesomelic shortening of limbs, distal digital hypoplasia, fibular hypoplasia, and clubfeet.

RED for this association as single, likely founder variant in the Brazilian population.; Changed publications: 31256876, 34400385; Changed phenotypes: Developmental and epileptic encephalopathy 80, MIM# 618580, Acrofrontofacionasal dysplasia 1, MIM# 201180
Mendeliome v2.487 10q24 duplication syndrome Split hand foot malformation 3 Sarah Milton Classified Region: 10q24 duplication syndrome Split hand foot malformation 3 as Green List (high evidence)
Mendeliome v2.487 10q24 duplication syndrome Split hand foot malformation 3 Sarah Milton Region: 10q24 duplication syndrome split hand foot malformation 3 has been classified as Green List (High Evidence).
Mendeliome v2.486 10q24 duplication syndrome Split hand foot malformation 3 Sarah Milton Marked Region: 10q24 duplication syndrome Split hand foot malformation 3 as ready
Mendeliome v2.486 10q24 duplication syndrome Split hand foot malformation 3 Sarah Milton Region: 10q24 duplication syndrome split hand foot malformation 3 has been classified as Red List (Low Evidence).
Mendeliome v2.486 10q24 duplication syndrome Split hand foot malformation 3 Sarah Milton Region: 10q24 duplication syndrome Split hand foot malformation 3 was added
Region: 10q24 duplication syndrome Split hand foot malformation 3 was added to Mendeliome. Sources: Literature
Mode of inheritance for Region: 10q24 duplication syndrome Split hand foot malformation 3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to 30622331; 27600068; 38168117; 35908152; 23596994
Phenotypes for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to Split-hand/foot malformation 3, gene duplication syndrome, MIM#246560
Penetrance for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to Incomplete
Review for Region: 10q24 duplication syndrome Split hand foot malformation 3 was set to GREEN
Added comment: Tandem genomic duplications at chromosome 10q24 have been reported in at least 50 affected individuals from over 30 families with split hand foot malformation.

Duplications encompassed protein coding genes FBXW4, BTRC and ranged in size from 120kb to 597kb. Interestingly very large duplications did not seem to recapitulate the phenotype.

The critical gene/molecular mechanism remains unclear. Expression analysis showed BTRC and SUFU were overexpressed in patient cells and as such a beta catenin signalling pathway defect was proposed. Regulatory element disruption and positional effect was also noted as a possibility given all causative CNV’s were duplications.

Some reduced penetrance noted.
Sources: Literature
Mendeliome v2.485 KATNA1 Sangavi Sivagnanasundram Classified gene: KATNA1 as Amber List (moderate evidence)
Mendeliome v2.485 KATNA1 Sangavi Sivagnanasundram Gene: katna1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.484 KATNA1 Sangavi Sivagnanasundram gene: KATNA1 was added
gene: KATNA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KATNA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KATNA1 were set to 42466416
Phenotypes for gene: KATNA1 were set to Macular dystrophy, non-syndromic MONDO:0020242
Review for gene: KATNA1 was set to AMBER
Added comment: This pre-print publication reports >10 unrelated families with rare heterozygous missense variants in KATNA1. Affected individuals presented with non-syndromic macular dystrophy with a range of severity (some early onset and some late onset).
Given this publication is a pre-print and there are no other evidence of reports, GDA to remain AMBER.
Sources: Literature
Speech apraxia v2.2 CHD3 chirag patel Phenotypes for gene: CHD3 were changed from Snijders Blok-Campeau syndrome MIM#618205 to Snijders Blok-Campeau syndrome, MONDO:0032600
Intellectual disability syndromic and non-syndromic v2.116 CHD3 chirag patel Phenotypes for gene: CHD3 were changed from Snijders Blok-Campeau syndrome, MIM#618205 to Snijders Blok-Campeau syndrome, MONDO:0032600
Genetic Epilepsy v2.36 CHD3 chirag patel Phenotypes for gene: CHD3 were changed from Snijders Blok-Campeau syndrome MIM#618205 to Snijders Blok-Campeau syndrome, MONDO:0032600
Craniosynostosis v2.6 CHD3 chirag patel Phenotypes for gene: CHD3 were changed from Snijders Blok-Campeau syndrome, MIM#618205 to Snijders Blok-Campeau syndrome, MONDO:0032600
Mendeliome v2.483 CHD3 chirag patel Phenotypes for gene: CHD3 were changed from Snijders Blok-Campeau syndrome (618205) to Snijders Blok-Campeau syndrome, MONDO:0032600
Macrocephaly_Megalencephaly v1.8 CHD3 chirag patel Marked gene: CHD3 as ready
Macrocephaly_Megalencephaly v1.8 CHD3 chirag patel Gene: chd3 has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v1.8 CHD3 chirag patel Mode of inheritance for gene: CHD3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Macrocephaly_Megalencephaly v1.7 CHD3 chirag patel Publications for gene: CHD3 were set to
Macrocephaly_Megalencephaly v1.6 CHD3 chirag patel Phenotypes for gene: CHD3 were changed from to Snijders Blok-Campeau syndrome, MONDO:0032600
Speech apraxia v2.1 chirag patel Added reviews for gene CHD3 from panel Intellectual disability syndromic and non-syndromic
Macrocephaly_Megalencephaly v1.5 chirag patel Added reviews for gene CHD3 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.115 chirag patel Added reviews for gene CHD3 from panel Mendeliome
Genetic Epilepsy v2.35 chirag patel Added reviews for gene CHD3 from panel Mendeliome
Craniosynostosis v2.5 chirag patel Added reviews for gene CHD3 from panel Mendeliome
Macrocephaly_Megalencephaly v1.4 chirag patel Added reviews for gene CHD3 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.482 CHD3 chirag patel reviewed gene: CHD3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Snijders Blok-Campeau syndrome, MONDO:0032600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe Combined Immunodeficiency v2.4 Sarah Milton Copied gene GTF3A from panel Mendeliome
Severe Combined Immunodeficiency v2.4 GTF3A Sarah Milton gene: GTF3A was added
gene: GTF3A was added to Severe Combined Immunodeficiency. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: GTF3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3A were set to 36399538
Phenotypes for gene: GTF3A were set to herpes simplex encephalitis MONDO:0012521
Combined Immunodeficiency v2.8 Sarah Milton Copied gene GTF3A from panel Mendeliome
Combined Immunodeficiency v2.8 GTF3A Sarah Milton gene: GTF3A was added
gene: GTF3A was added to Combined Immunodeficiency. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: GTF3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3A were set to 36399538
Phenotypes for gene: GTF3A were set to herpes simplex encephalitis MONDO:0012521
Mendeliome v2.482 GTF3A Sarah Milton Classified gene: GTF3A as Green List (high evidence)
Mendeliome v2.482 GTF3A Sarah Milton Gene: gtf3a has been classified as Green List (High Evidence).
Mendeliome v2.481 GTF3A Sarah Milton Classified gene: GTF3A as Green List (high evidence)
Mendeliome v2.481 GTF3A Sarah Milton Gene: gtf3a has been classified as Green List (High Evidence).
Mendeliome v2.480 GTF3A Sarah Milton reviewed gene: GTF3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 42428087, 36399538; Phenotypes: Inborn error of immunity, MONDO:0003778, GTF3A-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.480 ATL2 chirag patel Marked gene: ATL2 as ready
Mendeliome v2.480 ATL2 chirag patel Gene: atl2 has been classified as Red List (Low Evidence).
Cerebellar and Pontocerebellar Hypoplasia v2.5 ATL2 chirag patel Marked gene: ATL2 as ready
Cerebellar and Pontocerebellar Hypoplasia v2.5 ATL2 chirag patel Gene: atl2 has been classified as Red List (Low Evidence).
Mendeliome v2.480 chirag patel Copied gene ATL2 from panel Ataxia
Mendeliome v2.480 ATL2 chirag patel gene: ATL2 was added
gene: ATL2 was added to Mendeliome. Sources: Expert Review Red,Other
Mode of inheritance for gene: ATL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ATL2 were set to Cerebellar ataxia, MONDO:0000437, ATL2-related
Mode of pathogenicity for gene: ATL2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Cerebellar and Pontocerebellar Hypoplasia v2.5 chirag patel Copied gene ATL2 from panel Ataxia
Cerebellar and Pontocerebellar Hypoplasia v2.5 ATL2 chirag patel gene: ATL2 was added
gene: ATL2 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review Red,Other
Mode of inheritance for gene: ATL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ATL2 were set to Cerebellar ataxia, MONDO:0000437, ATL2-related
Mode of pathogenicity for gene: ATL2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Ataxia v2.14 ATL2 chirag patel Marked gene: ATL2 as ready
Ataxia v2.14 ATL2 chirag patel Gene: atl2 has been classified as Red List (Low Evidence).
Ataxia v2.14 ATL2 chirag patel gene: ATL2 was added
gene: ATL2 was added to Ataxia. Sources: Other
Mode of inheritance for gene: ATL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ATL2 were set to Cerebellar ataxia, MONDO:0000437, ATL2-related
Mode of pathogenicity for gene: ATL2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: ATL2 was set to RED
Added comment: ESHG 2026

7 living individuals from 1 large multigeneration family presenting with early onset (<20yrs but slowly progressive) ataxia, dysarthria, and cerebellar atrophy. WGS (SR and LR) identified a rare heterozygous 2-bp deletion variant in the ATL2 gene. The variant is deeply intronic in the canonical transcript but leads to a frameshift in an alternate transcript (ATL2-2, NM_001330461.2:c.1208_1209del, p.(Arg403Thrfs*6)), which is predominantly expressed in the brain and cerebellum.

The same variant seen in 2 other unrelated families with dominant cerebellar ataxia.

The variant is positioned in the last exon of this transcript, and it is not expected to cause nonsense-mediated decay but likely leads to a protein with an altered C-terminus. Functional analyses were conducted in ATL2/3 double knockout Cos7 cells with different ATL2 isoforms being reintroduced and subsequent measurements of GTPase activity and confocal imaging. These suggested a gain-of-function effect with increased GTPase activity and altered endoplasmatic reticulum morphology. The proposed disease mechanism is a transcript-specific heterozygous gain-of-function.
Sources: Other
Hereditary Spastic Paraplegia v2.5 GSN chirag patel Marked gene: GSN as ready
Hereditary Spastic Paraplegia v2.5 GSN chirag patel Gene: gsn has been classified as Red List (Low Evidence).
Hereditary Spastic Paraplegia v2.5 GSN chirag patel Publications for gene: GSN were set to 2176164; 28139293
Hereditary Spastic Paraplegia v2.4 GSN chirag patel Phenotypes for gene: GSN were changed from Spastic ataxia, MONDO:0017845, GSN-related to Spastic ataxia, MONDO:0017845, GSN-related
Hereditary Spastic Paraplegia v2.4 GSN chirag patel Mode of inheritance for gene: GSN was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Spastic Paraplegia v2.4 GSN chirag patel Mode of inheritance for gene: GSN was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Spastic Paraplegia v2.3 GSN chirag patel Phenotypes for gene: GSN were changed from Amyloidosis, Finnish type, MIM# 105120; Spastic ataxia, MONDO:0017845, GSN-related to Spastic ataxia, MONDO:0017845, GSN-related
Hereditary Spastic Paraplegia v2.3 GSN chirag patel Classified gene: GSN as Red List (low evidence)
Hereditary Spastic Paraplegia v2.3 GSN chirag patel Gene: gsn has been classified as Red List (Low Evidence).
Ataxia v2.13 GSN chirag patel Marked gene: GSN as ready
Ataxia v2.13 GSN chirag patel Gene: gsn has been classified as Red List (Low Evidence).
Ataxia v2.13 GSN chirag patel Phenotypes for gene: GSN were changed from Spastic ataxia, MONDO:0017845, GSN-related to Spastic ataxia, MONDO:0017845, GSN-related
Ataxia v2.13 GSN chirag patel Phenotypes for gene: GSN were changed from Amyloidosis, Finnish type, MIM# 105120; Spastic ataxia, MONDO:0017845, GSN-related to Spastic ataxia, MONDO:0017845, GSN-related
Ataxia v2.12 GSN chirag patel Publications for gene: GSN were set to 2176164; 28139293
Ataxia v2.11 GSN chirag patel Mode of inheritance for gene: GSN was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia v2.10 GSN chirag patel Classified gene: GSN as Red List (low evidence)
Ataxia v2.10 GSN chirag patel Gene: gsn has been classified as Red List (Low Evidence).
Hereditary Spastic Paraplegia v2.2 chirag patel Copied gene GSN from panel Mendeliome
Hereditary Spastic Paraplegia v2.2 GSN chirag patel gene: GSN was added
gene: GSN was added to Hereditary Spastic Paraplegia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GSN was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: GSN were set to 2176164; 28139293
Phenotypes for gene: GSN were set to Amyloidosis, Finnish type, MIM# 105120; Spastic ataxia, MONDO:0017845, GSN-related
Ataxia v2.9 chirag patel Copied gene GSN from panel Mendeliome
Ataxia v2.9 GSN chirag patel gene: GSN was added
gene: GSN was added to Ataxia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GSN was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: GSN were set to 2176164; 28139293
Phenotypes for gene: GSN were set to Amyloidosis, Finnish type, MIM# 105120; Spastic ataxia, MONDO:0017845, GSN-related
Mendeliome v2.479 GSN chirag patel Phenotypes for gene: GSN were changed from Amyloidosis, Finnish type, MIM# 105120 to Amyloidosis, Finnish type, MIM# 105120; Spastic ataxia, MONDO:0017845, GSN-related
Mendeliome v2.478 GSN chirag patel reviewed gene: GSN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic ataxia, MONDO:0017845, GSN-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy v2.29 GSN chirag patel Publications for gene: GSN were set to 8684801; 228009; 3513049
Hereditary Neuropathy v2.28 chirag patel Added reviews for gene GSN from panel Amyloidosis
Corneal Dystrophy v2.4 GSN chirag patel Publications for gene: GSN were set to 2176164
Corneal Dystrophy v2.3 GSN chirag patel Mode of inheritance for gene: GSN 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
Corneal Dystrophy v2.2 GSN chirag patel reviewed gene: GSN: Rating: GREEN; Mode of pathogenicity: None; Publications: 2176164, 28139293; Phenotypes: Amyloidosis, Finnish type, MIM# 105120; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Corneal Dystrophy v2.2 chirag patel Added reviews for gene GSN from panel Mendeliome
Amyloidosis v2.2 GSN chirag patel Publications for gene: GSN were set to PubMed: 8395367; 2176164; 8684801; 6975851; 29167514
Amyloidosis v2.1 GSN chirag patel Mode of inheritance for gene: GSN 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
Fetal anomalies v2.59 IRS1 chirag patel Marked gene: IRS1 as ready
Fetal anomalies v2.59 IRS1 chirag patel Gene: irs1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v2.59 chirag patel Copied gene IRS1 from panel Mendeliome
Fetal anomalies v2.59 IRS1 chirag patel gene: IRS1 was added
gene: IRS1 was added to Fetal anomalies. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: IRS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IRS1 were set to Syndromic disease, MONDO: 0002254, IRS1-related
Growth failure v2.18 IRS1 chirag patel Marked gene: IRS1 as ready
Growth failure v2.18 IRS1 chirag patel Gene: irs1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.114 IRS1 chirag patel Marked gene: IRS1 as ready
Intellectual disability syndromic and non-syndromic v2.114 IRS1 chirag patel Gene: irs1 has been classified as Amber List (Moderate Evidence).
Lipodystrophy_Lipoatrophy v2.11 IRS1 chirag patel Marked gene: IRS1 as ready
Lipodystrophy_Lipoatrophy v2.11 IRS1 chirag patel Gene: irs1 has been classified as Amber List (Moderate Evidence).
Lipodystrophy_Lipoatrophy v2.11 chirag patel Copied gene IRS1 from panel Mendeliome
Lipodystrophy_Lipoatrophy v2.11 IRS1 chirag patel gene: IRS1 was added
gene: IRS1 was added to Lipodystrophy_Lipoatrophy. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: IRS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IRS1 were set to Syndromic disease, MONDO: 0002254, IRS1-related
Intellectual disability syndromic and non-syndromic v2.114 chirag patel Copied gene IRS1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.114 IRS1 chirag patel gene: IRS1 was added
gene: IRS1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: IRS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IRS1 were set to Syndromic disease, MONDO: 0002254, IRS1-related
Growth failure v2.18 chirag patel Copied gene IRS1 from panel Mendeliome
Growth failure v2.18 IRS1 chirag patel gene: IRS1 was added
gene: IRS1 was added to Growth failure. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: IRS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IRS1 were set to Syndromic disease, MONDO: 0002254, IRS1-related
Mendeliome v2.478 IRS1 chirag patel changed review comment from: ESHG 2026

9 individuals from 4 unrelated families with homozygous variants in the IRS1 gene (p.F222del, p.His598Alafs*13). Segregation data not presented. All individuals presented with severe pre/postnatal growth failure (HT/WT/OFC <-3SD), severe insulin resistance, lipoatrophy, osteopenia, developmental delay, intellectual disability, and triangular facies with bulbous nose. Biochemical analysis showed low leptin levels, elevated adiponectin, mildly increased IGFBP3, low/normal cholesterol.

IRS1 is a key adaptor in insulin and IGF-1 signalling pathways. Patient-derived fibroblast demonstrated preserved IRS1 expression and intracellular localization for the variants, but impaired IRS1-mediated signalling, characterized by reduced ERK phosphorylation and increased FOXO1 expression. Variant-specific IRS1 mouse models exhibited severe growth restriction, insulin resistance, reduced adipocyte volume, and reduced bone strength.; to: ESHG 2026

9 individuals from 4 Turkish families with homozygous variants in the IRS1 gene (p.F222del, p.His598Alafs*13). Segregation data not presented. All individuals presented with severe pre/postnatal growth failure (HT/WT/OFC <-3SD), severe insulin resistance, lipoatrophy, osteopenia, developmental delay, intellectual disability, and triangular facies with bulbous nose. Biochemical analysis showed low leptin levels, elevated adiponectin, mildly increased IGFBP3, low/normal cholesterol.

IRS1 is a key adaptor in insulin and IGF-1 signalling pathways. Patient-derived fibroblast demonstrated preserved IRS1 expression and intracellular localization for the variants, but impaired IRS1-mediated signalling, characterized by reduced ERK phosphorylation and increased FOXO1 expression. Variant-specific IRS1 mouse models exhibited severe growth restriction, insulin resistance, reduced adipocyte volume, and reduced bone strength.
Mendeliome v2.478 IRS1 chirag patel Phenotypes for gene: IRS1 were changed from {Coronary artery disease, susceptibility to}; {Type 2 diabetes mellitus, susceptibility to}, MIM# 125853 to Syndromic disease, MONDO: 0002254, IRS1-related
Mendeliome v2.477 IRS1 chirag patel Mode of inheritance for gene: IRS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.476 IRS1 chirag patel Classified gene: IRS1 as Amber List (moderate evidence)
Mendeliome v2.476 IRS1 chirag patel Gene: irs1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.475 IRS1 chirag patel reviewed gene: IRS1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Syndromic disease, MONDO: 0002254, IRS1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.116 Sarah Milton Copied gene HAPLN1 from panel Mendeliome
Skeletal dysplasia v1.116 HAPLN1 Sarah Milton gene: HAPLN1 was added
gene: HAPLN1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: HAPLN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HAPLN1 were set to 42381221
Phenotypes for gene: HAPLN1 were set to Skeletal dysplasia, MONDO:0018230, HAPLN1-related
Mendeliome v2.475 HAPLN1 Sarah Milton gene: HAPLN1 was added
gene: HAPLN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HAPLN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HAPLN1 were set to 42381221
Phenotypes for gene: HAPLN1 were set to Skeletal dysplasia, MONDO:0018230, HAPLN1-related
Review for gene: HAPLN1 was set to RED
Added comment: HAPLN1 encodes hyaluronan and proteoglycan link protein 1 and is a extracellular matrix protein (ECM), required for maintaining tissue architecture and integrity.

PMID 42381221 reports 4 individuals from 1 consanguineous family with a biallelic missense variant presenting with autosomal recessive skeletal dysplasia characterised by rhizomelic‑mesomelic limb shortening, platyspondyly, square iliac wings, short metacarpals. No supportive functional evidence in this paper.

Previous studies cited in above paper have noted skeletal phenotypes in mouse and zebrafish knockout models. Remains a candidate gene.
Sources: Literature
Mendeliome v2.474 LRRFIP1 chirag patel Marked gene: LRRFIP1 as ready
Mendeliome v2.474 LRRFIP1 chirag patel Gene: lrrfip1 has been classified as Red List (Low Evidence).
Mendeliome v2.474 chirag patel Copied gene LRRFIP1 from panel Skeletal dysplasia
Mendeliome v2.474 LRRFIP1 chirag patel gene: LRRFIP1 was added
gene: LRRFIP1 was added to Mendeliome. Sources: Expert Review Red,Other
deep intronic tags were added to gene: LRRFIP1.
Mode of inheritance for gene: LRRFIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: LRRFIP1 were set to Spondylodysplastic-erosive early-onset scoliosis
Skeletal dysplasia v1.115 LRRFIP1 chirag patel Marked gene: LRRFIP1 as ready
Skeletal dysplasia v1.115 LRRFIP1 chirag patel Gene: lrrfip1 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.115 LRRFIP1 chirag patel gene: LRRFIP1 was added
gene: LRRFIP1 was added to Skeletal dysplasia. Sources: Other
deep intronic tags were added to gene: LRRFIP1.
Mode of inheritance for gene: LRRFIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: LRRFIP1 were set to Spondylodysplastic-erosive early-onset scoliosis
Review for gene: LRRFIP1 was set to RED
Added comment: ESHG 2026

Multiple individuals from 1 large multigenerational family with early-onset scoliosis, with a unique pattern of spondylodysplastic elements and progressive endplate erosion. Penetrance was 100% in the family. Linkage analysis and WGS identified a rare noncoding variant in the regulatory element in intron 1 of the LRRFIP1 gene (c.96+34737C>T). The variant segregated with disease in the family.

Short- and long-read RNA sequencing in patient fibroblasts showed altered transcription factor binding and alteration of relative LRRFIP1-isoform expression. Differential gene expression analyses in patient fibroblasts showed alterations in Wnt-signaling during somitogenesis, extracellular matrix organization and TNF-a/NF-kb signaling, partially overlapping with features of common spinal disorders such as Ankylosing Spondylitis. Lrrfip1-knockout mouse had a significantly increased prevalence of kyphoscoliosis.

Rare variant enrichment analysis using genome data from UK Biobank participants showed significant enrichment of LRRFIP1-variants in individuals with idiopathic scoliosis.
Sources: Other
Infertility and Recurrent Pregnancy Loss v2.41 Sarah Milton Copied gene PRRC2A from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v2.41 PRRC2A Sarah Milton gene: PRRC2A was added
gene: PRRC2A was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PRRC2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRRC2A were set to 42411761
Phenotypes for gene: PRRC2A were set to Spermatogenic failure, MONDO:0004983, PRRC2A-related
Mendeliome v2.473 PRRC2A Sarah Milton Marked gene: PRRC2A as ready
Mendeliome v2.473 PRRC2A Sarah Milton Gene: prrc2a has been classified as Amber List (Moderate Evidence).
Mendeliome v2.473 PRRC2A Sarah Milton Classified gene: PRRC2A as Amber List (moderate evidence)
Mendeliome v2.473 PRRC2A Sarah Milton Gene: prrc2a has been classified as Amber List (Moderate Evidence).
Mendeliome v2.472 PRRC2A Sarah Milton gene: PRRC2A was added
gene: PRRC2A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRRC2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRRC2A were set to 42411761
Phenotypes for gene: PRRC2A were set to Spermatogenic failure, MONDO:0004983, PRRC2A-related
Review for gene: PRRC2A was set to AMBER
Added comment: PRRC2A encodes proline rich coiled coil protein 2A which is involved in reading modified RNA specifically N6-methyladenosine (m6A). It is thought to have a role in meiotic progression.

PMID 42411761 reports three individuals from two families with biallelic missense PRRC2A variants presenting with severe male factor infertility (non‑obstructive azoospermia or severe oligozoospermia).

Testicular tissue shows markedly reduced PRRC2A protein, meiotic metaphase arrest, and disrupted m6A‑dependent RNA processing.

Presumably loss of function is proposed mechanism, PMID: 30514900 reports a knockout mouse of PRR2CA resulting in significantly hypomyelination and cognitive deficits, as such unclear if a more multisystem phenotype would be expected with biallelic LOF variants in humans.

Requires further literature to establish gene disease assocation.
Sources: Literature
Hand and foot malformations v1.7 S1PR2 chirag patel Marked gene: S1PR2 as ready
Hand and foot malformations v1.7 S1PR2 chirag patel Gene: s1pr2 has been classified as Green List (High Evidence).
Mendeliome v2.471 S1PR2 chirag patel Phenotypes for gene: S1PR2 were changed from Deafness, autosomal recessive 68, MIM# 610419 to Sensorineural hearing loss disorder MONDO:0020678, S1PR2-related; Congenital limb malformation, MONDO:0019054, S1PR2-related
Skeletal dysplasia v1.114 S1PR2 chirag patel Marked gene: S1PR2 as ready
Skeletal dysplasia v1.114 S1PR2 chirag patel Gene: s1pr2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.114 chirag patel Copied gene S1PR2 from panel Deafness_IsolatedAndComplex
Skeletal dysplasia v1.114 S1PR2 chirag patel gene: S1PR2 was added
gene: S1PR2 was added to Skeletal dysplasia. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: S1PR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: S1PR2 were set to 26805784; 29776397; 27383011
Phenotypes for gene: S1PR2 were set to Sensorineural hearing loss disorder MONDO:0020678, S1PR2-related; Congenital limb malformation, MONDO:0019054, S1PR2-related
Mendeliome v2.470 chirag patel Added reviews for gene S1PR2 from panel Deafness_IsolatedAndComplex
Hand and foot malformations v1.7 chirag patel Copied gene S1PR2 from panel Deafness_IsolatedAndComplex
Hand and foot malformations v1.7 S1PR2 chirag patel gene: S1PR2 was added
gene: S1PR2 was added to Hand and foot malformations. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: S1PR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: S1PR2 were set to 26805784; 29776397; 27383011
Phenotypes for gene: S1PR2 were set to Sensorineural hearing loss disorder MONDO:0020678, S1PR2-related; Congenital limb malformation, MONDO:0019054, S1PR2-related
Deafness_IsolatedAndComplex v2.10 S1PR2 chirag patel Phenotypes for gene: S1PR2 were changed from Deafness, autosomal recessive 68, MIM# 610419 to Sensorineural hearing loss disorder MONDO:0020678, S1PR2-related; Congenital limb malformation, MONDO:0019054, S1PR2-related
Deafness_IsolatedAndComplex v2.9 S1PR2 chirag patel reviewed gene: S1PR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26805784, 29776397; Phenotypes: Sensorineural hearing loss disorder MONDO:0020678, S1PR2-related, Congenital limb malformation, MONDO:0019054, S1PR2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v2.113 FRY chirag patel Phenotypes for gene: FRY were changed from Intellectual disability; no OMIM number yet to Sensorineural hearing loss disorder, MONDO:0020678; Neurodevelopmental disorder, MONDO:0700092, FRY-related
Intellectual disability syndromic and non-syndromic v2.112 FRY chirag patel Publications for gene: FRY were set to PMID: 31487712; 27457812; 21937992
Intellectual disability syndromic and non-syndromic v2.111 FRY chirag patel edited their review of gene: FRY: Added comment: ESHG 2026

18 individuals with 6 unrelated families with biallelic variants in the FRY gene (3 nonsense, 3 missense, 1 multiexon deletion). All variants segregated with disease. The 6 families include 4 families previously reported (31487712, 27457812, 21937992, 33098347). Individuals had moderate sensorineural hearing loss (13/18), developmental/speech delay (10/18), intellectual disability (18/18), ASD (9/10), and dysmorphism (7/10).

FRY encodes a scaffolding protein involved in kinase signalling and cytoskeletal dynamics in the HIPPO signalling pathway, which regulates YAP (a transcription coactivator). YAP variants are associated with multisystem disease with SNHL. Mouse studies showed robust expression of FRY in the cochlea and brain. The Fry null/null homozygous knockout mouse also displays moderate sensorineural hearing-loss consistent with the human phenotype.; Changed publications: 31487712, 27457812, 21937992, 33098347; Changed phenotypes: Sensorineural hearing loss disorder, MONDO:0020678, Neurodevelopmental disorder, MONDO:0700092, FRY-related
Deafness_IsolatedAndComplex v2.9 FRY chirag patel Marked gene: FRY as ready
Deafness_IsolatedAndComplex v2.9 FRY chirag patel Gene: fry has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.111 chirag patel Added reviews for gene FRY from panel Mendeliome
Deafness_IsolatedAndComplex v2.9 chirag patel Copied gene FRY from panel Mendeliome
Deafness_IsolatedAndComplex v2.9 FRY chirag patel gene: FRY was added
gene: FRY was added to Deafness_IsolatedAndComplex. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: FRY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRY were set to 31487712, 27457812, 21937992, 33098347
Phenotypes for gene: FRY were set to Sensorineural hearing loss disorder, MONDO:0020678, FRY-related; Neurodevelopmental disorder, MONDO:0700092, FRY-related
Mendeliome v2.469 FRY chirag patel Phenotypes for gene: FRY were changed from Neurodevelopmental disorder MONDO:0700092 to Sensorineural hearing loss disorder, MONDO:0020678, FRY-related; Neurodevelopmental disorder, MONDO:0700092, FRY-related
Mendeliome v2.468 FRY chirag patel Publications for gene: FRY were set to 31487712; 27457812; 21937992
Mendeliome v2.467 FRY chirag patel reviewed gene: FRY: Rating: AMBER; Mode of pathogenicity: None; Publications: 31487712, 27457812, 21937992, 33098347; Phenotypes: Sensorineural hearing loss disorder, MONDO:0020678, Neurodevelopmental disorder, MONDO:0700092, FRY-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v2.8 DDX41 chirag patel Marked gene: DDX41 as ready
Ataxia v2.8 DDX41 chirag patel Gene: ddx41 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.110 DDX41 chirag patel Marked gene: DDX41 as ready
Intellectual disability syndromic and non-syndromic v2.110 DDX41 chirag patel Gene: ddx41 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v2.4 DDX41 chirag patel Marked gene: DDX41 as ready
Cerebellar and Pontocerebellar Hypoplasia v2.4 DDX41 chirag patel Gene: ddx41 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.110 chirag patel Copied gene DDX41 from panel Syndromic Retinopathy
Intellectual disability syndromic and non-syndromic v2.110 DDX41 chirag patel gene: DDX41 was added
gene: DDX41 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
preprint tags were added to gene: DDX41.
Mode of inheritance for gene: DDX41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDX41 were set to 41646732
Phenotypes for gene: DDX41 were set to Inherited retinal dystrophy, MONDO:0019118, DDX41-related
Cerebellar and Pontocerebellar Hypoplasia v2.4 chirag patel Copied gene DDX41 from panel Syndromic Retinopathy
Cerebellar and Pontocerebellar Hypoplasia v2.4 DDX41 chirag patel gene: DDX41 was added
gene: DDX41 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review Green,Literature
preprint tags were added to gene: DDX41.
Mode of inheritance for gene: DDX41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDX41 were set to 41646732
Phenotypes for gene: DDX41 were set to Inherited retinal dystrophy, MONDO:0019118, DDX41-related
Ataxia v2.8 chirag patel Copied gene DDX41 from panel Syndromic Retinopathy
Ataxia v2.8 DDX41 chirag patel gene: DDX41 was added
gene: DDX41 was added to Ataxia. Sources: Expert Review Green,Literature
preprint tags were added to gene: DDX41.
Mode of inheritance for gene: DDX41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDX41 were set to 41646732
Phenotypes for gene: DDX41 were set to Inherited retinal dystrophy, MONDO:0019118, DDX41-related
Syndromic Retinopathy v1.2 DDX41 chirag patel reviewed gene: DDX41: Rating: GREEN; Mode of pathogenicity: None; Publications: 41646732; Phenotypes: Inherited retinal dystrophy, MONDO:0019118, DDX41-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.77 DTNA Zornitza Stark changed review comment from: PMID 38551768 reports a sinlge individual with a heterozygous DTNA missense variant (p.Gln201Arg) presenting with hypertrophic cardiomyopathy; PMID 29118297 reports another individual with a heterozygous DTNA missense variant (p.N49S) presenting with left ventricular noncompaction cardiomyopathy; a transgenic mouse model overexpressing p.N49S recapitulates LVNC‑like hyper‑trabeculation and dilated cardiomyopathy.; to: PMID 38551768 reports a sinlge individual with a heterozygous DTNA missense variant (p.Gln201Arg) presenting with hypertrophic cardiomyopathy; PMID 29118297 reports another individual with a heterozygous DTNA missense variant (p.N49S) presenting with left ventricular noncompaction cardiomyopathy; a transgenic mouse model overexpressing p.N49S recapitulates LVNC‑like hyper‑trabeculation and dilated cardiomyopathy.

Note association with CHD is DISPUTED.
Cardiomyopathy_Paediatric v1.77 DTNA Zornitza Stark Marked gene: DTNA as ready
Cardiomyopathy_Paediatric v1.77 DTNA Zornitza Stark Gene: dtna has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.77 DTNA Zornitza Stark Phenotypes for gene: DTNA were changed from Left ventricular noncompaction 1, with or without congenital heart defects, to Left ventricular noncompaction 1, with or without congenital heart defects, MIM# 604169
Cardiomyopathy_Paediatric v1.76 DTNA Zornitza Stark Publications for gene: DTNA were set to
Cardiomyopathy_Paediatric v1.75 DTNA Zornitza Stark reviewed gene: DTNA: Rating: RED; Mode of pathogenicity: None; Publications: 38551768, 29118297; Phenotypes: left ventricular noncompaction 1, MONDO:0011403; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.75 MIB1 Zornitza Stark Publications for gene: MIB1 were set to 30322850; 23314057
Fetal anomalies v2.58 TK1 chirag patel Marked gene: TK1 as ready
Fetal anomalies v2.58 TK1 chirag patel Gene: tk1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.467 TK1 chirag patel Marked gene: TK1 as ready
Mendeliome v2.467 TK1 chirag patel Gene: tk1 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.74 MIB1 Zornitza Stark edited their review of gene: MIB1: Added comment: PMID 36325906: Two families (R530X nonsense; V943F missense) reported a third novel frameshift family was reported in PMID 34564127 (c.1582_1589delinsGAGCCC). Variant‑specific rescue in patient‑derived cardiomyocytes (V943F) and a Mib1 knockout mouse model recapitulate the LVNC phenotype.

However, R530X has 64 hets in gnomADv4; V943F has 161 hets.; Changed publications: 40334239, 36325906, 34564127; Changed phenotypes: left ventricular noncompaction 7, MONDO:0014042, MIB1-related
Mendeliome v2.467 chirag patel Copied gene TK1 from panel Skeletal dysplasia
Mendeliome v2.467 TK1 chirag patel gene: TK1 was added
gene: TK1 was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: TK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TK1 were set to Thoracolaryngopelvic dysplasia, MONDO:0008551
Fetal anomalies v2.58 chirag patel Copied gene TK1 from panel Skeletal dysplasia
Fetal anomalies v2.58 TK1 chirag patel gene: TK1 was added
gene: TK1 was added to Fetal anomalies. Sources: Expert Review Amber,Other
Mode of inheritance for gene: TK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TK1 were set to Thoracolaryngopelvic dysplasia, MONDO:0008551
Skeletal dysplasia v1.113 TK1 chirag patel Marked gene: TK1 as ready
Skeletal dysplasia v1.113 TK1 chirag patel Gene: tk1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.113 TK1 chirag patel Classified gene: TK1 as Amber List (moderate evidence)
Skeletal dysplasia v1.113 TK1 chirag patel Gene: tk1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.112 TK1 chirag patel gene: TK1 was added
gene: TK1 was added to Skeletal dysplasia. Sources: Other
Mode of inheritance for gene: TK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TK1 were set to Thoracolaryngopelvic dysplasia, MONDO:0008551
Review for gene: TK1 was set to AMBER
Added comment: ESHG 2026

Barnes syndrome (thoraco-laryngo-pelvic dysplasia/TLPD) is a very rare autosomal dominant skeletal dysplasia, clinically characterised by thoracic dystrophy, narrow pelvis and laryngeal stenosis.

They report 3 unrelated individuals with TLPD with neonatal hypotonia, thoracic dystrophy with short ribs, subglottic stenosis/tracheal hypoplasia requiring tracheostomy, and narrow pelvis with delayed ossification of pubic rami. Trio WGS identified 2 different rare heterozygous de novo variants (1 x p.Phe29Leu and 2 x p.Lys170del) in TK1 gene.

TK1 gene codes for cytosolic thymidine kinase, which phosphorylates thymidine and plays role in DNA synthesis and cell proliferation. Functional studies in lymphoblastoid cell lines suggest a significant reduction of TK1 activity. Further studies are needed to clarify the role of TK1 in bone morphogenesis.
Sources: Other
Palmoplantar Keratoderma and Erythrokeratoderma v1.4 ERO1A chirag patel Marked gene: ERO1A as ready
Palmoplantar Keratoderma and Erythrokeratoderma v1.4 ERO1A chirag patel Gene: ero1a has been classified as Amber List (Moderate Evidence).
Osteogenesis Imperfecta and Osteoporosis v2.8 ERO1A chirag patel Marked gene: ERO1A as ready
Osteogenesis Imperfecta and Osteoporosis v2.8 ERO1A chirag patel Gene: ero1a has been classified as Amber List (Moderate Evidence).
Mendeliome v2.466 ERO1A chirag patel Marked gene: ERO1A as ready
Mendeliome v2.466 ERO1A chirag patel Gene: ero1a has been classified as Amber List (Moderate Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v1.4 chirag patel Copied gene ERO1A from panel Ichthyosis and Porokeratosis
Palmoplantar Keratoderma and Erythrokeratoderma v1.4 ERO1A chirag patel gene: ERO1A was added
gene: ERO1A was added to Palmoplantar Keratoderma and Erythrokeratoderma. Sources: Expert Review Amber,Other
Mode of inheritance for gene: ERO1A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERO1A were set to Ichthyosis, keratoderma and bone fragility
Osteogenesis Imperfecta and Osteoporosis v2.8 chirag patel Copied gene ERO1A from panel Ichthyosis and Porokeratosis
Osteogenesis Imperfecta and Osteoporosis v2.8 ERO1A chirag patel gene: ERO1A was added
gene: ERO1A was added to Osteogenesis Imperfecta and Osteoporosis. Sources: Expert Review Amber,Other
Mode of inheritance for gene: ERO1A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERO1A were set to Ichthyosis, keratoderma and bone fragility
Mendeliome v2.466 chirag patel Copied gene ERO1A from panel Ichthyosis and Porokeratosis
Mendeliome v2.466 ERO1A chirag patel gene: ERO1A was added
gene: ERO1A was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: ERO1A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERO1A were set to Ichthyosis, keratoderma and bone fragility
Ichthyosis and Porokeratosis v2.4 ERO1A chirag patel Marked gene: ERO1A as ready
Ichthyosis and Porokeratosis v2.4 ERO1A chirag patel Gene: ero1a has been classified as Amber List (Moderate Evidence).
Ichthyosis and Porokeratosis v2.4 ERO1A chirag patel Classified gene: ERO1A as Amber List (moderate evidence)
Ichthyosis and Porokeratosis v2.4 ERO1A chirag patel Gene: ero1a has been classified as Amber List (Moderate Evidence).
Ichthyosis and Porokeratosis v2.3 ERO1A chirag patel gene: ERO1A was added
gene: ERO1A was added to Ichthyosis and Porokeratosis. Sources: Other
Mode of inheritance for gene: ERO1A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERO1A were set to Ichthyosis, keratoderma and bone fragility
Review for gene: ERO1A was set to AMBER
Added comment: ESHG 2026

3 individuals from 2 unrelated families (1 consanguineous) with homozygous variants in ERO1A ((p.His22Glnfs19) and p.(Gln154*)). They presented with ichthyosis (3), palmoplantar keratoderma (3), sparse eyebrows (2), fragile nails (2), microcephaly (2), low bone mineral density (1), and recurrent long bone fractures in early childhood (2). The variants segregated in the families.

Endoplasmic reticulum (ER) oxidoreductase 1α (ERO1A) oxidizes the protein disulfide isomerase (PDI) and promotes disulfide bond formation in newly synthesized polypeptides such as collagen I. The 3 patient-derived fibroblasts showed significantly reduced ERO1A mRNA levels, indicating nonsense-mediated mRNA decay. This was accompanied by absence of ERO1A protein and increased PDI levels. In whole-cell lysates from fibroblasts of 2 patients, collagen I was detected as a triple band, whereas only two bands were observed in control cells. They found disordered collagen I aggregates in the extracellular matrix of all patient-derived fibroblasts. As a possible compensatory response, mRNA and protein levels for the collagen-specific ER chaperone HSP47 were increased in patient cells.
Sources: Other
Aortopathy_Connective Tissue Disorders v2.8 chirag patel Added reviews for gene PMEPA1 from panel Mendeliome
Mendeliome v2.465 PMEPA1 chirag patel reviewed gene: PMEPA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hereditary disorder of connective tissue, MONDO:0023603, PMEPA1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.74 ANK2 Zornitza Stark Publications for gene: ANK2 were set to
Cardiomyopathy_Paediatric v1.73 ANK2 Zornitza Stark Tag disputed tag was added to gene: ANK2.
Cardiomyopathy_Paediatric v1.73 ANK2 Zornitza Stark reviewed gene: ANK2: Rating: RED; Mode of pathogenicity: None; Publications: 39866811, 37123301, 31264976, 28196901; Phenotypes: Cardiac arrhythmia, ankyrin-B-related MIM#600919; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy v1.9 SUPV3L1 Zornitza Stark Marked gene: SUPV3L1 as ready
Leukodystrophy v1.9 SUPV3L1 Zornitza Stark Gene: supv3l1 has been classified as Green List (High Evidence).
Microcephaly v2.24 SUPV3L1 Zornitza Stark Marked gene: SUPV3L1 as ready
Microcephaly v2.24 SUPV3L1 Zornitza Stark Gene: supv3l1 has been classified as Green List (High Evidence).
Microcephaly v2.24 Zornitza Stark Copied gene SUPV3L1 from panel Regression
Microcephaly v2.24 SUPV3L1 Zornitza Stark gene: SUPV3L1 was added
gene: SUPV3L1 was added to Microcephaly. Sources: Expert Review Green,Literature,Literature
Mode of inheritance for gene: SUPV3L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUPV3L1 were set to 39596606; 35023579; 42466401; 10.21203/rs.3.rs-4356120; 36344539; 34946966
Phenotypes for gene: SUPV3L1 were set to Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Leukodystrophy v1.9 Zornitza Stark Copied gene SUPV3L1 from panel Regression
Leukodystrophy v1.9 SUPV3L1 Zornitza Stark gene: SUPV3L1 was added
gene: SUPV3L1 was added to Leukodystrophy. Sources: Expert Review Green,Literature,Literature
Mode of inheritance for gene: SUPV3L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUPV3L1 were set to 39596606; 35023579; 42466401; 10.21203/rs.3.rs-4356120; 36344539; 34946966
Phenotypes for gene: SUPV3L1 were set to Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Regression v1.6 SUPV3L1 Zornitza Stark Publications for gene: SUPV3L1 were set to 39596606; 35023579
Regression v1.5 SUPV3L1 Zornitza Stark Phenotypes for gene: SUPV3L1 were changed from Mitochondrial disease, MONDO:0044970 to Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Regression v1.4 SUPV3L1 Zornitza Stark Classified gene: SUPV3L1 as Green List (high evidence)
Regression v1.4 SUPV3L1 Zornitza Stark Gene: supv3l1 has been classified as Green List (High Evidence).
Regression v1.3 SUPV3L1 Zornitza Stark edited their review of gene: SUPV3L1: Added comment: Six studies have now identified over 20 families with biallelic SUPV3L1 variants, expanding the phenotype to a variable neurodevelopmental/mitochondrial disorder characterised by infant‑onset motor delay, intellectual disability, microcephaly, spasticity, leukodystrophy, optic atrophy and skin hypopigmentation. Functional data include variant‑specific dsRNA‑clearance assays for missense alleles, lentiviral rescue of the mitochondrial RNA‑processing defect in patient fibroblasts, and a supv3l1 knockout zebrafish model that recapitulates mitochondrial dysfunction and interferon activation.; Changed rating: GREEN; Changed publications: 39596606, 35023579, 42466401, 10.21203/rs.3.rs-4356120, 36344539, 34946966; Changed phenotypes: Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Mitochondrial disease v2.4 SUPV3L1 Zornitza Stark Phenotypes for gene: SUPV3L1 were changed from Mitochondrial disease, MONDO:0044970 to Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Mitochondrial disease v2.3 SUPV3L1 Zornitza Stark Publications for gene: SUPV3L1 were set to 39596606; 35023579
Mitochondrial disease v2.2 SUPV3L1 Zornitza Stark Classified gene: SUPV3L1 as Green List (high evidence)
Mitochondrial disease v2.2 SUPV3L1 Zornitza Stark Gene: supv3l1 has been classified as Green List (High Evidence).
Mitochondrial disease v2.1 SUPV3L1 Zornitza Stark edited their review of gene: SUPV3L1: Added comment: Six studies have now identified over 20 families with biallelic SUPV3L1 variants, expanding the phenotype to a variable neurodevelopmental/mitochondrial disorder characterised by infant‑onset motor delay, intellectual disability, microcephaly, spasticity, leukodystrophy, optic atrophy and skin hypopigmentation. Functional data include variant‑specific dsRNA‑clearance assays for missense alleles, lentiviral rescue of the mitochondrial RNA‑processing defect in patient fibroblasts, and a supv3l1 knockout zebrafish model that recapitulates mitochondrial dysfunction and interferon activation.; Changed rating: GREEN; Changed publications: 39596606, 35023579, 42466401, 10.21203/rs.3.rs-4356120, 36344539, 34946966; Changed phenotypes: Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Optic Atrophy v2.4 SUPV3L1 Zornitza Stark Phenotypes for gene: SUPV3L1 were changed from Mitochondrial disease, MONDO:0044970 to Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Optic Atrophy v2.3 SUPV3L1 Zornitza Stark Publications for gene: SUPV3L1 were set to 39596606; 35023579
Optic Atrophy v2.2 SUPV3L1 Zornitza Stark Classified gene: SUPV3L1 as Green List (high evidence)
Optic Atrophy v2.2 SUPV3L1 Zornitza Stark Gene: supv3l1 has been classified as Green List (High Evidence).
Optic Atrophy v2.1 SUPV3L1 Zornitza Stark edited their review of gene: SUPV3L1: Added comment: Six studies have now identified over 20 families with biallelic SUPV3L1 variants, expanding the phenotype to a variable neurodevelopmental/mitochondrial disorder characterised by infant‑onset motor delay, intellectual disability, microcephaly, spasticity, leukodystrophy, optic atrophy and skin hypopigmentation. Functional data include variant‑specific dsRNA‑clearance assays for missense alleles, lentiviral rescue of the mitochondrial RNA‑processing defect in patient fibroblasts, and a supv3l1 knockout zebrafish model that recapitulates mitochondrial dysfunction and interferon activation.; Changed rating: GREEN; Changed publications: 39596606, 35023579, 42466401, 10.21203/rs.3.rs-4356120, 36344539, 34946966; Changed phenotypes: Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Mendeliome v2.465 SUPV3L1 Zornitza Stark Phenotypes for gene: SUPV3L1 were changed from Mitochondrial disease, MONDO:0044970 to Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Mendeliome v2.464 SUPV3L1 Zornitza Stark Publications for gene: SUPV3L1 were set to 39596606; 35023579
Mendeliome v2.463 SUPV3L1 Zornitza Stark Classified gene: SUPV3L1 as Green List (high evidence)
Mendeliome v2.463 SUPV3L1 Zornitza Stark Gene: supv3l1 has been classified as Green List (High Evidence).
Mendeliome v2.462 SUPV3L1 Zornitza Stark Tag preprint tag was added to gene: SUPV3L1.
Mendeliome v2.462 SUPV3L1 Zornitza Stark edited their review of gene: SUPV3L1: Added comment: Six studies have now identified over 20 families with biallelic SUPV3L1 variants, expanding the phenotype to a variable neurodevelopmental/mitochondrial disorder characterised by infant‑onset motor delay, intellectual disability, microcephaly, spasticity, leukodystrophy, optic atrophy and skin hypopigmentation. Functional data include variant‑specific dsRNA‑clearance assays for missense alleles, lentiviral rescue of the mitochondrial RNA‑processing defect in patient fibroblasts, and a supv3l1 knockout zebrafish model that recapitulates mitochondrial dysfunction and interferon activation.; Changed rating: GREEN; Changed publications: 42466401, 10.21203/rs.3.rs-4356120, 39596606, 36344539, 35023579, 34946966; Changed phenotypes: Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Intellectual disability syndromic and non-syndromic v2.109 MORF4L1 Zornitza Stark Marked gene: MORF4L1 as ready
Intellectual disability syndromic and non-syndromic v2.109 MORF4L1 Zornitza Stark Gene: morf4l1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v2.109 Zornitza Stark Copied gene MORF4L1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.109 MORF4L1 Zornitza Stark gene: MORF4L1 was added
gene: MORF4L1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Red,Literature
Mode of inheritance for gene: MORF4L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MORF4L1 were set to 42457791
Phenotypes for gene: MORF4L1 were set to Neurodevelopmental disorder, MONDO:0700092, MORF4L1-related
Mendeliome v2.462 MORF4L1 Zornitza Stark Marked gene: MORF4L1 as ready
Mendeliome v2.462 MORF4L1 Zornitza Stark Gene: morf4l1 has been classified as Red List (Low Evidence).
Mendeliome v2.462 MORF4L1 Zornitza Stark gene: MORF4L1 was added
gene: MORF4L1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MORF4L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MORF4L1 were set to 42457791
Phenotypes for gene: MORF4L1 were set to Neurodevelopmental disorder, MONDO:0700092, MORF4L1-related
Review for gene: MORF4L1 was set to RED
Added comment: PMID 42457791 reports two individuals from a single family with a homozygous missense MORF4L1 variant (c.491T>C, p.Leu164Pro) presenting with a neurodevelopmental disorder characterised by trigonocephaly, dysmorphic facial features, global developmental delay, obesity and multi‑system anomalies. The variant is absent from gnomAD, and causes ~99 % reduction of MORF4L1 protein in patient fibroblasts; zebrafish loss‑of‑function mutants recapitulate growth restriction and skeletal defects, although knock‑in models appear phenotypically normal.
Sources: Literature
Autism v1.17 USP15 Zornitza Stark Marked gene: USP15 as ready
Autism v1.17 USP15 Zornitza Stark Gene: usp15 has been classified as Red List (Low Evidence).
Autism v1.17 Zornitza Stark Copied gene USP15 from panel Mendeliome
Autism v1.17 USP15 Zornitza Stark gene: USP15 was added
gene: USP15 was added to Autism. Sources: Expert Review Red,Literature
Mode of inheritance for gene: USP15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: USP15 were set to 42526765; 28344757
Phenotypes for gene: USP15 were set to Neurodevelopmental disorder, MONDO:0700092, USP15-related
Mendeliome v2.461 USP15 Zornitza Stark Marked gene: USP15 as ready
Mendeliome v2.461 USP15 Zornitza Stark Gene: usp15 has been classified as Red List (Low Evidence).
Mendeliome v2.461 USP15 Zornitza Stark gene: USP15 was added
gene: USP15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: USP15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: USP15 were set to 42526765; 28344757
Phenotypes for gene: USP15 were set to Neurodevelopmental disorder, MONDO:0700092, USP15-related
Review for gene: USP15 was set to RED
Added comment: PMID 42526765 reports a single individual with a de novo start‑codon loss‑of‑function USP15 variant and autism spectrum disorder; PMID 28344757 reports another individual with a de novo loss‑of‑function USP15 variant and autism spectrum disorder but variant details not provided. The PMID 42526765 study demonstrated progenitor‑centric transcriptional dysregulation and neuronal maturation defects in isogenic hiPSC‑derived cortical organoids harbouring the heterozygous variant.
Sources: Literature
Incidentalome v1.10 RRAD Zornitza Stark Marked gene: RRAD as ready
Incidentalome v1.10 RRAD Zornitza Stark Gene: rrad has been classified as Red List (Low Evidence).
Incidentalome v1.10 Zornitza Stark Copied gene RRAD from panel Brugada syndrome
Incidentalome v1.10 RRAD Zornitza Stark gene: RRAD was added
gene: RRAD was added to Incidentalome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: RRAD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RRAD were set to 34185406; 31114854
Phenotypes for gene: RRAD were set to Brugada syndrome, MONDO:0015263, RRAD-related
Brugada syndrome v1.4 RRAD Zornitza Stark Marked gene: RRAD as ready
Brugada syndrome v1.4 RRAD Zornitza Stark Gene: rrad has been classified as Red List (Low Evidence).
Brugada syndrome v1.4 RRAD Zornitza Stark gene: RRAD was added
gene: RRAD was added to Brugada syndrome. Sources: Literature
Mode of inheritance for gene: RRAD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RRAD were set to 34185406; 31114854
Phenotypes for gene: RRAD were set to Brugada syndrome, MONDO:0015263, RRAD-related
Review for gene: RRAD was set to RED
Added comment: RRAD encodes the RAD GTPase, a member of the RGK subfamily involved in regulation of cardiac ion channels and cytoskeletal dynamics.

PMID 31114854 reports five affected members of a three‑generation French family carrying a rare missense variant p.R211H in RRAD, present in 3 hets in gnomAD v4. iPSC‑derived cardiomyocytes from two affected relatives, as well as a CRISPR‑edited isogenic line, showed reduced Na⁺ peak current, increased persistent Na⁺ current, prolonged action potentials and cytoskeletal disorganisation, supporting a gain‑of‑function effect of the mutant GTPase. Screening of 186 unrelated BrS patients identified three additional rare RRAD missense variants without functional validation and with much higher gnomAD counts.
Sources: Literature
Mendeliome v2.460 B4GALT5 Rylee Peters Marked gene: B4GALT5 as ready
Mendeliome v2.460 B4GALT5 Rylee Peters Gene: b4galt5 has been classified as Red List (Low Evidence).
Mendeliome v2.460 B4GALT5 Rylee Peters gene: B4GALT5 was added
gene: B4GALT5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: B4GALT5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B4GALT5 were set to 42425491
Phenotypes for gene: B4GALT5 were set to Syndromic disease, MONDO:0002254, B4GALT5-related
Review for gene: B4GALT5 was set to RED
Added comment: PMID: 42425491 reports 1 individual from 1 family with biallelic loss-of-function missense variants presenting with a congenital disorder of glycosylation characterised by microcephaly, mild cognitive impairment and bilateral cataracts. Enzymatic activity of the identified B4GALT5 variants were measured in B4GALT5/6 double KO cell model. Cells transfected with each mutant B4GALT5 lacked LacCer synthase activity, whereas WT rescued activity.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v2.40 LRGUK Rylee Peters Marked gene: LRGUK as ready
Infertility and Recurrent Pregnancy Loss v2.40 LRGUK Rylee Peters Gene: lrguk has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v2.40 Rylee Peters Copied gene LRGUK from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v2.40 LRGUK Rylee Peters gene: LRGUK was added
gene: LRGUK was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: LRGUK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRGUK were set to 42493466; 38884051
Phenotypes for gene: LRGUK were set to Infertility disorder, MONDO:0005047, LRGUK-related
Congenital Heart Defect v1.31 PFKP Rylee Peters Marked gene: PFKP as ready
Congenital Heart Defect v1.31 PFKP Rylee Peters Gene: pfkp has been classified as Amber List (Moderate Evidence).
Mendeliome v2.459 LRGUK Rylee Peters Marked gene: LRGUK as ready
Mendeliome v2.459 LRGUK Rylee Peters Gene: lrguk has been classified as Amber List (Moderate Evidence).
Mendeliome v2.459 LRGUK Rylee Peters Classified gene: LRGUK as Amber List (moderate evidence)
Mendeliome v2.459 LRGUK Rylee Peters Gene: lrguk has been classified as Amber List (Moderate Evidence).
Mendeliome v2.458 LRGUK Rylee Peters gene: LRGUK was added
gene: LRGUK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LRGUK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRGUK were set to 42493466; 38884051
Phenotypes for gene: LRGUK were set to Infertility disorder, MONDO:0005047, LRGUK-related
Review for gene: LRGUK was set to AMBER
Added comment: PMID: 38884051 and PMID: 42493466 report 3 individuals from 2 families with biallelic loss-of-function LRGUK variants presenting with male infertility (asthenozoospermia and multiple morphological abnormalities of the sperm flagella). Functional studies show loss of LRGUK protein and flagellar ultrastructural defects.
Sources: Literature
Arthrogryposis v2.2 TTN Sarah Milton reviewed gene: TTN: Rating: AMBER; Mode of pathogenicity: None; Publications: 39277846, 37935568; Phenotypes: TTN-related myopathy, dominant-negative TTNsv, MONDO:1060225; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Muscular dystrophy and myopathy_Paediatric v2.7 Sarah Milton Added reviews for gene TTN from panel Limb-Girdle Muscular Dystrophy and Distal Myopathy
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.0 TTN Sarah Milton reviewed gene: TTN: Rating: GREEN; Mode of pathogenicity: None; Publications: 39277846, 37935568; Phenotypes: TTN-related myopathy, dominant-negative TTNsv, MONDO:1060225; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v2.57 chirag patel Added reviews for gene LDB1 from panel Intellectual disability syndromic and non-syndromic
Fetal anomalies v2.56 LDB1 chirag patel Phenotypes for gene: LDB1 were changed from Congenital hydrocephalus MONDO:0016349 to Congenital hydrocephalus MONDO:0016349; Neurodevelopmental disorder, MONDO:0700092, LDB1-related
Mendeliome v2.457 LDB1 chirag patel Phenotypes for gene: LDB1 were changed from Congenital hydrocephalus MONDO:0016349 to Congenital hydrocephalus MONDO:0016349; Neurodevelopmental disorder, MONDO:0700092, LDB1-related
Hydrocephalus_Ventriculomegaly v1.12 LDB1 chirag patel Phenotypes for gene: LDB1 were changed from Congenital hydrocephalus MONDO:0016349 to Congenital hydrocephalus MONDO:0016349; Neurodevelopmental disorder, MONDO:0700092, LDB1-related
Mendeliome v2.456 chirag patel Added reviews for gene LDB1 from panel Intellectual disability syndromic and non-syndromic
Hydrocephalus_Ventriculomegaly v1.11 chirag patel Added reviews for gene LDB1 from panel Intellectual disability syndromic and non-syndromic
Intellectual disability syndromic and non-syndromic v2.108 LDB1 chirag patel Marked gene: LDB1 as ready
Intellectual disability syndromic and non-syndromic v2.108 LDB1 chirag patel Gene: ldb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.108 LDB1 chirag patel Classified gene: LDB1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.108 LDB1 chirag patel Gene: ldb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.107 LDB1 chirag patel gene: LDB1 was added
gene: LDB1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: LDB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: LDB1 were set to Neurodevelopmental disorder, MONDO:0700092, LDB1-related
Review for gene: LDB1 was set to AMBER
Added comment: ESHG 2026

16 unrelated individuals with 16 different rare heterozygous de novo variants (missense, nonsense, frameshift, gene deletions) in the LDB1 gene. Eleven variants affect the whole gene or the N-terminal dimerization domain and 5 variants affect only the C-terminus. All individuals presented with developmental delay and behaviour issues, but individuals with C-terminal variants also presented with ventriculomegaly.

LDB1 encodes transcriptional regulator protein LIM-domain-binding protein 1, which plays an important role in neurogenesis. In vitro assays showed the N-terminal missense variants disrupted homodimerization of LDB1 (likely leading to a loss of function) but the C-terminal variants impaired interaction with the essential partner LHX2 (in a dominant-negative fashion). Toxicity of overexpressed human LDB1 in Drosophila was not seen for N-terminal missense variants but was exacerbated by C-terminal variants. Phenotypes associated with LDB1/chi loss in Drosophila were a) rescued by overexpression of wild-type LDB1, b) not rescued by N-terminal missense variants, and c) worsened by C-terminal variants. This suggests 2 distinct pathomechanisms of LDB1-related NDDs.
Sources: Other
Congenital Heart Defect v1.31 Rylee Peters Copied gene PFKP from panel Mendeliome
Congenital Heart Defect v1.31 PFKP Rylee Peters gene: PFKP was added
gene: PFKP was added to Congenital Heart Defect. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PFKP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PFKP were set to 42385441
Phenotypes for gene: PFKP were set to Congenital heart disease, MONDO:0005453, PFKP-related
Mendeliome v2.455 PFKP Rylee Peters Marked gene: PFKP as ready
Mendeliome v2.455 PFKP Rylee Peters Gene: pfkp has been classified as Amber List (Moderate Evidence).
Mendeliome v2.455 PFKP Rylee Peters Classified gene: PFKP as Amber List (moderate evidence)
Mendeliome v2.455 PFKP Rylee Peters Gene: pfkp has been classified as Amber List (Moderate Evidence).
Mendeliome v2.454 PFKP Rylee Peters gene: PFKP was added
gene: PFKP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PFKP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PFKP were set to 42385441
Phenotypes for gene: PFKP were set to Congenital heart disease, MONDO:0005453, PFKP-related
Review for gene: PFKP was set to AMBER
Added comment: PMID: 42385441 reports >10 individuals from 2 families with a heterozygous missense PFKP p.(R755W) variant (gnomAD v4: 3 hets) presenting with a congenital heart malformation syndrome characterised by prenatal ventricular wall thinning and septal defects. Heterozygous mutant (PfkpR754W/+) mice did not show significant structural abnormalities whilst homozygous mutant (PfkpR754W/R754W) mice recapitulated the core phenotypes including significantly thinned ventricular walls.
Sources: Literature
Mendeliome v2.453 MACROH2A1 chirag patel Marked gene: MACROH2A1 as ready
Mendeliome v2.453 MACROH2A1 chirag patel Gene: macroh2a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.453 chirag patel Copied gene MACROH2A1 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.453 MACROH2A1 chirag patel gene: MACROH2A1 was added
gene: MACROH2A1 was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: MACROH2A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MACROH2A1 were set to Neurodevelopmental disorder, MONDO:0700092, MACROH2A1-related
Intellectual disability syndromic and non-syndromic v2.106 MACROH2A1 chirag patel Marked gene: MACROH2A1 as ready
Intellectual disability syndromic and non-syndromic v2.106 MACROH2A1 chirag patel Gene: macroh2a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.106 MACROH2A1 chirag patel Classified gene: MACROH2A1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.106 MACROH2A1 chirag patel Gene: macroh2a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.105 MACROH2A1 chirag patel gene: MACROH2A1 was added
gene: MACROH2A1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: MACROH2A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MACROH2A1 were set to Neurodevelopmental disorder, MONDO:0700092, MACROH2A1-related
Review for gene: MACROH2A1 was set to AMBER
Added comment: ESHG 2026

5 unrelated individuals with 3 different rare heterozygous de novo missense variants in H2A-like domain in MACROH2A1 gene. Two missense variants affected the same amino acid in 4 individuals (p.Arg27Gln and p.Arg27Trp). Individuals presented with global developmental delay (5/5), intellectual disability (5/5), hypotonia (4/4), microcephaly (3/5), seizures (2/5), brain abnormalities (3/4), and dysmorphism (5/5).

MACROH2A1 is a distinctive H2A variant involved in transcriptional regulation, chromatin organization, and neuronal differentiation. Structural modeling indicated that variants destabilize the nucleosome and impair MACROH2A1-DNA interactions. Transcriptomic profiling of patient-derived fibroblasts highlighted dysregulation of the actin cytoskeleton organization and cell-matrix interaction dynamics, ER-related trafficking, and neuronal differentiation programs. Patient fibroblasts exhibited disorganized F-actin with defective focal adhesions and ER disorganization with lumen dilation. Patient fibroblasts also showed impaired fibroblast-to-neuronal reprogramming with reduced TuJ1-positive cells, and abnormal neurite morphology. Methylation profiling revealed a distinct episignature discriminating affected individuals from controls, consistent with global epigenetic dysregulation.
Sources: Other
Kabuki syndrome v1.1 RLF chirag patel Marked gene: RLF as ready
Kabuki syndrome v1.1 RLF chirag patel Gene: rlf has been classified as Amber List (Moderate Evidence).
Mendeliome v2.452 RLF chirag patel Marked gene: RLF as ready
Mendeliome v2.452 RLF chirag patel Gene: rlf has been classified as Amber List (Moderate Evidence).
Mendeliome v2.452 chirag patel Copied gene RLF from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.452 RLF chirag patel gene: RLF was added
gene: RLF was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: RLF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RLF were set to Neurodevelopmental disorder, MONDO:0700092, RLF-related
Kabuki syndrome v1.1 chirag patel Copied gene RLF from panel Intellectual disability syndromic and non-syndromic
Kabuki syndrome v1.1 RLF chirag patel gene: RLF was added
gene: RLF was added to Kabuki syndrome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: RLF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RLF were set to Neurodevelopmental disorder, MONDO:0700092, RLF-related
Intellectual disability syndromic and non-syndromic v2.104 RLF chirag patel Marked gene: RLF as ready
Intellectual disability syndromic and non-syndromic v2.104 RLF chirag patel Gene: rlf has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.104 RLF chirag patel Classified gene: RLF as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.104 RLF chirag patel Gene: rlf has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.103 RLF chirag patel gene: RLF was added
gene: RLF was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: RLF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RLF were set to Neurodevelopmental disorder, MONDO:0700092, RLF-related
Review for gene: RLF was set to AMBER
Added comment: ESHG 2026

22 unrelated individuals with rare heterozygous de novo variants (14 frameshift, 8 nonsense) located in the last exon of RLF gene. Individuals presented with developmental delay, intellectual disability, autism-type behaviour, and Kabuki syndrome-like facial features.

RLF is a poly-ZNF protein which acts as a transcription factor. In vitro assays showed the variants profoundly altered the epigenome, the transcriptome and the DNA secondary structure. ONT whole genome sequencing in patient IPSCs showed hypermethylation and hypo-5-hydroxymethylation at multiple CpG sites. ATAC-seq demonstrated altered chromatin accessibility at promoters and enhancers in patient IPSCs. RNA-seq unveiled several differentially expressed genes enriched for disease-relevant gene ontology terms. RLP variants upregulated neuronal differentiation genes. RLF-ChIP-seq data showed a marked reduction in G4 access signal in patient iPSCs. Methylation arrays revealed a distinct methylation profile overlapping with Kabuki syndrome.
Sources: Other
Mendeliome v2.451 DHX36 chirag patel Marked gene: DHX36 as ready
Mendeliome v2.451 DHX36 chirag patel Gene: dhx36 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.451 DHX36 chirag patel Classified gene: DHX36 as Amber List (moderate evidence)
Mendeliome v2.451 DHX36 chirag patel Gene: dhx36 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.102 DHX36 chirag patel Marked gene: DHX36 as ready
Intellectual disability syndromic and non-syndromic v2.102 DHX36 chirag patel Gene: dhx36 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.102 DHX36 chirag patel Classified gene: DHX36 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.102 DHX36 chirag patel Gene: dhx36 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.450 chirag patel Copied gene DHX36 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.450 DHX36 chirag patel gene: DHX36 was added
gene: DHX36 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: DHX36 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DHX36 were set to Neurodevelopmental disorder, MONDO:0700092, DHX36-related
Mode of pathogenicity for gene: DHX36 was set to Other
Intellectual disability syndromic and non-syndromic v2.101 DHX36 chirag patel gene: DHX36 was added
gene: DHX36 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: DHX36 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DHX36 were set to Neurodevelopmental disorder, MONDO:0700092, DHX36-related
Mode of pathogenicity for gene: DHX36 was set to Other
Review for gene: DHX36 was set to AMBER
Added comment: ESHG 2026

3 unrelated individuals with 3 heterozygous de novo variants (2 missense, 1 in-frame deletion) located in the helicase domain of DHX36 gene. Individuals presented with global developmental delay (3), hypotonia (3), microcephaly (2), cleft palate (2), respiratory defects (3), cardiovascular abnormalities (3), and hearing impairment (2).

DHX36 is an ATP-dependent G4 helicase which regulates G-quadruplexes (G4s), which are bulky DNA secondary structures that form naturally in GC-rich regions and can pose threats to genome integrity. Functional studies performed in in vitro, Xenopus egg extract and human cell based assays. DHX36 mutant proteins showed reduced ATPase and G4 unwinding activity, but retained G4 binding affinity. Mutant DHX36 also interfered with wild-type helicase activity, exerting a dominant-negative mechanism.
Sources: Other
Microcephaly v2.23 chirag patel Added reviews for gene CUL1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.100 chirag patel Added reviews for gene CUL1 from panel Mendeliome
Mendeliome v2.449 CUL1 chirag patel reviewed gene: CUL1: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CUL1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v2.34 THAP12 chirag patel Marked gene: THAP12 as ready
Genetic Epilepsy v2.34 THAP12 chirag patel Gene: thap12 has been classified as Red List (Low Evidence).
Microcephaly v2.22 THAP12 chirag patel Marked gene: THAP12 as ready
Microcephaly v2.22 THAP12 chirag patel Gene: thap12 has been classified as Red List (Low Evidence).
Mendeliome v2.449 THAP12 chirag patel Marked gene: THAP12 as ready
Mendeliome v2.449 THAP12 chirag patel Gene: thap12 has been classified as Red List (Low Evidence).
Microcephaly v2.22 chirag patel Copied gene THAP12 from panel Intellectual disability syndromic and non-syndromic
Microcephaly v2.22 THAP12 chirag patel gene: THAP12 was added
gene: THAP12 was added to Microcephaly. Sources: Expert Review Red,Other
Mode of inheritance for gene: THAP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: THAP12 were set to Neurodevelopmental disorder, MONDO:0700092, THAP12-related
Mendeliome v2.449 chirag patel Copied gene THAP12 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.449 THAP12 chirag patel gene: THAP12 was added
gene: THAP12 was added to Mendeliome. Sources: Expert Review Red,Other
Mode of inheritance for gene: THAP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: THAP12 were set to Neurodevelopmental disorder, MONDO:0700092, THAP12-related
Genetic Epilepsy v2.34 chirag patel Copied gene THAP12 from panel Intellectual disability syndromic and non-syndromic
Genetic Epilepsy v2.34 THAP12 chirag patel gene: THAP12 was added
gene: THAP12 was added to Genetic Epilepsy. Sources: Expert Review Red,Other
Mode of inheritance for gene: THAP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: THAP12 were set to Neurodevelopmental disorder, MONDO:0700092, THAP12-related
Intellectual disability syndromic and non-syndromic v2.99 THAP12 chirag patel Marked gene: THAP12 as ready
Intellectual disability syndromic and non-syndromic v2.99 THAP12 chirag patel Gene: thap12 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v2.99 THAP12 chirag patel gene: THAP12 was added
gene: THAP12 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: THAP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: THAP12 were set to Neurodevelopmental disorder, MONDO:0700092, THAP12-related
Review for gene: THAP12 was set to RED
Added comment: ESHG 2026

2 siblings from 1 family with compound heterozygous variants in THAP12 (1 missense, 1 frameshift), presenting with refractory early onset epilepsy, severe developmental delay and hypotonia, and microcephaly.

ChIP-seq confirmed the role of THAP12 as a transcriptional activator of genes essential for proliferation, apoptosis, and mitochondrial function in HEK293FT cells. In silico predictions (AlphaFold 3) showed that THAP12 forms homodimers, enabling it to bind DNA. The patient variants were shown to lead to a significant reduction in THAP12 protein level, suggesting a loss-of-function mechanism. Mouse models show embryonic lethality in both Thap12-KO and models harbouring patient specific alleles. Zebrafish models showed THAP12 is primarily expressed in cycling neural progenitors, and loss-of-function models phenocopy the clinical presentation with microcephaly, abnormal neural activity, and seizure like-behaviour.
Sources: Other
Intellectual disability syndromic and non-syndromic v2.98 Richard Lin Copied gene EHMT2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.98 EHMT2 Richard Lin gene: EHMT2 was added
gene: EHMT2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EHMT2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: EHMT2 were set to 42434347; 42386776; 39674972
Phenotypes for gene: EHMT2 were set to Kleefstra syndrome, MONDO:0012455, EHMT2-related
Congenital Heart Defect v1.30 Richard Lin Copied gene EHMT2 from panel Mendeliome
Congenital Heart Defect v1.30 EHMT2 Richard Lin gene: EHMT2 was added
gene: EHMT2 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: EHMT2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: EHMT2 were set to 42434347; 42386776; 39674972
Phenotypes for gene: EHMT2 were set to Kleefstra syndrome, MONDO:0012455, EHMT2-related
Mendeliome v2.448 EHMT2 Richard Lin changed review comment from: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1.

PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 missense and inframe deletion variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, structural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips and protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Episignature partially overlaps with Kleefstra syndrome 1 but was reported to form its own distinct profile. Biochemical assays show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with Ehmt2 +/del_1076-1079 recapitulated the neurobehavioural and craniofacial phenotype. In vitro studies show that patient variants encode for structurally stable G9a proteins which are catalytically incompetent due to aberrant interactions either with histone H3 tail or with S-adenosylmethionine. The proposed mechanism is dominant negative effect on the GLP/G9a complexes.

PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients.
Sources: Literature; to: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1.

PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 missense and inframe deletion variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, structural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips and protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Episignature partially overlaps with Kleefstra syndrome 1 but was reported to form its own distinct profile. Biochemical assays show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with a patient derived variant (Ehmt2 +/del_1076-1079) recapitulated the neurobehavioural and craniofacial phenotype. In vitro studies show that patient variants encode for structurally stable G9a proteins which are catalytically incompetent due to aberrant interactions either with histone H3 tail or with S-adenosylmethionine. The proposed mechanism is dominant negative effect on the GLP/G9a complexes.

PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients.
Sources: Literature
Mendeliome v2.448 EHMT2 Richard Lin changed review comment from: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1.

PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 missense and inframe deletion variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, structural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips and protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Biochemical assays show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with Ehmt2 +/del_1076-1079 recapitulated the neurobehavioural and craniofacial phenotype. In vitro studies show that patient variants encode for structurally stable G9a proteins which are catalytically incompetent due to aberrant interactions either with histone H3 tail or with S-adenosylmethionine. The proposed mechanism is dominant negative effect on the GLP/G9a complexes.

PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients.
Sources: Literature; to: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1.

PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 missense and inframe deletion variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, structural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips and protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Episignature partially overlaps with Kleefstra syndrome 1 but was reported to form its own distinct profile. Biochemical assays show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with Ehmt2 +/del_1076-1079 recapitulated the neurobehavioural and craniofacial phenotype. In vitro studies show that patient variants encode for structurally stable G9a proteins which are catalytically incompetent due to aberrant interactions either with histone H3 tail or with S-adenosylmethionine. The proposed mechanism is dominant negative effect on the GLP/G9a complexes.

PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients.
Sources: Literature
Mendeliome v2.448 DDX1 chirag patel Marked gene: DDX1 as ready
Mendeliome v2.448 DDX1 chirag patel Gene: ddx1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.448 chirag patel Copied gene DDX1 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.448 DDX1 chirag patel gene: DDX1 was added
gene: DDX1 was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: DDX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DDX1 were set to Neurodevelopmental disorder, MONDO:0700092, DDX1-related
Intellectual disability syndromic and non-syndromic v2.97 DDX1 chirag patel Marked gene: DDX1 as ready
Intellectual disability syndromic and non-syndromic v2.97 DDX1 chirag patel Gene: ddx1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.97 DDX1 chirag patel Classified gene: DDX1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.97 DDX1 chirag patel Gene: ddx1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.96 DDX1 chirag patel gene: DDX1 was added
gene: DDX1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: DDX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DDX1 were set to Neurodevelopmental disorder, MONDO:0700092, DDX1-related
Review for gene: DDX1 was set to AMBER
Added comment: ESHG 2026

9 unrelated individuals with 7 different rare heterozygous de novo variants (6 missense, 1 splice) involving conserved residues in critical domains of DDX1 gene. Individuals presented with developmental delay, hypotonia (9/9), distinctive facial gestalt (9/9), behavioral dysregulation (8/9), hand/foot skeletal anomalies (7/9), seizures (4/9), spasticity (4/9), and ataxia (3/9).

DEAD/DExH-box RNA (DDX) helicases are key regulators of RNA metabolism and cellular stress responses, and their dysfunction has been associated with distinct neurodevelopmental syndromes. DDX1 regulates RNA metabolism and genome integrity, and is an essential regulator of cellular responses to genotoxic and environmental stress. In silico analysis predicted all variants decrease protein stability. Patient-derived fibroblasts showed impaired radiation-induced DNA double-strand break repair, defective protection of specific target mRNAs under oxidative stress conditions, increased production of reactive oxygen species, and reduced mitochondrial function.
Sources: Other
Mendeliome v2.447 EHMT2 Richard Lin changed review comment from: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1.

PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, strcutural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips anrd protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Biochemical assay show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with Ehmt2 +/del_1076-1079 recapitulated the neurobehavioural and craniofacial phenotype.

PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients.
Sources: Literature; to: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1.

PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 missense and inframe deletion variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, structural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips and protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Biochemical assays show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with Ehmt2 +/del_1076-1079 recapitulated the neurobehavioural and craniofacial phenotype. In vitro studies show that patient variants encode for structurally stable G9a proteins which are catalytically incompetent due to aberrant interactions either with histone H3 tail or with S-adenosylmethionine. The proposed mechanism is dominant negative effect on the GLP/G9a complexes.

PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients.
Sources: Literature
Mendeliome v2.447 EHMT2 Richard Lin gene: EHMT2 was added
gene: EHMT2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EHMT2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: EHMT2 were set to 42434347; 42386776; 39674972
Phenotypes for gene: EHMT2 were set to Kleefstra syndrome, MONDO:0012455, EHMT2-related
Review for gene: EHMT2 was set to GREEN
Added comment: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1.

PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, strcutural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips anrd protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Biochemical assay show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with Ehmt2 +/del_1076-1079 recapitulated the neurobehavioural and craniofacial phenotype.

PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients.
Sources: Literature
Mendeliome v2.446 XPO7 chirag patel Marked gene: XPO7 as ready
Mendeliome v2.446 XPO7 chirag patel Gene: xpo7 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.446 chirag patel Copied gene XPO7 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.446 XPO7 chirag patel gene: XPO7 was added
gene: XPO7 was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: XPO7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: XPO7 were set to Neurodevelopmental disorder, MONDO:0700092, XPO7-related
Intellectual disability syndromic and non-syndromic v2.95 XPO7 chirag patel Marked gene: XPO7 as ready
Intellectual disability syndromic and non-syndromic v2.95 XPO7 chirag patel Gene: xpo7 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.95 XPO7 chirag patel Classified gene: XPO7 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.95 XPO7 chirag patel Gene: xpo7 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.94 XPO7 chirag patel gene: XPO7 was added
gene: XPO7 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: XPO7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: XPO7 were set to Neurodevelopmental disorder, MONDO:0700092, XPO7-related
Review for gene: XPO7 was set to AMBER
Added comment: ESHG 2026

25 unrelated individuals with 19 different heterozygous variants in XPO7 (10 missense, 3 splice, 6 truncating). The R756W variant occurred in 6 unrelated individuals. Inheritance of variants was de novo (21), inherited (2), or unknown (1). Individuals presented with mild to severe developmental delay/intellectual disability (24/25), behavioural disturbances (17/24), nonspecific brain abnormalities (9/17), epilepsy (4/25), overweight (7/22), and other variable congenital anomalies.

XPO7 encodes a nuclear transport receptor. The R756W knock-in mouse model exhibited reduced XPO7 protein levels, reduced brain volume, decreased dendritic complexity, diminished excitatory synaptic transmission, and altered anxiety-related behaviour.
Sources: Other
Microcephaly v2.21 CENPT chirag patel Marked gene: CENPT as ready
Microcephaly v2.21 CENPT chirag patel Gene: cenpt has been classified as Amber List (Moderate Evidence).
Growth failure v2.17 CENPT chirag patel Marked gene: CENPT as ready
Growth failure v2.17 CENPT chirag patel Gene: cenpt has been classified as Amber List (Moderate Evidence).
Fetal anomalies v2.55 CENPT chirag patel Marked gene: CENPT as ready
Fetal anomalies v2.55 CENPT chirag patel Gene: cenpt has been classified as Amber List (Moderate Evidence).
Eye Anterior Segment Abnormalities v2.1 CENPT chirag patel Marked gene: CENPT as ready
Eye Anterior Segment Abnormalities v2.1 CENPT chirag patel Gene: cenpt has been classified as Amber List (Moderate Evidence).
Microcephaly v2.21 chirag patel Copied gene CENPT from panel Mendeliome
Microcephaly v2.21 CENPT chirag patel gene: CENPT was added
gene: CENPT was added to Microcephaly. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CENPT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPT were set to 29228025
Phenotypes for gene: CENPT were set to Syndromic disease, MONDO: 0002254, CENPT-related
Growth failure v2.17 chirag patel Copied gene CENPT from panel Mendeliome
Growth failure v2.17 CENPT chirag patel gene: CENPT was added
gene: CENPT was added to Growth failure. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CENPT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPT were set to 29228025
Phenotypes for gene: CENPT were set to Syndromic disease, MONDO: 0002254, CENPT-related
Fetal anomalies v2.55 chirag patel Copied gene CENPT from panel Mendeliome
Fetal anomalies v2.55 CENPT chirag patel gene: CENPT was added
gene: CENPT was added to Fetal anomalies. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CENPT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPT were set to 29228025
Phenotypes for gene: CENPT were set to Syndromic disease, MONDO: 0002254, CENPT-related
Eye Anterior Segment Abnormalities v2.1 chirag patel Copied gene CENPT from panel Mendeliome
Eye Anterior Segment Abnormalities v2.1 CENPT chirag patel gene: CENPT was added
gene: CENPT was added to Eye Anterior Segment Abnormalities. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CENPT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPT were set to 29228025
Phenotypes for gene: CENPT were set to Syndromic disease, MONDO: 0002254, CENPT-related
Mendeliome v2.445 CENPT chirag patel Phenotypes for gene: CENPT were changed from short stature and microcephaly with genital anomalies MONDO:0032875 to Syndromic disease, MONDO: 0002254, CENPT-related
Mendeliome v2.444 CENPT chirag patel Classified gene: CENPT as Amber List (moderate evidence)
Mendeliome v2.444 CENPT chirag patel Gene: cenpt has been classified as Amber List (Moderate Evidence).
Mendeliome v2.443 CENPT chirag patel reviewed gene: CENPT: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Syndromic disease, MONDO: 0002254, CENPT-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital ophthalmoplegia v2.1 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from Fibrosis of extraocular muscles, congenital, 3A 600638; CFEOM3A to Fibrosis of extraocular muscles, congenital, 3A 600638; CFEOM3A; Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay MIM#621655; Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Congenital ophthalmoplegia v2.0 TUBB3 Zornitza Stark edited their review of gene: TUBB3: Changed phenotypes: Fibrosis of extraocular muscles, congenital, 3A, MIM# 600638, Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay MIM#621655, Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Hypogonadotropic hypogonadism v1.16 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from TUBB3-related tubulinopathy, MONDO:0100154 to TUBB3-related tubulinopathy, MONDO:0100154; Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay, MIM#621655
Hypogonadotropic hypogonadism v1.15 TUBB3 Zornitza Stark reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay, MIM#621655; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v1.19 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from TUBB3-related tubulinopathy, MONDO:0100154 to TUBB3-related tubulinopathy, MONDO:0100154; Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay, MIM#621655
Pituitary hormone deficiency v1.18 TUBB3 Zornitza Stark reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay, MIM#621655; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v2.93 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from complex cortical dysplasia with other brain malformations 1 MONDO:0013541; Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay MIM#621655 Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666 to complex cortical dysplasia with other brain malformations 1 MONDO:0013541; Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay; MIM#621655 Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Intellectual disability syndromic and non-syndromic v2.92 TUBB3 Zornitza Stark edited their review of gene: TUBB3: Changed phenotypes: Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay MIM#621655, Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Intellectual disability syndromic and non-syndromic v2.92 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from complex cortical dysplasia with other brain malformations 1 MONDO:0013541 to complex cortical dysplasia with other brain malformations 1 MONDO:0013541; Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay MIM#621655 Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Intellectual disability syndromic and non-syndromic v2.91 TUBB3 Zornitza Stark commented on gene: TUBB3: CFEOM: multiple families reported, some affected individuals show additional features, including developmental delay or learning disabilities associated with dysgenesis of the corpus callosum. Other variable features include facial weakness and peripheral axonal neuropathy, sometimes associated with wrist and finger contractures. OMIM have split into three disorders.

Complex cortical dysplasia with other brain malformations (CDCBM), MIM#614039 is a disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have mild to severe DD/ID, strabismus, axial hypotonia, and spasticity. Brain imaging shows variable malformations of cortical development, including polymicrogyria, gyral disorganization, and fusion of the basal ganglia, as well as thin corpus callosum, hypoplastic brainstem, and dysplastic cerebellar vermis.

Unclear if the four disorders are distinct or part of a spectrum of TUBB3-associated abnormalities.
Intellectual disability syndromic and non-syndromic v2.91 TUBB3 Zornitza Stark reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay MIM#621655 Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy v2.27 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from Fibrosis of extraocular muscles, congenital, 3A (MIM#600638); Neuropathy to Fibrosis of extraocular muscles, congenital, 3A (MIM#600638); Neuropathy; Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Hereditary Neuropathy v2.26 TUBB3 Zornitza Stark edited their review of gene: TUBB3: Changed phenotypes: Fibrosis of extraocular muscles, congenital, 3A (MIM#600638), Neuropathy, Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Arthrogryposis v2.2 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from Fibrosis of extraocular muscles, congenital, 3A (MIM#600638); Neuropathy to Fibrosis of extraocular muscles, congenital, 3A (MIM#600638); Neuropathy; Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Arthrogryposis v2.1 TUBB3 Zornitza Stark edited their review of gene: TUBB3: Changed phenotypes: Fibrosis of extraocular muscles, congenital, 3A (MIM#600638), Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Mendeliome v2.443 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039; Fibrosis of extraocular muscles, congenital, 3A, MIM# 600638 to Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039; Fibrosis of extraocular muscles, congenital, 3A, MIM# 600638; Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay MIM#621655; Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Mendeliome v2.442 TUBB3 Zornitza Stark edited their review of gene: TUBB3: Changed phenotypes: Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039, Fibrosis of extraocular muscles, congenital, 3A, MIM# 600638, Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay MIM#621655, Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Mendeliome v2.442 CSMD2 chirag patel Phenotypes for gene: CSMD2 were changed from Neurodevelopmental disorder, MONDO:0700092, CSMD2-related to Neurodevelopmental disorder, MONDO:0700092, CSMD2-related
Mendeliome v2.441 CSMD2 chirag patel Phenotypes for gene: CSMD2 were changed from Neurodevelopmental disorder, MONDO:0700092, CSMD2-related to Neurodevelopmental disorder, MONDO:0700092, CSMD2-related
Mendeliome v2.441 CSMD2 chirag patel Phenotypes for gene: CSMD2 were changed from Focal epilepsy - MONDO:0005384, CSMD1-related to Neurodevelopmental disorder, MONDO:0700092, CSMD2-related
Mendeliome v2.440 CSMD2 chirag patel Mode of inheritance for gene: CSMD2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v2.439 CSMD2 chirag patel Mode of inheritance for gene: CSMD2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v2.438 CSMD2 chirag patel Classified gene: CSMD2 as Amber List (moderate evidence)
Mendeliome v2.438 CSMD2 chirag patel Gene: csmd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.437 chirag patel Added reviews for gene CSMD2 from panel Intellectual disability syndromic and non-syndromic
Intellectual disability syndromic and non-syndromic v2.91 CSMD2 chirag patel Phenotypes for gene: CSMD2 were changed from Focal epilepsy - MONDO:0005384, CSMD2-related to Neurodevelopmental disorder, MONDO:0700092, CSMD2-related
Intellectual disability syndromic and non-syndromic v2.90 CSMD2 chirag patel Mode of inheritance for gene: CSMD2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v2.89 CSMD2 chirag patel Classified gene: CSMD2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.89 CSMD2 chirag patel Gene: csmd2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.88 CSMD2 chirag patel reviewed gene: CSMD2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CSMD2-related; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v2.88 DLGAP1 chirag patel Marked gene: DLGAP1 as ready
Intellectual disability syndromic and non-syndromic v2.88 DLGAP1 chirag patel Gene: dlgap1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.88 chirag patel Copied gene DLGAP1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.88 DLGAP1 chirag patel gene: DLGAP1 was added
gene: DLGAP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Other
Mode of inheritance for gene: DLGAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DLGAP1 were set to Neurodevelopmental disorder, MONDO:0700092, DLGAP1-related
Mendeliome v2.436 DLGAP1 chirag patel Marked gene: DLGAP1 as ready
Mendeliome v2.436 DLGAP1 chirag patel Gene: dlgap1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.436 DLGAP1 chirag patel Classified gene: DLGAP1 as Amber List (moderate evidence)
Mendeliome v2.436 DLGAP1 chirag patel Gene: dlgap1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.435 DLGAP1 chirag patel gene: DLGAP1 was added
gene: DLGAP1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: DLGAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DLGAP1 were set to Neurodevelopmental disorder, MONDO:0700092, DLGAP1-related
Review for gene: DLGAP1 was set to AMBER
Added comment: ESHG 2026

14 unrelated individuals with 13 different rare heterozygous de novo variants (missense, nonsense, splice, frameshift) throughout DLGAP1 gene. Individuals presented with developmental delay (14), intellectual disability (7), ASD (11), seizures (5) and other non-specific features.

DLGAP1 (GKAP) encodes a postsynaptic scaffold protein bridging DLG4 to SHANK3. Disruption of other synaptic scaffolding proteins (DLG4 and SHANK3) is well known to cause neurodevelopmental disorders. Expression experiments revealed no gross instability of the mutant proteins. However, co-immunoprecipitation assays demonstrated impaired binding between DLGAP1 and DLG4 for the p.(Arg343Gln) variant and complete loss of SHANK interaction for the frameshift mutant, indicating a disruption of postsynaptic scaffold integrity.
Sources: Other
Mendeliome v2.434 UBE2I chirag patel Marked gene: UBE2I as ready
Mendeliome v2.434 UBE2I chirag patel Gene: ube2i has been classified as Amber List (Moderate Evidence).
Mendeliome v2.434 chirag patel Copied gene UBE2I from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.434 UBE2I chirag patel gene: UBE2I was added
gene: UBE2I was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: UBE2I was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UBE2I were set to Neurodevelopmental disorder, MONDO:0700092, UBE2I-related
Intellectual disability syndromic and non-syndromic v2.87 UBE2I chirag patel Marked gene: UBE2I as ready
Intellectual disability syndromic and non-syndromic v2.87 UBE2I chirag patel Gene: ube2i has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.87 UBE2I chirag patel Classified gene: UBE2I as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.87 UBE2I chirag patel Gene: ube2i has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.86 UBE2I chirag patel gene: UBE2I was added
gene: UBE2I was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: UBE2I was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UBE2I were set to Neurodevelopmental disorder, MONDO:0700092, UBE2I-related
Review for gene: UBE2I was set to AMBER
Added comment: ESHG 2026

10 unrelated individuals with 10 different heterozygous missense variants throughout UBE2I gene (9 confirmed de novo) presenting with developmental delay (10), intellectual disability (4), ASD (5), microcephaly (3), hearing loss (3), and dysmorphism.

UBE2I encodes the only human E2 enzyme UBC9. SUMOylation is a critical post-translational modification regulating protein function, localization, and stability through E1, E2, and E3 enzymes. SUMOylation pathway is key regulator of neurodevelopment processes. Structural modeling for all variants suggested possible protein destabilization, disruption of the catalytic core, and altered SUMO binding. LCLs from patient with 2 variants (p.W53L and p.N124I) showed normal UBE2I mRNA levels, whereas protein levels were markedly reduced, and accompanied by decreased global SUMOylation. Yeast-based assays showed reduced protein stability for the p.W53L variant.
Sources: Other
Growth failure v2.16 SMC6 chirag patel Marked gene: SMC6 as ready
Growth failure v2.16 SMC6 chirag patel Gene: smc6 has been classified as Amber List (Moderate Evidence).
Microcephaly v2.20 SMC6 chirag patel Marked gene: SMC6 as ready
Microcephaly v2.20 SMC6 chirag patel Gene: smc6 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.433 SMC6 chirag patel Marked gene: SMC6 as ready
Mendeliome v2.433 SMC6 chirag patel Gene: smc6 has been classified as Amber List (Moderate Evidence).
Chromosome Breakage Disorders v2.3 SMC6 chirag patel Marked gene: SMC6 as ready
Chromosome Breakage Disorders v2.3 SMC6 chirag patel Gene: smc6 has been classified as Amber List (Moderate Evidence).
Microcephaly v2.20 chirag patel Copied gene SMC6 from panel Intellectual disability syndromic and non-syndromic
Microcephaly v2.20 SMC6 chirag patel gene: SMC6 was added
gene: SMC6 was added to Microcephaly. Sources: Expert Review Amber,Other
Mode of inheritance for gene: SMC6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMC6 were set to Neurodevelopmental disorder, MONDO:0700092, SMC6-related
Mendeliome v2.433 chirag patel Copied gene SMC6 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.433 SMC6 chirag patel gene: SMC6 was added
gene: SMC6 was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: SMC6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMC6 were set to Neurodevelopmental disorder, MONDO:0700092, SMC6-related
Growth failure v2.16 chirag patel Copied gene SMC6 from panel Intellectual disability syndromic and non-syndromic
Growth failure v2.16 SMC6 chirag patel gene: SMC6 was added
gene: SMC6 was added to Growth failure. Sources: Expert Review Amber,Other
Mode of inheritance for gene: SMC6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMC6 were set to Neurodevelopmental disorder, MONDO:0700092, SMC6-related
Chromosome Breakage Disorders v2.3 chirag patel Copied gene SMC6 from panel Intellectual disability syndromic and non-syndromic
Chromosome Breakage Disorders v2.3 SMC6 chirag patel gene: SMC6 was added
gene: SMC6 was added to Chromosome Breakage Disorders. Sources: Expert Review Amber,Other
Mode of inheritance for gene: SMC6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMC6 were set to Neurodevelopmental disorder, MONDO:0700092, SMC6-related
Intellectual disability syndromic and non-syndromic v2.85 SMC6 chirag patel Marked gene: SMC6 as ready
Intellectual disability syndromic and non-syndromic v2.85 SMC6 chirag patel Gene: smc6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.85 SMC6 chirag patel Classified gene: SMC6 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.85 SMC6 chirag patel Gene: smc6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.84 SMC6 chirag patel gene: SMC6 was added
gene: SMC6 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: SMC6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMC6 were set to Neurodevelopmental disorder, MONDO:0700092, SMC6-related
Review for gene: SMC6 was set to AMBER
Added comment: ESHG 2026

17 affected individuals from 2 families (1 consanguineous family with 16 individuals) with biallelic variants in SMC6 (3 missense) which segregated with disease. Phenotype included microcephaly (1 family), short stature, DD/ID (1 family), dysmorphism (Seckel like), haematological anomalies (1 family), and lung disease (1 family).

SMC5/6 complex is a highly conserved multi-subunit protein complex essential for repairing DNA damage and preventing replication stress. SMC5 has been associated with a developmental disorder. SMC6 patient-derived cell lines display a shared cellular phenotype (to SMC5) typified by chromosome instability with elevated replication stress and genome instability, exacerbated when exposed to genotoxins that stabilise G-quadruplex structures. Zebrafish models showed microcephaly and reduced length.
Sources: Other
Intellectual disability syndromic and non-syndromic v2.83 CMIP Eleanor Ludington Marked gene: CMIP as ready
Intellectual disability syndromic and non-syndromic v2.83 CMIP Eleanor Ludington Gene: cmip has been classified as Green List (High Evidence).
Genetic Epilepsy v2.33 CMIP Eleanor Ludington Marked gene: CMIP as ready
Genetic Epilepsy v2.33 CMIP Eleanor Ludington Gene: cmip has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.83 Eleanor Ludington Copied gene CMIP from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.83 CMIP Eleanor Ludington gene: CMIP was added
gene: CMIP was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CMIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CMIP were set to 42386996; 28504353; 22689534
Phenotypes for gene: CMIP were set to Neurodevelopmental disorder, MONDO:0700092
Genetic Epilepsy v2.33 Eleanor Ludington Copied gene CMIP from panel Mendeliome
Genetic Epilepsy v2.33 CMIP Eleanor Ludington gene: CMIP was added
gene: CMIP was added to Genetic Epilepsy. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CMIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CMIP were set to 42386996; 28504353; 22689534
Phenotypes for gene: CMIP were set to Neurodevelopmental disorder, MONDO:0700092
Mendeliome v2.432 CMIP Eleanor Ludington Marked gene: CMIP as ready
Mendeliome v2.432 CMIP Eleanor Ludington Gene: cmip has been classified as Green List (High Evidence).
Mendeliome v2.432 CMIP Eleanor Ludington Classified gene: CMIP as Green List (high evidence)
Mendeliome v2.432 CMIP Eleanor Ludington Gene: cmip has been classified as Green List (High Evidence).
Mendeliome v2.431 CMIP Eleanor Ludington gene: CMIP was added
gene: CMIP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CMIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CMIP were set to 42386996; 28504353; 22689534
Phenotypes for gene: CMIP were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: CMIP was set to GREEN
Added comment: PMID 42386996 reports 7 individuals from 7 families with de novo heterozygous loss-of-function SNVs in CMIP presenting with developmental delay, intellectual disability, autism spectrum disorder and epilepsy (childhood‑onset). Earlier studies (PMID 28504353; PMID 22689534) described de novo heterozygous deletions of CMIP in individuals with autism spectrum disorder and developmental delay. Functional evidence includes a zebrafish loss‑of-function model showing reduced locomotion and increased spontaneous epileptiform activity.
Sources: Literature
Mendeliome v2.430 GTF3C1 chirag patel Marked gene: GTF3C1 as ready
Mendeliome v2.430 GTF3C1 chirag patel Gene: gtf3c1 has been classified as Amber List (Moderate Evidence).
Callosome v1.23 GTF3C1 chirag patel Marked gene: GTF3C1 as ready
Callosome v1.23 GTF3C1 chirag patel Gene: gtf3c1 has been classified as Amber List (Moderate Evidence).
Microcephaly v2.19 GTF3C1 chirag patel Marked gene: GTF3C1 as ready
Microcephaly v2.19 GTF3C1 chirag patel Gene: gtf3c1 has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v2.3 GTF3C1 chirag patel Marked gene: GTF3C1 as ready
Cerebellar and Pontocerebellar Hypoplasia v2.3 GTF3C1 chirag patel Gene: gtf3c1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.430 chirag patel Copied gene GTF3C1 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.430 GTF3C1 chirag patel gene: GTF3C1 was added
gene: GTF3C1 was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: GTF3C1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GTF3C1 were set to Neurodevelopmental disorder, MONDO:0700092, GTF3C1-related
Microcephaly v2.19 chirag patel Copied gene GTF3C1 from panel Intellectual disability syndromic and non-syndromic
Microcephaly v2.19 GTF3C1 chirag patel gene: GTF3C1 was added
gene: GTF3C1 was added to Microcephaly. Sources: Expert Review Amber,Other
Mode of inheritance for gene: GTF3C1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GTF3C1 were set to Neurodevelopmental disorder, MONDO:0700092, GTF3C1-related
Cerebellar and Pontocerebellar Hypoplasia v2.3 chirag patel Copied gene GTF3C1 from panel Intellectual disability syndromic and non-syndromic
Cerebellar and Pontocerebellar Hypoplasia v2.3 GTF3C1 chirag patel gene: GTF3C1 was added
gene: GTF3C1 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review Amber,Other
Mode of inheritance for gene: GTF3C1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GTF3C1 were set to Neurodevelopmental disorder, MONDO:0700092, GTF3C1-related
Callosome v1.23 chirag patel Copied gene GTF3C1 from panel Intellectual disability syndromic and non-syndromic
Callosome v1.23 GTF3C1 chirag patel gene: GTF3C1 was added
gene: GTF3C1 was added to Callosome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: GTF3C1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GTF3C1 were set to Neurodevelopmental disorder, MONDO:0700092, GTF3C1-related
Intellectual disability syndromic and non-syndromic v2.82 GTF3C1 chirag patel Marked gene: GTF3C1 as ready
Intellectual disability syndromic and non-syndromic v2.82 GTF3C1 chirag patel Gene: gtf3c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.82 GTF3C1 chirag patel Classified gene: GTF3C1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.82 GTF3C1 chirag patel Gene: gtf3c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.81 GTF3C1 chirag patel Classified gene: GTF3C1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.81 GTF3C1 chirag patel Gene: gtf3c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.80 GTF3C1 chirag patel gene: GTF3C1 was added
gene: GTF3C1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: GTF3C1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GTF3C1 were set to Neurodevelopmental disorder, MONDO:0700092, GTF3C1-related
Review for gene: GTF3C1 was set to AMBER
Added comment: ESHG 2026

6 individuals from 6 unrelated families (4 consanguineous) with biallelic variants in GTF3C1 which segregated with disease (6 missense, 1 nonsense). Phenotype included developmental delay, intellectual disability, microcephaly, cerebellar atrophy/hypoplasia, abnormal corpus callosum, arthrogryposis, and variable craniofacial features.

GTF3C1 encodes a subunit within the general Transcription Factor IIIC (TFIIIC), which is involved general transcription factor activity via recruitment of RNA polymerase III for target gene transcription. Two other TFIIIC subunits, GTF3C3 and GTF3C5, have been implicated in neurodevelopmental disorders. Molecular modelling suggested missense variants disrupt intramolecular interactions, causing instability of the TFIIIC complex. Proteomic analysis using patient cell lines revealed significantly reduced GTF3C1 protein. A relative complex abundance assay demonstrated the five other subunits of the TFIIIC complex were also reduced, and suggests a loss-of-function mechanism. Gtf3c1 knockdown in mouse brain revealed impaired neuronal production and cell cycle exit.
Sources: Other
Cerebellar and Pontocerebellar Hypoplasia v2.2 GTF3C5 chirag patel Marked gene: GTF3C5 as ready
Cerebellar and Pontocerebellar Hypoplasia v2.2 GTF3C5 chirag patel Gene: gtf3c5 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v2.2 chirag patel Copied gene GTF3C5 from panel Intellectual disability syndromic and non-syndromic
Cerebellar and Pontocerebellar Hypoplasia v2.2 GTF3C5 chirag patel gene: GTF3C5 was added
gene: GTF3C5 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review Green,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
Cerebellar and Pontocerebellar Hypoplasia v2.1 GTF3C3 chirag patel Marked gene: GTF3C3 as ready
Cerebellar and Pontocerebellar Hypoplasia v2.1 GTF3C3 chirag patel Gene: gtf3c3 has been classified as Green List (High Evidence).
Callosome v1.22 GTF3C3 chirag patel Marked gene: GTF3C3 as ready
Callosome v1.22 GTF3C3 chirag patel Gene: gtf3c3 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v2.1 chirag patel Copied gene GTF3C3 from panel Intellectual disability syndromic and non-syndromic
Cerebellar and Pontocerebellar Hypoplasia v2.1 GTF3C3 chirag patel gene: GTF3C3 was added
gene: GTF3C3 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: GTF3C3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C3 were set to 28940097; 28097321; 30552426
Phenotypes for gene: GTF3C3 were set to Neurodevelopmental disorder with dysmorphic facies, brain anomalies, and seizures, MIM# 621201
Callosome v1.22 chirag patel Copied gene GTF3C3 from panel Intellectual disability syndromic and non-syndromic
Callosome v1.22 GTF3C3 chirag patel gene: GTF3C3 was added
gene: GTF3C3 was added to Callosome. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: GTF3C3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C3 were set to 28940097; 28097321; 30552426
Phenotypes for gene: GTF3C3 were set to Neurodevelopmental disorder with dysmorphic facies, brain anomalies, and seizures, MIM# 621201
Intellectual disability syndromic and non-syndromic v2.79 NUAK1 chirag patel changed review comment from: 7 individuals from 5 unrelated consanguineous families with craniofacial dysmorphism (hypertelorism, DSPF, dental anomalies), neurodevelopmental issues, and omphalocele (2 families with LOF variants). WES identified 5 different homozygous variants (3 missense, 1 nonsense, 1 splice) which segregated with disease.

NUAK1 has a kinase function and all variants were located in the kinase domain. Patient fibroblast assays showed reduced transcript and loss of NUAK1 protein for LOF variants. The missense variants had increased transcript and protein levels but had reduced kinase activity. Mouse models show abdominal wall defects. Xenopus models showed craniofacial defects and ventral body wall defects.
Sources: Other; to: ESHG 2026

7 individuals from 5 unrelated consanguineous families with craniofacial dysmorphism (hypertelorism, DSPF, dental anomalies), neurodevelopmental issues, and omphalocele (2 families with LOF variants). WES identified 5 different homozygous variants (3 missense, 1 nonsense, 1 splice) which segregated with disease.

NUAK1 has a kinase function and all variants were located in the kinase domain. Patient fibroblast assays showed reduced transcript and loss of NUAK1 protein for LOF variants. The missense variants had increased transcript and protein levels but had reduced kinase activity. Mouse models show abdominal wall defects. Xenopus models showed craniofacial defects and ventral body wall defects.
Sources: Other
Fetal anomalies v2.54 NUAK1 chirag patel changed review comment from: 7 individuals from 5 unrelated consanguineous families with craniofacial dysmorphism (hypertelorism, DSPF, dental anomalies), neurodevelopmental issues, and omphalocele (2 families with LOF variants). WES identified 5 different homozygous variants (3 missense, 1 nonsense, 1 splice) which segregated with disease.

NUAK1 has a kinase function and all variants were located in the kinase domain. Patient fibroblast assays showed reduced transcript and loss of NUAK1 protein for LOF variants. The missense variants had increased transcript and protein levels but had reduced kinase activity. Mouse models show abdominal wall defects. Xenopus models showed craniofacial defects and ventral body wall defects.
Sources: Other; to: ESHG 2026

7 individuals from 5 unrelated consanguineous families with craniofacial dysmorphism (hypertelorism, DSPF, dental anomalies), neurodevelopmental issues, and omphalocele (2 families with LOF variants). WES identified 5 different homozygous variants (3 missense, 1 nonsense, 1 splice) which segregated with disease.

NUAK1 has a kinase function and all variants were located in the kinase domain. Patient fibroblast assays showed reduced transcript and loss of NUAK1 protein for LOF variants. The missense variants had increased transcript and protein levels but had reduced kinase activity. Mouse models show abdominal wall defects. Xenopus models showed craniofacial defects and ventral body wall defects.
Sources: Other
Fetal anomalies v2.54 NUAK1 chirag patel Marked gene: NUAK1 as ready
Fetal anomalies v2.54 NUAK1 chirag patel Gene: nuak1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.429 NUAK1 chirag patel Marked gene: NUAK1 as ready
Mendeliome v2.429 NUAK1 chirag patel Gene: nuak1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.429 NUAK1 chirag patel changed review comment from: 7 individuals from 5 unrelated consanguineous families with craniofacial dysmorphism (hypertelorism, DSPF, dental anomalies), neurodevelopmental issues, and omphalocele (2 families with LOF variants). WES identified 5 different homozygous variants (3 missense, 1 nonsense, 1 splice) which segregated with disease.

NUAK1 has a kinase function and all variants were located in the kinase domain. Patient fibroblast assays showed reduced transcript and loss of NUAK1 protein for LOF variants. The missense variants had increased transcript and protein levels but had reduced kinase activity. Mouse models show abdominal wall defects. Xenopus models showed craniofacial defects and ventral body wall defects.
Sources: Other; to: ESHG 2026

7 individuals from 5 unrelated consanguineous families with craniofacial dysmorphism (hypertelorism, DSPF, dental anomalies), neurodevelopmental issues, and omphalocele (2 families with LOF variants). WES identified 5 different homozygous variants (3 missense, 1 nonsense, 1 splice) which segregated with disease.

NUAK1 has a kinase function and all variants were located in the kinase domain. Patient fibroblast assays showed reduced transcript and loss of NUAK1 protein for LOF variants. The missense variants had increased transcript and protein levels but had reduced kinase activity. Mouse models show abdominal wall defects. Xenopus models showed craniofacial defects and ventral body wall defects.
Sources: Other
Mendeliome v2.429 chirag patel Copied gene NUAK1 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.429 NUAK1 chirag patel gene: NUAK1 was added
gene: NUAK1 was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: NUAK1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NUAK1 were set to Syndromic disease, MONDO: 0002254
Fetal anomalies v2.54 chirag patel Copied gene NUAK1 from panel Intellectual disability syndromic and non-syndromic
Fetal anomalies v2.54 NUAK1 chirag patel gene: NUAK1 was added
gene: NUAK1 was added to Fetal anomalies. Sources: Expert Review Amber,Other
Mode of inheritance for gene: NUAK1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NUAK1 were set to Syndromic disease, MONDO: 0002254
Intellectual disability syndromic and non-syndromic v2.79 NUAK1 chirag patel Marked gene: NUAK1 as ready
Intellectual disability syndromic and non-syndromic v2.79 NUAK1 chirag patel Gene: nuak1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.79 NUAK1 chirag patel Classified gene: NUAK1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.79 NUAK1 chirag patel Gene: nuak1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.78 NUAK1 chirag patel gene: NUAK1 was added
gene: NUAK1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: NUAK1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NUAK1 were set to Syndromic disease, MONDO: 0002254
Review for gene: NUAK1 was set to AMBER
Added comment: 7 individuals from 5 unrelated consanguineous families with craniofacial dysmorphism (hypertelorism, DSPF, dental anomalies), neurodevelopmental issues, and omphalocele (2 families with LOF variants). WES identified 5 different homozygous variants (3 missense, 1 nonsense, 1 splice) which segregated with disease.

NUAK1 has a kinase function and all variants were located in the kinase domain. Patient fibroblast assays showed reduced transcript and loss of NUAK1 protein for LOF variants. The missense variants had increased transcript and protein levels but had reduced kinase activity. Mouse models show abdominal wall defects. Xenopus models showed craniofacial defects and ventral body wall defects.
Sources: Other
Retinitis pigmentosa v1.11 Sangavi Sivagnanasundram Copied gene ATRAID from panel Mendeliome
Retinitis pigmentosa v1.11 ATRAID Sangavi Sivagnanasundram gene: ATRAID was added
gene: ATRAID was added to Retinitis pigmentosa. Sources: Literature
Mode of inheritance for gene: ATRAID was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATRAID were set to 42417592
Phenotypes for gene: ATRAID were set to ATRAID-related retinitis pigmentosa, MONDO:0019200
Mendeliome v2.428 ATRAID Sangavi Sivagnanasundram gene: ATRAID was added
gene: ATRAID was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATRAID was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATRAID were set to 42417592
Phenotypes for gene: ATRAID were set to ATRAID-related retinitis pigmentosa, MONDO:0019200
Review for gene: ATRAID was set to RED
Added comment: PMID 42417592 reports six individuals from four Norwegian families (one family is consanguineous) with biallelic frameshift variants presenting with late‑onset, non‑syndromic retinitis pigmentosa. Clinical features include mid‑peripheral chorioretinal atrophy, bone‑spicule pigmentation and rod‑cone dysfunction.

LoF is not an established mechanism of disease for this gene yet. gnomAD v4.1 pLI = 0
o/e = 0.9 (0.66 - 1.25) and there are no reported pathogenic LoF variants reported in ClinVar.
Sources: Literature
Mendeliome v2.427 ACTRT3 Zornitza Stark Publications for gene: ACTRT3 were set to 42330090
Mendeliome v2.426 ACTRT3 Zornitza Stark Classified gene: ACTRT3 as Green List (high evidence)
Mendeliome v2.426 ACTRT3 Zornitza Stark Gene: actrt3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v2.39 ACTRT3 Zornitza Stark Classified gene: ACTRT3 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v2.39 ACTRT3 Zornitza Stark Gene: actrt3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v2.38 ACTRT3 Zornitza Stark edited their review of gene: ACTRT3: Added comment: PMID 42391565 reports another individual with a homozygous nonsense ACTRT3 c.712C>T variant causing male infertility characterised by severe teratozoospermia, acrosomal ultrastructural defects, fertilisation failure and embryonic arrest.; Changed rating: GREEN; Changed publications: 42330090, 42391565
Mendeliome v2.425 ACTRT3 Zornitza Stark edited their review of gene: ACTRT3: Changed rating: GREEN
Mendeliome v2.425 ACTRT3 Zornitza Stark edited their review of gene: ACTRT3: Added comment: PMID 42391565 reports another individual with a homozygous nonsense ACTRT3 c.712C>T variant causing male infertility characterised by severe teratozoospermia, acrosomal ultrastructural defects, fertilisation failure and embryonic arrest.; Changed publications: 42330090, 42391565
Ciliopathies v2.16 DNAJC16 Zornitza Stark Marked gene: DNAJC16 as ready
Ciliopathies v2.16 DNAJC16 Zornitza Stark Gene: dnajc16 has been classified as Red List (Low Evidence).
Ciliopathies v2.16 Zornitza Stark Copied gene DNAJC16 from panel Mendeliome
Ciliopathies v2.16 DNAJC16 Zornitza Stark gene: DNAJC16 was added
gene: DNAJC16 was added to Ciliopathies. Sources: Expert Review Red,Literature
Mode of inheritance for gene: DNAJC16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC16 were set to 42434812
Phenotypes for gene: DNAJC16 were set to ciliopathy, MONDO:0005308
Mendeliome v2.425 DNAJC16 Zornitza Stark Marked gene: DNAJC16 as ready
Mendeliome v2.425 DNAJC16 Zornitza Stark Gene: dnajc16 has been classified as Red List (Low Evidence).
Mendeliome v2.425 DNAJC16 Zornitza Stark gene: DNAJC16 was added
gene: DNAJC16 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNAJC16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC16 were set to 42434812
Phenotypes for gene: DNAJC16 were set to ciliopathy, MONDO:0005308
Review for gene: DNAJC16 was set to RED
Added comment: PMID 42434812 reports ?three families with homozygous loss-of-function DNAJC16 variants causing a ciliopathy phenotype. Minimal phenotypic or genetic detail, part of a large paper putting forward multiple novel gene-disease associations.
Sources: Literature
Mendeliome v2.423 USH1C Michelle Torres reviewed gene: USH1C: Rating: AMBER; Mode of pathogenicity: None; Publications: 31858762, 37973466, 37206537; Phenotypes: Usher syndrome, type 1C, MIM#276904, Deafness, autosomal recessive 18A, MIM#602092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v2.423 KRT16 Sangavi Sivagnanasundram reviewed gene: KRT16: Rating: AMBER; Mode of pathogenicity: None; Publications: 38170465, 42476612; Phenotypes: palmoplantar keratoderma, nonepidermolytic, focal 1, MONDO:0013073; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Tubulopathies and related disorders v2.7 KCNA1 Lucy Spencer Publications for gene: KCNA1 were set to 32316562; 11026449
Renal Tubulopathies and related disorders v2.6 KCNA1 Lucy Spencer Phenotypes for gene: KCNA1 were changed from Epilepsy, MONDO:0005027, KCNA1-related; Episodic ataxia/myokymia syndrome, MIM# 160120 to Episodic ataxia/myokymia syndrome MIM#160120
Renal Tubulopathies and related disorders v2.5 KCNA1 Lucy Spencer reviewed gene: KCNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34784661, 32316562; Phenotypes: Episodic ataxia/myokymia syndrome MIM#160120; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.111 PEX6 chirag patel Marked gene: PEX6 as ready
Skeletal dysplasia v1.111 PEX6 chirag patel Gene: pex6 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.111 PEX6 chirag patel changed review comment from: Variants in this gene account for 14.5% of Zellweger Spectrum Disorder patients according to GeneReviews (https://www.ncbi.nlm.nih.gov/books/NBK1448/) Genetic spectrum of 77 patients reviewed in PMID: 19877282.; to: Variants in this gene account for 14.5% of Zellweger Spectrum Disorder patients according to GeneReviews (https://www.ncbi.nlm.nih.gov/books/NBK1448/) Genetic spectrum of 77 patients reviewed in PMID: 19877282.

Newborns may have bony stippling (chondrodysplasia punctata) of the patella(e) and other long bones.
Skeletal dysplasia v1.111 chirag patel Copied gene PEX6 from panel Peroxisomal Disorders
Skeletal dysplasia v1.111 PEX6 chirag patel gene: PEX6 was added
gene: PEX6 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PEX6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX6 were set to 20301621, 19877282
Phenotypes for gene: PEX6 were set to Peroxisome biogenesis disorder 4A (Zellweger), MIM# 614862
Leukodystrophy v1.8 PEX6 chirag patel Marked gene: PEX6 as ready
Leukodystrophy v1.8 PEX6 chirag patel Gene: pex6 has been classified as Green List (High Evidence).
Leukodystrophy v1.8 PEX6 chirag patel Phenotypes for gene: PEX6 were changed from Peroxisome biogenesis disorder 4A (Zellweger), 614862; Peroxisome biogenesis disorder 4B, 614863 to Peroxisome biogenesis disorder 4A (Zellweger), MIM# 614862
Leukodystrophy v1.7 PEX6 chirag patel Publications for gene: PEX6 were set to
Leukodystrophy v1.6 PEX6 chirag patel Mode of inheritance for gene: PEX6 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy v1.5 PEX6 chirag patel changed review comment from: Variants in this gene account for 14.5% of Zellweger Spectrum Disorder patients according to GeneReviews (https://www.ncbi.nlm.nih.gov/books/NBK1448/) Genetic spectrum of 77 patients reviewed in PMID: 19877282.; to: Variants in this gene account for 14.5% of Zellweger Spectrum Disorder patients according to GeneReviews (https://www.ncbi.nlm.nih.gov/books/NBK1448/) Genetic spectrum of 77 patients reviewed in PMID: 19877282.

Intermediate/milder ZSD is a progressive disorder with hearing and vision worsening with time. Some individuals may develop progressive degeneration of CNS myelin, a leukodystrophy, which may lead to loss of previously acquired skills and ultimately death.
Leukodystrophy v1.5 chirag patel Added reviews for gene PEX6 from panel Peroxisomal Disorders
Peroxisomal Disorders v1.8 PEX6 chirag patel Marked gene: PEX6 as ready
Peroxisomal Disorders v1.8 PEX6 chirag patel Gene: pex6 has been classified as Green List (High Evidence).
Peroxisomal Disorders v1.8 PEX6 chirag patel Phenotypes for gene: PEX6 were changed from to Peroxisome biogenesis disorder 4A (Zellweger), MIM# 614862
Peroxisomal Disorders v1.7 PEX6 chirag patel Publications for gene: PEX6 were set to
Peroxisomal Disorders v1.6 PEX6 chirag patel Mode of inheritance for gene: PEX6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Peroxisomal Disorders v1.5 PEX6 chirag patel reviewed gene: PEX6: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301621, 19877282; Phenotypes: Peroxisome biogenesis disorder 4A (Zellweger), MIM# 614862; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v1.21 PEX6 chirag patel Marked gene: PEX6 as ready
Callosome v1.21 PEX6 chirag patel Gene: pex6 has been classified as Red List (Low Evidence).
Callosome v1.21 PEX6 chirag patel Mode of inheritance for gene: PEX6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Callosome v1.20 PEX6 chirag patel Phenotypes for gene: PEX6 were changed from to Peroxisome biogenesis disorder 4A (Zellweger), MIM# 614862
Callosome v1.19 PEX6 chirag patel Classified gene: PEX6 as Red List (low evidence)
Callosome v1.19 PEX6 chirag patel Gene: pex6 has been classified as Red List (Low Evidence).
Callosome v1.18 PEX6 chirag patel reviewed gene: PEX6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 4A (Zellweger), MIM# 614862; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hydrops fetalis v1.3 PEX6 chirag patel Marked gene: PEX6 as ready
Hydrops fetalis v1.3 PEX6 chirag patel Gene: pex6 has been classified as Red List (Low Evidence).
Hydrops fetalis v1.3 PEX6 chirag patel Phenotypes for gene: PEX6 were changed from to Peroxisome biogenesis disorder 4A (Zellweger), MIM# 614862
Hydrops fetalis v1.2 PEX6 chirag patel Mode of inheritance for gene: PEX6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Hydrops fetalis v1.1 PEX6 chirag patel Classified gene: PEX6 as Red List (low evidence)
Hydrops fetalis v1.1 PEX6 chirag patel Gene: pex6 has been classified as Red List (Low Evidence).
Hydrops fetalis v1.0 PEX6 chirag patel reviewed gene: PEX6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 4A (Zellweger), MIM# 614862; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.110 PLCB4 chirag patel Marked gene: PLCB4 as ready
Skeletal dysplasia v1.110 PLCB4 chirag patel Gene: plcb4 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.110 chirag patel Copied gene PLCB4 from panel Mandibulofacial Acrofacial dysostosis
Skeletal dysplasia v1.110 PLCB4 chirag patel gene: PLCB4 was added
gene: PLCB4 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PLCB4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PLCB4 were set to 22560091; 23315542; 33131036; 32201334; 28328130; 27007857; 23913798
Phenotypes for gene: PLCB4 were set to Auriculocondylar syndrome 2A, MIM# 614669; Auriculocondylar syndrome 2B, MIM# 620458
Mode of pathogenicity for gene: PLCB4 was set to Other
Deafness_IsolatedAndComplex v2.8 PAX1 chirag patel Phenotypes for gene: PAX1 were changed from Otofaciocervical syndrome 2, MIM# 615560 to Otofaciocervical syndrome 2 with T-cell deficiency, MIM #615560
Severe Combined Immunodeficiency v2.3 PAX1 chirag patel Phenotypes for gene: PAX1 were changed from Syndromic SCID; dysmorphism; ear abnormalities; Otofaciocervical syndrome 2, MIM# 615560 to Otofaciocervical syndrome 2 with T-cell deficiency, MIM #615560
Intellectual disability syndromic and non-syndromic v2.77 PAX1 chirag patel Classified gene: PAX1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v2.77 PAX1 chirag patel Gene: pax1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.77 PAX1 chirag patel Classified gene: PAX1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v2.77 PAX1 chirag patel Gene: pax1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.76 PAX1 chirag patel Phenotypes for gene: PAX1 were changed from Otofaciocervical syndrome 2, 615560 to Otofaciocervical syndrome 2 with T-cell deficiency, MIM #615560
Mendeliome v2.423 PAX1 chirag patel Phenotypes for gene: PAX1 were changed from Otofaciocervical syndrome 2, MIM#615560; Syndromic SCID to Otofaciocervical syndrome 2 with T-cell deficiency, MIM #615560
Intellectual disability syndromic and non-syndromic v2.75 PAX1 chirag patel Publications for gene: PAX1 were set to 29681087; 23851939; 28657137
Severe Combined Immunodeficiency v2.2 PAX1 chirag patel Publications for gene: PAX1 were set to 32111619
Deafness_IsolatedAndComplex v2.7 PAX1 chirag patel Publications for gene: PAX1 were set to 23851939; 29681087
Mendeliome v2.422 PAX1 chirag patel Publications for gene: PAX1 were set to 29681087; 28657137; 23851939; 32111619
Severe Combined Immunodeficiency v2.1 chirag patel Added reviews for gene PAX1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.74 chirag patel Added reviews for gene PAX1 from panel Mendeliome
Deafness_IsolatedAndComplex v2.6 chirag patel Added reviews for gene PAX1 from panel Mendeliome
Mendeliome v2.421 PAX1 chirag patel reviewed gene: PAX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681087, 37924468, 37689091, 32111619, 29681087, 28657137, 23851939; Phenotypes: Otofaciocervical syndrome 2 with T-cell deficiency, MIM #615560; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v2.73 PDS5B Zornitza Stark Publications for gene: PDS5B were set to 41810376
Intellectual disability syndromic and non-syndromic v2.72 PDS5B Zornitza Stark Classified gene: PDS5B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v2.72 PDS5B Zornitza Stark Gene: pds5b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.71 PDS5B Zornitza Stark reviewed gene: PDS5B: Rating: GREEN; Mode of pathogenicity: None; Publications: 42431198; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, PDS5B-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v2.421 PDS5B Zornitza Stark Publications for gene: PDS5B were set to 41810376
Mendeliome v2.420 PDS5B Zornitza Stark Classified gene: PDS5B as Green List (high evidence)
Mendeliome v2.420 PDS5B Zornitza Stark Gene: pds5b has been classified as Green List (High Evidence).
Mendeliome v2.419 PDS5B Zornitza Stark reviewed gene: PDS5B: Rating: GREEN; Mode of pathogenicity: None; Publications: 42431198; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, PDS5B-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v2.71 PDS5A Zornitza Stark Publications for gene: PDS5A were set to 30158690; 41810376
Intellectual disability syndromic and non-syndromic v2.70 PDS5A Zornitza Stark Classified gene: PDS5A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v2.70 PDS5A Zornitza Stark Gene: pds5a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.69 PDS5A Zornitza Stark reviewed gene: PDS5A: Rating: GREEN; Mode of pathogenicity: None; Publications: 42431198; Phenotypes: Complex neurodevelopmental disorder, MONDO:0100038, PDS5A-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v2.419 PDS5A Zornitza Stark Publications for gene: PDS5A were set to 30158690; 41810376
Mendeliome v2.418 PDS5A Zornitza Stark Classified gene: PDS5A as Green List (high evidence)
Mendeliome v2.418 PDS5A Zornitza Stark Gene: pds5a has been classified as Green List (High Evidence).
Mendeliome v2.417 PDS5A Zornitza Stark reviewed gene: PDS5A: Rating: GREEN; Mode of pathogenicity: None; Publications: 42431198; Phenotypes: Complex neurodevelopmental disorder, MONDO:0100038, PDS5A-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v2.69 WAPL Zornitza Stark Publications for gene: WAPL were set to 10.64898/2026.02.23.26346364; 30158690
Intellectual disability syndromic and non-syndromic v2.68 WAPL Zornitza Stark Tag preprint was removed from gene: WAPL.
Intellectual disability syndromic and non-syndromic v2.68 WAPL Zornitza Stark edited their review of gene: WAPL: Added comment: Now published PMID 42431198: 27 probands reported.; Changed publications: 42431198, 30158690
Mendeliome v2.417 WAPL Zornitza Stark Tag preprint was removed from gene: WAPL.
Mendeliome v2.417 WAPL Zornitza Stark Publications for gene: WAPL were set to 10.64898/2026.02.23.26346364; 30158690
Mendeliome v2.416 WAPL Zornitza Stark edited their review of gene: WAPL: Added comment: Now published PMID 42431198: 27 probands reported.; Changed publications: 42431198, 30158690
Hydrocephalus_Ventriculomegaly v1.10 PPP2R5D chirag patel Marked gene: PPP2R5D as ready
Hydrocephalus_Ventriculomegaly v1.10 PPP2R5D chirag patel Gene: ppp2r5d has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v1.10 PPP2R5D chirag patel Phenotypes for gene: PPP2R5D were changed from to Houge-Janssens syndrome 1, MONDO:0014602
Hydrocephalus_Ventriculomegaly v1.9 PPP2R5D chirag patel Mode of inheritance for gene: PPP2R5D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hydrocephalus_Ventriculomegaly v1.8 PPP2R5D chirag patel Publications for gene: PPP2R5D were set to
Hydrocephalus_Ventriculomegaly v1.7 PPP2R5D chirag patel Classified gene: PPP2R5D as Green List (high evidence)
Hydrocephalus_Ventriculomegaly v1.7 PPP2R5D chirag patel Gene: ppp2r5d has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v1.6 PPP2R5D chirag patel reviewed gene: PPP2R5D: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Houge-Janssens syndrome 1, MONDO:0014602; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hydrocephalus_Ventriculomegaly v1.6 chirag patel Added reviews for gene PPP2R5D from panel Intellectual disability syndromic and non-syndromic
Pulmonary Fibrosis_Interstitial Lung Disease v2.5 STAT2 Zornitza Stark Marked gene: STAT2 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v2.5 STAT2 Zornitza Stark Gene: stat2 has been classified as Amber List (Moderate Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v2.5 STAT2 Zornitza Stark Classified gene: STAT2 as Amber List (moderate evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v2.5 STAT2 Zornitza Stark Gene: stat2 has been classified as Amber List (Moderate Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v2.4 STAT2 Zornitza Stark gene: STAT2 was added
gene: STAT2 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature
Mode of inheritance for gene: STAT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STAT2 were set to 42461263
Phenotypes for gene: STAT2 were set to Inborn error of immunity, MONDO:0003778, STAT2-related
Review for gene: STAT2 was set to AMBER
Added comment: Variants in this gene are associated with immune system disorders, particularly causing auto inflammation.

Report of 3 siblings presenting with early-onset, life-threatening pulmonary alveolar proteinosis (PAP) and autoinflammation; novel homozygous variant (R223Q) in STAT2 identified. R223Q STAT2 preserved signal transduction and viral control in vitro. However, cells homozygous for the R223Q variant failed to terminate IFN-I responses, owing to impaired localization of USP18. GM-CSF signaling remained intact. Instead, persistent IFN-I signaling antagonized monocyte migration toward chemokines essential for lung trafficking. The youngest sibling received JAK inhibitor and anti-IFN-I receptor therapy with marked clinical improvement.
Sources: Literature
Hydrocephalus_Ventriculomegaly v1.5 PPP2R5D chirag patel Deleted their review
Hydrocephalus_Ventriculomegaly v1.5 PPP2R5D chirag patel changed review comment from: Very rare feature of condition; to: Hydrocephalus or mild-moderate ventricular dilation reported in some cases
Hydrocephalus_Ventriculomegaly v1.5 PPP2R5D chirag patel changed review comment from: Not common feature of condition; to: Very rare feature of condition
Autoinflammatory Disorders v3.14 STAT2 Zornitza Stark edited their review of gene: STAT2: Changed phenotypes: Pseudo-TORCH syndrome 3, MIM# 618886
Callosome v1.18 PPP2R5D chirag patel Classified gene: PPP2R5D as Red List (low evidence)
Callosome v1.18 PPP2R5D chirag patel Gene: ppp2r5d has been classified as Red List (Low Evidence).
Callosome v1.17 PPP2R5D chirag patel commented on gene: PPP2R5D: Not feature of condition
Callosome v1.17 PPP2R5D chirag patel reviewed gene: PPP2R5D: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Houge-Janssens syndrome 1, MONDO:0014602; Mode of inheritance: None
Hydrocephalus_Ventriculomegaly v1.5 PPP2R5D chirag patel Classified gene: PPP2R5D as Red List (low evidence)
Hydrocephalus_Ventriculomegaly v1.5 PPP2R5D chirag patel Gene: ppp2r5d has been classified as Red List (Low Evidence).
Autism v1.16 PPP2R5D chirag patel Classified gene: PPP2R5D as Red List (low evidence)
Autism v1.16 PPP2R5D chirag patel Gene: ppp2r5d has been classified as Red List (Low Evidence).
Autism v1.15 PPP2R5D chirag patel reviewed gene: PPP2R5D: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Houge-Janssens syndrome 1, MONDO:0014602; Mode of inheritance: None
Hydrocephalus_Ventriculomegaly v1.4 PPP2R5D chirag patel reviewed gene: PPP2R5D: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Houge-Janssens syndrome 1, MONDO:0014602; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v2.68 SYTL4 Zornitza Stark Marked gene: SYTL4 as ready
Intellectual disability syndromic and non-syndromic v2.68 SYTL4 Zornitza Stark Gene: sytl4 has been classified as Amber List (Moderate Evidence).
Autism v1.15 SYTL4 Zornitza Stark Marked gene: SYTL4 as ready
Autism v1.15 SYTL4 Zornitza Stark Gene: sytl4 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v2.53 PRIM1 chirag patel Tag deep intronic was removed from gene: PRIM1.
Tag founder was removed from gene: PRIM1.
Intellectual disability syndromic and non-syndromic v2.68 Zornitza Stark Copied gene SYTL4 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.68 SYTL4 Zornitza Stark gene: SYTL4 was added
gene: SYTL4 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: SYTL4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SYTL4 were set to 42531028
Phenotypes for gene: SYTL4 were set to Neurodevelopmental disorder, MONDO:0700092, SYTL4-related
Growth failure v2.15 PRIM1 chirag patel Tag deep intronic was removed from gene: PRIM1.
Tag founder was removed from gene: PRIM1.
Autism v1.15 Zornitza Stark Copied gene SYTL4 from panel Mendeliome
Autism v1.15 SYTL4 Zornitza Stark gene: SYTL4 was added
gene: SYTL4 was added to Autism. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: SYTL4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SYTL4 were set to 42531028
Phenotypes for gene: SYTL4 were set to Neurodevelopmental disorder, MONDO:0700092, SYTL4-related
Microcephaly v2.18 PRIM1 chirag patel Tag deep intronic was removed from gene: PRIM1.
Tag founder was removed from gene: PRIM1.
Mendeliome v2.416 SYTL4 Zornitza Stark Marked gene: SYTL4 as ready
Mendeliome v2.416 SYTL4 Zornitza Stark Gene: sytl4 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.416 SYTL4 Zornitza Stark Classified gene: SYTL4 as Amber List (moderate evidence)
Mendeliome v2.416 SYTL4 Zornitza Stark Gene: sytl4 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.415 SYTL4 Zornitza Stark gene: SYTL4 was added
gene: SYTL4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SYTL4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SYTL4 were set to 42531028
Phenotypes for gene: SYTL4 were set to Neurodevelopmental disorder, MONDO:0700092, SYTL4-related
Review for gene: SYTL4 was set to AMBER
Added comment: Reports a recurrent hemizygous missense variant, R126H, located within the Rab-binding domain of SYTL4 in four unrelated male individuals, consistent with an X-linked recessive mode of ASD. R126H knock-in male mice exhibit ASD-relevant behavioural abnormalities accompanied by synaptic deficits in the medial prefrontal cortex.

Amber rating as all evidence relates to a single variant -- exercise caution in reporting any other variants.
Sources: Literature
Mendeliome v2.414 PRIM1 chirag patel Tag deep intronic was removed from gene: PRIM1.
Tag founder was removed from gene: PRIM1.
Lipodystrophy_Lipoatrophy v2.10 PRIM1 chirag patel Phenotypes for gene: PRIM1 were changed from Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005 to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MONDO:0859276
Microcephaly v2.18 PRIM1 chirag patel Phenotypes for gene: PRIM1 were changed from Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005 to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MONDO:0859276
Combined Immunodeficiency v2.7 PRIM1 chirag patel Phenotypes for gene: PRIM1 were changed from primordial dwarfism-immunodeficiency-lipodystrophy syndrome MONDO:0859276 to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MONDO:0859276
Growth failure v2.15 PRIM1 chirag patel Marked gene: PRIM1 as ready
Growth failure v2.15 PRIM1 chirag patel Gene: prim1 has been classified as Green List (High Evidence).
Growth failure v2.15 PRIM1 chirag patel Phenotypes for gene: PRIM1 were changed from Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005 to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MONDO:0859276
Fetal anomalies v2.53 PRIM1 chirag patel Phenotypes for gene: PRIM1 were changed from Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005 to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MONDO:0859276
Mendeliome v2.414 PRIM1 chirag patel Phenotypes for gene: PRIM1 were changed from Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005 to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MONDO:0859276
Fetal anomalies v2.52 PRIM1 chirag patel Publications for gene: PRIM1 were set to 33060134
Fetal anomalies v2.51 PRIM1 chirag patel Classified gene: PRIM1 as Green List (high evidence)
Fetal anomalies v2.51 PRIM1 chirag patel Gene: prim1 has been classified as Green List (High Evidence).
Growth failure v2.14 PRIM1 chirag patel Publications for gene: PRIM1 were set to 33060134
Microcephaly v2.17 PRIM1 chirag patel Publications for gene: PRIM1 were set to 33060134
Microcephaly v2.16 PRIM1 chirag patel Classified gene: PRIM1 as Green List (high evidence)
Microcephaly v2.16 PRIM1 chirag patel Gene: prim1 has been classified as Green List (High Evidence).
Mendeliome v2.413 PRIM1 chirag patel Publications for gene: PRIM1 were set to 33060134
Lipodystrophy_Lipoatrophy v2.9 PRIM1 chirag patel Publications for gene: PRIM1 were set to 33060134
Lipodystrophy_Lipoatrophy v2.8 PRIM1 chirag patel Classified gene: PRIM1 as Green List (high evidence)
Lipodystrophy_Lipoatrophy v2.8 PRIM1 chirag patel Gene: prim1 has been classified as Green List (High Evidence).
Fetal anomalies v2.50 chirag patel Added reviews for gene PRIM1 from panel Mendeliome
Growth failure v2.13 chirag patel Copied gene PRIM1 from panel Mendeliome
Growth failure v2.13 PRIM1 chirag patel gene: PRIM1 was added
gene: PRIM1 was added to Growth failure. Sources: Expert Review Green,Literature
deep intronic, founder tags were added to gene: PRIM1.
Mode of inheritance for gene: PRIM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRIM1 were set to 33060134
Phenotypes for gene: PRIM1 were set to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005
Combined Immunodeficiency v2.6 chirag patel Added reviews for gene PRIM1 from panel Mendeliome
Microcephaly v2.15 chirag patel Added reviews for gene PRIM1 from panel Mendeliome
Lipodystrophy_Lipoatrophy v2.7 chirag patel Added reviews for gene PRIM1 from panel Mendeliome
Mendeliome v2.412 NOTCH3 chirag patel Marked gene: NOTCH3 as ready
Mendeliome v2.412 NOTCH3 chirag patel Gene: notch3 has been classified as Green List (High Evidence).
Congenital Heart Defect v1.29 NOTCH3 chirag patel Marked gene: NOTCH3 as ready
Congenital Heart Defect v1.29 NOTCH3 chirag patel Gene: notch3 has been classified as Green List (High Evidence).
Mendeliome v2.412 chirag patel Copied gene NOTCH3 from panel Skeletal dysplasia
Mendeliome v2.412 NOTCH3 chirag patel gene: NOTCH3 was added
gene: NOTCH3 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NOTCH3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH3 were set to 25394726,40256810; 32141180; 26754023
Phenotypes for gene: NOTCH3 were set to Lateral meningocele syndrome, MONDO:0007537
Congenital Heart Defect v1.29 chirag patel Copied gene NOTCH3 from panel Skeletal dysplasia
Congenital Heart Defect v1.29 NOTCH3 chirag patel gene: NOTCH3 was added
gene: NOTCH3 was added to Congenital Heart Defect. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NOTCH3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH3 were set to 25394726,40256810; 32141180; 26754023
Phenotypes for gene: NOTCH3 were set to Lateral meningocele syndrome, MONDO:0007537
Skeletal dysplasia v1.109 NOTCH3 chirag patel Marked gene: NOTCH3 as ready
Skeletal dysplasia v1.109 NOTCH3 chirag patel Gene: notch3 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.109 NOTCH3 chirag patel Classified gene: NOTCH3 as Green List (high evidence)
Skeletal dysplasia v1.109 NOTCH3 chirag patel Gene: notch3 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.108 NOTCH3 chirag patel gene: NOTCH3 was added
gene: NOTCH3 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: NOTCH3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH3 were set to 25394726,40256810; 32141180; 26754023
Phenotypes for gene: NOTCH3 were set to Lateral meningocele syndrome, MONDO:0007537
Review for gene: NOTCH3 was set to GREEN
Added comment: 9 unrelated individuals with lateral meningocele syndrome and de novo heterozygous truncating variants in exon 33 of NOTCH3. This is a congenital skeletal dysplasia characterised by lateral spinal meningoceles, distinctive facial dysmorphism, joint hypermobility, congenital cardiac anomalies and vertebral anomalies (scoliosis, vertebral scalloping, vertebral fusion). No variant‑specific functional assays.
Sources: Literature
Mendeliome v2.411 STXBP2 Zornitza Stark Publications for gene: STXBP2 were set to 19804848
Mendeliome v2.410 STXBP2 Zornitza Stark edited their review of gene: STXBP2: Added comment: PMID 25564401: four unrelated families (P1‑P4) harbouring heterozygous (monoallelic) or biallelic STXBP2 miss‑sense variants at codon 65 (R65Q or R65W) that cause familial haemophagocytic lymphohistiocytosis (F‑HLH). Functional assays (patient CTL/NK cytotoxicity, degranulation, forced expression in control cells, liposome‑fusion assays) demonstrate that the R65Q/W mutants act in a dominant‑negative manner to inhibit SNARE‑complex assembly and membrane fusion. Two families carry heterozygous variants (monoallelic disease) and two families carry biallelic variants (homozygous R65Q or compound‑heterozygous R65Q + G541S). Insufficient evidence for monoallelic MOI except for variants at this specific codon.; Changed publications: 19804848, 25564401, 32542393
Disorders of immune dysregulation v2.9 STXBP2 Zornitza Stark Publications for gene: STXBP2 were set to 19804848
Disorders of immune dysregulation v2.8 STXBP2 Zornitza Stark edited their review of gene: STXBP2: Changed publications: 19804848, 25564401, 32542393
Disorders of immune dysregulation v2.8 STXBP2 Zornitza Stark edited their review of gene: STXBP2: Added comment: PMID 25564401: four unrelated families (P1‑P4) harbouring heterozygous (monoallelic) or biallelic STXBP2 miss‑sense variants at codon 65 (R65Q or R65W) that cause familial haemophagocytic lymphohistiocytosis (F‑HLH). Functional assays (patient CTL/NK cytotoxicity, degranulation, forced expression in control cells, liposome‑fusion assays) demonstrate that the R65Q/W mutants act in a dominant‑negative manner to inhibit SNARE‑complex assembly and membrane fusion. Two families carry heterozygous variants (monoallelic disease) and two families carry biallelic variants (homozygous R65Q or compound‑heterozygous R65Q + G541S).

Insufficient evidence for monoallelic MOI except for variants at this specific codon.; Changed publications: 19804848, 25564401
Disorders of immune dysregulation v2.8 STXBP2 Zornitza Stark Marked gene: STXBP2 as ready
Disorders of immune dysregulation v2.8 STXBP2 Zornitza Stark Gene: stxbp2 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v2.8 STXBP2 Zornitza Stark Phenotypes for gene: STXBP2 were changed from to Haemophagocytic lymphohistiocytosis, familial, 5, with or without microvillus inclusion disease MIM#613101
Disorders of immune dysregulation v2.7 STXBP2 Zornitza Stark Publications for gene: STXBP2 were set to
Disorders of immune dysregulation v2.6 STXBP2 Zornitza Stark Mode of inheritance for gene: STXBP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.410 PRDM1 chirag patel Marked gene: PRDM1 as ready
Mendeliome v2.410 PRDM1 chirag patel Gene: prdm1 has been classified as Green List (High Evidence).
Mendeliome v2.410 chirag patel Copied gene PRDM1 from panel Skeletal dysplasia
Mendeliome v2.410 PRDM1 chirag patel gene: PRDM1 was added
gene: PRDM1 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PRDM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRDM1 were set to 38456586; 37083955
Phenotypes for gene: PRDM1 were set to Split hand-foot malformation MONDO:0016576, PRDM1-related
Skeletal dysplasia v1.107 PRDM1 chirag patel Classified gene: PRDM1 as Green List (high evidence)
Skeletal dysplasia v1.107 PRDM1 chirag patel Gene: prdm1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.106 PRDM1 chirag patel Marked gene: PRDM1 as ready
Skeletal dysplasia v1.106 PRDM1 chirag patel Gene: prdm1 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.106 PRDM1 chirag patel gene: PRDM1 was added
gene: PRDM1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: PRDM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRDM1 were set to 38456586; 37083955
Phenotypes for gene: PRDM1 were set to Split hand-foot malformation MONDO:0016576, PRDM1-related
Review for gene: PRDM1 was set to GREEN
Added comment: PMID 38456586 (and PMID 37083955) report 3 families with split hand/foot malformation (SHFM) caused by heterozygous PRDM1 variants. The frameshift variant (c.712_713insT) segregated in a multigenerational family (3 affected individuals) with variable penetrance (2 unaffected individuals). The 2 missense variants (p.T524R and p.T819A) were de novo (but the p.T819A variant exceeds population‑frequency thresholds). Zebrafish rescue assays showing loss‑of‑function, as wild‑type human PRDM1 rescues fin defects, whereas each mutant mRNA fails to rescue.
Sources: Literature
Hand and foot malformations v1.6 Sarah Milton Copied Region BMP2 downstream regulatory region from panel Mendeliome
Hand and foot malformations v1.6 BMP2 downstream regulatory region Sarah Milton Region: BMP2 downstream regulatory region was added
Region: BMP2 downstream regulatory region was added to Hand and foot malformations. Sources: Expert Review Green,Literature
regulatory region tags were added to Region: BMP2 downstream regulatory region.
Mode of inheritance for Region: BMP2 downstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: BMP2 downstream regulatory region were set to 19327734; 24710560; 35227291; 21357617
Phenotypes for Region: BMP2 downstream regulatory region were set to Brachydactyly, type A2 MIM#112600
Clefting disorders v1.22 PIGA chirag patel commented on gene: PIGA
Clefting disorders v1.22 PIGA chirag patel Marked gene: PIGA as ready
Clefting disorders v1.22 PIGA chirag patel Gene: piga has been classified as Red List (Low Evidence).
Clefting disorders v1.22 PIGA chirag patel Publications for gene: PIGA were set to 22305531; 22514539
Mendeliome v2.409 BMP2 downstream regulatory region Sarah Milton Classified Region: BMP2 downstream regulatory region as Green List (high evidence)
Mendeliome v2.409 BMP2 downstream regulatory region Sarah Milton Region: bmp2 downstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v2.409 BMP2 downstream regulatory region Sarah Milton Classified Region: BMP2 downstream regulatory region as Green List (high evidence)
Mendeliome v2.409 BMP2 downstream regulatory region Sarah Milton Region: bmp2 downstream regulatory region has been classified as Green List (High Evidence).
Clefting disorders v1.21 PIGA chirag patel Phenotypes for gene: PIGA were changed from MCAHS2; MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2 to Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM# 300868, MONDO:0010466
Mendeliome v2.408 BMP2 downstream regulatory region Sarah Milton Region: BMP2 downstream regulatory region was added
Region: BMP2 downstream regulatory region was added to Mendeliome. Sources: Literature
regulatory region tags were added to Region: BMP2 downstream regulatory region.
Mode of inheritance for Region: BMP2 downstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: BMP2 downstream regulatory region were set to 19327734; 24710560; 35227291; 21357617
Phenotypes for Region: BMP2 downstream regulatory region were set to Brachydactyly, type A2 MIM#112600
Added comment: BMP2 is part of the TGFb family and is a signalling protein primarily involved in promoting bone and cartilage formation.

Duplications in an evolutionary well conserved agenic region downstream of BMP2 have been reported in at least 5 unrelated families, with over 50 affected individuals presenting with brachydactyly type A2 characterised by by hypoplastic or aplastic middle phalanges of the second and fifth finger.

Duplications ranged from 4.6kb to 6.3mb and were generally located 110kb downstream of BMP2.

The molecular mechanism is postulated to be duplication of a cis acting limb specific enhancer resulting in altered equilibrium between GDF5 and BMPR1B and overall reduced BMPR1B signalling.

Note: The minimum duplication coordinates seen in an affected individual have been used for this entry.
Sources: Literature
Skeletal dysplasia v1.105 SF3B2 chirag patel Marked gene: SF3B2 as ready
Skeletal dysplasia v1.105 SF3B2 chirag patel Gene: sf3b2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.105 chirag patel Copied gene SF3B2 from panel Mandibulofacial Acrofacial dysostosis
Skeletal dysplasia v1.105 SF3B2 chirag patel gene: SF3B2 was added
gene: SF3B2 was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: SF3B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SF3B2 were set to 34344887
Phenotypes for gene: SF3B2 were set to Craniofacial microsomia, MIM#164210
Fetal anomalies v2.49 SCNM1 chirag patel Publications for gene: SCNM1 were set to 41291844; 36084634
Fetal anomalies v2.49 SCNM1 chirag patel Publications for gene: SCNM1 were set to 36084634
Polydactyly v1.18 SCNM1 chirag patel Publications for gene: SCNM1 were set to 36084634
Fetal anomalies v2.48 SCNM1 chirag patel Phenotypes for gene: SCNM1 were changed from Orofaciodigital syndrome XIX, MIM# 620107 to Orofaciodigital syndrome 19, MONDO:0859310
Polydactyly v1.17 SCNM1 chirag patel Phenotypes for gene: SCNM1 were changed from Orofaciodigital syndrome XIX, MIM# 620107 to Orofaciodigital syndrome 19, MONDO:0859310
Mendeliome v2.407 SCNM1 chirag patel Phenotypes for gene: SCNM1 were changed from Orofaciodigital syndrome 19, MONDO:0859310 to Orofaciodigital syndrome 19, MONDO:0859310
Mendeliome v2.406 SCNM1 chirag patel Phenotypes for gene: SCNM1 were changed from Orofaciodigital syndrome XIX, MIM# 620107 to Orofaciodigital syndrome 19, MONDO:0859310
Mendeliome v2.405 SCNM1 chirag patel Publications for gene: SCNM1 were set to PMID: 36084634
Ciliopathies v2.15 SCNM1 chirag patel Publications for gene: SCNM1 were set to PMID: 36084634
Ciliopathies v2.14 SCNM1 chirag patel Phenotypes for gene: SCNM1 were changed from Orofaciodigital syndrome XIX, MIM# 620107 to Orofaciodigital syndrome 19, MONDO:0859310
Polydactyly v1.16 chirag patel Added reviews for gene SCNM1 from panel Skeletal dysplasia
Mendeliome v2.404 chirag patel Added reviews for gene SCNM1 from panel Skeletal dysplasia
Fetal anomalies v2.47 chirag patel Added reviews for gene SCNM1 from panel Skeletal dysplasia
Ciliopathies v2.13 chirag patel Added reviews for gene SCNM1 from panel Skeletal dysplasia
Skeletal dysplasia v1.104 SCNM1 chirag patel changed review comment from: PMID 36084634 and PMID 41291844 report a total of 9 individuals from 7 independent consanguineous families with biallelic loss‑of‑function SCNM1 variants presenting with orofaciodigital syndrome 19. Clinical features included: bilateral postaxial polydactyly, foot syndactyly, short limbs, tongue hamartomas, micro/retrognathia, arched/cleft palate, hypo/microdontia with missing incisors, talipes equinovarus, delayed speech and brain anomalies. Variants were frameshift, missense, splice, and AluYc1 sequence insertion) with segregation confirmed in all families. Functional studies including a minigene splice assay, SCNM1 knock‑out/knock‑down in RPE‑1 cells and patient‑fibroblast rescue experiments demonstrate reduced SCNM1 protein, defective U12‑type intron splicing, elongated primary cilia and impaired Hedgehog signalling, confirming loss‑of‑function as the disease mechanism.
Sources: Literature; to: PMID 36084634 and PMID 41291844 report a total of 9 individuals from 7 independent consanguineous families with biallelic loss‑of‑function SCNM1 variants presenting with orofaciodigital syndrome 19. Clinical features included: bilateral postaxial polydactyly, foot syndactyly, bifid halluces, short limbs, tongue hamartomas, micro/retrognathia, arched/cleft palate, hypo/microdontia with missing incisors, talipes equinovarus, developmental delay and brain anomalies. Variants were frameshift, missense, splice, and AluYc1 sequence insertion) with segregation confirmed in all families. Functional studies including a minigene splice assay, SCNM1 knock‑out/knock‑down in RPE‑1 cells and patient‑fibroblast rescue experiments demonstrate reduced SCNM1 protein, defective U12‑type intron splicing, elongated primary cilia and impaired Hedgehog signalling, confirming loss‑of‑function as the disease mechanism.
Sources: Literature
Skeletal dysplasia v1.104 SCNM1 chirag patel changed review comment from: PMID 36084634 and PMID 41291844 report a total of 5 individuals from 4 independent consanguineous families with biallelic loss‑of‑function SCNM1 variants presenting with orofaciodigital syndrome 19, a disorder characterised by oral, facial and digital anomalies, limb shortening, polydactyly, tibial hemimelia and neurodevelopmental delay. Variants were frameshift, missense, splice, and AluYc1 sequence insertion) with segregation confirmed in all families. Functional studies including a minigene splice assay, SCNM1 knock‑out/knock‑down in RPE‑1 cells and patient‑fibroblast rescue experiments demonstrate reduced SCNM1 protein, defective U12‑type intron splicing, elongated primary cilia and impaired Hedgehog signalling, confirming loss‑of‑function as the disease mechanism.
Sources: Literature; to: PMID 36084634 and PMID 41291844 report a total of 9 individuals from 7 independent consanguineous families with biallelic loss‑of‑function SCNM1 variants presenting with orofaciodigital syndrome 19. Clinical features included: bilateral postaxial polydactyly, foot syndactyly, short limbs, tongue hamartomas, micro/retrognathia, arched/cleft palate, hypo/microdontia with missing incisors, talipes equinovarus, delayed speech and brain anomalies. Variants were frameshift, missense, splice, and AluYc1 sequence insertion) with segregation confirmed in all families. Functional studies including a minigene splice assay, SCNM1 knock‑out/knock‑down in RPE‑1 cells and patient‑fibroblast rescue experiments demonstrate reduced SCNM1 protein, defective U12‑type intron splicing, elongated primary cilia and impaired Hedgehog signalling, confirming loss‑of‑function as the disease mechanism.
Sources: Literature
Skeletal dysplasia v1.104 SCNM1 chirag patel Classified gene: SCNM1 as Green List (high evidence)
Skeletal dysplasia v1.104 SCNM1 chirag patel Gene: scnm1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.103 SCNM1 chirag patel Marked gene: SCNM1 as ready
Skeletal dysplasia v1.103 SCNM1 chirag patel Gene: scnm1 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.103 SCNM1 chirag patel gene: SCNM1 was added
gene: SCNM1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: SCNM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCNM1 were set to 41291844; 36084634
Phenotypes for gene: SCNM1 were set to Orofaciodigital syndrome 19, MONDO:0859310
Review for gene: SCNM1 was set to GREEN
Added comment: PMID 36084634 and PMID 41291844 report a total of 5 individuals from 4 independent consanguineous families with biallelic loss‑of‑function SCNM1 variants presenting with orofaciodigital syndrome 19, a disorder characterised by oral, facial and digital anomalies, limb shortening, polydactyly, tibial hemimelia and neurodevelopmental delay. Variants were frameshift, missense, splice, and AluYc1 sequence insertion) with segregation confirmed in all families. Functional studies including a minigene splice assay, SCNM1 knock‑out/knock‑down in RPE‑1 cells and patient‑fibroblast rescue experiments demonstrate reduced SCNM1 protein, defective U12‑type intron splicing, elongated primary cilia and impaired Hedgehog signalling, confirming loss‑of‑function as the disease mechanism.
Sources: Literature
Skeletal dysplasia v1.102 TMEM17 chirag patel Marked gene: TMEM17 as ready
Skeletal dysplasia v1.102 TMEM17 chirag patel Gene: tmem17 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.102 chirag patel Copied gene TMEM17 from panel Mendeliome
Skeletal dysplasia v1.102 TMEM17 chirag patel gene: TMEM17 was added
gene: TMEM17 was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TMEM17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM17 were set to 41054827, 40841990
Phenotypes for gene: TMEM17 were set to Meckel syndrome MONDO:0018921, TMEM17-related
Fetal anomalies v2.46 TXNDC15 chirag patel Publications for gene: TXNDC15 were set to 41518077; 39679447; 38156946; 38073519; 31411728; 30851085; 27894351
Fetal anomalies v2.46 TXNDC15 chirag patel Publications for gene: TXNDC15 were set to 30851085; 27894351
Renal Ciliopathies and Nephronophthisis v2.2 TXNDC15 chirag patel Publications for gene: TXNDC15 were set to 30851085; 27894351
Mendeliome v2.403 TXNDC15 chirag patel Publications for gene: TXNDC15 were set to 41518077; 39679447; 38156946; 38073519; 31411728; 30851085; 27894351
Mendeliome v2.402 TXNDC15 chirag patel Publications for gene: TXNDC15 were set to 30851085; 27894351
Joubert syndrome and other neurological ciliopathies v2.2 TXNDC15 chirag patel Publications for gene: TXNDC15 were set to 30851085; 27894351
Ciliopathies v2.12 TXNDC15 chirag patel Publications for gene: TXNDC15 were set to 30851085; 27894351
Renal Ciliopathies and Nephronophthisis v2.1 chirag patel Added reviews for gene TXNDC15 from panel Skeletal dysplasia
Mendeliome v2.401 chirag patel Added reviews for gene TXNDC15 from panel Skeletal dysplasia
Joubert syndrome and other neurological ciliopathies v2.1 chirag patel Added reviews for gene TXNDC15 from panel Skeletal dysplasia
Fetal anomalies v2.45 chirag patel Added reviews for gene TXNDC15 from panel Skeletal dysplasia
Ciliopathies v2.11 chirag patel Added reviews for gene TXNDC15 from panel Skeletal dysplasia
Skeletal dysplasia v1.101 TXNDC15 chirag patel Marked gene: TXNDC15 as ready
Skeletal dysplasia v1.101 TXNDC15 chirag patel Gene: txndc15 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.101 TXNDC15 chirag patel Classified gene: TXNDC15 as Green List (high evidence)
Skeletal dysplasia v1.101 TXNDC15 chirag patel Gene: txndc15 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.100 TXNDC15 chirag patel gene: TXNDC15 was added
gene: TXNDC15 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: TXNDC15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TXNDC15 were set to 41518077; 39679447; 38156946; 38073519; 31411728; 30851085; 27894351
Phenotypes for gene: TXNDC15 were set to Meckel syndrome 14, MIM# 619879
Review for gene: TXNDC15 was set to GREEN
Added comment: PMID 41518077, PMID 38073519, PMID 38156946, PMID 30851085, PMID 31411728 and PMID 27894351 report 8 families with biallelic loss‑of‑function TXNDC15 variants causing Meckel syndrome, a perinatally lethal autosomal recessive ciliopathy characterised by occipital encephalocele, polycystic kidneys, postaxial polydactyly and omphalocele. Segregation, ultra‑rare population frequencies and functional studies in patient cells and mouse models support the association.
Sources: Literature
Skeletal dysplasia v1.99 TRIM37 chirag patel changed review comment from: long‑bone dysplasia seen in condition; to: fibrous dysplasia of long bones (esp. tibia) seen in condition.
Skeletal dysplasia v1.99 TRIM37 chirag patel Marked gene: TRIM37 as ready
Skeletal dysplasia v1.99 TRIM37 chirag patel Gene: trim37 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.99 TRIM37 chirag patel reviewed gene: TRIM37: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mulibrey nanism, MIM# 253250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.99 chirag patel Copied gene TRIM37 from panel Mendeliome
Skeletal dysplasia v1.99 TRIM37 chirag patel gene: TRIM37 was added
gene: TRIM37 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TRIM37 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM37 were set to 10888877; 12754710; 15108285; 14757854; 27044324
Phenotypes for gene: TRIM37 were set to Mulibrey nanism, MIM# 253250
Peroxisomal Disorders v1.5 TRIM37 chirag patel Phenotypes for gene: TRIM37 were changed from Mulibrey nanism, MIM# 253250 to Mulibrey nanism, MIM# 253250
Peroxisomal Disorders v1.5 TRIM37 chirag patel Phenotypes for gene: TRIM37 were changed from Mulibrey nanism, MIM# 253250 to Mulibrey nanism, MIM# 253250
Peroxisomal Disorders v1.4 TRIM37 chirag patel Phenotypes for gene: TRIM37 were changed from Mulibrey nanism, MIM# 253250 to Mulibrey nanism, MIM# 253250
Peroxisomal Disorders v1.4 TRIM37 chirag patel Phenotypes for gene: TRIM37 were changed from to Mulibrey nanism, MIM# 253250
Peroxisomal Disorders v1.3 TRIM37 chirag patel Marked gene: TRIM37 as ready
Peroxisomal Disorders v1.3 TRIM37 chirag patel Gene: trim37 has been classified as Green List (High Evidence).
Peroxisomal Disorders v1.3 TRIM37 chirag patel Publications for gene: TRIM37 were set to
Peroxisomal Disorders v1.2 TRIM37 chirag patel Mode of inheritance for gene: TRIM37 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Peroxisomal Disorders v1.1 chirag patel Added reviews for gene TRIM37 from panel Mendeliome
Mandibulofacial Acrofacial dysostosis v2.9 VGLL2 chirag patel Publications for gene: VGLL2 were set to
Skeletal dysplasia v1.98 VGLL2 chirag patel Publications for gene: VGLL2 were set to
Mendeliome v2.400 VGLL2 chirag patel Publications for gene: VGLL2 were set to 37666660
Mendeliome v2.400 VGLL2 chirag patel Publications for gene: VGLL2 were set to
Mendeliome v2.399 VGLL2 chirag patel edited their review of gene: VGLL2: Added comment: PMID 37666660 reports the ESHG cases: 6 individuals from 4 families with biallelic VGLL2 variants presenting with isolated congenital bony syngnathia (jaw bone fusion, sometimes with cleft palate). The variants (p.Gln151Ter p.Glu67Ter) and segregated in all families, with founder effect in Turkish families. Zebrafish vgll2a and vgll4l knockouts and Vgll2‑/‑ mouse models showed no craniofacial defects, suggesting species‑specific compensation.; Changed publications: 37666660; Changed phenotypes: Syngnathia, MONDO:0015409, VGLL2-related
Skeletal dysplasia v1.97 VGLL2 chirag patel Marked gene: VGLL2 as ready
Skeletal dysplasia v1.97 VGLL2 chirag patel Gene: vgll2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.97 chirag patel Copied gene VGLL2 from panel Mandibulofacial Acrofacial dysostosis
Skeletal dysplasia v1.97 VGLL2 chirag patel gene: VGLL2 was added
gene: VGLL2 was added to Skeletal dysplasia. Sources: Expert Review Green,Other
Mode of inheritance for gene: VGLL2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VGLL2 were set to Syngnathia, MONDO:0015409, VGLL2-related
Mendeliome v2.399 chirag patel Added reviews for gene VGLL2 from panel Mandibulofacial Acrofacial dysostosis
Mandibulofacial Acrofacial dysostosis v2.8 VGLL2 chirag patel edited their review of gene: VGLL2: Added comment: PMID 37666660 reports the ESHG cases: 6 individuals from 4 families with biallelic VGLL2 variants presenting with isolated congenital bony syngnathia (jaw bone fusion, sometimes with cleft palate). The variants (p.Gln151Ter p.Glu67Ter) and segregated in all families, with founder effect in Turkish families. Zebrafish vgll2a and vgll4l knockouts and Vgll2‑/‑ mouse models showed no craniofacial defects, suggesting species‑specific compensation.; Changed publications: 37666660; Changed phenotypes: Syngnathia, MONDO:0015409, VGLL2-related
Mandibulofacial Acrofacial dysostosis v2.8 VGLL2 chirag patel changed review comment from: ESHG 2023:
4 families/7 affected individuals with isolated unilateral/bilateral syngnathia
biallelic truncating variants in VGLL2
But not phenotype in KO mouse or zebrafish models
Sources: Other; to: ESHG 2023:
4 families/7 affected individuals with isolated unilateral/bilateral syngnathia
biallelic truncating variants in VGLL2
But not phenotype in KO mouse or zebrafish models
Sources: Other
Skeletal dysplasia v1.96 VPS16 chirag patel Classified gene: VPS16 as Green List (high evidence)
Skeletal dysplasia v1.96 VPS16 chirag patel Gene: vps16 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.95 VPS16 chirag patel Marked gene: VPS16 as ready
Skeletal dysplasia v1.95 VPS16 chirag patel Gene: vps16 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.95 VPS16 chirag patel gene: VPS16 was added
gene: VPS16 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: VPS16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS16 were set to 34013567; 33938619
Phenotypes for gene: VPS16 were set to Mucopolysaccharidosis or mucopolysaccharidosis-like disorder, MONDO:0100365
Review for gene: VPS16 was set to GREEN
Added comment: PMID 34013567 reports a consanguineous Turkish‑Arab family with two siblings homozygous for a missense VPS16 p.Trp180Cys variant presenting with a mucopolysaccharidosis‑like multisystem disorder that includes short stature, coarse facies, spondylar dysplasia and severe neutropenia. PMID 33938619 identifies two unrelated families harbouring a homozygous intronic splice‑site c.2272-18C>A variant that causes a similar early‑onset mucopolysaccharidosis‑like disease with dysostosis multiplex, neurodevelopmental regression and hematological abnormalities. Functional studies show ~85 % loss of VPS16 protein in patient fibroblasts rescued by wild‑type VPS16 expression and a vps16‑deficient zebrafish recapitulating the neuro‑developmental and lysosomal phenotypes.
Sources: Literature
Callosome v1.17 WDR4 chirag patel reviewed gene: WDR4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Galloway-Mowat syndrome 1 MIM#251300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuria v1.2 WDR4 chirag patel Marked gene: WDR4 as ready
Proteinuria v1.2 WDR4 chirag patel Gene: wdr4 has been classified as Green List (High Evidence).
Proteinuria v1.2 WDR4 chirag patel Classified gene: WDR4 as Green List (high evidence)
Proteinuria v1.2 WDR4 chirag patel Gene: wdr4 has been classified as Green List (High Evidence).
Proteinuria v1.1 WDR4 chirag patel gene: WDR4 was added
gene: WDR4 was added to Proteinuria. Sources: Literature
Mode of inheritance for gene: WDR4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR4 were set to 30079490, 29597095, 28617965
Phenotypes for gene: WDR4 were set to Galloway-Mowat syndrome 6, OMIM #618347
Review for gene: WDR4 was set to GREEN
Added comment: Galloway-Mowat syndrome (GAMOS) is characterised by neurodevelopmental defects combined with nephrotic syndrome and proteinuria. Most patients with GAMOS6 also have growth deficiency with variable microcephaly, and the renal disease may be age-dependent.

1 family with 2 sibs with GMS and compound heterozygous mutations in the WDR4 gene, segregated with the disorder in the family. Functional studies of the variants and studies of patient cells were not performed.

1 family with 1 child with GMS and compound heterozygous mutations in the WDR4 gene, segregated with the disorder in the family. Functional studies of the variants and studies of patient cells were not performed.

1 family with 4 sibs with GMS and homozygous splice site mutation in the WDR4 gene. Functional studies of the variant and studies of patient cells were not performed.
Sources: Literature
Skeletal dysplasia v1.94 WDR4 chirag patel Classified gene: WDR4 as Green List (high evidence)
Skeletal dysplasia v1.94 WDR4 chirag patel Gene: wdr4 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.93 WDR4 chirag patel Marked gene: WDR4 as ready
Skeletal dysplasia v1.93 WDR4 chirag patel Gene: wdr4 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.93 WDR4 chirag patel gene: WDR4 was added
gene: WDR4 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: WDR4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR4 were set to 28617965; 26429597; 26416026
Phenotypes for gene: WDR4 were set to Microcephaly, growth deficiency, seizures, and brain malformations, MONDO:0032690
Review for gene: WDR4 was set to GREEN
Added comment: 6 individuals from 5 families with biallelic WDR4 variants causing microcephalic primordial dwarfism characterised by severe growth deficiency, microcephaly, brain malformations, seizures and facial dysmorphism. Skeletal features include: unossified pubic bones, short long bones, and broad metaphyses. Patient lymphoblastoid cells show reduced tRNA m7G46 methylation. Yeast models with orthologous WDR4 mutations display temperature‑sensitive growth defects.
Sources: Literature
Microcephaly v2.14 WDR4 chirag patel Phenotypes for gene: WDR4 were changed from Microcephaly, growth deficiency, seizures, and brain malformations, OMIM #618346; Microcephaly, growth deficiency, seizures, and brain malformations, OMIM #618346 to Galloway-Mowat syndrome 6 MIM#618347; Microcephaly, growth deficiency, seizures, and brain malformations, OMIM #618346
Microcephaly v2.13 WDR4 chirag patel Phenotypes for gene: WDR4 were changed from Microcephaly, growth deficiency, seizures, and brain malformations, OMIM #618346 to Microcephaly, growth deficiency, seizures, and brain malformations, OMIM #618346; Microcephaly, growth deficiency, seizures, and brain malformations, OMIM #618346
Microcephaly v2.12 chirag patel Added reviews for gene WDR4 from panel Mendeliome
Microcephaly v2.11 WDR4 chirag patel Phenotypes for gene: WDR4 were changed from Galloway-Mowat syndrome 6 MIM#618347 to Microcephaly, growth deficiency, seizures, and brain malformations, OMIM #618346
Mendeliome v2.398 YY1AP1 chirag patel Phenotypes for gene: YY1AP1 were changed from Grange syndrome, MIM# 602531 to Grange syndrome, MIM# 602531
Mendeliome v2.397 YY1AP1 chirag patel Phenotypes for gene: YY1AP1 were changed from Grange syndrome, MIM# 602531; stenosis/occlusion of multiple arteries to Grange syndrome, MIM# 602531
Skeletal dysplasia v1.92 YY1AP1 chirag patel Phenotypes for gene: YY1AP1 were changed from Grange syndrome, MIM# 602531; stenosis/occlusion of multiple arteries to Grange syndrome, MIM# 602531
Skeletal dysplasia v1.91 YY1AP1 chirag patel Marked gene: YY1AP1 as ready
Skeletal dysplasia v1.91 YY1AP1 chirag patel Gene: yy1ap1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.91 YY1AP1 chirag patel reviewed gene: YY1AP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Grange syndrome, MIM# 602531; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.91 chirag patel Copied gene YY1AP1 from panel Mendeliome
Skeletal dysplasia v1.91 YY1AP1 chirag patel gene: YY1AP1 was added
gene: YY1AP1 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: YY1AP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YY1AP1 were set to 31633303; 30356112; 31270375; 22987684; 16691574; 27939641; 30556293
Phenotypes for gene: YY1AP1 were set to Grange syndrome, MIM# 602531; stenosis/occlusion of multiple arteries
Skeletal dysplasia v1.90 ZRSR2 chirag patel Marked gene: ZRSR2 as ready
Skeletal dysplasia v1.90 ZRSR2 chirag patel Gene: zrsr2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.90 ZRSR2 chirag patel reviewed gene: ZRSR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Orofaciodigital syndrome XXI, MIM# 301132; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Skeletal dysplasia v1.90 chirag patel Copied gene ZRSR2 from panel Mendeliome
Skeletal dysplasia v1.90 ZRSR2 chirag patel gene: ZRSR2 was added
gene: ZRSR2 was added to Skeletal dysplasia. Sources: Expert Review Green,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 Orofaciodigital syndrome XXI, MIM# 301132
Skeletal dysplasia v1.89 SATB2 chirag patel Publications for gene: SATB2 were set to 29023086; 28151491; 32446642
Skeletal dysplasia v1.88 SATB2 chirag patel Marked gene: SATB2 as ready
Skeletal dysplasia v1.88 SATB2 chirag patel Gene: satb2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.88 SATB2 chirag patel reviewed gene: SATB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35241104; Phenotypes: Glass syndrome, MONDO:0100147; Mode of inheritance: None
Skeletal dysplasia v1.88 chirag patel Copied gene SATB2 from panel Mendeliome
Skeletal dysplasia v1.88 SATB2 chirag patel gene: SATB2 was added
gene: SATB2 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SATB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SATB2 were set to 29023086; 28151491; 32446642
Phenotypes for gene: SATB2 were set to Glass syndrome, MIM# 612313; MONDO:0100147
Cardiomyopathy_Paediatric v1.73 MT-ND6 Lucy Spencer Classified gene: MT-ND6 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.73 MT-ND6 Lucy Spencer Gene: mt-nd6 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.72 MT-ND6 Lucy Spencer gene: MT-ND6 was added
gene: MT-ND6 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene gene: MT-ND6 was set to MITOCHONDRIAL
Publications for gene: MT-ND6 were set to 34933128
Phenotypes for gene: MT-ND6 were set to Mitochondrial disease (MONDO:0044970), MT-ND6-related
Review for gene: MT-ND6 was set to AMBER
Added comment: PMID 34933128 reports 4 new patients and reviews the literature for individuals with Leigh syndrome and m.14453G>A in MT-ND6. 2 of the individuals were noted to have childhood/infantile onset HCM.
Sources: Literature
Genomic newborn screening: BabyScreen+ v2.1 FBN2 Zornitza Stark Mode of inheritance for gene: FBN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v2.0 FBN2 Zornitza Stark edited their review of gene: FBN2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v2.44 FBN2 Zornitza Stark Mode of inheritance for gene: FBN2 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.87 FBN2 Zornitza Stark Mode of inheritance for gene: FBN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.86 FBN2 Zornitza Stark edited their review of gene: FBN2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v2.1 FBN2 Zornitza Stark Mode of inheritance for gene: FBN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v2.7 FBN2 Zornitza Stark Mode of inheritance for gene: FBN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v2.6 FBN2 Zornitza Stark edited their review of gene: FBN2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v2.396 FBN2 Zornitza Stark Mode of inheritance for gene: FBN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v2.395 FBN2 Zornitza Stark edited their review of gene: FBN2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.86 COL9A1 Zornitza Stark Marked gene: COL9A1 as ready
Skeletal dysplasia v1.86 COL9A1 Zornitza Stark Gene: col9a1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.86 COL9A1 Zornitza Stark Publications for gene: COL9A1 were set to
Skeletal dysplasia v1.85 COL9A1 Zornitza Stark Mode of inheritance for gene: COL9A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.395 VMA21 Sangavi Sivagnanasundram reviewed gene: VMA21: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: congenital disorder of glycosylation MONDO:0015286; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v2.395 SPNS2 Sangavi Sivagnanasundram reviewed gene: SPNS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 36494063; Phenotypes: hearing loss, autosomal recessive 115 MONDO:0032762; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Complement Deficiencies v2.7 C2 Zornitza Stark Marked gene: C2 as ready
Complement Deficiencies v2.7 C2 Zornitza Stark Gene: c2 has been classified as Green List (High Evidence).
Complement Deficiencies v2.7 C2 Zornitza Stark Phenotypes for gene: C2 were changed from to C2 deficiency MIM#217000
Complement Deficiencies v2.6 C2 Zornitza Stark Publications for gene: C2 were set to
Complement Deficiencies v2.5 C2 Zornitza Stark Mode of inheritance for gene: C2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.395 CIDEC Sangavi Sivagnanasundram Phenotypes for gene: CIDEC were changed from Lipodystrophy, familial partial, type 5, MIM# 615238 to CIDEC-related familial partial lipodystrophy MONDO:0014098
Mendeliome v2.394 CIDEC Sangavi Sivagnanasundram Classified gene: CIDEC as Amber List (moderate evidence)
Mendeliome v2.394 CIDEC Sangavi Sivagnanasundram Gene: cidec has been classified as Amber List (Moderate Evidence).
Mendeliome v2.393 CIDEC Sangavi Sivagnanasundram reviewed gene: CIDEC: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: CIDEC-related familial partial lipodystrophy MONDO:0014098; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v2.32 SYNCRIP Rylee Peters Classified gene: SYNCRIP as Green List (high evidence)
Genetic Epilepsy v2.32 SYNCRIP Rylee Peters Gene: syncrip has been classified as Green List (High Evidence).
Genetic Epilepsy v2.31 SYNCRIP Rylee Peters changed review comment from: Two additional reports of individuals with SYNCRIP-related neurodevelopmental disorder with seizures (https://doi.org/10.1016/j.rare.2024.100052).; to: Two additional reports of individuals with SYNCRIP-related neurodevelopmental disorder including seizures (https://doi.org/10.1016/j.rare.2024.100052).
Genetic Epilepsy v2.31 SYNCRIP Rylee Peters reviewed gene: SYNCRIP: Rating: GREEN; Mode of pathogenicity: None; Publications: https://doi.org/10.1016/j.rare.2024.100052; Phenotypes: SYNCRIP-related neurodevelopmental disorder, MONDO:0800456; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Periventricular Grey Matter Heterotopia v2.2 SYNCRIP Rylee Peters Publications for gene: SYNCRIP were set to 34157790
Periventricular Grey Matter Heterotopia v2.1 SYNCRIP Rylee Peters Classified gene: SYNCRIP as Amber List (moderate evidence)
Periventricular Grey Matter Heterotopia v2.1 SYNCRIP Rylee Peters Gene: syncrip has been classified as Amber List (Moderate Evidence).
Periventricular Grey Matter Heterotopia v2.0 SYNCRIP Rylee Peters reviewed gene: SYNCRIP: Rating: AMBER; Mode of pathogenicity: None; Publications: 39487702; Phenotypes: SYNCRIP-related neurodevelopmental disorder, MONDO:0800456; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v2.43 SYNCRIP Rylee Peters Publications for gene: SYNCRIP were set to 34157790
Fetal anomalies v2.42 SYNCRIP Rylee Peters Classified gene: SYNCRIP as Green List (high evidence)
Fetal anomalies v2.42 SYNCRIP Rylee Peters Gene: syncrip has been classified as Green List (High Evidence).
Fetal anomalies v2.41 SYNCRIP Rylee Peters reviewed gene: SYNCRIP: Rating: GREEN; Mode of pathogenicity: None; Publications: 39487702, https://doi.org/10.1016/j.rare.2024.100052; Phenotypes: SYNCRIP-related neurodevelopmental disorder, MONDO:0800456; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.84 Sarah Milton Copied Region HOXD cluster regulatory region from panel Mendeliome
Skeletal dysplasia v1.84 HOXD cluster regulatory region Sarah Milton Region: HOXD cluster regulatory region was added
Region: HOXD cluster regulatory region was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
regulatory region tags were added to Region: HOXD cluster regulatory region.
Mode of inheritance for Region: HOXD cluster regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: HOXD cluster regulatory region were set to 20648051; 36990510; 34408147; 31591517; 20577005; 29517766
Phenotypes for Region: HOXD cluster regulatory region were set to Mesomelic dysplasia, Kantaputra type, MIM#156232
Mendeliome v2.393 HOXD cluster regulatory region Sarah Milton Marked Region: HOXD cluster regulatory region as ready
Mendeliome v2.393 HOXD cluster regulatory region Sarah Milton Region: hoxd cluster regulatory region has been classified as Green List (High Evidence).
Mendeliome v2.393 HOXD cluster regulatory region Sarah Milton Classified Region: HOXD cluster regulatory region as Green List (high evidence)
Mendeliome v2.393 HOXD cluster regulatory region Sarah Milton Region: hoxd cluster regulatory region has been classified as Green List (High Evidence).
Mendeliome v2.392 HOXD cluster regulatory region Sarah Milton changed review comment from: The HOXD cluster of genes including HOXD1, HOXD3, HOXD4, HOXD8, HOXD9, HOXD10, HOXD11, HOXD12, HOXD13 are involved in embryonic patterning in developing limb buds.

Multiple publications report copy number changes in the 2q31 region involving the HOXD cluster resulting in Mesomelic dysplasia, Kantaputra type characterised by marked shortening of the upper and lower limbs and progressive flexion contractures of PIP joints.

Copy number changes in affected individuals included deletions, duplications and inversions ranging from 93kb to 1mb, many individuals had more than one structural variant within the region.

The proposed molecular mechanism is repositioning of the HOX genes in relation to up and downstream enhancers resulting in misexpression.

It should be noted deletions of the HOX gene cluster don't recapitulate the phenotype as it is thought there is compensation from HOXA genes.

Functional studies in a mouse model showed inappropriate expression of HOXD13 in the middle segment of limb (ulnar/radius/tibia/fibula) and loss of normal expression in hand/foot, as well as loss of normal HOXD11 expression in the middle segment of the limb.
This is thought to occur as each enhancer region normally acts on different precursor cells in normal physiology thus rearranging the region results in misexpression.

Note: coordinates used for the above entry were the minimum seen in an affected individual (duplication).
Authors of above publications did note if the copy number variant is too large it did not recapitulate the phenotype.
Sources: Literature; to: The HOXD cluster of genes including HOXD1, HOXD3, HOXD4, HOXD8, HOXD9, HOXD10, HOXD11, HOXD12, HOXD13 are involved in embryonic patterning in developing limb buds.

Multiple publications report copy number changes in the 2q31 region involving the HOXD cluster resulting in Mesomelic dysplasia, Kantaputra type characterised by marked shortening of the upper and lower limbs and progressive flexion contractures of PIP joints.

Copy number changes in affected individuals included deletions, duplications and inversions ranging from 93kb to 1mb, many individuals had more than one structural variant within the region.

The proposed molecular mechanism is repositioning of the HOX genes in relation to up and downstream enhancers resulting in misexpression.

It should be noted deletions of the HOX gene cluster don't recapitulate the phenotype as it is thought there is compensation from HOXA genes.

Functional studies in a mouse model showed inappropriate expression of HOXD13 in the middle segment of limb (ulnar/radius/tibia/fibula) and loss of normal expression in hand/foot, as well as loss of normal HOXD11 expression in the middle segment of the limb.
This is thought to occur as each enhancer region acts on different precursor cells in normal physiology thus rearranging the region results in misexpression.

Note: coordinates used for the above entry were the minimum seen in an affected individual (duplication).
Authors of above publications did note if the copy number variant is too large it did not recapitulate the phenotype.
Sources: Literature
Mendeliome v2.392 HOXD cluster regulatory region Sarah Milton changed review comment from: The HOXD cluster of genes including HOXD1, HOXD3, HOXD4, HOXD8, HOXD9, HOXD10, HOXD11, HOXD12, HOXD13 are involved in embryonic patterning in developing limb buds.

Multiple publications report copy number changes in the 2q31 region involving the HOXD cluster resulting in Mesomelic dysplasia, Kantaputra type characterised by marked shortening of the upper and lower limbs and progressive flexion contractures of PIP joints.

Copy number changes in affected individuals included deletions, duplications and inversions ranging from 93kb to 1mb, many individuals had more than one structural variant within the region.

The proposed molecular mechanism is repositioning of the HOX genes in relation to up and downstream enhancers resulting in misexpression.

It should be noted deletions of the HOX gene cluster don't recapitulate the phenotype as it is thought there is compensation from HOXA genes.

Functional studies in a mouse model showed inappropriate expression of HOXD13 in the middle segment of limb (ulnar/radius/tibia/fibula) and loss of normal expression in hand/foot, as well as loss of normal HOXD11 expression in the middle segment of the limb.
This is thought to occur as each enhancer region normally acts on different precursor cells but repositioning of genes in the region results in misexpression.

Note: coordinates used for the above entry were the minimum seen in an affected individual (duplication).
Authors of above publications did note if the copy number variant is too large it did not recapitulate the phenotype.
Sources: Literature; to: The HOXD cluster of genes including HOXD1, HOXD3, HOXD4, HOXD8, HOXD9, HOXD10, HOXD11, HOXD12, HOXD13 are involved in embryonic patterning in developing limb buds.

Multiple publications report copy number changes in the 2q31 region involving the HOXD cluster resulting in Mesomelic dysplasia, Kantaputra type characterised by marked shortening of the upper and lower limbs and progressive flexion contractures of PIP joints.

Copy number changes in affected individuals included deletions, duplications and inversions ranging from 93kb to 1mb, many individuals had more than one structural variant within the region.

The proposed molecular mechanism is repositioning of the HOX genes in relation to up and downstream enhancers resulting in misexpression.

It should be noted deletions of the HOX gene cluster don't recapitulate the phenotype as it is thought there is compensation from HOXA genes.

Functional studies in a mouse model showed inappropriate expression of HOXD13 in the middle segment of limb (ulnar/radius/tibia/fibula) and loss of normal expression in hand/foot, as well as loss of normal HOXD11 expression in the middle segment of the limb.
This is thought to occur as each enhancer region normally acts on different precursor cells in normal physiology thus rearranging the region results in misexpression.

Note: coordinates used for the above entry were the minimum seen in an affected individual (duplication).
Authors of above publications did note if the copy number variant is too large it did not recapitulate the phenotype.
Sources: Literature
Mendeliome v2.392 HOXD cluster regulatory region Sarah Milton Region: HOXD cluster regulatory region was added
Region: HOXD cluster regulatory region was added to Mendeliome. Sources: Literature
regulatory region tags were added to Region: HOXD cluster regulatory region.
Mode of inheritance for Region: HOXD cluster regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: HOXD cluster regulatory region were set to 20648051; 36990510; 34408147; 31591517; 20577005; 29517766
Phenotypes for Region: HOXD cluster regulatory region were set to Mesomelic dysplasia, Kantaputra type, MIM#156232
Review for Region: HOXD cluster regulatory region was set to GREEN
Added comment: The HOXD cluster of genes including HOXD1, HOXD3, HOXD4, HOXD8, HOXD9, HOXD10, HOXD11, HOXD12, HOXD13 are involved in embryonic patterning in developing limb buds.

Multiple publications report copy number changes in the 2q31 region involving the HOXD cluster resulting in Mesomelic dysplasia, Kantaputra type characterised by marked shortening of the upper and lower limbs and progressive flexion contractures of PIP joints.

Copy number changes in affected individuals included deletions, duplications and inversions ranging from 93kb to 1mb, many individuals had more than one structural variant within the region.

The proposed molecular mechanism is repositioning of the HOX genes in relation to up and downstream enhancers resulting in misexpression.

It should be noted deletions of the HOX gene cluster don't recapitulate the phenotype as it is thought there is compensation from HOXA genes.

Functional studies in a mouse model showed inappropriate expression of HOXD13 in the middle segment of limb (ulnar/radius/tibia/fibula) and loss of normal expression in hand/foot, as well as loss of normal HOXD11 expression in the middle segment of the limb.
This is thought to occur as each enhancer region normally acts on different precursor cells but repositioning of genes in the region results in misexpression.

Note: coordinates used for the above entry were the minimum seen in an affected individual (duplication).
Authors of above publications did note if the copy number variant is too large it did not recapitulate the phenotype.
Sources: Literature
Mendeliome v2.391 OTOF Sangavi Sivagnanasundram reviewed gene: OTOF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: nonsyndromic genetic hearing loss MONDO:0019497; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy v2.26 FBXO38 Sangavi Sivagnanasundram reviewed gene: FBXO38: Rating: AMBER; Mode of pathogenicity: None; Publications: 34103343; Phenotypes: distal hereditary motor neuropathy MONDO:0018894; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.71 TANGO2 Lucy Spencer Classified gene: TANGO2 as Green List (high evidence)
Cardiomyopathy_Paediatric v1.71 TANGO2 Lucy Spencer Gene: tango2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.70 TANGO2 Lucy Spencer gene: TANGO2 was added
gene: TANGO2 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: TANGO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TANGO2 were set to 40156300; 35568137
Phenotypes for gene: TANGO2 were set to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration MIM#616878
Review for gene: TANGO2 was set to GREEN
Added comment: PMID: 40156300 reports 2 probands with biallelic TANGO2 variants with cardiomyopathy as part of a broader TANGO2-associated phenotype.

PMID: 35568137 Cohort of 27 children with TANGO2 deficiency disorder, 19 developed cardiomyopathy
Sources: Literature
Cardiomyopathy_Paediatric v1.69 TREX1 Lucy Spencer Classified gene: TREX1 as Green List (high evidence)
Cardiomyopathy_Paediatric v1.69 TREX1 Lucy Spencer Gene: trex1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.68 TREX1 Lucy Spencer gene: TREX1 was added
gene: TREX1 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: TREX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TREX1 were set to 25604658; 36581356
Phenotypes for gene: TREX1 were set to Aicardi-Goutieres syndrome 1, dominant and recessive MIM#225750
Review for gene: TREX1 was set to GREEN
Added comment: PMID: 25604658 infantile onset hypertrophic cardiomyopathy reported in 9/79 individuals with TREX1 related Aicardi-Goutieres syndrome. This paper includes both recessive and dominant TREX1 patients, it is unclear which have HCM.

PMID 36581356 reports one proband with Aicardi-Goutieres syndrome diagnosed with cardiomyopathy in utero. The proband was homozygous for a TREX1 frameshift variant.
Sources: Literature
Microcephaly v2.10 ATP6V0C Vivek Kumar reviewed gene: ATP6V0C: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Mendeliome v2.391 TKFC Rylee Peters Publications for gene: TKFC were set to 32004446
Mendeliome v2.390 TKFC Rylee Peters reviewed gene: TKFC: Rating: AMBER; Mode of pathogenicity: None; Publications: 39251934; Phenotypes: Triokinase and FMN cyclase deficiency syndrome, MIM#618805; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.67 TKFC Rylee Peters Marked gene: TKFC as ready
Cardiomyopathy_Paediatric v1.67 TKFC Rylee Peters Gene: tkfc has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.67 TKFC Rylee Peters Classified gene: TKFC as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.67 TKFC Rylee Peters Gene: tkfc has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.66 TKFC Rylee Peters gene: TKFC was added
gene: TKFC was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: TKFC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TKFC were set to 39251934; 32004446
Phenotypes for gene: TKFC were set to Triokinase and FMN cyclase deficiency syndrome, MIM#618805
Review for gene: TKFC was set to AMBER
Added comment: PMID: 32004446 reports 4 individuals from 2 consanguineous families with homozygous variants in TKFC. The first family had 2 children with phenotypes including cataract, lactic acidosis, cardiomyopathy. The second family had one child with cataracts and poor weight gain and one child with isolated delayed speech and learning difficulties.

PMID: 39251934 reports 2 individuals from 1 consanguineous family with a homozygous TKFC missense variant presenting with severe skeletal abnormalities, fetal cerebral hypoplasia,
fetal reduced movements, liver dysfunction, and fatal hypertrophic cardiomyopathy. They were also homozygous for a TYR LoF variant.
Sources: Literature
Cardiomyopathy_Paediatric v1.65 NAA10 Rylee Peters Marked gene: NAA10 as ready
Cardiomyopathy_Paediatric v1.65 NAA10 Rylee Peters Gene: naa10 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.65 NAA10 Rylee Peters Classified gene: NAA10 as Green List (high evidence)
Cardiomyopathy_Paediatric v1.65 NAA10 Rylee Peters Gene: naa10 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.64 NAA10 Rylee Peters gene: NAA10 was added
gene: NAA10 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: NAA10 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: NAA10 were set to 40304357; 40234403; 38335407; 37441566; 37130971; 33335012; 32864149
Phenotypes for gene: NAA10 were set to NAA10-related syndrome, MONDO:0100124
Review for gene: NAA10 was set to GREEN
Added comment: NAA10-related neurodevelopmental syndrome phenotypic spectrum includes variable levels of intellectual disability, delayed milestones, autism spectrum disorder, craniofacial dysmorphology, cardiac anomalies, seizures, and visual abnormalities. Multiple families also reported with early‑onset cardiomyopathy, predominantly hypertrophic cardiopmyopathy phenotype.
Sources: Literature
Congenital Heart Defect v1.28 NAA10 Rylee Peters Marked gene: NAA10 as ready
Congenital Heart Defect v1.28 NAA10 Rylee Peters Gene: naa10 has been classified as Green List (High Evidence).
Congenital Heart Defect v1.28 NAA10 Rylee Peters Classified gene: NAA10 as Green List (high evidence)
Congenital Heart Defect v1.28 NAA10 Rylee Peters Gene: naa10 has been classified as Green List (High Evidence).
Congenital Heart Defect v1.27 NAA10 Rylee Peters gene: NAA10 was added
gene: NAA10 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: NAA10 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: NAA10 were set to 37130971
Phenotypes for gene: NAA10 were set to NAA10-related syndrome MONDO:0100124
Review for gene: NAA10 was set to GREEN
Added comment: PMID: 37130971 – Cohort of individuals with NAA10-related neurodevelopmental syndrome. Phenotypic spectrum includes variable levels of intellectual disability, delayed milestones, autism spectrum disorder, craniofacial dysmorphology, cardiac anomalies, seizures, and visual abnormalities. Congenital heart defects including (ASD, VSD) occur in >10 individuals.
Sources: Literature
Cardiomyopathy_Paediatric v1.63 POPDC2 Rylee Peters Marked gene: POPDC2 as ready
Cardiomyopathy_Paediatric v1.63 POPDC2 Rylee Peters Gene: popdc2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.63 POPDC2 Rylee Peters Classified gene: POPDC2 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.63 POPDC2 Rylee Peters Gene: popdc2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.62 POPDC2 Rylee Peters gene: POPDC2 was added
gene: POPDC2 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: POPDC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POPDC2 were set to 41456958; 40409267
Phenotypes for gene: POPDC2 were set to Cardiac conduction disease with or without cardiomyopathy 2, MIM# 621367
Review for gene: POPDC2 was set to AMBER
Added comment: Multiple families reported with cardiac conduction and hypertrophic cardiomyopathy (rated GREEN).
AMBER rating given to this panel as there are only 2 reports of paediatric onset of HCM and cardiac conduction disorder (PMIDs: 41456958, 40409267).
Sources: Literature
Fetal anomalies v2.41 CDK20 Zornitza Stark Marked gene: CDK20 as ready
Fetal anomalies v2.41 CDK20 Zornitza Stark Gene: cdk20 has been classified as Green List (High Evidence).
Clefting disorders v1.20 CDK20 Zornitza Stark Marked gene: CDK20 as ready
Clefting disorders v1.20 CDK20 Zornitza Stark Gene: cdk20 has been classified as Green List (High Evidence).
Polydactyly v1.15 CDK20 Zornitza Stark Marked gene: CDK20 as ready
Polydactyly v1.15 CDK20 Zornitza Stark Gene: cdk20 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v1.4 CDK20 Zornitza Stark Marked gene: CDK20 as ready
Hydrocephalus_Ventriculomegaly v1.4 CDK20 Zornitza Stark Gene: cdk20 has been classified as Green List (High Evidence).
Ciliopathies v2.10 CDK20 Zornitza Stark Marked gene: CDK20 as ready
Ciliopathies v2.10 CDK20 Zornitza Stark Gene: cdk20 has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v2.4 CDK20 Zornitza Stark Marked gene: CDK20 as ready
Anophthalmia_Microphthalmia_Coloboma v2.4 CDK20 Zornitza Stark Gene: cdk20 has been classified as Green List (High Evidence).
Polydactyly v1.15 Zornitza Stark Copied gene CDK20 from panel Mendeliome
Polydactyly v1.15 CDK20 Zornitza Stark gene: CDK20 was added
gene: CDK20 was added to Polydactyly. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CDK20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK20 were set to 42409022
Phenotypes for gene: CDK20 were set to Ciliopathy, MONDO:0005308, CDK20-related
Hydrocephalus_Ventriculomegaly v1.4 Zornitza Stark Copied gene CDK20 from panel Mendeliome
Hydrocephalus_Ventriculomegaly v1.4 CDK20 Zornitza Stark gene: CDK20 was added
gene: CDK20 was added to Hydrocephalus_Ventriculomegaly. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CDK20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK20 were set to 42409022
Phenotypes for gene: CDK20 were set to Ciliopathy, MONDO:0005308, CDK20-related
Fetal anomalies v2.41 Zornitza Stark Copied gene CDK20 from panel Mendeliome
Fetal anomalies v2.41 CDK20 Zornitza Stark gene: CDK20 was added
gene: CDK20 was added to Fetal anomalies. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CDK20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK20 were set to 42409022
Phenotypes for gene: CDK20 were set to Ciliopathy, MONDO:0005308, CDK20-related
Clefting disorders v1.20 Zornitza Stark Copied gene CDK20 from panel Mendeliome
Clefting disorders v1.20 CDK20 Zornitza Stark gene: CDK20 was added
gene: CDK20 was added to Clefting disorders. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CDK20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK20 were set to 42409022
Phenotypes for gene: CDK20 were set to Ciliopathy, MONDO:0005308, CDK20-related
Ciliopathies v2.10 Zornitza Stark Copied gene CDK20 from panel Mendeliome
Ciliopathies v2.10 CDK20 Zornitza Stark gene: CDK20 was added
gene: CDK20 was added to Ciliopathies. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CDK20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK20 were set to 42409022
Phenotypes for gene: CDK20 were set to Ciliopathy, MONDO:0005308, CDK20-related
Anophthalmia_Microphthalmia_Coloboma v2.4 Zornitza Stark Copied gene CDK20 from panel Mendeliome
Anophthalmia_Microphthalmia_Coloboma v2.4 CDK20 Zornitza Stark gene: CDK20 was added
gene: CDK20 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CDK20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK20 were set to 42409022
Phenotypes for gene: CDK20 were set to Ciliopathy, MONDO:0005308, CDK20-related
Mendeliome v2.390 CDK20 Zornitza Stark Marked gene: CDK20 as ready
Mendeliome v2.390 CDK20 Zornitza Stark Gene: cdk20 has been classified as Green List (High Evidence).
Mendeliome v2.390 CDK20 Zornitza Stark Classified gene: CDK20 as Green List (high evidence)
Mendeliome v2.390 CDK20 Zornitza Stark Gene: cdk20 has been classified as Green List (High Evidence).
Mendeliome v2.389 CDK20 Zornitza Stark gene: CDK20 was added
gene: CDK20 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CDK20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK20 were set to 42409022
Phenotypes for gene: CDK20 were set to Ciliopathy, MONDO:0005308, CDK20-related
Review for gene: CDK20 was set to GREEN
Added comment: Seven individuals from five unrelated families with bi-allelic variants in CDK20 and an overlapping phenotype of ventriculomegaly or hydrocephalus, midline brain anomalies, abnormal nose, midline cleft lip and/or palate, cryptophthalmos or anophthalmia, postaxial polydactyly, and a sandal toe gap. Immunoblot analysis of fibroblasts derived from two affected fetuses with a homozygous CDK20 c.687+6T>C (p.?) variant demonstrated reduced CDK20 levels. Fibroblasts derived from these affected fetuses were also significantly deficient in cilium formation and function, with abnormal cilium morphology and significantly decreased Hedgehog responsiveness.
Sources: Literature
Fetal anomalies v2.40 DMRTA2 Zornitza Stark Marked gene: DMRTA2 as ready
Fetal anomalies v2.40 DMRTA2 Zornitza Stark Gene: dmrta2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.67 DMRTA2 Zornitza Stark Marked gene: DMRTA2 as ready
Intellectual disability syndromic and non-syndromic v2.67 DMRTA2 Zornitza Stark Gene: dmrta2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.67 Zornitza Stark Copied gene DMRTA2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.67 DMRTA2 Zornitza Stark gene: DMRTA2 was added
gene: DMRTA2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: DMRTA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DMRTA2 were set to 40541527; 26757254
Phenotypes for gene: DMRTA2 were set to Microcephaly, MONDO:0001149, DMRTA2-related
Fetal anomalies v2.40 Zornitza Stark Copied gene DMRTA2 from panel Mendeliome
Fetal anomalies v2.40 DMRTA2 Zornitza Stark gene: DMRTA2 was added
gene: DMRTA2 was added to Fetal anomalies. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: DMRTA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DMRTA2 were set to 40541527; 26757254
Phenotypes for gene: DMRTA2 were set to Microcephaly, MONDO:0001149, DMRTA2-related
Mendeliome v2.388 DMRTA2 Zornitza Stark Classified gene: DMRTA2 as Amber List (moderate evidence)
Mendeliome v2.388 DMRTA2 Zornitza Stark Gene: dmrta2 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.387 DMRTA2 Zornitza Stark changed review comment from: Single family reported with three affected siblings and bi-allelic LoF variant. Newly published functional data but no further reports.
Sources: Literature; to: Two families reported: PMID 26757254: two siblings from a Bedouin family, with hmz variant 1197delG. Both presented antenatally with abnormal imaging. Third sibling also likely affected in utero but not tested.
PMID 40541527: reports 3 members of a consanguineous Pakistani family, born in different sibships. Hmz missense variant R116P identified. Clinical features included: global developmental delay, dysarthria, muscle atrophy, aggressive behavior, and peripheral neuropathy as well as microcephaly.
Sources: Literature
Mendeliome v2.387 DMRTA2 Zornitza Stark edited their review of gene: DMRTA2: Changed rating: AMBER
Microcephaly v2.10 DMRTA2 Zornitza Stark Classified gene: DMRTA2 as Amber List (moderate evidence)
Microcephaly v2.10 DMRTA2 Zornitza Stark Gene: dmrta2 has been classified as Amber List (Moderate Evidence).
Microcephaly v2.9 DMRTA2 Zornitza Stark edited their review of gene: DMRTA2: Changed rating: AMBER
Microcephaly v2.9 DMRTA2 Zornitza Stark changed review comment from: Single family reported with three affected siblings and bi-allelic LoF variant. Newly published functional data but no further reports.
Sources: Literature; to: Two families reported:
PMID 26757254: two siblings from a Bedouin family, with hmz variant 1197delG. Both presented antenatally with abnormal imaging. Third sibling also likely affected in utero but not tested.
PMID 40541527: reports 3 members of a consanguineous Pakistani family, born in different sibships. Hmz missense variant R116P identified. Clinical features included: global developmental delay, dysarthria, muscle atrophy, aggressive behavior, and peripheral neuropathy as well as microcephaly.

Sources: Literature
Intellectual disability syndromic and non-syndromic v2.66 ELAVL2 Zornitza Stark Marked gene: ELAVL2 as ready
Intellectual disability syndromic and non-syndromic v2.66 ELAVL2 Zornitza Stark Gene: elavl2 has been classified as Green List (High Evidence).
Genetic Epilepsy v2.31 ELAVL2 Zornitza Stark Marked gene: ELAVL2 as ready
Genetic Epilepsy v2.31 ELAVL2 Zornitza Stark Gene: elavl2 has been classified as Green List (High Evidence).
Autism v1.14 ELAVL2 Zornitza Stark Marked gene: ELAVL2 as ready
Autism v1.14 ELAVL2 Zornitza Stark Gene: elavl2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.66 Zornitza Stark Copied gene ELAVL2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.66 ELAVL2 Zornitza Stark gene: ELAVL2 was added
gene: ELAVL2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ELAVL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ELAVL2 were set to 42556336
Phenotypes for gene: ELAVL2 were set to Neurodevelopmental disorder, MONDO:0700092, ELAVL2-related
Genetic Epilepsy v2.31 Zornitza Stark Copied gene ELAVL2 from panel Mendeliome
Genetic Epilepsy v2.31 ELAVL2 Zornitza Stark gene: ELAVL2 was added
gene: ELAVL2 was added to Genetic Epilepsy. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ELAVL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ELAVL2 were set to 42556336
Phenotypes for gene: ELAVL2 were set to Neurodevelopmental disorder, MONDO:0700092, ELAVL2-related
Autism v1.14 Zornitza Stark Copied gene ELAVL2 from panel Mendeliome
Autism v1.14 ELAVL2 Zornitza Stark gene: ELAVL2 was added
gene: ELAVL2 was added to Autism. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ELAVL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ELAVL2 were set to 42556336
Phenotypes for gene: ELAVL2 were set to Neurodevelopmental disorder, MONDO:0700092, ELAVL2-related
Mendeliome v2.387 ELAVL2 Zornitza Stark Marked gene: ELAVL2 as ready
Mendeliome v2.387 ELAVL2 Zornitza Stark Gene: elavl2 has been classified as Green List (High Evidence).
Mendeliome v2.387 ELAVL2 Zornitza Stark Classified gene: ELAVL2 as Green List (high evidence)
Mendeliome v2.387 ELAVL2 Zornitza Stark Gene: elavl2 has been classified as Green List (High Evidence).
Mendeliome v2.386 ELAVL2 Zornitza Stark gene: ELAVL2 was added
gene: ELAVL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ELAVL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ELAVL2 were set to 42556336
Phenotypes for gene: ELAVL2 were set to Neurodevelopmental disorder, MONDO:0700092, ELAVL2-related
Review for gene: ELAVL2 was set to GREEN
Added comment: 16 individuals with a neurodevelopmental disorder and de novo heterozygous variants in ELAVL2 reported. ELAVL2 encodes an RNA-binding protein. The cohort presented with developmental delay, intellectual disability, autism spectrum disorder, seizures, sleep problems, sensory processing issues, emotional instability, and difficulty with socialization. Over half of the variants reported are LoF, supporting haploinsufficiency as the mechanism of disease. Drosophila loss-of-function models provide further independent evidence for a conserved role in the regulation of seizure-like behavior, sensory processing, and sleep. Some of the missense variants are also shown to be deleterious, leading to decreased protein levels.
Sources: Literature
Disorders of immune dysregulation v2.5 ISCA-37433-Loss Krithika Murali Marked Region: ISCA-37433-Loss as ready
Disorders of immune dysregulation v2.5 ISCA-37433-Loss Krithika Murali Region: isca-37433-loss has been classified as Green List (High Evidence).
Disorders of immune dysregulation v2.5 Krithika Murali Copied Region ISCA-37433-Loss from panel Common deletion and duplication syndromes
Disorders of immune dysregulation v2.5 ISCA-37433-Loss Krithika Murali Region: ISCA-37433-Loss was added
Region: ISCA-37433-Loss was added to Disorders of immune dysregulation. Sources: Expert Review Green,Expert list
Mode of inheritance for Region: ISCA-37433-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for Region: ISCA-37433-Loss were set to DiGeorge syndrome MIM#188400
Deafness_IsolatedAndComplex v2.5 ISCA-37392-Loss Krithika Murali Marked Region: ISCA-37392-Loss as ready
Deafness_IsolatedAndComplex v2.5 ISCA-37392-Loss Krithika Murali Region: isca-37392-loss has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v2.5 Krithika Murali Copied Region ISCA-37392-Loss from panel Common deletion and duplication syndromes
Deafness_IsolatedAndComplex v2.5 ISCA-37392-Loss Krithika Murali Region: ISCA-37392-Loss was added
Region: ISCA-37392-Loss was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Expert Review
SV/CNV tags were added to Region: ISCA-37392-Loss.
Mode of inheritance for Region: ISCA-37392-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: ISCA-37392-Loss were set to 20301427
Phenotypes for Region: ISCA-37392-Loss were set to Williams-Beuren syndrome, MIM# 194050; intellectual disability; growth retardation; cardiovascular disease
Skeletal dysplasia v1.83 FAR1 chirag patel Marked gene: FAR1 as ready
Skeletal dysplasia v1.83 FAR1 chirag patel Gene: far1 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.83 FAR1 chirag patel Mode of inheritance for gene: FAR1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.82 FAR1 chirag patel Publications for gene: FAR1 were set to 25439727; 33239752
Skeletal dysplasia v1.81 FAR1 chirag patel Phenotypes for gene: FAR1 were changed from Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154; Cataracts, spastic paraparesis, and speech delay, MIM#619338 to Fatty acyl-CoA reductase 1 deficiency MONDO:0014510
Skeletal dysplasia v1.80 FAR1 chirag patel Classified gene: FAR1 as Red List (low evidence)
Skeletal dysplasia v1.80 FAR1 chirag patel Gene: far1 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.79 FAR1 chirag patel reviewed gene: FAR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Fatty acyl-CoA reductase 1 deficiency MONDO:0014510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.79 chirag patel Copied gene FAR1 from panel Mendeliome
Skeletal dysplasia v1.79 FAR1 chirag patel gene: FAR1 was added
gene: FAR1 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FAR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: FAR1 were set to 25439727; 33239752
Phenotypes for gene: FAR1 were set to Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154; Cataracts, spastic paraparesis, and speech delay, MIM#619338
Hand and foot malformations v1.5 CCNQ chirag patel Marked gene: CCNQ as ready
Hand and foot malformations v1.5 CCNQ chirag patel Gene: ccnq has been classified as Green List (High Evidence).
Hand and foot malformations v1.5 CCNQ chirag patel Phenotypes for gene: CCNQ were changed from STAR syndrome 300707 to syndactyly-telecanthus-anogenital and renal malformations syndrome MONDO:0010408
Hand and foot malformations v1.4 CCNQ chirag patel Publications for gene: CCNQ were set to
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.13 CCNQ chirag patel Phenotypes for gene: CCNQ were changed from STAR syndrome, MIM# 300707 to syndactyly-telecanthus-anogenital and renal malformations syndrome MONDO:0010408
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.12 CCNQ chirag patel Publications for gene: CCNQ were set to 28225384; 18297069
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.11 CCNQ chirag patel Mode of inheritance for gene: CCNQ 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)
Hand and foot malformations v1.3 chirag patel Added reviews for gene CCNQ from panel Skeletal dysplasia
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.10 chirag patel Added reviews for gene CCNQ from panel Skeletal dysplasia
Skeletal dysplasia v1.78 CCNQ chirag patel Publications for gene: CCNQ were set to
Skeletal dysplasia v1.77 CCNQ chirag patel Marked gene: CCNQ as ready
Skeletal dysplasia v1.77 CCNQ chirag patel Gene: ccnq has been classified as Green List (High Evidence).
Skeletal dysplasia v1.77 CCNQ chirag patel Phenotypes for gene: CCNQ were changed from STAR syndrome 300707; STAR syndrome 300707 to syndactyly-telecanthus-anogenital and renal malformations syndrome MONDO:0010408
Skeletal dysplasia v1.76 B9D2 chirag patel Marked gene: B9D2 as ready
Skeletal dysplasia v1.76 B9D2 chirag patel Gene: b9d2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.76 B9D2 chirag patel Publications for gene: B9D2 were set to
Skeletal dysplasia v1.75 B9D2 chirag patel Phenotypes for gene: B9D2 were changed from Meckel syndrome 10 614175 to Joubert syndrome 34, MIM#614175; Meckel syndrome 10, MIM#614175
Skeletal dysplasia v1.74 B9D2 chirag patel Classified gene: B9D2 as Green List (high evidence)
Skeletal dysplasia v1.74 B9D2 chirag patel Gene: b9d2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.73 chirag patel Added reviews for gene B9D2 from panel Polydactyly
Skeletal dysplasia v1.72 AKT3 chirag patel Marked gene: AKT3 as ready
Skeletal dysplasia v1.72 AKT3 chirag patel Gene: akt3 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.72 chirag patel Copied gene AKT3 from panel Mendeliome
Skeletal dysplasia v1.72 AKT3 chirag patel gene: AKT3 was added
gene: AKT3 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: AKT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AKT3 were set to PMID: 22729224
Phenotypes for gene: AKT3 were set to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 MIM#615937
Mode of pathogenicity for gene: AKT3 was set to Other
Polydactyly v1.14 AKT3 chirag patel Mode of pathogenicity for gene: AKT3 was changed from to Other
Polydactyly v1.13 AKT3 chirag patel Publications for gene: AKT3 were set to
Polydactyly v1.12 chirag patel Added reviews for gene AKT3 from panel Mendeliome
Polydactyly v1.11 AHI1 chirag patel Classified gene: AHI1 as Red List (low evidence)
Polydactyly v1.11 AHI1 chirag patel Gene: ahi1 has been classified as Red List (Low Evidence).
Polydactyly v1.10 AHI1 chirag patel reviewed gene: AHI1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Joubert syndrome 3, MIM# 608629; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.71 AHI1 chirag patel reviewed gene: AHI1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v1.71 CENPE chirag patel Marked gene: CENPE as ready
Skeletal dysplasia v1.71 CENPE chirag patel Gene: cenpe has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.71 CENPE chirag patel changed review comment from: skeletal findings were not characteristic of a specific bone dysplasia; to: skeletal findings are not characteristic of a specific bone dysplasia
Skeletal dysplasia v1.71 CENPE chirag patel reviewed gene: CENPE: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v1.71 chirag patel Copied gene CENPE from panel Mendeliome
Skeletal dysplasia v1.71 CENPE chirag patel gene: CENPE was added
gene: CENPE was added to Skeletal dysplasia. Sources: Expert Review Red,Victorian Clinical Genetics Services
Mode of inheritance for gene: CENPE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPE were set to 24748105; 30086807
Phenotypes for gene: CENPE were set to Microcephaly 13, primary, autosomal recessive (MIM#616051)
Fetal anomalies v2.39 ZIC1 chirag patel changed review comment from: 5 families with heterozygous mutations located in the final (third) exon of ZIC1 who have a distinct phenotype in which severe craniosynostosis, specifically involving the coronal sutures, and variable learning disability are the most characteristic features. The location of the nonsense mutations predicts escape of mutant ZIC1 transcripts from nonsense-mediated decay, which was confirmed in a cell line from an affected individual. Both nonsense and missense mutations are associated with altered and/or enhanced expression of a target gene, engrailed-2, in a Xenopus embryo assay. Analysis of mouse embryos revealed a localized domain of Zic1 expression at embryonic days 11.5-12.5 in a region overlapping the supraorbital regulatory center, which patterns the coronal suture.

2 sibs with BAIDCS, Vandervore et al. (2018) identified heterozygosity for a frameshift mutation in the ZIC1 gene. Neither parent had evidence of the mutation by whole-exome sequencing, suggesting that gonadal mosaicism for the mutation was present in one of the parents. Expression of the mutated allele was detected in patient fibroblasts by RT-PCR, evidence that the mutant mRNA did not undergo nonsense-mediated decay and probably generates an abnormal protein.


Also heterozygous deletions of ZIC1 on chromosome 3q25.1 are associated with Dandy-Walker malformation of the cerebellum. Loss of the orthologous Zic1 gene in the mouse causes cerebellar hypoplasia and vertebral defects.
Sources: Expert list; to: Individuals with BAIDCS have microcephaly, brain anomalies (esp corpus callosum), intellectual disability (moderate to severe), and bicoronal synostosis.

5 families with heterozygous mutations located in the final (third) exon of ZIC1 who have a distinct phenotype in which severe craniosynostosis, specifically involving the coronal sutures, and variable learning disability are the most characteristic features. The location of the nonsense mutations predicts escape of mutant ZIC1 transcripts from nonsense-mediated decay, which was confirmed in a cell line from an affected individual. Both nonsense and missense mutations are associated with altered and/or enhanced expression of a target gene, engrailed-2, in a Xenopus embryo assay. Analysis of mouse embryos revealed a localized domain of Zic1 expression at embryonic days 11.5-12.5 in a region overlapping the supraorbital regulatory center, which patterns the coronal suture.

2 sibs with BAIDCS, Vandervore et al. (2018) identified heterozygosity for a frameshift mutation in the ZIC1 gene. Neither parent had evidence of the mutation by whole-exome sequencing, suggesting that gonadal mosaicism for the mutation was present in one of the parents. Expression of the mutated allele was detected in patient fibroblasts by RT-PCR, evidence that the mutant mRNA did not undergo nonsense-mediated decay and probably generates an abnormal protein.


Also heterozygous deletions of ZIC1 on chromosome 3q25.1 are associated with Dandy-Walker malformation of the cerebellum. Loss of the orthologous Zic1 gene in the mouse causes cerebellar hypoplasia and vertebral defects.
Sources: Expert list
Callosome v1.17 ZIC1 chirag patel Marked gene: ZIC1 as ready
Callosome v1.17 ZIC1 chirag patel Gene: zic1 has been classified as Green List (High Evidence).
Callosome v1.17 ZIC1 chirag patel Phenotypes for gene: ZIC1 were changed from to Structural brain anomalies with impaired intellectual development and craniosynostosis; OMIM #618736
Callosome v1.16 ZIC1 chirag patel Publications for gene: ZIC1 were set to
Callosome v1.15 ZIC1 chirag patel Mode of inheritance for gene: ZIC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v2.9 ZIC1 chirag patel Marked gene: ZIC1 as ready
Microcephaly v2.9 ZIC1 chirag patel Gene: zic1 has been classified as Green List (High Evidence).
Microcephaly v2.9 chirag patel Copied gene ZIC1 from panel Intellectual disability syndromic and non-syndromic
Microcephaly v2.9 ZIC1 chirag patel gene: ZIC1 was added
gene: ZIC1 was added to Microcephaly. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ZIC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZIC1 were set to PMID: 26340333, 30391508
Phenotypes for gene: ZIC1 were set to Structural brain anomalies with impaired intellectual development and craniosynostosis; OMIM #618736 
Fetal anomalies v2.39 chirag patel Added reviews for gene ZIC1 from panel Intellectual disability syndromic and non-syndromic
Craniosynostosis v2.4 chirag patel Added reviews for gene ZIC1 from panel Intellectual disability syndromic and non-syndromic
Callosome v1.14 chirag patel Added reviews for gene ZIC1 from panel Intellectual disability syndromic and non-syndromic
Intellectual disability syndromic and non-syndromic v2.65 ZIC1 chirag patel changed review comment from: 5 families with heterozygous mutations located in the final (third) exon of ZIC1 who have a distinct phenotype in which severe craniosynostosis, specifically involving the coronal sutures, and variable learning disability are the most characteristic features. The location of the nonsense mutations predicts escape of mutant ZIC1 transcripts from nonsense-mediated decay, which was confirmed in a cell line from an affected individual. Both nonsense and missense mutations are associated with altered and/or enhanced expression of a target gene, engrailed-2, in a Xenopus embryo assay. Analysis of mouse embryos revealed a localized domain of Zic1 expression at embryonic days 11.5-12.5 in a region overlapping the supraorbital regulatory center, which patterns the coronal suture.

2 sibs with BAIDCS, Vandervore et al. (2018) identified heterozygosity for a frameshift mutation in the ZIC1 gene. Neither parent had evidence of the mutation by whole-exome sequencing, suggesting that gonadal mosaicism for the mutation was present in one of the parents. Expression of the mutated allele was detected in patient fibroblasts by RT-PCR, evidence that the mutant mRNA did not undergo nonsense-mediated decay and probably generates an abnormal protein.


Also heterozygous deletions of ZIC1 on chromosome 3q25.1 are associated with Dandy-Walker malformation of the cerebellum. Loss of the orthologous Zic1 gene in the mouse causes cerebellar hypoplasia and vertebral defects.
Sources: Expert list; to: Individuals with BAIDCS have microcephaly, brain anomalies (esp corpus callosum), intellectual disability (moderate to severe), and bicoronal synostosis.

5 families with heterozygous mutations located in the final (third) exon of ZIC1 who have a distinct phenotype in which severe craniosynostosis, specifically involving the coronal sutures, and variable learning disability are the most characteristic features. The location of the nonsense mutations predicts escape of mutant ZIC1 transcripts from nonsense-mediated decay, which was confirmed in a cell line from an affected individual. Both nonsense and missense mutations are associated with altered and/or enhanced expression of a target gene, engrailed-2, in a Xenopus embryo assay. Analysis of mouse embryos revealed a localized domain of Zic1 expression at embryonic days 11.5-12.5 in a region overlapping the supraorbital regulatory center, which patterns the coronal suture.

2 sibs with BAIDCS, Vandervore et al. (2018) identified heterozygosity for a frameshift mutation in the ZIC1 gene. Neither parent had evidence of the mutation by whole-exome sequencing, suggesting that gonadal mosaicism for the mutation was present in one of the parents. Expression of the mutated allele was detected in patient fibroblasts by RT-PCR, evidence that the mutant mRNA did not undergo nonsense-mediated decay and probably generates an abnormal protein.


Also heterozygous deletions of ZIC1 on chromosome 3q25.1 are associated with Dandy-Walker malformation of the cerebellum. Loss of the orthologous Zic1 gene in the mouse causes cerebellar hypoplasia and vertebral defects.
Sources: Expert list
Fetal anomalies v2.38 VCP chirag patel Marked gene: VCP as ready
Fetal anomalies v2.38 VCP chirag patel Gene: vcp has been classified as Green List (High Evidence).
Hand and foot malformations v1.2 VCP chirag patel Marked gene: VCP as ready
Hand and foot malformations v1.2 VCP chirag patel Gene: vcp has been classified as Green List (High Evidence).
Pulmonary Arterial Hypertension v2.3 VCP chirag patel Marked gene: VCP as ready
Pulmonary Arterial Hypertension v2.3 VCP chirag patel Gene: vcp has been classified as Green List (High Evidence).
Congenital Heart Defect v1.26 VCP chirag patel Marked gene: VCP as ready
Congenital Heart Defect v1.26 VCP chirag patel Gene: vcp has been classified as Green List (High Evidence).
Mendeliome v2.385 VCP chirag patel Marked gene: VCP as ready
Mendeliome v2.385 VCP chirag patel Gene: vcp has been classified as Green List (High Evidence).
Mendeliome v2.385 VCP chirag patel Phenotypes for gene: VCP were changed from Neurodevelopmental disorder (MONDO: 0700092), VCP-related to Neurodevelopmental disorder (MONDO: 0700092), VCP-related; Adams-Oliver syndrome MONDO:0007034, VCP-related
Mendeliome v2.384 VCP chirag patel Publications for gene: VCP were set to PMID: 37883978, 41979051
Mendeliome v2.383 VCP chirag patel Publications for gene: VCP were set to PMID: 37883978
Pulmonary Arterial Hypertension v2.3 chirag patel Copied gene VCP from panel Skeletal dysplasia
Pulmonary Arterial Hypertension v2.3 VCP chirag patel gene: VCP was added
gene: VCP was added to Pulmonary Arterial Hypertension. Sources: Expert Review Green,Literature
Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCP were set to 41979051
Phenotypes for gene: VCP were set to Adams-Oliver syndrome MONDO:0007034, VCP-related
Mendeliome v2.382 chirag patel Added reviews for gene VCP from panel Skeletal dysplasia
Hand and foot malformations v1.2 chirag patel Copied gene VCP from panel Skeletal dysplasia
Hand and foot malformations v1.2 VCP chirag patel gene: VCP was added
gene: VCP was added to Hand and foot malformations. Sources: Expert Review Green,Literature
Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCP were set to 41979051
Phenotypes for gene: VCP were set to Adams-Oliver syndrome MONDO:0007034, VCP-related
Fetal anomalies v2.38 chirag patel Copied gene VCP from panel Skeletal dysplasia
Fetal anomalies v2.38 VCP chirag patel gene: VCP was added
gene: VCP was added to Fetal anomalies. Sources: Expert Review Green,Literature
Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCP were set to 41979051
Phenotypes for gene: VCP were set to Adams-Oliver syndrome MONDO:0007034, VCP-related
Congenital Heart Defect v1.26 chirag patel Copied gene VCP from panel Skeletal dysplasia
Congenital Heart Defect v1.26 VCP chirag patel gene: VCP was added
gene: VCP was added to Congenital Heart Defect. Sources: Expert Review Green,Literature
Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCP were set to 41979051
Phenotypes for gene: VCP were set to Adams-Oliver syndrome MONDO:0007034, VCP-related
Skeletal dysplasia v1.70 VCP chirag patel changed review comment from: Adams-Oliver syndrome (AOS) is a rare developmental disorder defined by the combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects (e.g., amputations, syndactyly, brachydactyly, or oligodactyly).

PMID 41979051 reports 7 families with Adams-Oliver syndrome and rare heterozygous missense VCP variants (4 de novo, 2 inherited from affected parent, 1 presumed inherited). Variant‑specific functional assays support pathogenicity as they were hypermorphic for ATPase activity. Pulmonary hypertension seen in 5/7 families. 3 families had features of multisystem proteinopathy 1 (MSP1) - progressive myopathy (2 families), neuropathy (1 family), lytic bone lesions (1 family), and frontotemporal dementia (1 family) - and had offspring with AOS and severe or fatal PH, suggesting these conditions form a spectrum of VCP-related disease.
Sources: Literature; to: Adams-Oliver syndrome (AOS) is a rare developmental disorder defined by the combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects (e.g., amputations, syndactyly, brachydactyly, or oligodactyly).

PMID 41979051 reports 7 families with Adams-Oliver syndrome and rare heterozygous missense VCP variants (4 de novo, 2 inherited from affected parent, 1 presumed inherited). Variant‑specific functional assays support pathogenicity as they were hypermorphic for ATPase activity. Congenital heart defects seen in 6/7 and pulmonary hypertension seen in 5/7 families. 3 families had features of multisystem proteinopathy 1 (MSP1) - progressive myopathy (2 families), neuropathy (1 family), lytic bone lesions (1 family), and frontotemporal dementia (1 family) - and had offspring with AOS and severe or fatal PH, suggesting these conditions form a spectrum of VCP-related disease.
Sources: Literature
Skeletal dysplasia v1.70 VCP chirag patel Marked gene: VCP as ready
Skeletal dysplasia v1.70 VCP chirag patel Gene: vcp has been classified as Green List (High Evidence).
Skeletal dysplasia v1.70 VCP chirag patel Classified gene: VCP as Green List (high evidence)
Skeletal dysplasia v1.70 VCP chirag patel Gene: vcp has been classified as Green List (High Evidence).
Skeletal dysplasia v1.69 VCP chirag patel gene: VCP was added
gene: VCP was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCP were set to 41979051
Phenotypes for gene: VCP were set to Adams-Oliver syndrome MONDO:0007034, VCP-related
Review for gene: VCP was set to GREEN
Added comment: Adams-Oliver syndrome (AOS) is a rare developmental disorder defined by the combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects (e.g., amputations, syndactyly, brachydactyly, or oligodactyly).

PMID 41979051 reports 7 families with Adams-Oliver syndrome and rare heterozygous missense VCP variants (4 de novo, 2 inherited from affected parent, 1 presumed inherited). Variant‑specific functional assays support pathogenicity as they were hypermorphic for ATPase activity. Pulmonary hypertension seen in 5/7 families. 3 families had features of multisystem proteinopathy 1 (MSP1) - progressive myopathy (2 families), neuropathy (1 family), lytic bone lesions (1 family), and frontotemporal dementia (1 family) - and had offspring with AOS and severe or fatal PH, suggesting these conditions form a spectrum of VCP-related disease.
Sources: Literature
Pulmonary Arterial Hypertension v2.2 ARHGAP31 chirag patel Marked gene: ARHGAP31 as ready
Pulmonary Arterial Hypertension v2.2 ARHGAP31 chirag patel Gene: arhgap31 has been classified as Green List (High Evidence).
Pulmonary Arterial Hypertension v2.2 chirag patel Copied gene ARHGAP31 from panel Mendeliome
Pulmonary Arterial Hypertension v2.2 ARHGAP31 chirag patel gene: ARHGAP31 was added
gene: ARHGAP31 was added to Pulmonary Arterial Hypertension. Sources: Expert Review Green,Genetic Health Queensland,Victorian Clinical Genetics Services,Victorian Clinical Genetics Services
Mode of inheritance for gene: ARHGAP31 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ARHGAP31 were set to PMID: 33655927; 29924900
Phenotypes for gene: ARHGAP31 were set to Adams-Oliver syndrome 1, MIM#100300
Mendeliome v2.381 ARHGAP31 chirag patel reviewed gene: ARHGAP31: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Adams-Oliver syndrome 1, MIM#100300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v1.25 ARHGAP31 chirag patel Marked gene: ARHGAP31 as ready
Congenital Heart Defect v1.25 ARHGAP31 chirag patel Gene: arhgap31 has been classified as Green List (High Evidence).
Congenital Heart Defect v1.25 ARHGAP31 chirag patel Classified gene: ARHGAP31 as Green List (high evidence)
Congenital Heart Defect v1.25 ARHGAP31 chirag patel Gene: arhgap31 has been classified as Green List (High Evidence).
Congenital Heart Defect v1.24 ARHGAP31 chirag patel Source Expert Review was added to ARHGAP31.
Rating Changed from No List (delete) to Red List (low evidence)
Congenital Heart Defect v1.23 ARHGAP31 chirag patel All sources for gene: ARHGAP31 were removed
Congenital Heart Defect v1.22 ARHGAP31 chirag patel reviewed gene: ARHGAP31: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Congenital Heart Defect v1.22 chirag patel Copied gene ARHGAP31 from panel Skeletal dysplasia
Congenital Heart Defect v1.22 ARHGAP31 chirag patel gene: ARHGAP31 was added
gene: ARHGAP31 was added to Congenital Heart Defect. Sources: Expert Review Green,Illumina TruGenome Clinical Sequencing Services,UKGTN,Radboud University Medical Center, Nijmegen,Expert Review Green,NHS GMS,Expert list,Emory Genetics Laboratory,Genetic Health Queensland,Victorian Clinical Genetics Services,Victorian Clinical Genetics Services
Mode of inheritance for gene: ARHGAP31 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARHGAP31 were set to 21565291; 29924900
Phenotypes for gene: ARHGAP31 were set to Adams-Oliver syndrome 1 100300
Mendeliome v2.381 chirag patel Copied gene VCP from panel Macrocephaly_Megalencephaly
Mendeliome v2.381 VCP chirag patel gene: VCP was added
gene: VCP was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCP were set to PMID: 37883978
Phenotypes for gene: VCP were set to Neurodevelopmental disorder (MONDO: 0700092), VCP-related
Macrocephaly_Megalencephaly v1.3 VCP chirag patel Phenotypes for gene: VCP were changed from Neurodevelopmental disorder (MONDO: 0700092) to Neurodevelopmental disorder (MONDO: 0700092), VCP-related
Intellectual disability syndromic and non-syndromic v2.65 VCP chirag patel Phenotypes for gene: VCP were changed from Neurodevelopmental disorder (MONDO: 0700092) to Neurodevelopmental disorder (MONDO: 0700092), VCP-related
Skeletal dysplasia v1.68 SMS chirag patel Marked gene: SMS as ready
Skeletal dysplasia v1.68 SMS chirag patel Gene: sms has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v2.7 SMS chirag patel Marked gene: SMS as ready
Osteogenesis Imperfecta and Osteoporosis v2.7 SMS chirag patel Gene: sms has been classified as Green List (High Evidence).
Skeletal dysplasia v1.68 chirag patel Copied gene SMS from panel Mendeliome
Skeletal dysplasia v1.68 SMS chirag patel gene: SMS was added
gene: SMS was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SMS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SMS were set to 30237987; 34177437; 32838743; 23805436
Phenotypes for gene: SMS were set to Intellectual developmental disorder, X-linked syndromic, Snyder-Robinson type, MIM# 309583; Syndromic X-linked intellectual disability Snyder type, MONDO:0010664
Osteogenesis Imperfecta and Osteoporosis v2.7 chirag patel Copied gene SMS from panel Mendeliome
Osteogenesis Imperfecta and Osteoporosis v2.7 SMS chirag patel gene: SMS was added
gene: SMS was added to Osteogenesis Imperfecta and Osteoporosis. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SMS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SMS were set to 30237987; 34177437; 32838743; 23805436
Phenotypes for gene: SMS were set to Intellectual developmental disorder, X-linked syndromic, Snyder-Robinson type, MIM# 309583; Syndromic X-linked intellectual disability Snyder type, MONDO:0010664
Skeletal dysplasia v1.67 SMO chirag patel Marked gene: SMO as ready
Skeletal dysplasia v1.67 SMO chirag patel Gene: smo has been classified as Green List (High Evidence).
Skeletal dysplasia v1.67 chirag patel Copied gene SMO from panel Congenital Heart Defect
Skeletal dysplasia v1.67 SMO chirag patel gene: SMO was added
gene: SMO was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: SMO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMO were set to 32413283
Phenotypes for gene: SMO were set to Microcephaly, congenital heart disease, polydactyly, aganglionosis; Pallister-Hall-like syndrome , MIM#241800
Fetal anomalies v2.37 SMO chirag patel Publications for gene: SMO were set to 27236920; 24859340
Fetal anomalies v2.36 SMO chirag patel Phenotypes for gene: SMO were changed from Curry-Jones syndrome, somatic mosaic, MIM#601707 to Curry-Jones syndrome, somatic mosaic, MIM#601707; Pallister-Hall-like syndrome, MIM# 241800
Callosome v1.13 SMO chirag patel Mode of pathogenicity for gene: SMO 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
Callosome v1.12 SMO chirag patel Mode of inheritance for gene: SMO was changed from Other to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v1.10 chirag patel Added reviews for gene SMO from panel Anophthalmia_Microphthalmia_Coloboma
Craniosynostosis v2.3 chirag patel Added reviews for gene SMO from panel Anophthalmia_Microphthalmia_Coloboma
Callosome v1.11 chirag patel Added reviews for gene SMO from panel Anophthalmia_Microphthalmia_Coloboma
Anophthalmia_Microphthalmia_Coloboma v2.3 SMO chirag patel reviewed gene: SMO: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Curry-Jones syndrome, somatic mosaic, MIM#601707; Mode of inheritance: None
Polymicrogyria and Schizencephaly v1.4 SMO chirag patel Mode of inheritance for gene: SMO was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Anophthalmia_Microphthalmia_Coloboma v2.3 SMO chirag patel Mode of pathogenicity for gene: SMO 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
Anophthalmia_Microphthalmia_Coloboma v2.2 SMO chirag patel Mode of inheritance for gene: SMO was changed from Other to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.66 SLC25A24 chirag patel reviewed gene: SLC25A24: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v1.66 SLC25A24 chirag patel Marked gene: SLC25A24 as ready
Skeletal dysplasia v1.66 SLC25A24 chirag patel Gene: slc25a24 has been classified as Green List (High Evidence).
Hypertrichosis syndromes v1.6 SLC25A24 chirag patel Phenotypes for gene: SLC25A24 were changed from to FONTAINE PROGEROID SYNDROME, MIM#612289
Hypertrichosis syndromes v1.5 SLC25A24 chirag patel Publications for gene: SLC25A24 were set to
Hypertrichosis syndromes v1.4 SLC25A24 chirag patel Mode of inheritance for gene: SLC25A24 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrichosis syndromes v1.3 SLC25A24 chirag patel Mode of inheritance for gene: SLC25A24 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrichosis syndromes v1.2 SLC25A24 chirag patel Marked gene: SLC25A24 as ready
Hypertrichosis syndromes v1.2 SLC25A24 chirag patel Gene: slc25a24 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.66 chirag patel Copied gene SLC25A24 from panel Fetal anomalies
Skeletal dysplasia v1.66 SLC25A24 chirag patel gene: SLC25A24 was added
gene: SLC25A24 was added to Skeletal dysplasia. Sources: Expert Review Green,Genomics England PanelApp,Genetic Health Queensland
Mode of inheritance for gene: SLC25A24 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC25A24 were set to 29100093; 29100094; 29100094; 31775791; 32732226; 32860237
Phenotypes for gene: SLC25A24 were set to Fontaine progeroid syndrome, MIM#612289
Hypertrichosis syndromes v1.2 chirag patel Added reviews for gene SLC25A24 from panel Fetal anomalies
Skeletal dysplasia v1.65 SGMS2 chirag patel Marked gene: SGMS2 as ready
Skeletal dysplasia v1.65 SGMS2 chirag patel Gene: sgms2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.65 chirag patel Copied gene SGMS2 from panel Osteogenesis Imperfecta and Osteoporosis
Skeletal dysplasia v1.65 SGMS2 chirag patel gene: SGMS2 was added
gene: SGMS2 was added to Skeletal dysplasia. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: SGMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGMS2 were set to 30779713; 32028018
Phenotypes for gene: SGMS2 were set to Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia MIM#126550
Mendeliome v2.380 chirag patel Added reviews for gene SGMS2 from panel Osteogenesis Imperfecta and Osteoporosis
Osteogenesis Imperfecta and Osteoporosis v2.6 SGMS2 chirag patel reviewed gene: SGMS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v1.64 RNU12 chirag patel Publications for gene: RNU12 were set to 34085356; 27863452
Skeletal dysplasia v1.63 RNU12 chirag patel Marked gene: RNU12 as ready
Skeletal dysplasia v1.63 RNU12 chirag patel Gene: rnu12 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.63 chirag patel Copied gene RNU12 from panel Mendeliome
Skeletal dysplasia v1.63 RNU12 chirag patel gene: RNU12 was added
gene: RNU12 was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
non-coding gene tags were added to gene: RNU12.
Mode of inheritance for gene: RNU12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU12 were set to 34085356; 27863452
Phenotypes for gene: RNU12 were set to Craniosynostosis-anal anomalies-porokeratosis syndrome MONDO:0011287
Fetal anomalies v2.35 chirag patel Added reviews for gene RNU12 from panel Mendeliome
Craniosynostosis v2.2 chirag patel Added reviews for gene RNU12 from panel Mendeliome
Mendeliome v2.379 RNU12 chirag patel reviewed gene: RNU12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Craniosynostosis-anal anomalies-porokeratosis syndrome MONDO:0011287; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.379 RNU12 chirag patel Phenotypes for gene: RNU12 were changed from Craniosynostosis-anal anomalies-porokeratosis syndrome MONDO:0011287 to Craniosynostosis-anal anomalies-porokeratosis syndrome MONDO:0011287
Mendeliome v2.379 RNU12 chirag patel Phenotypes for gene: RNU12 were changed from CDAGS syndrome MIM#603116; Craniosynostosis, Delayed closure of the fontanelles, cranial defects, clavicular hypoplasia, Anal and Genitourinary malformations, and Skin manifestations to Craniosynostosis-anal anomalies-porokeratosis syndrome MONDO:0011287
Craniosynostosis v2.1 RNU12 chirag patel Phenotypes for gene: RNU12 were changed from CDAGS syndrome MIM#603116; Craniosynostosis, Delayed closure of the fontanelles, cranial defects, clavicular hypoplasia, Anal and Genitourinary malformations, and Skin manifestations to Craniosynostosis-anal anomalies-porokeratosis syndrome MONDO:0011287
Fetal anomalies v2.34 RNU12 chirag patel Phenotypes for gene: RNU12 were changed from craniosynostosis-anal anomalies-porokeratosis syndrome MONDO:0011287 to Craniosynostosis-anal anomalies-porokeratosis syndrome MONDO:0011287
Fetal anomalies v2.33 RNU12 chirag patel Phenotypes for gene: RNU12 were changed from CDAGS syndrome MIM#603116; Craniosynostosis, Delayed closure of the fontanelles, cranial defects, clavicular hypoplasia, Anal and Genitourinary malformations, and Skin manifestations to craniosynostosis-anal anomalies-porokeratosis syndrome MONDO:0011287
Skeletal dysplasia v1.62 RSPO2 chirag patel Marked gene: RSPO2 as ready
Skeletal dysplasia v1.62 RSPO2 chirag patel Gene: rspo2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.62 chirag patel Copied gene RSPO2 from panel Mendeliome
Skeletal dysplasia v1.62 RSPO2 chirag patel gene: RSPO2 was added
gene: RSPO2 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RSPO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RSPO2 were set to 29769720; 32457899
Phenotypes for gene: RSPO2 were set to Tetraamelia syndrome 2, MIM# 618021
Skeletal dysplasia v1.61 PRRX1 chirag patel Marked gene: PRRX1 as ready
Skeletal dysplasia v1.61 PRRX1 chirag patel Gene: prrx1 has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v2.4 PRRX1 chirag patel Marked gene: PRRX1 as ready
Holoprosencephaly and septo-optic dysplasia v2.4 PRRX1 chirag patel Gene: prrx1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.61 chirag patel Copied gene PRRX1 from panel Mandibulofacial Acrofacial dysostosis
Skeletal dysplasia v1.61 PRRX1 chirag patel gene: PRRX1 was added
gene: PRRX1 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PRRX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PRRX1 were set to 21294718; 22211708; 22674740; 23444262
Phenotypes for gene: PRRX1 were set to Agnathia-otocephaly complex, MIM# 202650
Holoprosencephaly and septo-optic dysplasia v2.4 chirag patel Copied gene PRRX1 from panel Mandibulofacial Acrofacial dysostosis
Holoprosencephaly and septo-optic dysplasia v2.4 PRRX1 chirag patel gene: PRRX1 was added
gene: PRRX1 was added to Holoprosencephaly and septo-optic dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PRRX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PRRX1 were set to 21294718; 22211708; 22674740; 23444262
Phenotypes for gene: PRRX1 were set to Agnathia-otocephaly complex, MIM# 202650
Fetal anomalies v2.32 PRRX1 chirag patel Mode of inheritance for gene: PRRX1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v2.378 PRRX1 chirag patel Phenotypes for gene: PRRX1 were changed from Agnathia-otocephaly complex, MIM# 202650; Craniosynostosis, MONDO:0015469, PRRX1-related to Agnathia-otocephaly complex, MIM# 202650; Craniosynostosis, MONDO:0015469, PRRX1-related
Mendeliome v2.377 PRRX1 chirag patel Phenotypes for gene: PRRX1 were changed from Agnathia-otocephaly complex, MIM# 202650 to Agnathia-otocephaly complex, MIM# 202650; Craniosynostosis, MONDO:0015469, PRRX1-related
Mendeliome v2.376 PRRX1 chirag patel Mode of inheritance for gene: PRRX1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal Ciliopathies v2.5 PRKACB chirag patel Marked gene: PRKACB as ready
Skeletal Ciliopathies v2.5 PRKACB chirag patel Gene: prkacb has been classified as Green List (High Evidence).
Fetal anomalies v2.31 PRKACB chirag patel Phenotypes for gene: PRKACB were changed from Cardioacrofacial dysplasia 2, MONDO:0030877 to Cardioacrofacial dysplasia 2, MONDO:0030877
Fetal anomalies v2.30 PRKACB chirag patel Phenotypes for gene: PRKACB were changed from Cardioacrofacial dysplasia 2 - MIM#619143 to Cardioacrofacial dysplasia 2, MONDO:0030877
Skeletal dysplasia v1.60 PRKACB chirag patel Marked gene: PRKACB as ready
Skeletal dysplasia v1.60 PRKACB chirag patel Gene: prkacb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.64 PRKACB chirag patel Phenotypes for gene: PRKACB were changed from Cardioacrofacial dysplasia 2, MIM# 619143; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 2, MONDO:0030877
Polydactyly v1.9 PRKACB chirag patel Phenotypes for gene: PRKACB were changed from Cardioacrofacial dysplasia 2, MIM# 619143; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 2, MONDO:0030877
Ciliopathies v2.9 PRKACB chirag patel Phenotypes for gene: PRKACB were changed from Cardioacrofacial dysplasia 2, MIM# 619143; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 2, MONDO:0030877
Congenital Heart Defect v1.21 PRKACB chirag patel Phenotypes for gene: PRKACB were changed from Cardioacrofacial dysplasia 2, MIM# 619143; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 2, MONDO:0030877
Skeletal dysplasia v1.60 chirag patel Copied gene PRKACB from panel Mendeliome
Skeletal dysplasia v1.60 PRKACB chirag patel gene: PRKACB was added
gene: PRKACB was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACB were set to 33058759
Phenotypes for gene: PRKACB were set to Cardioacrofacial dysplasia 2, MONDO:0030877
Penetrance for gene: PRKACB were set to unknown
Mode of pathogenicity for gene: PRKACB was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Skeletal Ciliopathies v2.5 chirag patel Copied gene PRKACB from panel Mendeliome
Skeletal Ciliopathies v2.5 PRKACB chirag patel gene: PRKACB was added
gene: PRKACB was added to Skeletal Ciliopathies. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACB were set to 33058759
Phenotypes for gene: PRKACB were set to Cardioacrofacial dysplasia 2, MONDO:0030877
Penetrance for gene: PRKACB were set to unknown
Mode of pathogenicity for gene: PRKACB was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Polydactyly v1.8 chirag patel Added reviews for gene PRKACB from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.63 chirag patel Added reviews for gene PRKACB from panel Mendeliome
Fetal anomalies v2.29 chirag patel Added reviews for gene PRKACB from panel Mendeliome
Congenital Heart Defect v1.20 chirag patel Added reviews for gene PRKACB from panel Mendeliome
Ciliopathies v2.8 chirag patel Added reviews for gene PRKACB from panel Mendeliome
Mendeliome v2.375 PRKACB chirag patel Phenotypes for gene: PRKACB were changed from Cardioacrofacial dysplasia 2, MIM# 619143; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 2, MONDO:0030877
Mendeliome v2.374 PRKACB chirag patel reviewed gene: PRKACB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardioacrofacial dysplasia 2, MONDO:0030877; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v2.28 PRKACA chirag patel Publications for gene: PRKACA were set to 33058759
Fetal anomalies v2.27 PRKACA chirag patel Phenotypes for gene: PRKACA were changed from Cardioacrofacial dysplasia 1, MONDO:0030876 to Cardioacrofacial dysplasia 1, MONDO:0030876
Fetal anomalies v2.26 PRKACA chirag patel Phenotypes for gene: PRKACA were changed from Cardioacrofacial dysplasia 1-MIM#619142 to Cardioacrofacial dysplasia 1, MONDO:0030876
Skeletal dysplasia v1.59 PRKACA chirag patel Marked gene: PRKACA as ready
Skeletal dysplasia v1.59 PRKACA chirag patel Gene: prkaca has been classified as Green List (High Evidence).
Skeletal dysplasia v1.59 PRKACA chirag patel Phenotypes for gene: PRKACA were changed from Cardioacrofacial dysplasia 1, MIM# 619142; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 1, MONDO:0030876
Skeletal dysplasia v1.58 PRKACA chirag patel Publications for gene: PRKACA were set to 33058759; 31130284
Skeletal Ciliopathies v2.4 PRKACA chirag patel Marked gene: PRKACA as ready
Skeletal Ciliopathies v2.4 PRKACA chirag patel Gene: prkaca has been classified as Green List (High Evidence).
Skeletal Ciliopathies v2.4 PRKACA chirag patel Phenotypes for gene: PRKACA were changed from Cardioacrofacial dysplasia 1, MIM# 619142; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 1, MONDO:0030876
Skeletal Ciliopathies v2.3 PRKACA chirag patel Publications for gene: PRKACA were set to 33058759; 31130284
Polydactyly v1.7 PRKACA chirag patel Publications for gene: PRKACA were set to 33058759; 31130284
Polydactyly v1.6 PRKACA chirag patel Phenotypes for gene: PRKACA were changed from Cardioacrofacial dysplasia 1, MIM# 619142; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 1, MONDO:0030876
Ciliopathies v2.7 PRKACA chirag patel Publications for gene: PRKACA were set to 33058759; 31130284
Ciliopathies v2.6 PRKACA chirag patel Phenotypes for gene: PRKACA were changed from Cardioacrofacial dysplasia 1, MIM# 619142; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 1, MONDO:0030876
Congenital Heart Defect v1.19 PRKACA chirag patel Phenotypes for gene: PRKACA were changed from Cardioacrofacial dysplasia 1, MIM# 619142; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 1, MONDO:0030876
Congenital Heart Defect v1.18 PRKACA chirag patel Publications for gene: PRKACA were set to 33058759; 31130284
Skeletal dysplasia v1.57 chirag patel Copied gene PRKACA from panel Polydactyly
Skeletal dysplasia v1.57 PRKACA chirag patel gene: PRKACA was added
gene: PRKACA was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACA were set to 33058759; 31130284
Phenotypes for gene: PRKACA were set to Cardioacrofacial dysplasia 1, MIM# 619142; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACA were set to Complete
Mode of pathogenicity for gene: PRKACA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Skeletal Ciliopathies v2.2 chirag patel Copied gene PRKACA from panel Polydactyly
Skeletal Ciliopathies v2.2 PRKACA chirag patel gene: PRKACA was added
gene: PRKACA was added to Skeletal Ciliopathies. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACA were set to 33058759; 31130284
Phenotypes for gene: PRKACA were set to Cardioacrofacial dysplasia 1, MIM# 619142; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACA were set to Complete
Mode of pathogenicity for gene: PRKACA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Polydactyly v1.5 chirag patel Added reviews for gene PRKACA from panel Polydactyly
Fetal anomalies v2.25 chirag patel Added reviews for gene PRKACA from panel Polydactyly
Congenital Heart Defect v1.17 chirag patel Added reviews for gene PRKACA from panel Polydactyly
Ciliopathies v2.5 chirag patel Added reviews for gene PRKACA from panel Polydactyly
Mendeliome v2.374 PRKACA chirag patel Phenotypes for gene: PRKACA were changed from Cardioacrofacial dysplasia 1, MIM# 619142; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability; Pigmented nodular adrenocortical disease, primary, 4, MONDO:0014359 to Cardioacrofacial dysplasia 1, MIM# 619142; Pigmented nodular adrenocortical disease, primary, 4, MONDO:0014359
Mendeliome v2.373 PRKACA chirag patel reviewed gene: PRKACA: 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: 24571724, 25924874; Phenotypes: Pigmented nodular adrenocortical disease, primary, 4, MONDO:0014359; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v2.373 PRKACA chirag patel Deleted their review
Polydactyly v1.4 PRKACA chirag patel reviewed gene: PRKACA: 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: 33058759, 38357848; Phenotypes: Cardioacrofacial dysplasia 1, MONDO:0030876; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v2.373 PRKACA chirag patel changed review comment from: Numerous cases reported with ACTH-independent Cushing syndrome due to macronodular bilateral adrenal hyperplasia or adrenal adenomas.

All individuals have chromosome duplications/triplications involving 19p13 region and PRKACA gene.

Patient cells showed increased protein levels of the PKA catalytic subunit as well as increased basal protein kinase A activity, consistent with a gain of function.; to: Numerous cases reported with ACTH-independent Cushing syndrome due to macronodular bilateral adrenal hyperplasia or adrenal adenomas.

All individuals have chromosome duplications/triplications involving 19p13 region and PRKACA gene.

Patient cells showed increased protein levels of the PKA catalytic subunit as well as increased basal protein kinase A activity, consistent with a gain of function.
Mendeliome v2.373 PRKACA chirag patel edited their review of gene: PRKACA: Added comment: Cardioacrofacial dysplasia-1 (CAFD1) is characterized by congenital cardiac defects, primarily common atrium or atrioventricular septal defect; limb anomalies, including short limbs, brachydactyly, and postaxial polydactyly; and dysmorphic facial features.; 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: 33058759, 38357848; Changed phenotypes: Cardioacrofacial dysplasia 1, MONDO:0030876
Clefting disorders v1.19 PORCN chirag patel Marked gene: PORCN as ready
Clefting disorders v1.19 PORCN chirag patel Gene: porcn has been classified as Green List (High Evidence).
Clefting disorders v1.19 PORCN chirag patel Phenotypes for gene: PORCN were changed from Focal dermal hypoplasia, MIM# 305600 to Focal dermal hypoplasia, MIM# 305600
Clefting disorders v1.19 PORCN chirag patel Phenotypes for gene: PORCN were changed from GOLTZ SYNDROME; Focal dermal hypoplasia, 305600 to Focal dermal hypoplasia, MIM# 305600
Clefting disorders v1.18 PORCN chirag patel reviewed gene: PORCN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301712; Phenotypes: Focal dermal hypoplasia, MIM# 305600; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Clefting disorders v1.18 PORCN chirag patel Deleted their review
Clefting disorders v1.18 PORCN chirag patel Deleted their comment
Clefting disorders v1.18 PORCN chirag patel reviewed gene: PORCN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Clefting disorders v1.18 chirag patel Added reviews for gene PORCN from panel Skeletal dysplasia
Skeletal dysplasia v1.56 PORCN chirag patel Marked gene: PORCN as ready
Skeletal dysplasia v1.56 PORCN chirag patel Gene: porcn has been classified as Green List (High Evidence).
Skeletal dysplasia v1.56 chirag patel Copied gene PORCN from panel Mendeliome
Skeletal dysplasia v1.56 PORCN chirag patel gene: PORCN was added
gene: PORCN was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PORCN was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: PORCN were set to Focal dermal hypoplasia, MIM# 305600
Skeletal dysplasia v1.55 POLE chirag patel Marked gene: POLE as ready
Skeletal dysplasia v1.55 POLE chirag patel Gene: pole has been classified as Green List (High Evidence).
Skeletal dysplasia v1.55 chirag patel Copied gene POLE from panel Adrenal insufficiency
Skeletal dysplasia v1.55 POLE chirag patel gene: POLE was added
gene: POLE was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: POLE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLE were set to 30503519
Phenotypes for gene: POLE were set to IMAGE-I syndrome, MONDO:0032684
Mendeliome v2.373 chirag patel Added reviews for gene PDGFRB from panel Skeletal dysplasia
Lipodystrophy_Lipoatrophy v2.6 PDGFRB chirag patel Marked gene: PDGFRB as ready
Lipodystrophy_Lipoatrophy v2.6 PDGFRB chirag patel Gene: pdgfrb has been classified as Green List (High Evidence).
Lipodystrophy_Lipoatrophy v2.6 chirag patel Copied gene PDGFRB from panel Skeletal dysplasia
Lipodystrophy_Lipoatrophy v2.6 PDGFRB chirag patel gene: PDGFRB was added
gene: PDGFRB was added to Lipodystrophy_Lipoatrophy. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PDGFRB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDGFRB were set to 30573803, 26279204, 40248971, 9056558
Phenotypes for gene: PDGFRB were set to Premature aging syndrome, Penttinen type, 601812
Mode of pathogenicity for gene: PDGFRB was set to Other
Skeletal dysplasia v1.54 PDGFRB chirag patel Phenotypes for gene: PDGFRB were changed from Basal ganglia calcification, idiopathic, 4, MIM# 615007; Kosaki overgrowth syndrome, MIM# 616592; Myeloproliferative disorder with eosinophilia, MIM# 131440; Myofibromatosis, infantile, 1, MIM# 228550; Premature ageing syndrome, Penttinen type, MIM# 601812; Ocular pterygium-digital keloid dysplasia syndrome, MIM# 621091 to Premature aging syndrome, Penttinen type, 601812
Skeletal dysplasia v1.53 PDGFRB chirag patel Marked gene: PDGFRB as ready
Skeletal dysplasia v1.53 PDGFRB chirag patel Gene: pdgfrb has been classified as Green List (High Evidence).
Skeletal dysplasia v1.53 PDGFRB chirag patel Publications for gene: PDGFRB were set to 30573803; 26279204; 33450762
Skeletal dysplasia v1.52 PDGFRB chirag patel reviewed gene: PDGFRB: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30573803, 26279204, 40248971, 9056558; Phenotypes: Premature aging syndrome, Penttinen type, 601812; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.52 chirag patel Copied gene PDGFRB from panel Mendeliome
Skeletal dysplasia v1.52 PDGFRB chirag patel gene: PDGFRB was added
gene: PDGFRB was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PDGFRB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDGFRB were set to 30573803; 26279204; 33450762
Phenotypes for gene: PDGFRB were set to Basal ganglia calcification, idiopathic, 4, MIM# 615007; Kosaki overgrowth syndrome, MIM# 616592; Myeloproliferative disorder with eosinophilia, MIM# 131440; Myofibromatosis, infantile, 1, MIM# 228550; Premature ageing syndrome, Penttinen type, MIM# 601812; Ocular pterygium-digital keloid dysplasia syndrome, MIM# 621091
Mode of pathogenicity for gene: PDGFRB was set to Other
Macrocephaly_Megalencephaly v1.2 PDGFRB chirag patel Classified gene: PDGFRB as Red List (low evidence)
Macrocephaly_Megalencephaly v1.2 PDGFRB chirag patel Gene: pdgfrb has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v2.1 PDGFRB chirag patel Phenotypes for gene: PDGFRB were changed from aneurysm; scoliosis; atrophic skin; stroke; infantile myofibromatosis to Kosaki overgrowth syndrome MIM#616592
Regression v1.3 PDGFRB chirag patel Classified gene: PDGFRB as Red List (low evidence)
Regression v1.3 PDGFRB chirag patel Gene: pdgfrb has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v2.6 PDGFRB chirag patel Phenotypes for gene: PDGFRB were changed from Kosaki overgrowth syndrome, MIM# 616592 to Kosaki overgrowth syndrome, MIM# 616592
Aortopathy_Connective Tissue Disorders v2.5 PDGFRB chirag patel Phenotypes for gene: PDGFRB were changed from aneurysm; scoliosis; atrophic skin; stroke; infantile myofibromatosis to Kosaki overgrowth syndrome, MIM# 616592
Skeletal dysplasia v1.51 NPR3 chirag patel Marked gene: NPR3 as ready
Skeletal dysplasia v1.51 NPR3 chirag patel Gene: npr3 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v2.4 NPR3 chirag patel Publications for gene: NPR3 were set to 30032985
Aortopathy_Connective Tissue Disorders v2.3 NPR3 chirag patel Phenotypes for gene: NPR3 were changed from Boudin-Mortier syndrome, MIM#619543; Tall stature, skeletal abnormalities, aortic dilatation to Boudin-Mortier syndrome, MONDO:0859194
Skeletal dysplasia v1.51 chirag patel Copied gene NPR3 from panel Mendeliome
Skeletal dysplasia v1.51 NPR3 chirag patel gene: NPR3 was added
gene: NPR3 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NPR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPR3 were set to 40171685; 35233476; 30032985
Phenotypes for gene: NPR3 were set to Boudin-Mortier syndrome, MONDO:0859194
Aortopathy_Connective Tissue Disorders v2.2 chirag patel Added reviews for gene NPR3 from panel Mendeliome
Mendeliome v2.372 NPR3 chirag patel Phenotypes for gene: NPR3 were changed from Boudin-Mortier syndrome, MONDO:0859194 to Boudin-Mortier syndrome, MONDO:0859194
Mendeliome v2.371 NPR3 chirag patel Phenotypes for gene: NPR3 were changed from Boudin-Mortier syndrome, MIM#619543; Tall stature, skeletal abnormalities, aortic dilatation to Boudin-Mortier syndrome, MONDO:0859194
Mendeliome v2.370 NPR3 chirag patel Publications for gene: NPR3 were set to 30032985
Mendeliome v2.369 NPR3 chirag patel reviewed gene: NPR3: Rating: GREEN; Mode of pathogenicity: None; Publications: 40171685, 35233476, 30032985; Phenotypes: Boudin-Mortier syndrome, MONDO:0859194; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.50 NADSYN1 chirag patel Marked gene: NADSYN1 as ready
Skeletal dysplasia v1.50 NADSYN1 chirag patel Gene: nadsyn1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.50 chirag patel Copied gene NADSYN1 from panel Mendeliome
Skeletal dysplasia v1.50 NADSYN1 chirag patel gene: NADSYN1 was added
gene: NADSYN1 was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NADSYN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NADSYN1 were set to 31883644
Phenotypes for gene: NADSYN1 were set to Vertebral, cardiac, renal, and limb defects syndrome 3, MONDO:0030077; Vertebral, cardiac, renal, and limb defects syndrome 3, OMIM:618845
Fetal anomalies v2.24 chirag patel Added reviews for gene NADSYN1 from panel Mendeliome
Congenital Heart Defect v1.16 chirag patel Added reviews for gene NADSYN1 from panel Mendeliome
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.9 chirag patel Added reviews for gene NADSYN1 from panel Mendeliome
Mendeliome v2.369 NADSYN1 chirag patel commented on gene: NADSYN1
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.8 MBTPS2 chirag patel Marked gene: MBTPS2 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.8 MBTPS2 chirag patel Gene: mbtps2 has been classified as Green List (High Evidence).
Hirschsprung disease v1.1 MBTPS2 chirag patel Marked gene: MBTPS2 as ready
Hirschsprung disease v1.1 MBTPS2 chirag patel Gene: mbtps2 has been classified as Green List (High Evidence).
Hirschsprung disease v1.1 chirag patel Copied gene MBTPS2 from panel Clefting disorders
Hirschsprung disease v1.1 MBTPS2 chirag patel gene: MBTPS2 was added
gene: MBTPS2 was added to Hirschsprung disease. Sources: Expert Review Green
Mode of inheritance for gene: MBTPS2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MBTPS2 were set to https://search.clinicalgenome.org/CCID:005345
Phenotypes for gene: MBTPS2 were set to IFAP syndrome with or without BRESHECK syndrome MONDO:0100213
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.8 chirag patel Copied gene MBTPS2 from panel Clefting disorders
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.8 MBTPS2 chirag patel gene: MBTPS2 was added
gene: MBTPS2 was added to Congenital anomalies of the kidney and urinary tract (CAKUT). Sources: Expert Review Green
Mode of inheritance for gene: MBTPS2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MBTPS2 were set to https://search.clinicalgenome.org/CCID:005345
Phenotypes for gene: MBTPS2 were set to IFAP syndrome with or without BRESHECK syndrome MONDO:0100213
Clefting disorders v1.17 MBTPS2 chirag patel Publications for gene: MBTPS2 were set to
Clefting disorders v1.16 MBTPS2 chirag patel Marked gene: MBTPS2 as ready
Clefting disorders v1.16 MBTPS2 chirag patel Gene: mbtps2 has been classified as Green List (High Evidence).
Clefting disorders v1.16 MBTPS2 chirag patel reviewed gene: MBTPS2: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005345; Phenotypes: IFAP syndrome with or without BRESHECK syndrome MONDO:0100213; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Clefting disorders v1.16 MBTPS2 chirag patel Phenotypes for gene: MBTPS2 were changed from IFAP SYNDROME WITH OR WITHOUT BRESHECK SYNDROME to IFAP syndrome with or without BRESHECK syndrome MONDO:0100213
Callosome v1.10 MBTPS2 chirag patel Marked gene: MBTPS2 as ready
Callosome v1.10 MBTPS2 chirag patel Gene: mbtps2 has been classified as Green List (High Evidence).
Callosome v1.10 MBTPS2 chirag patel Phenotypes for gene: MBTPS2 were changed from to IFAP syndrome 1, with or without BRESHECK syndrome MONDO:0100213
Callosome v1.9 MBTPS2 chirag patel Publications for gene: MBTPS2 were set to
Callosome v1.8 MBTPS2 chirag patel Mode of inheritance for gene: MBTPS2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Callosome v1.7 chirag patel Added reviews for gene MBTPS2 from panel Intellectual disability syndromic and non-syndromic
Polydactyly v1.4 MBTPS2 chirag patel Marked gene: MBTPS2 as ready
Polydactyly v1.4 MBTPS2 chirag patel Gene: mbtps2 has been classified as Red List (Low Evidence).
Polydactyly v1.4 MBTPS2 chirag patel Classified gene: MBTPS2 as Red List (low evidence)
Polydactyly v1.4 MBTPS2 chirag patel Gene: mbtps2 has been classified as Red List (Low Evidence).
Polydactyly v1.3 MBTPS2 chirag patel reviewed gene: MBTPS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v1.49 MBTPS2 chirag patel Marked gene: MBTPS2 as ready
Skeletal dysplasia v1.49 MBTPS2 chirag patel Gene: mbtps2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.49 MBTPS2 chirag patel Classified gene: MBTPS2 as Green List (high evidence)
Skeletal dysplasia v1.49 MBTPS2 chirag patel Gene: mbtps2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.48 MBTPS2 chirag patel gene: MBTPS2 was added
gene: MBTPS2 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: MBTPS2 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: MBTPS2 were set to 37305034; 34093655; 27380894
Phenotypes for gene: MBTPS2 were set to Osteogenesis imperfecta, type 19, MONDO:0049223
Review for gene: MBTPS2 was set to GREEN
Added comment: PMID 27380894 and PMID 37305034 report X-linked osteogenesis imperfecta caused by MBTPS2 missense variants. PMID 27380894 describes 8 affected individuals from two unrelated families with variants p.N459S and p.L505F; PMID 37305034 adds a third family with a p.Glu172Asp variant and includes the earlier families as controls. All three families present prenatal fractures, short stature, bowing of long bones, scoliosis and blue/white sclerae.

Patient fibroblasts/osteoblasts show impaired regulated intramembrane proteolysis, reduced type I collagen secretion and altered ER morphology. CHO‑M19 luciferase reporter assays demonstrate reduced ATF6 activation. RNA‑seq, lipidomic profiling and electron microscopy reveal transcriptomic and cellular deficits. qRT‑PCR of bone‑development genes and immunocytochemistry show reduced collagen deposition.
Sources: Literature
Skeletal dysplasia v1.47 KIAA0825 chirag patel Marked gene: KIAA0825 as ready
Skeletal dysplasia v1.47 KIAA0825 chirag patel Gene: kiaa0825 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.47 KIAA0825 chirag patel Classified gene: KIAA0825 as Green List (high evidence)
Skeletal dysplasia v1.47 KIAA0825 chirag patel Gene: kiaa0825 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.46 KIAA0825 chirag patel gene: KIAA0825 was added
gene: KIAA0825 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: KIAA0825 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0825 were set to 41010063; 37107627; 35886013; 32147526; 30982135
Phenotypes for gene: KIAA0825 were set to Postaxial polydactyly type A, MONDO:0019673
Review for gene: KIAA0825 was set to GREEN
Added comment: PMID 30982135 reports 6 individuals from 2 families, PMID 32147526 reports 2 individuals from 1 family, PMID 35886013 reports a prenatally detected case (1 individual, 1 family), PMID 37107627 reports 2 individuals from 1 family, and PMID 41010063 reports 10 individuals from 4 families, totalling 21 patients from 9 families (8 independent) with autosomal recessive postaxial polydactyly type A. Mouse knockout shows reduced bone mineral density (PMID 30982135, PMID 41010063); minigene splice assays demonstrate loss‑of‑function for splice variants (PMID 35886013); protein structural modelling predicts destabilisation for missense variants (PMID 32147526, PMID 37107627, PMID 41010063).
Sources: Literature
Skeletal dysplasia v1.45 KDELR2 chirag patel Marked gene: KDELR2 as ready
Skeletal dysplasia v1.45 KDELR2 chirag patel Gene: kdelr2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.45 chirag patel Copied gene KDELR2 from panel Mendeliome
Skeletal dysplasia v1.45 KDELR2 chirag patel gene: KDELR2 was added
gene: KDELR2 was added to Skeletal dysplasia. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: KDELR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KDELR2 were set to 33053334
Phenotypes for gene: KDELR2 were set to Osteogenesis imperfecta 21, MIM# 619131
Mendeliome v2.369 KDELR2 chirag patel Phenotypes for gene: KDELR2 were changed from Osteogenesis imperfecta 21, MIM# 619131 to Osteogenesis imperfecta 21, MIM# 619131
Mendeliome v2.369 KDELR2 chirag patel Phenotypes for gene: KDELR2 were changed from Osteogenesis imperfecta 21, MIM# 619131; Increased susceptibility to fractures; joint hypermobility; Scoliosis; Bowing of the legs; Bowing of the arms to Osteogenesis imperfecta 21, MIM# 619131
Osteogenesis Imperfecta and Osteoporosis v2.6 KDELR2 chirag patel Phenotypes for gene: KDELR2 were changed from Osteogenesis imperfecta 21, MIM# 619131; Increased susceptibility to fractures; joint hypermobility; Scoliosis; Bowing of the legs; Bowing of the arms to Osteogenesis imperfecta 21, MIM# 619131
Skeletal dysplasia v1.44 IL6ST chirag patel Marked gene: IL6ST as ready
Skeletal dysplasia v1.44 IL6ST chirag patel Gene: il6st has been classified as Green List (High Evidence).
Skeletal dysplasia v1.44 IL6ST chirag patel Classified gene: IL6ST as Green List (high evidence)
Skeletal dysplasia v1.44 IL6ST chirag patel Gene: il6st has been classified as Green List (High Evidence).
Skeletal dysplasia v1.43 IL6ST chirag patel gene: IL6ST was added
gene: IL6ST was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: IL6ST was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL6ST were set to 40835206; 38133879; 31914175
Phenotypes for gene: IL6ST were set to Stuve-Wiedemann syndrome 2, MONDO:0030756
Review for gene: IL6ST was set to GREEN
Added comment: PMID 38133879, PMID 31914175 and PMID 40835206 together report 11 individuals from 7 families with homozygous truncating or splice IL6ST variants presenting with bent long bones, respiratory failure and perinatal lethality. Patient‑derived cells (amniocytes, EBV‑LCLs) lack GP130 surface expression and IL‑6/IL‑11 signalling, rescued by lentiviral WT GP130 (PMID 31914175). HEK293 GP130‑KO cells transfected with mutant constructs fail to signal (PMID 31914175).
Sources: Literature
Congenital Heart Defect v1.15 HSPA9 chirag patel Phenotypes for gene: HSPA9 were changed from Even-plus syndrome, MIM# 616854; skeletal anomalies; congenital cardiac and renal anomalies: marked small nose to Even-plus syndrome, MONDO:0014801
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.7 HSPA9 chirag patel Phenotypes for gene: HSPA9 were changed from Even-plus syndrome, MIM# 616854; skeletal anomalies; congenital cardiac and renal anomalies: marked small nose to Even-plus syndrome, MONDO:0014801
Intellectual disability syndromic and non-syndromic v2.62 HSPA9 chirag patel Phenotypes for gene: HSPA9 were changed from Even-plus syndrome, OMIM 616854; skeletal anomalies; congenital cardiac and renal anom to Even-plus syndrome, MONDO:0014801
Mendeliome v2.368 HSPA9 chirag patel Phenotypes for gene: HSPA9 were changed from Anemia, sideroblastic, 4, MIM# 182170; Even-plus syndrome, MONDO:0014801 to Anemia, sideroblastic, 4, MIM# 182170; Even-plus syndrome, MONDO:0014801
Mendeliome v2.367 HSPA9 chirag patel Phenotypes for gene: HSPA9 were changed from Anemia, sideroblastic, 4, MIM# 182170; Even-plus syndrome, MIM#616854; skeletal anomalies; congenital cardiac and renal anomalies: marked small nose to Anemia, sideroblastic, 4, MIM# 182170; Even-plus syndrome, MONDO:0014801
Skeletal dysplasia v1.42 HSPA9 chirag patel Phenotypes for gene: HSPA9 were changed from Even-plus syndrome, MIM# 616854; skeletal anomalies; congenital cardiac and renal anomalies: marked small nose to Even-plus syndrome, MONDO:0014801
Skeletal dysplasia v1.41 HSPA9 chirag patel Marked gene: HSPA9 as ready
Skeletal dysplasia v1.41 HSPA9 chirag patel Gene: hspa9 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.41 chirag patel Copied gene HSPA9 from panel Congenital anomalies of the kidney and urinary tract (CAKUT)
Skeletal dysplasia v1.41 HSPA9 chirag patel gene: HSPA9 was added
gene: HSPA9 was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: HSPA9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HSPA9 were set to 26598328; 32869452
Phenotypes for gene: HSPA9 were set to Even-plus syndrome, MIM# 616854; skeletal anomalies; congenital cardiac and renal anomalies: marked small nose
Skeletal dysplasia v1.40 GRK2 chirag patel Marked gene: GRK2 as ready
Skeletal dysplasia v1.40 GRK2 chirag patel Gene: grk2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.40 chirag patel Copied gene GRK2 from panel Skeletal Ciliopathies
Skeletal dysplasia v1.40 GRK2 chirag patel gene: GRK2 was added
gene: GRK2 was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: GRK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRK2 were set to 33200460; 38647386
Phenotypes for gene: GRK2 were set to Jeune asphyxiating thoracic dystrophy (ATD), MONDO:0018770
Skeletal dysplasia v1.39 GPC4 chirag patel reviewed gene: GPC4: Rating: GREEN; Mode of pathogenicity: None; Publications: 30982611; Phenotypes: Keipert syndrome OMIM# 301026; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Skeletal dysplasia v1.39 GPC4 chirag patel Marked gene: GPC4 as ready
Skeletal dysplasia v1.39 GPC4 chirag patel Gene: gpc4 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.39 chirag patel Copied gene GPC4 from panel Mendeliome
Skeletal dysplasia v1.39 GPC4 chirag patel gene: GPC4 was added
gene: GPC4 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GPC4 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: GPC4 were set to 30982611
Phenotypes for gene: GPC4 were set to Keipert syndrome OMIM# 301026
Mendeliome v2.366 GNAI3 chirag patel Publications for gene: GNAI3 were set to 22560091; 16114046
Clefting disorders v1.15 GNAI3 chirag patel Classified gene: GNAI3 as Green List (high evidence)
Clefting disorders v1.15 GNAI3 chirag patel Gene: gnai3 has been classified as Green List (High Evidence).
Fetal anomalies v2.23 GNAI3 chirag patel Publications for gene: GNAI3 were set to 22560091
Skeletal dysplasia v1.38 GNAI3 chirag patel Marked gene: GNAI3 as ready
Skeletal dysplasia v1.38 GNAI3 chirag patel Gene: gnai3 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.38 GNAI3 chirag patel Publications for gene: GNAI3 were set to 22560091
Mendeliome v2.365 GNAI3 chirag patel Publications for gene: GNAI3 were set to 22560091; 16114046
Mendeliome v2.364 GNAI3 chirag patel Publications for gene: GNAI3 were set to 22560091
Mandibulofacial Acrofacial dysostosis v2.8 GNAI3 chirag patel Publications for gene: GNAI3 were set to 22560091; 16114046
Mandibulofacial Acrofacial dysostosis v2.7 GNAI3 chirag patel Publications for gene: GNAI3 were set to 22560091
Pierre Robin Sequence v1.5 GNAI3 chirag patel Publications for gene: GNAI3 were set to 22560091
Pierre Robin Sequence v1.4 GNAI3 chirag patel Marked gene: GNAI3 as ready
Pierre Robin Sequence v1.4 GNAI3 chirag patel Gene: gnai3 has been classified as Green List (High Evidence).
Pierre Robin Sequence v1.4 GNAI3 chirag patel Publications for gene: GNAI3 were set to
Pierre Robin Sequence v1.3 GNAI3 chirag patel Phenotypes for gene: GNAI3 were changed from to Auriculocondylar syndrome 1, OMIM #602483
Pierre Robin Sequence v1.2 GNAI3 chirag patel Mode of inheritance for gene: GNAI3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.37 chirag patel Copied gene GNAI3 from panel Mendeliome
Skeletal dysplasia v1.37 GNAI3 chirag patel gene: GNAI3 was added
gene: GNAI3 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GNAI3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNAI3 were set to 22560091
Phenotypes for gene: GNAI3 were set to Auriculocondylar syndrome 1, OMIM #602483
Pierre Robin Sequence v1.1 chirag patel Added reviews for gene GNAI3 from panel Mendeliome
Skeletal dysplasia v1.36 GLI1 chirag patel Marked gene: GLI1 as ready
Skeletal dysplasia v1.36 GLI1 chirag patel Gene: gli1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.36 chirag patel Copied gene GLI1 from panel Mendeliome
Skeletal dysplasia v1.36 GLI1 chirag patel gene: GLI1 was added
gene: GLI1 was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: GLI1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GLI1 were set to 34721536; 31621941; 31549748; 30620395
Phenotypes for gene: GLI1 were set to Postaxial polydactyly MONDO:0020927, GLI1-related; Polydactyly, postaxial, type A8 MIM#618123; Polydactyly, preaxial I MIM#174400
Penetrance for gene: GLI1 were set to unknown
Skeletal dysplasia v1.35 GBA1 chirag patel Phenotypes for gene: GBA1 were changed from Gaucher disease, perinatal lethal, MIM# 608013; Gaucher disease, type I, MIM# 230800; Gaucher disease, type II, MIM# 230900; Gaucher disease, type III, MIM# 231000; Gaucher disease, type IIIC, MIM# 231005 to Gaucher disease, MONDO:0018150
Skeletal dysplasia v1.34 GBA1 chirag patel Publications for gene: GBA1 were set to
Skeletal dysplasia v1.33 GBA1 chirag patel Marked gene: GBA1 as ready
Skeletal dysplasia v1.33 GBA1 chirag patel Gene: gba1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.33 GBA1 chirag patel reviewed gene: GBA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301446; Phenotypes: Gaucher disease, MONDO:0018150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.363 GBA1 chirag patel Marked gene: GBA1 as ready
Mendeliome v2.363 GBA1 chirag patel Gene: gba1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.33 chirag patel Copied gene GBA1 from panel Lysosomal Storage Disorder
Skeletal dysplasia v1.33 GBA1 chirag patel gene: GBA1 was added
gene: GBA1 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GBA1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GBA1 were set to Gaucher disease, perinatal lethal, MIM# 608013; Gaucher disease, type I, MIM# 230800; Gaucher disease, type II, MIM# 230900; Gaucher disease, type III, MIM# 231000; Gaucher disease, type IIIC, MIM# 231005
Mendeliome v2.363 chirag patel Copied gene GBA1 from panel Lysosomal Storage Disorder
Mendeliome v2.363 GBA1 chirag patel gene: GBA1 was added
gene: GBA1 was added to Mendeliome. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GBA1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GBA1 were set to Gaucher disease, perinatal lethal, MIM# 608013; Gaucher disease, type I, MIM# 230800; Gaucher disease, type II, MIM# 230900; Gaucher disease, type III, MIM# 231000; Gaucher disease, type IIIC, MIM# 231005
Congenital Heart Defect v1.14 FGD1 chirag patel Marked gene: FGD1 as ready
Congenital Heart Defect v1.14 FGD1 chirag patel Gene: fgd1 has been classified as Green List (High Evidence).
Congenital Heart Defect v1.14 FGD1 chirag patel changed review comment from: Heart defects seen in 16% - mostly ventricular & atrial septal defects; ; to: Heart defects seen in 16% - mostly ventricular & atrial septal defects
Congenital Heart Defect v1.14 FGD1 chirag patel changed review comment from: Cleft lip & palate seen in 6%; to: Heart defects seen in 16% - mostly ventricular & atrial septal defects;
Congenital Heart Defect v1.14 chirag patel Copied gene FGD1 from panel Clefting disorders
Congenital Heart Defect v1.14 FGD1 chirag patel gene: FGD1 was added
gene: FGD1 was added to Congenital Heart Defect. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FGD1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FGD1 were set to 7954831; 20082460; 41704117
Phenotypes for gene: FGD1 were set to Aarskog-Scott syndrome, X-linked, MONDO:0010589
Clefting disorders v1.14 FGD1 chirag patel Marked gene: FGD1 as ready
Clefting disorders v1.14 FGD1 chirag patel Gene: fgd1 has been classified as Green List (High Evidence).
Clefting disorders v1.14 FGD1 chirag patel Phenotypes for gene: FGD1 were changed from AARSKOG-SCOTT SYNDROME; AAS to Aarskog-Scott syndrome, X-linked, MONDO:0010589
Clefting disorders v1.13 FGD1 chirag patel Publications for gene: FGD1 were set to 20082460
Clefting disorders v1.12 FGD1 chirag patel reviewed gene: FGD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41704117; Phenotypes: Aarskog-Scott syndrome, X-linked, MONDO:0010589; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Clefting disorders v1.12 chirag patel Added reviews for gene FGD1 from panel Mendeliome
Skeletal dysplasia v1.32 FGD1 chirag patel Marked gene: FGD1 as ready
Skeletal dysplasia v1.32 FGD1 chirag patel Gene: fgd1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.32 chirag patel Copied gene FGD1 from panel Mendeliome
Skeletal dysplasia v1.32 FGD1 chirag patel gene: FGD1 was added
gene: FGD1 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FGD1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FGD1 were set to 7954831; 20082460
Phenotypes for gene: FGD1 were set to Aarskog-Scott syndrome, MIM # 305400; Mental retardation, X-linked syndromic 16, MIM# 305400
Skeletal dysplasia v1.31 EIF4A3 chirag patel Marked gene: EIF4A3 as ready
Skeletal dysplasia v1.31 EIF4A3 chirag patel Gene: eif4a3 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.31 chirag patel Copied gene EIF4A3 from panel Mendeliome
Skeletal dysplasia v1.31 EIF4A3 chirag patel gene: EIF4A3 was added
gene: EIF4A3 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
STR tags were added to gene: EIF4A3.
Mode of inheritance for gene: EIF4A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF4A3 were set to 24360810
Phenotypes for gene: EIF4A3 were set to Robin sequence with cleft mandible and limb anomalies, MIM# 268305; Richieri-Costa-Pereira syndrome
Clefting disorders v1.11 EFNB1 chirag patel Marked gene: EFNB1 as ready
Clefting disorders v1.11 EFNB1 chirag patel Gene: efnb1 has been classified as Green List (High Evidence).
Clefting disorders v1.11 EFNB1 chirag patel Phenotypes for gene: EFNB1 were changed from CRANIOFRONTONASAL SYNDROME; CFNS to Craniofrontonasal dysplasia, MIM# 304110
Clefting disorders v1.10 EFNB1 chirag patel Publications for gene: EFNB1 were set to
Clefting disorders v1.9 chirag patel Added reviews for gene EFNB1 from panel Mendeliome
Skeletal dysplasia v1.30 EFNB1 chirag patel Marked gene: EFNB1 as ready
Skeletal dysplasia v1.30 EFNB1 chirag patel Gene: efnb1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.30 chirag patel Copied gene EFNB1 from panel Frontonasal dysplasia
Skeletal dysplasia v1.30 EFNB1 chirag patel gene: EFNB1 was added
gene: EFNB1 was added to Skeletal dysplasia. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: EFNB1 was set to Other
Publications for gene: EFNB1 were set to 15166289
Phenotypes for gene: EFNB1 were set to Craniofrontonasal dysplasia, MIM# 304110
Clefting disorders v1.8 EDNRA chirag patel Phenotypes for gene: EDNRA were changed from MANDIBULOFACIAL DYSOSTOSIS WITH ALOPECIA; MFDA; Cleft palate to Mandibulofacial dysostosis with alopecia, MIM# 616367
Clefting disorders v1.7 EDNRA chirag patel Mode of inheritance for gene: EDNRA was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting disorders v1.6 EDNRA chirag patel Publications for gene: EDNRA were set to
Clefting disorders v1.5 EDNRA chirag patel Marked gene: EDNRA as ready
Clefting disorders v1.5 EDNRA chirag patel Gene: ednra has been classified as Green List (High Evidence).
Skeletal dysplasia v1.29 EDNRA chirag patel Marked gene: EDNRA as ready
Skeletal dysplasia v1.29 EDNRA chirag patel Gene: ednra has been classified as Green List (High Evidence).
Clefting disorders v1.5 chirag patel Added reviews for gene EDNRA from panel Mendeliome
Skeletal dysplasia v1.29 chirag patel Copied gene EDNRA from panel Mendeliome
Skeletal dysplasia v1.29 EDNRA chirag patel gene: EDNRA was added
gene: EDNRA was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: EDNRA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EDNRA were set to 25772936; 27671791
Phenotypes for gene: EDNRA were set to Mandibulofacial dysostosis with alopecia, MIM# 616367
Skeletal dysplasia v1.28 DSE chirag patel Marked gene: DSE as ready
Skeletal dysplasia v1.28 DSE chirag patel Gene: dse has been classified as Green List (High Evidence).
Skeletal dysplasia v1.28 DSE chirag patel reviewed gene: DSE: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ehlers-Danlos syndrome, musculocontractural type 2 - MIM#615539; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.28 chirag patel Copied gene DSE from panel Mendeliome
Skeletal dysplasia v1.28 DSE chirag patel gene: DSE was added
gene: DSE was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DSE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DSE were set to 28306229; 23704329; 25703627; 32130795
Phenotypes for gene: DSE were set to Ehlers-Danlos syndrome, musculocontractural type 2 - MIM#615539
Skeletal dysplasia v1.27 ASAH1 chirag patel Marked gene: ASAH1 as ready
Skeletal dysplasia v1.27 ASAH1 chirag patel Gene: asah1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.27 chirag patel Copied gene ASAH1 from panel Fetal anomalies
Skeletal dysplasia v1.27 ASAH1 chirag patel gene: ASAH1 was added
gene: ASAH1 was added to Skeletal dysplasia. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: ASAH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASAH1 were set to 11241842
Phenotypes for gene: ASAH1 were set to Farber lipogranulomatosis, MIM# 228000
Genomic screening in children: BabyScreen+ v1.0 APC Gene migrated from ENSG00000134982 to ENSG00000134982 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 SMARCAL1 Gene migrated from ENSG00000138375 to ENSG00000138375 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 SPTLC1 Gene migrated from ENSG00000090054 to ENSG00000090054 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 CDC73 Gene migrated from ENSG00000134371 to ENSG00000134371 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 NF2 Gene migrated from ENSG00000186575 to ENSG00000186575 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 AIP Gene migrated from ENSG00000110711 to ENSG00000110711 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 TTN Gene migrated from ENSG00000155657 to ENSG00000155657 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 ZBTB24 Gene migrated from ENSG00000112365 to ENSG00000112365 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 VWF Gene migrated from ENSG00000110799 to ENSG00000110799 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 ABCC8 Gene migrated from ENSG00000006071 to ENSG00000006071 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 GCK Gene migrated from ENSG00000106633 to ENSG00000106633 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 SCN5A Gene migrated from ENSG00000183873 to ENSG00000183873 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 STK11 Gene migrated from ENSG00000118046 to ENSG00000118046 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 PRKG1 Gene migrated from ENSG00000185532 to ENSG00000185532 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 TECRL Gene migrated from ENSG00000205678 to ENSG00000205678 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 TNFRSF11B Gene migrated from ENSG00000164761 to ENSG00000164761 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 TRDN Gene migrated from ENSG00000186439 to ENSG00000186439 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 PKP2 Gene migrated from ENSG00000057294 to ENSG00000057294 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 KCNJ11 Gene migrated from ENSG00000187486 to ENSG00000187486 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 LDLR Gene migrated from ENSG00000130164 to ENSG00000130164 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 LDLRAP1 Gene migrated from ENSG00000157978 to ENSG00000157978 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 PCSK9 Gene migrated from ENSG00000169174 to ENSG00000169174 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 NEUROD1 Gene migrated from ENSG00000162992 to ENSG00000162992 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 INS Gene migrated from ENSG00000254647 to ENSG00000254647 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 RFX6 Gene migrated from ENSG00000185002 to ENSG00000185002 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 CEL Gene migrated from ENSG00000170835 to ENSG00000170835 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 MYH11 Gene migrated from ENSG00000133392 to ENSG00000133392 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 MEN1 Gene migrated from ENSG00000133895 to ENSG00000133895 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 LOX Gene migrated from ENSG00000113083 to ENSG00000113083 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 LAMP2 Gene migrated from ENSG00000005893 to ENSG00000005893 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 DMD Gene migrated from ENSG00000198947 to ENSG00000198947 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 HNF4A Gene migrated from ENSG00000101076 to ENSG00000101076 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 HNF1A Gene migrated from ENSG00000135100 to ENSG00000135100 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 DSC2 Gene migrated from ENSG00000134755 to ENSG00000134755 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 CASQ2 Gene migrated from ENSG00000118729 to ENSG00000118729 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 CALM2 Gene migrated from ENSG00000143933 to ENSG00000143933 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 HGD Gene migrated from ENSG00000113924 to ENSG00000113924 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 DSP Gene migrated from ENSG00000096696 to ENSG00000096696 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 COL3A1 Gene migrated from ENSG00000168542 to ENSG00000168542 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 CALM1 Gene migrated from ENSG00000198668 to ENSG00000198668 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 DSG2 Gene migrated from ENSG00000046604 to ENSG00000046604 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 APOB Gene migrated from ENSG00000084674 to ENSG00000084674 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 HNF1B Gene migrated from ENSG00000275410 to ENSG00000275410 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 JUP Gene migrated from ENSG00000173801 to ENSG00000173801 (gene set migration)
Genomic screening in children: BabyScreen+ v1.0 Panel migrated to gene set Ensemblv115. Source version: v0.99
Cardiomyopathy_Paediatric v1.61 DST Rylee Peters Marked gene: DST as ready
Cardiomyopathy_Paediatric v1.61 DST Rylee Peters Gene: dst has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.61 DST Rylee Peters Classified gene: DST as Green List (high evidence)
Cardiomyopathy_Paediatric v1.61 DST Rylee Peters Gene: dst has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.60 DST Rylee Peters gene: DST was added
gene: DST was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: DST was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DST were set to 40497796
Phenotypes for gene: DST were set to Congenital myopathy 29 with contractures, MIM#621510
Review for gene: DST was set to GREEN
Added comment: PMID: 40497796 reports several unrelated families with biallelic loss‑of‑function DST‑b variants presenting with severe congenital myopathy, arthrogryposis, neonatal hypotonia and cardiomyopathy (DCM was identified in 9/14 individuals). Most required respiratory support in infancy, seven died before age three from heart failure.
Sources: Literature
Cardiomyopathy_Paediatric v1.59 BOLA3 Rylee Peters Marked gene: BOLA3 as ready
Cardiomyopathy_Paediatric v1.59 BOLA3 Rylee Peters Gene: bola3 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.59 BOLA3 Rylee Peters Classified gene: BOLA3 as Green List (high evidence)
Cardiomyopathy_Paediatric v1.59 BOLA3 Rylee Peters Gene: bola3 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.58 BOLA3 Rylee Peters gene: BOLA3 was added
gene: BOLA3 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: BOLA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BOLA3 were set to 40273865
Phenotypes for gene: BOLA3 were set to Multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia, MIM#614299
Review for gene: BOLA3 was set to GREEN
Added comment: PMID: 40273865 describes several unrelated families with biallelic BOLA3 variants causing early‑infantile multiple mitochondrial dysfunction syndrome 2 (MMDS2) that frequently includes hypertrophic cardiomyopathy.
Sources: Literature
Cardiomyopathy_Paediatric v1.57 C10orf71 Sarah Milton Classified gene: C10orf71 as Green List (high evidence)
Cardiomyopathy_Paediatric v1.57 C10orf71 Sarah Milton Gene: c10orf71 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.56 C10orf71 Sarah Milton gene: C10orf71 was added
gene: C10orf71 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: C10orf71 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: C10orf71 were set to 38950288
Phenotypes for gene: C10orf71 were set to Cardiomyopathy, dilated, 1QQ, MIM# 621251
Review for gene: C10orf71 was set to GREEN
Added comment: Loss of function variants in C10ORF71 have been associated with adult onset dilated cardiomyopathy, PMID 38950288 reports 3 cases of paediatric onset DCM ages 7-12 from 3 separate families.
Sources: Literature
Cardiomyopathy_Paediatric v1.55 TRIM37 Sarah Milton Classified gene: TRIM37 as Green List (high evidence)
Cardiomyopathy_Paediatric v1.55 TRIM37 Sarah Milton Gene: trim37 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.54 TRIM37 Sarah Milton edited their review of gene: TRIM37: Changed phenotypes: Mulibrey nanism, MIM#253250
Cardiomyopathy_Paediatric v1.54 TRIM37 Sarah Milton gene: TRIM37 was added
gene: TRIM37 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: TRIM37 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM37 were set to 41702694; 38116000; 36742244
Phenotypes for gene: TRIM37 were set to mulibrey nanism, MONDO:0009664
Review for gene: TRIM37 was set to GREEN
Added comment: Mulibrey nanism (MUL) is a rare autosomal recessive growth disorder with prenatal onset and characteristic facial features, along with occasional restrictive cardiomyopathy/restrictive pericarditis, failure of sexual maturation, insulin resistance with type 2 diabetes, and an increased risk for Wilms tumor. Numerous case reports with biallelic variants in the TRIM37 gene, which encodes a peroxisomal protein.
Sources: Literature
Mendeliome v2.362 PYCR1 chirag patel Phenotypes for gene: PYCR1 were changed from cutis laxa to Cutis laxa, autosomal recessive, type IIB, MIM# 612940; Cutis laxa, autosomal recessive, type IIIB, MIM# 614438
Mendeliome v2.361 THRB Lucy Spencer reviewed gene: THRB: Rating: AMBER; Mode of pathogenicity: None; Publications: 1991834, 1653889; Phenotypes: Thyroid hormone resistance, autosomal recessive, MIM# 274300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy v2.26 AR_SBMA_CAG Bryony Thompson Publications for STR: AR_SBMA_CAG were set to 2062380; 20301508; 29325606
Hereditary Neuropathy v2.25 AR_SBMA_CAG Bryony Thompson Classified STR: AR_SBMA_CAG as Green List (high evidence)
Hereditary Neuropathy v2.25 AR_SBMA_CAG Bryony Thompson Added comment: Comment on list classification: Sensory neuropathy is a feature of the condition
Hereditary Neuropathy v2.25 AR_SBMA_CAG Bryony Thompson Str: ar_sbma_cag has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.24 Bryony Thompson Copied STR AR_SBMA_CAG from panel Repeat Disorders
Hereditary Neuropathy v2.24 AR_SBMA_CAG Bryony Thompson STR: AR_SBMA_CAG was added
STR: AR_SBMA_CAG was added to Hereditary Neuropathy. Sources: Expert Review Green,Expert list
adult-onset tags were added to STR: AR_SBMA_CAG.
Mode of inheritance for STR: AR_SBMA_CAG was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for STR: AR_SBMA_CAG were set to 2062380; 20301508; 29325606
Phenotypes for STR: AR_SBMA_CAG were set to Spinal and bulbar muscular atrophy of Kennedy MIM#313200
Predominantly Antibody Deficiency v2.9 Bryony Thompson Copied gene SOCS1 from panel Common Variable Immunodeficiency
Predominantly Antibody Deficiency v2.9 SOCS1 Bryony Thompson gene: SOCS1 was added
gene: SOCS1 was added to Predominantly Antibody Deficiency. Sources: Expert Review Green,Literature
Mode of inheritance for gene: SOCS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOCS1 were set to 32499645; 10490099; 10490100
Phenotypes for gene: SOCS1 were set to Autoinflammatory syndrome, familial, with or without immunodeficiency, MIM# 619375; Common variable immunodeficiency
Predominantly Antibody Deficiency v2.8 Bryony Thompson Copied gene PRKCD from panel Common Variable Immunodeficiency
Predominantly Antibody Deficiency v2.8 PRKCD Bryony Thompson gene: PRKCD was added
gene: PRKCD was added to Predominantly Antibody Deficiency. Sources: Expert Review Green,Melbourne Genomics Health Alliance Immunology Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: PRKCD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRKCD were set to 23319571; 23666743; 23430113; 11976687; 33047643; 29867916
Phenotypes for gene: PRKCD were set to Autoimmune lymphoproliferative syndrome, type III, MIM# 615559; CVID 9
Predominantly Antibody Deficiency v2.7 Bryony Thompson Copied gene PLCG2 from panel Common Variable Immunodeficiency
Predominantly Antibody Deficiency v2.7 PLCG2 Bryony Thompson gene: PLCG2 was added
gene: PLCG2 was added to Predominantly Antibody Deficiency. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PLCG2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLCG2 were set to 31853824; 32671674; 22236196
Phenotypes for gene: PLCG2 were set to Common variable immunodeficiency; Autoinflammation, antibody deficiency, and immune dysregulation syndrome MIM#614878
Mode of pathogenicity for gene: PLCG2 was set to Other
Predominantly Antibody Deficiency v2.6 Bryony Thompson Copied gene MAP3K14 from panel Common Variable Immunodeficiency
Predominantly Antibody Deficiency v2.6 MAP3K14 Bryony Thompson gene: MAP3K14 was added
gene: MAP3K14 was added to Predominantly Antibody Deficiency. Sources: Expert Review Green,Melbourne Genomics Health Alliance Immunology Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: MAP3K14 was set to Unknown
Publications for gene: MAP3K14 were set to 29230214; 11251123; 25406581
Phenotypes for gene: MAP3K14 were set to Immunodeficiency 112, MIM# 620449
Predominantly Antibody Deficiency v2.5 Bryony Thompson Copied gene LRBA from panel Common Variable Immunodeficiency
Predominantly Antibody Deficiency v2.5 LRBA Bryony Thompson gene: LRBA was added
gene: LRBA was added to Predominantly Antibody Deficiency. Sources: Expert Review Green,Literature
Mode of inheritance for gene: LRBA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRBA were set to 22608502; 32506362
Phenotypes for gene: LRBA were set to Immunodeficiency, common variable, 8, with autoimmunity MIM#614700
Predominantly Antibody Deficiency v2.4 Bryony Thompson Copied gene ICOS from panel Common Variable Immunodeficiency
Predominantly Antibody Deficiency v2.4 ICOS Bryony Thompson gene: ICOS was added
gene: ICOS was added to Predominantly Antibody Deficiency. Sources: Expert Review Green,Melbourne Genomics Health Alliance Immunology Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: ICOS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ICOS were set to 12577056; 15507387; 19380800; 28861081; 31858365; 11343122; 16982935
Phenotypes for gene: ICOS were set to Immunodeficiency, common variable, 1 MIM# 607594; recurrent bacterial respiratory/gastrointestinal infections; autoimmunity; gastroenteritis; low IgG/IgA; normal-low IgM; hypogammaglobulinaemia; low-normal B-cells; normal T-cells; Bronchitis; Lymphadenopathy; Hepatomegaly; Diarrhoea
Predominantly Antibody Deficiency v2.3 Bryony Thompson Copied gene CTLA4 from panel Common Variable Immunodeficiency
Predominantly Antibody Deficiency v2.3 CTLA4 Bryony Thompson gene: CTLA4 was added
gene: CTLA4 was added to Predominantly Antibody Deficiency. Sources: Expert Review Green,Melbourne Genomics Health Alliance Immunology Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: CTLA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTLA4 were set to 25213377; 25329329; 30377434
Phenotypes for gene: CTLA4 were set to Autoimmune lymphoproliferative syndrome, type V, MIM# 616100
Predominantly Antibody Deficiency v2.2 Bryony Thompson Copied gene CD27 from panel Common Variable Immunodeficiency
Predominantly Antibody Deficiency v2.2 CD27 Bryony Thompson gene: CD27 was added
gene: CD27 was added to Predominantly Antibody Deficiency. Sources: Expert Review Green,Melbourne Genomics Health Alliance Immunology Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: CD27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD27 were set to 22197273; 22801960; 22365582; 25843314; 11062504
Phenotypes for gene: CD27 were set to Lymphoproliferative syndrome 2; CD27-deficiency MIM# 615122; hepatosplenomegaly; reduced CD8+ T-cell function; lymphadenopathy; hepatosplenomegaly; fever; increased susceptibility to EBV infection; aplastic anaemia
Predominantly Antibody Deficiency v2.1 Bryony Thompson Copied gene ADA2 from panel Common Variable Immunodeficiency
Predominantly Antibody Deficiency v2.1 ADA2 Bryony Thompson gene: ADA2 was added
gene: ADA2 was added to Predominantly Antibody Deficiency. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ADA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADA2 were set to 26922074; 29963054; 32659374; 24552284; 28493328; 28493328
Phenotypes for gene: ADA2 were set to Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome MIM#615688; common variable immunodeficiency
Haematological malignancies v0.146 Bryony Thompson HPO terms changed from to Hematological neoplasm, HP:0004377
List of related panels changed from to Hematological neoplasm; HP:0004377
Panel status changed from internal to public
Haematological malignancies v0.143 Bryony Thompson Added reviews for gene XRCC2 from panel Mendeliome
Haematological malignancies v0.142 Bryony Thompson Added reviews for gene WRAP53 from panel Mendeliome
Haematological malignancies v0.141 Bryony Thompson Added reviews for gene WAS from panel Mendeliome
Haematological malignancies v0.140 UNC13D Bryony Thompson Marked gene: UNC13D as ready
Haematological malignancies v0.140 UNC13D Bryony Thompson Gene: unc13d has been classified as Red List (Low Evidence).
Haematological malignancies v0.140 UNC13D Bryony Thompson Classified gene: UNC13D as Red List (low evidence)
Haematological malignancies v0.140 UNC13D Bryony Thompson Gene: unc13d has been classified as Red List (Low Evidence).
Haematological malignancies v0.139 UNC13D Bryony Thompson reviewed gene: UNC13D: Rating: RED; Mode of pathogenicity: None; Publications: 39569186, 24309606, 24827398, 21370424, 30758854; Phenotypes: hereditary hemophagocytic lymphohistiocytosis MONDO:0015541; Mode of inheritance: None
Haematological malignancies v0.139 UBE2T Bryony Thompson Publications for gene: UBE2T were set to 28297620
Haematological malignancies v0.138 Bryony Thompson Added reviews for gene UBE2T from panel Mendeliome
Haematological malignancies v0.137 UBA2 Bryony Thompson Classified gene: UBA2 as Red List (low evidence)
Haematological malignancies v0.137 UBA2 Bryony Thompson Added comment: Comment on list classification: Somatic change not germline
Haematological malignancies v0.137 UBA2 Bryony Thompson Gene: uba2 has been classified as Red List (Low Evidence).
Haematological malignancies v0.136 TSR2 Bryony Thompson Publications for gene: TSR2 were set to 28297620
Haematological malignancies v0.135 Bryony Thompson Added reviews for gene TSR2 from panel Mendeliome
Haematological malignancies v0.134 TP53 Bryony Thompson Publications for gene: TP53 were set to 27881370; 28297620
Haematological malignancies v0.133 TP53 Bryony Thompson reviewed gene: TP53: Rating: GREEN; Mode of pathogenicity: None; Publications: 38203823; Phenotypes: Li-Fraumeni syndrome MONDO:0018875; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v3.31 HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT Bryony Thompson HSF_ET_CCCCGCNCCGCCT_CCNCGCCT was changed to HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT
Repeat Disorders v1.3 HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT Bryony Thompson HSF_ET_CCCCGCNCCGCCT_CCNCGCCT was changed to HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT
Mendeliome v2.361 HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT Bryony Thompson HSF_ET_CCCCGCNCCGCCT_CCNCGCCT was changed to HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT
Repeat Disorders v1.2 Bryony Thompson Copied STR HSF_ET_CCCCGCNCCGCCT_CCNCGCCT from panel Mendeliome
Repeat Disorders v1.2 HSF_ET_CCCCGCNCCGCCT_CCNCGCCT Bryony Thompson STR: HSF_ET_CCCCGCNCCGCCT_CCNCGCCT was added
STR: HSF_ET_CCCCGCNCCGCCT_CCNCGCCT was added to Repeat Disorders. Sources: Expert Review Green,Literature
Mode of inheritance for STR: HSF_ET_CCCCGCNCCGCCT_CCNCGCCT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: HSF_ET_CCCCGCNCCGCCT_CCNCGCCT were set to 40581632
Phenotypes for STR: HSF_ET_CCCCGCNCCGCCT_CCNCGCCT were set to Essential tremor, MONDO:0003233
Early-onset Parkinson disease v3.30 Bryony Thompson Copied STR HSF_ET_CCCCGCNCCGCCT_CCNCGCCT from panel Mendeliome
Early-onset Parkinson disease v3.30 HSF_ET_CCCCGCNCCGCCT_CCNCGCCT Bryony Thompson STR: HSF_ET_CCCCGCNCCGCCT_CCNCGCCT was added
STR: HSF_ET_CCCCGCNCCGCCT_CCNCGCCT was added to Early-onset Parkinson disease. Sources: Expert Review Green,Literature
Mode of inheritance for STR: HSF_ET_CCCCGCNCCGCCT_CCNCGCCT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: HSF_ET_CCCCGCNCCGCCT_CCNCGCCT were set to 40581632
Phenotypes for STR: HSF_ET_CCCCGCNCCGCCT_CCNCGCCT were set to Essential tremor, MONDO:0003233
Mendeliome v2.360 HSF_ET_CCCCGCNCCGCCT_CCNCGCCT Bryony Thompson Marked STR: HSF_ET_CCCCGCNCCGCCT_CCNCGCCT as ready
Mendeliome v2.360 HSF_ET_CCCCGCNCCGCCT_CCNCGCCT Bryony Thompson Str: hsf_et_ccccgcnccgcct_ccncgcct has been classified as Green List (High Evidence).
Mendeliome v2.360 HSF_ET_CCCCGCNCCGCCT_CCNCGCCT Bryony Thompson Classified STR: HSF_ET_CCCCGCNCCGCCT_CCNCGCCT as Green List (high evidence)
Mendeliome v2.360 HSF_ET_CCCCGCNCCGCCT_CCNCGCCT Bryony Thompson Str: hsf_et_ccccgcnccgcct_ccncgcct has been classified as Green List (High Evidence).
Mendeliome v2.359 HSF_ET_CCCCGCNCCGCCT_CCNCGCCT Bryony Thompson STR: HSF_ET_CCCCGCNCCGCCT_CCNCGCCT was added
STR: HSF_ET_CCCCGCNCCGCCT_CCNCGCCT was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: HSF_ET_CCCCGCNCCGCCT_CCNCGCCT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: HSF_ET_CCCCGCNCCGCCT_CCNCGCCT were set to 40581632
Phenotypes for STR: HSF_ET_CCCCGCNCCGCCT_CCNCGCCT were set to Essential tremor, MONDO:0003233
Review for STR: HSF_ET_CCCCGCNCCGCCT_CCNCGCCT was set to GREEN
Added comment: NOTE: bp rather than number of repeats is reported above
PMID 40581632 reports 33 individuals (27 individuals >700bp) from 18 families with heterozygous intronic VNTR expansions (a combination of two VNTRs, (CCCCGCNCCGCCT)n/(CCNCGCCT)n) in intron 10 of HSF1 that co‑segregate with adult‑onset essential tremor; the expansion reduces HSF1 mRNA and protein levels and Drosophila HSF knockdown recapitulates a tremor phenotype, supporting a loss‑of‑function (haploinsufficiency) mechanism with incomplete penetrance. The study screened 165 Chinese ET pedigrees and 666 normal controls. Expanded VNTR alleles were highly enriched in ET-affected individuals, and the length of VNTRs was positively correlated with disease severity. Most controls had a HSF1 repeat expansion allele size <500 bp most affected individuals had an expansion >700 bp.
Sources: Literature
Early-onset Parkinson disease v3.29 Bryony Thompson Copied STR HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT from panel Mendeliome
Early-onset Parkinson disease v3.29 HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT Bryony Thompson STR: HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT was added
STR: HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT was added to Early-onset Parkinson disease. Sources: Expert Review Green,Literature
Mode of inheritance for STR: HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT were set to 40581632
Phenotypes for STR: HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT were set to Essential tremor, MONDO:0003233
Mendeliome v2.358 HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT Bryony Thompson Classified STR: HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT as Green List (high evidence)
Mendeliome v2.358 HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT Bryony Thompson Str: hsf1_et_ccccgcnccgcct_ccncgcct has been classified as Green List (High Evidence).
Mendeliome v2.357 HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT Bryony Thompson STR: HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT was added
STR: HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT were set to 40581632
Phenotypes for STR: HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT were set to Essential tremor, MONDO:0003233
Review for STR: HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT was set to GREEN
Added comment: NOTE: bp rather than number of repeats is reported above
PMID 40581632 reports 33 individuals (27 individuals >700bp) from 18 families with heterozygous intronic VNTR expansions (a combination of two VNTRs, (CCCCGCNCCGCCT)n/(CCNCGCCT)n) in intron 10 of HSF1 that co‑segregate with adult‑onset essential tremor; the expansion reduces HSF1 mRNA and protein levels and Drosophila HSF knockdown recapitulates a tremor phenotype, supporting a loss‑of‑function (haploinsufficiency) mechanism with incomplete penetrance. The study screened 165 Chinese ET pedigrees and 666 normal controls. Expanded VNTR alleles were highly enriched in ET-affected individuals, and the length of VNTRs was positively correlated with disease severity. Most controls had a HSF1 repeat expansion allele size <500 bp most affected individuals had an expansion >700 bp.
Sources: Literature
Repeat Disorders v1.1 HSF1_ET_CCCCGCNCCGCCT_CCNCGCCT Bryony Thompson STR: HSF1_ET_CCCCGCNCCGCCT/CCNCGCCT was added
STR: HSF1_ET_CCCCGCNCCGCCT/CCNCGCCT was added to Repeat Disorders. Sources: Literature
Mode of inheritance for STR: HSF1_ET_CCCCGCNCCGCCT/CCNCGCCT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: HSF1_ET_CCCCGCNCCGCCT/CCNCGCCT were set to 40581632
Phenotypes for STR: HSF1_ET_CCCCGCNCCGCCT/CCNCGCCT were set to Essential tremor, MONDO:0003233
Review for STR: HSF1_ET_CCCCGCNCCGCCT/CCNCGCCT was set to GREEN
Added comment: NOTE: bp rather than number of repeats is reported above
PMID 40581632 reports 33 individuals (27 individuals >700bp) from 18 families with heterozygous intronic VNTR expansions (a combination of two VNTRs, (CCCCGCNCCGCCT)n/(CCNCGCCT)n) in intron 10 of HSF1 that co‑segregate with adult‑onset essential tremor; the expansion reduces HSF1 mRNA and protein levels and Drosophila HSF knockdown recapitulates a tremor phenotype, supporting a loss‑of‑function (haploinsufficiency) mechanism with incomplete penetrance. The study screened 165 Chinese ET pedigrees and 666 normal controls. Expanded VNTR alleles were highly enriched in ET-affected individuals, and the length of VNTRs was positively correlated with disease severity. Most controls had a HSF1 repeat expansion allele size <500 bp most affected individuals had an expansion >700 bp.
Sources: Literature
Intellectual disability syndromic and non-syndromic v2.61 Bryony Thompson Copied gene PTPRG from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.61 PTPRG Bryony Thompson gene: PTPRG was added
gene: PTPRG was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PTPRG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPRG were set to 37056996
Phenotypes for gene: PTPRG were set to Neurodevelopmental disorder, MONDO:0700092
Mendeliome v2.356 PTPRG Bryony Thompson Marked gene: PTPRG as ready
Mendeliome v2.356 PTPRG Bryony Thompson Gene: ptprg has been classified as Amber List (Moderate Evidence).
Mendeliome v2.356 PTPRG Bryony Thompson Classified gene: PTPRG as Amber List (moderate evidence)
Mendeliome v2.356 PTPRG Bryony Thompson Gene: ptprg has been classified as Amber List (Moderate Evidence).
Mendeliome v2.355 PTPRG Bryony Thompson gene: PTPRG was added
gene: PTPRG was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTPRG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPRG were set to 37056996
Phenotypes for gene: PTPRG were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: PTPRG was set to AMBER
Added comment: PMID 37056996 reports 4 de novo heterozygous missense variants (also common poly‑T region variants) presenting with a neurodevelopmental disorder characterised by global developmental delay. No variant‑specific functional assays were performed for the reported missense variants. 2 of the missense are present in gnomAD v4 although rare.
Sources: Literature
Clefting disorders v1.4 AXIN2 Zornitza Stark Marked gene: AXIN2 as ready
Clefting disorders v1.4 AXIN2 Zornitza Stark Gene: axin2 has been classified as Amber List (Moderate Evidence).
Clefting disorders v1.4 AXIN2 Zornitza Stark Classified gene: AXIN2 as Amber List (moderate evidence)
Clefting disorders v1.4 AXIN2 Zornitza Stark Gene: axin2 has been classified as Amber List (Moderate Evidence).
Choanal atresia v2.1 AXIN2 Zornitza Stark Marked gene: AXIN2 as ready
Choanal atresia v2.1 AXIN2 Zornitza Stark Gene: axin2 has been classified as Red List (Low Evidence).
Choanal atresia v2.1 AXIN2 Zornitza Stark Classified gene: AXIN2 as Red List (low evidence)
Choanal atresia v2.1 AXIN2 Zornitza Stark Gene: axin2 has been classified as Red List (Low Evidence).
Polydactyly v1.3 SETD5 Zornitza Stark Marked gene: SETD5 as ready
Polydactyly v1.3 SETD5 Zornitza Stark Gene: setd5 has been classified as Green List (High Evidence).
Polydactyly v1.3 SETD5 Zornitza Stark Classified gene: SETD5 as Green List (high evidence)
Polydactyly v1.3 SETD5 Zornitza Stark Gene: setd5 has been classified as Green List (High Evidence).
Hand and foot malformations v1.1 SETD5 Zornitza Stark Marked gene: SETD5 as ready
Hand and foot malformations v1.1 SETD5 Zornitza Stark Gene: setd5 has been classified as Green List (High Evidence).
Hand and foot malformations v1.1 SETD5 Zornitza Stark Classified gene: SETD5 as Green List (high evidence)
Hand and foot malformations v1.1 SETD5 Zornitza Stark Gene: setd5 has been classified as Green List (High Evidence).
Mendeliome v2.354 DNAJC17 Zornitza Stark Marked gene: DNAJC17 as ready
Mendeliome v2.354 DNAJC17 Zornitza Stark Gene: dnajc17 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.354 Zornitza Stark Copied gene DNAJC17 from panel Autoinflammatory Disorders
Mendeliome v2.354 DNAJC17 Zornitza Stark gene: DNAJC17 was added
gene: DNAJC17 was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: DNAJC17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC17 were set to PMID: 42495638
Phenotypes for gene: DNAJC17 were set to Inborn error of immunity, MONDO:0003778, DNAJC17-related
Autoinflammatory Disorders v3.14 Zornitza Stark Added reviews for gene DNAJC17 from panel Autoinflammatory Disorders
Autoinflammatory Disorders v3.13 DNAJC17 Zornitza Stark Marked gene: DNAJC17 as ready
Autoinflammatory Disorders v3.13 DNAJC17 Zornitza Stark Gene: dnajc17 has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v3.13 DNAJC17 Zornitza Stark Phenotypes for gene: DNAJC17 were changed from Combined Immune deficiency; retinopathy; autoinflammation to Inborn error of immunity, MONDO:0003778, DNAJC17-related
Autoinflammatory Disorders v3.12 DNAJC17 Zornitza Stark Classified gene: DNAJC17 as Amber List (moderate evidence)
Autoinflammatory Disorders v3.12 DNAJC17 Zornitza Stark Gene: dnajc17 has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v3.11 DNAJC17 Zornitza Stark reviewed gene: DNAJC17: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Inborn error of immunity, MONDO:0003778, DNAJC17-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.353 PCDHGB1 Zornitza Stark Marked gene: PCDHGB1 as ready
Mendeliome v2.353 PCDHGB1 Zornitza Stark Gene: pcdhgb1 has been classified as Green List (High Evidence).
Mendeliome v2.353 PCDHGB1 Zornitza Stark commented on gene: PCDHGB1: Over 50 individuals reported as part of a cohort study. However, only 6 of the variants are absent from gnomAD. Others are present at low frequencies and are over-represented in the dystonia cohort.
Dystonia and Chorea v1.9 PCDHGB1 Zornitza Stark commented on gene: PCDHGB1: Over 50 individuals reported as part of a cohort study. However, only 6 of the variants are absent from gnomAD. Others are present at low frequencies and are over-represented in the dystonia cohort.
Mendeliome v2.353 Zornitza Stark Copied gene PCDHGB1 from panel Dystonia and Chorea
Mendeliome v2.353 PCDHGB1 Zornitza Stark gene: PCDHGB1 was added
gene: PCDHGB1 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PCDHGB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PCDHGB1 were set to 42482420; 35229923
Phenotypes for gene: PCDHGB1 were set to Inherited dystonia, MONDO:0044807, PCDHGB1-related
Penetrance for gene: PCDHGB1 were set to unknown
Dystonia and Chorea v1.9 PCDHGB1 Zornitza Stark Marked gene: PCDHGB1 as ready
Dystonia and Chorea v1.9 PCDHGB1 Zornitza Stark Gene: pcdhgb1 has been classified as Green List (High Evidence).
Dystonia and Chorea v1.9 PCDHGB1 Zornitza Stark Phenotypes for gene: PCDHGB1 were changed from Dystonia (HP:0001332); Cervical dystonia (HP:0002481); Blepharospasm (HP:0000617); Oromandibular dystonia (HP:0007291); Laryngeal dystonia (HP:0001593); Focal dystonia (HP:0002515); Segmental dystonia (HP:0007328); Generalized dystonia (HP:0007329); Myoclonus (HP:0001336); Parkinsonism (HP:0001300); Ataxia (HP:0001251); External ophthalmoplegia (HP:0000605); Sensorineural hearing impairment (HP:0000407); Abnormal gait (HP:0001288); Tremor (HP:0001337); Adult onset (HP:0003581); Childhood onset (HP:0011463); Family history of dystonia (HP:0032371); Autosomal dominant inheritance (HP:0000006) to Inherited dystonia, MONDO:0044807, PCDHGB1-related
Dystonia and Chorea v1.8 PCDHGB1 Zornitza Stark Classified gene: PCDHGB1 as Green List (high evidence)
Dystonia and Chorea v1.8 PCDHGB1 Zornitza Stark Gene: pcdhgb1 has been classified as Green List (High Evidence).
Dystonia and Chorea v1.7 PCDHGB1 Zornitza Stark reviewed gene: PCDHGB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Inherited dystonia, MONDO:0044807, PCDHGB1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy v2.23 POLR3A Zornitza Stark Marked gene: POLR3A as ready
Hereditary Neuropathy v2.23 POLR3A Zornitza Stark Gene: polr3a has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.23 POLR3A Zornitza Stark Phenotypes for gene: POLR3A were changed from POLR3A-related disorder MONDO:0700276; Susceptibility to severe VZV infection; peripheral neuropathy, MONDO:0005244, POLR3A-related to peripheral neuropathy, MONDO:0005244, POLR3A-related
Hereditary Neuropathy v2.22 POLR3A Zornitza Stark Mode of inheritance for gene: POLR3A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy v2.21 Zornitza Stark Copied gene POLR3A from panel Mendeliome
Hereditary Neuropathy v2.21 POLR3A Zornitza Stark gene: POLR3A was added
gene: POLR3A was added to Hereditary Neuropathy. Sources: Expert Review Green,Literature,Expert Review Green,Victorian Clinical Genetics Services
deep intronic tags were added to gene: POLR3A.
Mode of inheritance for gene: POLR3A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: POLR3A were set to 31637490; 30414627; 30450527; 30323018; 21671373; 10607952; 42260910
Phenotypes for gene: POLR3A were set to POLR3A-related disorder MONDO:0700276; Susceptibility to severe VZV infection; peripheral neuropathy, MONDO:0005244, POLR3A-related
Mendeliome v2.352 POLR3A Zornitza Stark Phenotypes for gene: POLR3A were changed from POLR3A-related disorder MONDO:0700276; Susceptibility to severe VZV infection; POLR3A-related spastic ataxia to POLR3A-related disorder MONDO:0700276; Susceptibility to severe VZV infection; peripheral neuropathy, MONDO:0005244, POLR3A-related
Mendeliome v2.351 POLR3A Zornitza Stark Publications for gene: POLR3A were set to 31637490
Growth failure v2.12 ARCN1 Zornitza Stark Marked gene: ARCN1 as ready
Growth failure v2.12 ARCN1 Zornitza Stark Gene: arcn1 has been classified as Green List (High Evidence).
Growth failure v2.12 ARCN1 Zornitza Stark Phenotypes for gene: ARCN1 were changed from small stature; IUGR; cleft; genitourinary malformations; microcephaly; transient liver dysfunction; giant cell hepatitis; hepatoblastoma; cataracts; lethal skeletal manifestations to Short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay (MIM#617164)
Growth failure v2.11 ARCN1 Zornitza Stark Classified gene: ARCN1 as Green List (high evidence)
Growth failure v2.11 ARCN1 Zornitza Stark Gene: arcn1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.60 NPTN Zornitza Stark Marked gene: NPTN as ready
Intellectual disability syndromic and non-syndromic v2.60 NPTN Zornitza Stark Gene: nptn has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.60 Zornitza Stark Copied gene NPTN from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.60 NPTN Zornitza Stark gene: NPTN was added
gene: NPTN was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NPTN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NPTN were set to 42387534
Phenotypes for gene: NPTN were set to neurodevelopmental disorder, MONDO:0700092
Mendeliome v2.350 NPTN Zornitza Stark Marked gene: NPTN as ready
Mendeliome v2.350 NPTN Zornitza Stark Gene: nptn has been classified as Green List (High Evidence).
Mendeliome v2.350 NPTN Zornitza Stark Classified gene: NPTN as Green List (high evidence)
Mendeliome v2.350 NPTN Zornitza Stark Gene: nptn has been classified as Green List (High Evidence).
Combined Immunodeficiency v2.5 MYB Zornitza Stark Marked gene: MYB as ready
Combined Immunodeficiency v2.5 MYB Zornitza Stark Gene: myb has been classified as Green List (High Evidence).
Combined Immunodeficiency v2.5 Zornitza Stark Copied gene MYB from panel Mendeliome
Combined Immunodeficiency v2.5 MYB Zornitza Stark gene: MYB was added
gene: MYB was added to Combined Immunodeficiency. Sources: Expert Review Green,Literature
Mode of inheritance for gene: MYB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYB were set to 20130238; 27577878; 29654210; 36168523
Phenotypes for gene: MYB were set to combined immunodeficiency, MONDO:0015131
Mendeliome v2.349 MYB Zornitza Stark Marked gene: MYB as ready
Mendeliome v2.349 MYB Zornitza Stark Gene: myb has been classified as Green List (High Evidence).
Mendeliome v2.349 MYB Zornitza Stark Classified gene: MYB as Green List (high evidence)
Mendeliome v2.349 MYB Zornitza Stark Gene: myb has been classified as Green List (High Evidence).
Incidentalome v1.9 BRD9 Zornitza Stark Marked gene: BRD9 as ready
Incidentalome v1.9 BRD9 Zornitza Stark Gene: brd9 has been classified as Red List (Low Evidence).
Mendeliome v2.348 Zornitza Stark removed gene:BRD9 from the panel
Incidentalome v1.9 Zornitza Stark Copied gene BRD9 from panel Mendeliome
Incidentalome v1.9 BRD9 Zornitza Stark gene: BRD9 was added
gene: BRD9 was added to Incidentalome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: BRD9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRD9 were set to 40959972
Phenotypes for gene: BRD9 were set to Early onset Parkinson Disease MONDO:0017279
Mendeliome v2.347 BRD9 Zornitza Stark Marked gene: BRD9 as ready
Mendeliome v2.347 BRD9 Zornitza Stark Gene: brd9 has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v3.28 BRD9 Zornitza Stark Marked gene: BRD9 as ready
Early-onset Parkinson disease v3.28 BRD9 Zornitza Stark Gene: brd9 has been classified as Red List (Low Evidence).
Congenital Heart Defect v1.13 IQGAP1 Zornitza Stark Marked gene: IQGAP1 as ready
Congenital Heart Defect v1.13 IQGAP1 Zornitza Stark Gene: iqgap1 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v1.13 IQGAP1 Zornitza Stark Phenotypes for gene: IQGAP1 were changed from Tetralogy of Fallot MONDO:0008542; Annular Pancreas MONDO:0008183 to Tetralogy of Fallot MONDO:0008542
Congenital Heart Defect v1.12 Zornitza Stark Copied gene IQGAP1 from panel Mendeliome
Congenital Heart Defect v1.12 IQGAP1 Zornitza Stark gene: IQGAP1 was added
gene: IQGAP1 was added to Congenital Heart Defect. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: IQGAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IQGAP1 were set to 37635636; 34328347; 30232381
Phenotypes for gene: IQGAP1 were set to Tetralogy of Fallot MONDO:0008542; Annular Pancreas MONDO:0008183
Mendeliome v2.347 IQGAP1 Zornitza Stark Marked gene: IQGAP1 as ready
Mendeliome v2.347 IQGAP1 Zornitza Stark Gene: iqgap1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.347 IQGAP1 Zornitza Stark Classified gene: IQGAP1 as Amber List (moderate evidence)
Mendeliome v2.347 IQGAP1 Zornitza Stark Gene: iqgap1 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v2.20 AP5Z1 Zornitza Stark Marked gene: AP5Z1 as ready
Hereditary Neuropathy v2.20 AP5Z1 Zornitza Stark Gene: ap5z1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.20 AP5Z1 Zornitza Stark Classified gene: AP5Z1 as Green List (high evidence)
Hereditary Neuropathy v2.20 AP5Z1 Zornitza Stark Gene: ap5z1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.19 ERCC4 Zornitza Stark Marked gene: ERCC4 as ready
Hereditary Neuropathy v2.19 ERCC4 Zornitza Stark Gene: ercc4 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.19 ERCC4 Zornitza Stark Classified gene: ERCC4 as Green List (high evidence)
Hereditary Neuropathy v2.19 ERCC4 Zornitza Stark Gene: ercc4 has been classified as Green List (High Evidence).
Leukodystrophy v1.4 COL4A2 Zornitza Stark Marked gene: COL4A2 as ready
Leukodystrophy v1.4 COL4A2 Zornitza Stark Gene: col4a2 has been classified as Amber List (Moderate Evidence).
Leukodystrophy v1.4 COL4A2 Zornitza Stark Phenotypes for gene: COL4A2 were changed from Brain small vessel disease 2, 614483 to Brain small vessel disease 2B, autosomal recessive, MONDO:0980747
Leukodystrophy v1.3 COL4A2 Zornitza Stark Mode of inheritance for gene: COL4A2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy v1.2 COL4A2 Zornitza Stark Classified gene: COL4A2 as Amber List (moderate evidence)
Leukodystrophy v1.2 COL4A2 Zornitza Stark Gene: col4a2 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v2.18 IBA57 Zornitza Stark Marked gene: IBA57 as ready
Hereditary Neuropathy v2.18 IBA57 Zornitza Stark Gene: iba57 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.18 IBA57 Zornitza Stark Classified gene: IBA57 as Green List (high evidence)
Hereditary Neuropathy v2.18 IBA57 Zornitza Stark Gene: iba57 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.17 MADD Zornitza Stark Marked gene: MADD as ready
Hereditary Neuropathy v2.17 MADD Zornitza Stark Gene: madd has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.17 MADD Zornitza Stark Classified gene: MADD as Green List (high evidence)
Hereditary Neuropathy v2.17 MADD Zornitza Stark Gene: madd has been classified as Green List (High Evidence).
Mendeliome v2.346 SPMIP10 Zornitza Stark Marked gene: SPMIP10 as ready
Mendeliome v2.346 SPMIP10 Zornitza Stark Gene: spmip10 has been classified as Red List (Low Evidence).
Infertility and Recurrent Pregnancy Loss v2.38 SPMIP10 Zornitza Stark Marked gene: SPMIP10 as ready
Infertility and Recurrent Pregnancy Loss v2.38 SPMIP10 Zornitza Stark Gene: spmip10 has been classified as Red List (Low Evidence).
Mendeliome v2.346 DND1 Zornitza Stark Marked gene: DND1 as ready
Mendeliome v2.346 DND1 Zornitza Stark Gene: dnd1 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v2.38 DND1 Zornitza Stark Marked gene: DND1 as ready
Infertility and Recurrent Pregnancy Loss v2.38 DND1 Zornitza Stark Gene: dnd1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.346 ST6GALNAC1 Zornitza Stark Marked gene: ST6GALNAC1 as ready
Mendeliome v2.346 ST6GALNAC1 Zornitza Stark Gene: st6galnac1 has been classified as Red List (Low Evidence).
Inflammatory bowel disease v1.3 ST6GALNAC1 Zornitza Stark Marked gene: ST6GALNAC1 as ready
Inflammatory bowel disease v1.3 ST6GALNAC1 Zornitza Stark Gene: st6galnac1 has been classified as Red List (Low Evidence).
Mendeliome v2.346 DMXL2 Zornitza Stark Mode of inheritance for gene: DMXL2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v1.11 GJC1 Zornitza Stark Marked gene: GJC1 as ready
Congenital Heart Defect v1.11 GJC1 Zornitza Stark Gene: gjc1 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v2.16 ZC4H2 Zornitza Stark Classified gene: ZC4H2 as Green List (high evidence)
Hereditary Neuropathy v2.16 ZC4H2 Zornitza Stark Gene: zc4h2 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.15 VPS13A Zornitza Stark Marked gene: VPS13A as ready
Hereditary Neuropathy v2.15 VPS13A Zornitza Stark Gene: vps13a has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.15 VPS13A Zornitza Stark Classified gene: VPS13A as Green List (high evidence)
Hereditary Neuropathy v2.15 VPS13A Zornitza Stark Gene: vps13a has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.14 TOP3A Zornitza Stark Marked gene: TOP3A as ready
Hereditary Neuropathy v2.14 TOP3A Zornitza Stark Gene: top3a has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.14 TOP3A Zornitza Stark Classified gene: TOP3A as Green List (high evidence)
Hereditary Neuropathy v2.14 TOP3A Zornitza Stark Gene: top3a has been classified as Green List (High Evidence).
Early-onset Dementia v2.13 SORBS2 Zornitza Stark Marked gene: SORBS2 as ready
Early-onset Dementia v2.13 SORBS2 Zornitza Stark Gene: sorbs2 has been classified as Red List (Low Evidence).
Early-onset Dementia v2.13 SORBS2 Zornitza Stark Phenotypes for gene: SORBS2 were changed from congenital heart disease MONDO:0005453, SORBS2-related; familial Alzheimer disease MONDO:0100087, SORBS2-related to familial Alzheimer disease MONDO:0100087, SORBS2-related
Early-onset Dementia v2.12 SORBS2 Zornitza Stark Classified gene: SORBS2 as Red List (low evidence)
Early-onset Dementia v2.12 SORBS2 Zornitza Stark Gene: sorbs2 has been classified as Red List (Low Evidence).
Early-onset Dementia v2.11 SORBS2 Zornitza Stark reviewed gene: SORBS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: familial Alzheimer disease MONDO:0100087, SORBS2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.53 MAP3K7 Zornitza Stark Marked gene: MAP3K7 as ready
Cardiomyopathy_Paediatric v1.53 MAP3K7 Zornitza Stark Gene: map3k7 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.13 RNASEH1 Zornitza Stark Marked gene: RNASEH1 as ready
Hereditary Neuropathy v2.13 RNASEH1 Zornitza Stark Gene: rnaseh1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.13 RNASEH1 Zornitza Stark Classified gene: RNASEH1 as Green List (high evidence)
Hereditary Neuropathy v2.13 RNASEH1 Zornitza Stark Gene: rnaseh1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.53 MED12 Zornitza Stark Marked gene: MED12 as ready
Cardiomyopathy_Paediatric v1.53 MED12 Zornitza Stark Gene: med12 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.53 MTO1 Zornitza Stark Marked gene: MTO1 as ready
Cardiomyopathy_Paediatric v1.53 MTO1 Zornitza Stark Gene: mto1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.53 NEK8 Zornitza Stark Marked gene: NEK8 as ready
Cardiomyopathy_Paediatric v1.53 NEK8 Zornitza Stark Gene: nek8 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v2.12 PIGB Zornitza Stark Marked gene: PIGB as ready
Hereditary Neuropathy v2.12 PIGB Zornitza Stark Gene: pigb has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.12 PIGB Zornitza Stark Classified gene: PIGB as Green List (high evidence)
Hereditary Neuropathy v2.12 PIGB Zornitza Stark Gene: pigb has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.53 PIGA Zornitza Stark Marked gene: PIGA as ready
Cardiomyopathy_Paediatric v1.53 PIGA Zornitza Stark Gene: piga has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.53 SLC6A8 Zornitza Stark Marked gene: SLC6A8 as ready
Cardiomyopathy_Paediatric v1.53 SLC6A8 Zornitza Stark Gene: slc6a8 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v2.11 NRCAM Zornitza Stark Marked gene: NRCAM as ready
Hereditary Neuropathy v2.11 NRCAM Zornitza Stark Gene: nrcam has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.11 NRCAM Zornitza Stark Classified gene: NRCAM as Green List (high evidence)
Hereditary Neuropathy v2.11 NRCAM Zornitza Stark Gene: nrcam has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.53 ALG3 Zornitza Stark Marked gene: ALG3 as ready
Cardiomyopathy_Paediatric v1.53 ALG3 Zornitza Stark Gene: alg3 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.53 CHKB Zornitza Stark Marked gene: CHKB as ready
Cardiomyopathy_Paediatric v1.53 CHKB Zornitza Stark Gene: chkb has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.53 CHKB Zornitza Stark Classified gene: CHKB as Green List (high evidence)
Cardiomyopathy_Paediatric v1.53 CHKB Zornitza Stark Gene: chkb has been classified as Green List (High Evidence).
Fetal anomalies v2.22 GIT1 Zornitza Stark Marked gene: GIT1 as ready
Fetal anomalies v2.22 GIT1 Zornitza Stark Gene: git1 has been classified as Green List (High Evidence).
Fetal anomalies v2.22 Zornitza Stark Copied gene GIT1 from panel Growth failure
Fetal anomalies v2.22 GIT1 Zornitza Stark gene: GIT1 was added
gene: GIT1 was added to Fetal anomalies. Sources: Expert Review Green,Literature,Literature
Mode of inheritance for gene: GIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GIT1 were set to 42360756
Phenotypes for gene: GIT1 were set to Neurodevelopmental disorder, MONDO:0700092, GIT1-related
Growth failure v2.10 GIT1 Zornitza Stark Marked gene: GIT1 as ready
Growth failure v2.10 GIT1 Zornitza Stark Gene: git1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.59 GIT1 Zornitza Stark Marked gene: GIT1 as ready
Intellectual disability syndromic and non-syndromic v2.59 GIT1 Zornitza Stark Gene: git1 has been classified as Green List (High Evidence).
Genetic Epilepsy v2.30 GIT1 Zornitza Stark Marked gene: GIT1 as ready
Genetic Epilepsy v2.30 GIT1 Zornitza Stark Gene: git1 has been classified as Green List (High Evidence).
Mendeliome v2.345 GIT1 Zornitza Stark Marked gene: GIT1 as ready
Mendeliome v2.345 GIT1 Zornitza Stark Gene: git1 has been classified as Green List (High Evidence).
Microcephaly v2.8 GIT1 Zornitza Stark Marked gene: GIT1 as ready
Microcephaly v2.8 GIT1 Zornitza Stark Gene: git1 has been classified as Green List (High Evidence).
Mendeliome v2.345 ATG9B Zornitza Stark Marked gene: ATG9B as ready
Mendeliome v2.345 ATG9B Zornitza Stark Gene: atg9b has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v2.59 KLC1 Zornitza Stark Marked gene: KLC1 as ready
Intellectual disability syndromic and non-syndromic v2.59 KLC1 Zornitza Stark Gene: klc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.59 KLC1 Zornitza Stark reviewed gene: KLC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v2.345 KLC1 Zornitza Stark Marked gene: KLC1 as ready
Mendeliome v2.345 KLC1 Zornitza Stark Gene: klc1 has been classified as Green List (High Evidence).
Mendeliome v2.345 KLC1 Zornitza Stark reviewed gene: KLC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia and Chorea v1.7 KLC1 Zornitza Stark Marked gene: KLC1 as ready
Dystonia and Chorea v1.7 KLC1 Zornitza Stark Gene: klc1 has been classified as Green List (High Evidence).
Dystonia and Chorea v1.7 KLC1 Zornitza Stark changed review comment from: Three of the individuals had de novo missense variants affecting p.Asp253; to: Three of the individuals had de novo missense variants affecting p.Asp253. All variants are absent from gnomAD.
Dystonia and Chorea v1.7 KLC1 Zornitza Stark reviewed gene: KLC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: KLC1-related neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v2.345 ITPRID2 Zornitza Stark Marked gene: ITPRID2 as ready
Mendeliome v2.345 ITPRID2 Zornitza Stark Gene: itprid2 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.345 ITPRID2 Zornitza Stark Classified gene: ITPRID2 as Amber List (moderate evidence)
Mendeliome v2.345 ITPRID2 Zornitza Stark Gene: itprid2 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v2.38 ITPRID2 Zornitza Stark Marked gene: ITPRID2 as ready
Infertility and Recurrent Pregnancy Loss v2.38 ITPRID2 Zornitza Stark Gene: itprid2 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v2.38 ITPRID2 Zornitza Stark Classified gene: ITPRID2 as Amber List (moderate evidence)
Infertility and Recurrent Pregnancy Loss v2.38 ITPRID2 Zornitza Stark Gene: itprid2 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.344 MED20 Zornitza Stark Marked gene: MED20 as ready
Mendeliome v2.344 MED20 Zornitza Stark Gene: med20 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.59 MED20 Zornitza Stark Marked gene: MED20 as ready
Intellectual disability syndromic and non-syndromic v2.59 MED20 Zornitza Stark Gene: med20 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.344 USP34 Zornitza Stark Marked gene: USP34 as ready
Mendeliome v2.344 USP34 Zornitza Stark Gene: usp34 has been classified as Green List (High Evidence).
Autism v1.13 USP34 Zornitza Stark Marked gene: USP34 as ready
Autism v1.13 USP34 Zornitza Stark Gene: usp34 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.59 USP34 Zornitza Stark Marked gene: USP34 as ready
Intellectual disability syndromic and non-syndromic v2.59 USP34 Zornitza Stark Gene: usp34 has been classified as Green List (High Evidence).
Genetic Epilepsy v2.30 GSK3B Zornitza Stark Classified gene: GSK3B as Amber List (moderate evidence)
Genetic Epilepsy v2.30 GSK3B Zornitza Stark Gene: gsk3b has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v2.29 GSK3B Zornitza Stark edited their review of gene: GSK3B: Changed rating: AMBER
Genetic Epilepsy v2.29 GSK3B Zornitza Stark Deleted their comment
Genetic Epilepsy v2.29 GSK3B Zornitza Stark Classified gene: GSK3B as Green List (high evidence)
Genetic Epilepsy v2.29 GSK3B Zornitza Stark Gene: gsk3b has been classified as Green List (High Evidence).
Genetic Epilepsy v2.28 GSK3B Zornitza Stark reviewed gene: GSK3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 39472663; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, GSK3B-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.52 COQ2 Zornitza Stark Marked gene: COQ2 as ready
Cardiomyopathy_Paediatric v1.52 COQ2 Zornitza Stark Gene: coq2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.52 FBXL4 Zornitza Stark Marked gene: FBXL4 as ready
Cardiomyopathy_Paediatric v1.52 FBXL4 Zornitza Stark Gene: fbxl4 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.52 LETM1 Zornitza Stark Marked gene: LETM1 as ready
Cardiomyopathy_Paediatric v1.52 LETM1 Zornitza Stark Gene: letm1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.52 NDUFA5 Zornitza Stark Marked gene: NDUFA5 as ready
Cardiomyopathy_Paediatric v1.52 NDUFA5 Zornitza Stark Gene: ndufa5 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.52 NDUFA5 Zornitza Stark Phenotypes for gene: NDUFA5 were changed from Mitochondrial disease, MONDO:0044970 to Mitochondrial disease, MONDO:0044970, NDUFA5-related
Intellectual disability syndromic and non-syndromic v2.59 NDUFA5 Zornitza Stark edited their review of gene: NDUFA5: Changed phenotypes: Mitochondrial disease, MONDO:0044970, NDUFA5-related
Intellectual disability syndromic and non-syndromic v2.59 NDUFA5 Zornitza Stark Marked gene: NDUFA5 as ready
Intellectual disability syndromic and non-syndromic v2.59 NDUFA5 Zornitza Stark Gene: ndufa5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.59 NDUFA5 Zornitza Stark reviewed gene: NDUFA5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Inborn mitochondrial metabolism disorder MONDO:0004069, NDUFA5-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.51 QRSL1 Zornitza Stark Marked gene: QRSL1 as ready
Cardiomyopathy_Paediatric v1.51 QRSL1 Zornitza Stark Gene: qrsl1 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v1.4 CCDC201 Zornitza Stark Marked gene: CCDC201 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v1.4 CCDC201 Zornitza Stark Gene: ccdc201 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v1.4 Zornitza Stark Copied gene CCDC201 from panel Mendeliome
Primary Ovarian Insufficiency_Premature Ovarian Failure v1.4 CCDC201 Zornitza Stark gene: CCDC201 was added
gene: CCDC201 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Expert Review Red,Literature
Mode of inheritance for gene: CCDC201 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC201 were set to 39192094
Phenotypes for gene: CCDC201 were set to Infertility disorder, MONDO:0005047
Mendeliome v2.344 CCDC201 Zornitza Stark Marked gene: CCDC201 as ready
Mendeliome v2.344 CCDC201 Zornitza Stark Gene: ccdc201 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v2.59 ATP8B2 Zornitza Stark Marked gene: ATP8B2 as ready
Intellectual disability syndromic and non-syndromic v2.59 ATP8B2 Zornitza Stark Gene: atp8b2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.59 Zornitza Stark Copied gene ATP8B2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.59 ATP8B2 Zornitza Stark gene: ATP8B2 was added
gene: ATP8B2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: ATP8B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP8B2 were set to 39219493
Phenotypes for gene: ATP8B2 were set to Neurodevelopmental disorder MONDO:0700092, ATP8B2-related
Mendeliome v2.344 ATP8B2 Zornitza Stark Marked gene: ATP8B2 as ready
Mendeliome v2.344 ATP8B2 Zornitza Stark Gene: atp8b2 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v2.1 TES Zornitza Stark Marked gene: TES as ready
Aortopathy_Connective Tissue Disorders v2.1 TES Zornitza Stark Gene: tes has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v2.1 Zornitza Stark Copied gene TES from panel Mendeliome
Aortopathy_Connective Tissue Disorders v2.1 TES Zornitza Stark gene: TES was added
gene: TES was added to Aortopathy_Connective Tissue Disorders. Sources: Expert Review Red,Literature
Mode of inheritance for gene: TES was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TES were set to 33092471
Phenotypes for gene: TES were set to Thoracic aortic aneurysm, MONDO:0005396,TES-related
Intellectual disability syndromic and non-syndromic v2.58 YBX3 Zornitza Stark Marked gene: YBX3 as ready
Intellectual disability syndromic and non-syndromic v2.58 YBX3 Zornitza Stark Gene: ybx3 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v2.58 Zornitza Stark Copied gene YBX3 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.58 YBX3 Zornitza Stark gene: YBX3 was added
gene: YBX3 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Red,Literature
Mode of inheritance for gene: YBX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: YBX3 were set to 39423228; 38260399
Phenotypes for gene: YBX3 were set to Neurodevelopmental disorder, MONDO:0700092
Mendeliome v2.344 YBX3 Zornitza Stark Marked gene: YBX3 as ready
Mendeliome v2.344 YBX3 Zornitza Stark Gene: ybx3 has been classified as Red List (Low Evidence).
Fetal anomalies v2.21 RIPPLY3 Zornitza Stark Marked gene: RIPPLY3 as ready
Fetal anomalies v2.21 RIPPLY3 Zornitza Stark Gene: ripply3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v2.21 Zornitza Stark Copied gene RIPPLY3 from panel Mendeliome
Fetal anomalies v2.21 RIPPLY3 Zornitza Stark gene: RIPPLY3 was added
gene: RIPPLY3 was added to Fetal anomalies. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: RIPPLY3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RIPPLY3 were set to 30241482; 21177346
Phenotypes for gene: RIPPLY3 were set to Congenital heart disease, MONDO:0005453, RIPPLY3-related
Mendeliome v2.344 CHAF1A Zornitza Stark Marked gene: CHAF1A as ready
Mendeliome v2.344 CHAF1A Zornitza Stark Gene: chaf1a has been classified as Green List (High Evidence).
Fetal anomalies v2.20 CHAF1A Zornitza Stark Marked gene: CHAF1A as ready
Fetal anomalies v2.20 CHAF1A Zornitza Stark Gene: chaf1a has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v2.6 CHAF1A Zornitza Stark Marked gene: CHAF1A as ready
Mandibulofacial Acrofacial dysostosis v2.6 CHAF1A Zornitza Stark Gene: chaf1a has been classified as Green List (High Evidence).
Fetal anomalies v2.20 Zornitza Stark Copied gene CHAF1A from panel Mendeliome
Fetal anomalies v2.20 CHAF1A Zornitza Stark gene: CHAF1A was added
gene: CHAF1A was added to Fetal anomalies. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CHAF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHAF1A were set to 39333427
Phenotypes for gene: CHAF1A were set to oculoauriculovertebral spectrum with radial defects MONDO:0007712, CHAF1A-related
Mandibulofacial Acrofacial dysostosis v2.6 Zornitza Stark Copied gene CHAF1A from panel Mendeliome
Mandibulofacial Acrofacial dysostosis v2.6 CHAF1A Zornitza Stark gene: CHAF1A was added
gene: CHAF1A was added to Mandibulofacial Acrofacial dysostosis. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CHAF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHAF1A were set to 39333427
Phenotypes for gene: CHAF1A were set to oculoauriculovertebral spectrum with radial defects MONDO:0007712, CHAF1A-related
Clefting disorders v1.3 Zornitza Stark removed gene:CHAF1A from the panel
Ectodermal Dysplasia v1.7 Zornitza Stark removed gene:CHAF1A from the panel
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.6 CHAF1A Zornitza Stark Marked gene: CHAF1A as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.6 CHAF1A Zornitza Stark Gene: chaf1a has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.6 CHAF1A Zornitza Stark Classified gene: CHAF1A as Green List (high evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.6 CHAF1A Zornitza Stark Gene: chaf1a has been classified as Green List (High Evidence).
Mendeliome v2.344 FIBCD1 Zornitza Stark Marked gene: FIBCD1 as ready
Mendeliome v2.344 FIBCD1 Zornitza Stark Gene: fibcd1 has been classified as Amber List (Moderate Evidence).
Autism v1.13 FIBCD1 Zornitza Stark Marked gene: FIBCD1 as ready
Autism v1.13 FIBCD1 Zornitza Stark Gene: fibcd1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.57 FIBCD1 Zornitza Stark Marked gene: FIBCD1 as ready
Intellectual disability syndromic and non-syndromic v2.57 FIBCD1 Zornitza Stark Gene: fibcd1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.344 GAK Zornitza Stark Marked gene: GAK as ready
Mendeliome v2.344 GAK Zornitza Stark Gene: gak has been classified as Red List (Low Evidence).
Mendeliome v2.344 GAK Zornitza Stark Classified gene: GAK as Red List (low evidence)
Mendeliome v2.344 GAK Zornitza Stark Gene: gak has been classified as Red List (Low Evidence).
Mendeliome v2.343 GAK Zornitza Stark reviewed gene: GAK: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder MONDO:0700092, GAK-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v2.57 GAK Zornitza Stark Marked gene: GAK as ready
Intellectual disability syndromic and non-syndromic v2.57 GAK Zornitza Stark Gene: gak has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v2.57 GAK Zornitza Stark Classified gene: GAK as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v2.57 GAK Zornitza Stark Gene: gak has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v2.56 GAK Zornitza Stark reviewed gene: GAK: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder MONDO:0700092, GAK-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v2.343 ZC3H11A Zornitza Stark Classified gene: ZC3H11A as Red List (low evidence)
Mendeliome v2.343 ZC3H11A Zornitza Stark Gene: zc3h11a has been classified as Red List (Low Evidence).
Mendeliome v2.342 ZC3H11A Zornitza Stark reviewed gene: ZC3H11A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: myopia MONDO:0001384, ZC3H11A-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v2.342 ZC3H11A Zornitza Stark Marked gene: ZC3H11A as ready
Mendeliome v2.342 ZC3H11A Zornitza Stark Gene: zc3h11a has been classified as Amber List (Moderate Evidence).
Mendeliome v2.342 GPAT2 Zornitza Stark Marked gene: GPAT2 as ready
Mendeliome v2.342 GPAT2 Zornitza Stark Gene: gpat2 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.342 GPAT2 Zornitza Stark Classified gene: GPAT2 as Amber List (moderate evidence)
Mendeliome v2.342 GPAT2 Zornitza Stark Gene: gpat2 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.341 GPAT2 Zornitza Stark reviewed gene: GPAT2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: GPAT2-related non‑obstructive azoospermia/extreme oligozoospermia due to spermatogenic failure MONDO:0100459; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v2.37 GPAT2 Zornitza Stark Marked gene: GPAT2 as ready
Infertility and Recurrent Pregnancy Loss v2.37 GPAT2 Zornitza Stark Gene: gpat2 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v2.37 GPAT2 Zornitza Stark Classified gene: GPAT2 as Amber List (moderate evidence)
Infertility and Recurrent Pregnancy Loss v2.37 GPAT2 Zornitza Stark Gene: gpat2 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v2.36 GPAT2 Zornitza Stark reviewed gene: GPAT2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: GPAT2-related non‑obstructive azoospermia/extreme oligozoospermia due to spermatogenic failure MONDO:0100459; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypogonadotropic hypogonadism v1.15 PLEKHA6 Zornitza Stark Marked gene: PLEKHA6 as ready
Hypogonadotropic hypogonadism v1.15 PLEKHA6 Zornitza Stark Gene: plekha6 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v1.15 Zornitza Stark Copied gene PLEKHA6 from panel Mendeliome
Hypogonadotropic hypogonadism v1.15 PLEKHA6 Zornitza Stark gene: PLEKHA6 was added
gene: PLEKHA6 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Red,Literature
Mode of inheritance for gene: PLEKHA6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLEKHA6 were set to 10.64898/2026.04.10.26349358
Phenotypes for gene: PLEKHA6 were set to idiopathic hypogonadotropic hypogonadism MONDO:0018555
Mendeliome v2.341 PLEKHA6 Zornitza Stark Marked gene: PLEKHA6 as ready
Mendeliome v2.341 PLEKHA6 Zornitza Stark Gene: plekha6 has been classified as Red List (Low Evidence).
Mendeliome v2.341 PLEKHA6 Zornitza Stark Classified gene: PLEKHA6 as Red List (low evidence)
Mendeliome v2.341 PLEKHA6 Zornitza Stark Gene: plekha6 has been classified as Red List (Low Evidence).
Mendeliome v2.340 PLEKHA6 Zornitza Stark reviewed gene: PLEKHA6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: idiopathic hypogonadotropic hypogonadism MONDO:0018555; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v2.36 PLEKHA6 Zornitza Stark Marked gene: PLEKHA6 as ready
Infertility and Recurrent Pregnancy Loss v2.36 PLEKHA6 Zornitza Stark Gene: plekha6 has been classified as Red List (Low Evidence).
Infertility and Recurrent Pregnancy Loss v2.36 PLEKHA6 Zornitza Stark Classified gene: PLEKHA6 as Red List (low evidence)
Infertility and Recurrent Pregnancy Loss v2.36 PLEKHA6 Zornitza Stark Gene: plekha6 has been classified as Red List (Low Evidence).
Infertility and Recurrent Pregnancy Loss v2.35 PLEKHA6 Zornitza Stark reviewed gene: PLEKHA6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: idiopathic hypogonadotropic hypogonadism MONDO:0018555; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Stroke v2.1 PPIL4 Zornitza Stark Marked gene: PPIL4 as ready
Stroke v2.1 PPIL4 Zornitza Stark Gene: ppil4 has been classified as Amber List (Moderate Evidence).
Stroke v2.1 Zornitza Stark Copied gene PPIL4 from panel Mendeliome
Stroke v2.1 PPIL4 Zornitza Stark gene: PPIL4 was added
gene: PPIL4 was added to Stroke. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PPIL4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPIL4 were set to 34887573
Phenotypes for gene: PPIL4 were set to PPIL4-related intracranial saccular aneurysm MONDO:0016483
Mendeliome v2.340 PPIL4 Zornitza Stark Marked gene: PPIL4 as ready
Mendeliome v2.340 PPIL4 Zornitza Stark Gene: ppil4 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.340 GRIPAP1 Zornitza Stark Marked gene: GRIPAP1 as ready
Mendeliome v2.340 GRIPAP1 Zornitza Stark Gene: gripap1 has been classified as Red List (Low Evidence).
Mendeliome v2.340 GRIPAP1 Zornitza Stark Mode of inheritance for gene: GRIPAP1 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v2.339 GRIPAP1 Zornitza Stark Classified gene: GRIPAP1 as Red List (low evidence)
Mendeliome v2.339 GRIPAP1 Zornitza Stark Gene: gripap1 has been classified as Red List (Low Evidence).
Mendeliome v2.338 GRIPAP1 Zornitza Stark reviewed gene: GRIPAP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: GRIPAP1-related neurodevelopmental disorder MONDO:0001071; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v2.56 GRIPAP1 Zornitza Stark Marked gene: GRIPAP1 as ready
Intellectual disability syndromic and non-syndromic v2.56 GRIPAP1 Zornitza Stark Gene: gripap1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v2.56 GRIPAP1 Zornitza Stark Mode of inheritance for gene: GRIPAP1 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v2.55 GRIPAP1 Zornitza Stark Classified gene: GRIPAP1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v2.55 GRIPAP1 Zornitza Stark Gene: gripap1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v2.54 GRIPAP1 Zornitza Stark Tag disputed tag was added to gene: GRIPAP1.
Intellectual disability syndromic and non-syndromic v2.54 GRIPAP1 Zornitza Stark reviewed gene: GRIPAP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: GRIPAP1-related neurodevelopmental disorder MONDO:0001071; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v2.54 NFIC Zornitza Stark Marked gene: NFIC as ready
Intellectual disability syndromic and non-syndromic v2.54 NFIC Zornitza Stark Gene: nfic has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v1.1 NFIC Zornitza Stark Marked gene: NFIC as ready
Macrocephaly_Megalencephaly v1.1 NFIC Zornitza Stark Gene: nfic has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v1.1 Zornitza Stark Copied gene NFIC from panel Mendeliome
Macrocephaly_Megalencephaly v1.1 NFIC Zornitza Stark gene: NFIC was added
gene: NFIC was added to Macrocephaly_Megalencephaly. Sources: Expert Review Green,Literature
SV/CNV tags were added to gene: NFIC.
Mode of inheritance for gene: NFIC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFIC were set to 42498698
Phenotypes for gene: NFIC were set to Neurodevelopmental disorder, MONDO:0700092, NFIC-related
Intellectual disability syndromic and non-syndromic v2.54 Zornitza Stark Copied gene NFIC from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.54 NFIC Zornitza Stark gene: NFIC was added
gene: NFIC was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
SV/CNV tags were added to gene: NFIC.
Mode of inheritance for gene: NFIC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFIC were set to 42498698
Phenotypes for gene: NFIC were set to Neurodevelopmental disorder, MONDO:0700092, NFIC-related
Mendeliome v2.338 NFIC Zornitza Stark Marked gene: NFIC as ready
Mendeliome v2.338 NFIC Zornitza Stark Gene: nfic has been classified as Green List (High Evidence).
Mendeliome v2.338 NFIC Zornitza Stark Classified gene: NFIC as Green List (high evidence)
Mendeliome v2.338 NFIC Zornitza Stark Gene: nfic has been classified as Green List (High Evidence).
Mendeliome v2.337 NFIC Zornitza Stark gene: NFIC was added
gene: NFIC was added to Mendeliome. Sources: Literature
SV/CNV tags were added to gene: NFIC.
Mode of inheritance for gene: NFIC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFIC were set to 42498698
Phenotypes for gene: NFIC were set to Neurodevelopmental disorder, MONDO:0700092, NFIC-related
Review for gene: NFIC was set to GREEN
Added comment: 11 individuals reported with deletions (n=7) or sequence variants (n=4) and presenting with ID and macrocephaly.
Sources: Literature
Mendeliome v2.336 MYB Achchuthan Shanmugasundram gene: MYB was added
gene: MYB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MYB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYB were set to 20130238; 27577878; 29654210; 36168523
Phenotypes for gene: MYB were set to combined immunodeficiency, MONDO:0015131
Review for gene: MYB was set to GREEN
Added comment: PMID:27577878 (2016) reported a cohort of patients with primary immunodeficiency diseases from 278 families from 22 countries investigated using whole-exome sequencing, of which one patient (8 year-old female) with immunodeficiency, progressive bone marrow failure, short stature and dysmorphic facial features were identified with a heterozygous 3.4Mb deletion on chromosome 6 including Myb gene.

PMID:36168523 (2022) reported two patients presenting with a combined deficiency phenotype ((B-cell lymphocytopenia, hypogammaglobulinemia) that progressed into severe bone marrow dysfunction. Patient 1 (a 22-year old male of Dutch descent) additionally showed telomere shortening and Case 2 ( of French-Canadian descent) developed autoimmune-like features (polyarthritis, granulomatous dermatitis). They both were identified with de novo heterozygous variants in DNA-binding domain of MYB gene using trio exome sequnecing (patient 1: c.545A>G/ p.Lys182Arg; patient 2: c.383A>G/ p.Lys128Arg). Functional evidence is available for patient 1 (T-cell phenotyping, RT-PCR, flow cytometry) showing altered Zeb2/c-Myb/Tcf7 expression, particularly in CD8+ T cells.

There is also evidence available from mice models - Homozygous null variants of MYB in mice were shown to be lethal. But, heterozygous, temporal and local null models of the DNA-binding domain exon in mice and human cell lines have shown that its product, the c-Myb transcription factor, is crucial for pro- and pre-B cell differentiation by controlling the expression of interleukin-7 receptor-α, and recombinase activating gene (Rag) and the initiation of survival signals (PMIDs: 20130238 (2010) & 29654210 (2019)).

In summary, there are two unrelated patients with heterozygous SNVs in Myb gene and functional evidence including mouse models available from literature in support of the association of Myb with combined immunodeficiency. Hence, this gene can be promoted to green rating.
Sources: Literature
Severe early-onset obesity v2.2 NCOA1 Zornitza Stark Marked gene: NCOA1 as ready
Severe early-onset obesity v2.2 NCOA1 Zornitza Stark Gene: ncoa1 has been classified as Amber List (Moderate Evidence).
Severe early-onset obesity v2.2 Zornitza Stark Copied gene NCOA1 from panel Mendeliome
Severe early-onset obesity v2.2 NCOA1 Zornitza Stark gene: NCOA1 was added
gene: NCOA1 was added to Severe early-onset obesity. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: NCOA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NCOA1 were set to 35137184; 30979869
Phenotypes for gene: NCOA1 were set to Inherited obesity, MONDO:0019182, NCOA1-related
Mendeliome v2.336 NCOA1 Zornitza Stark Marked gene: NCOA1 as ready
Mendeliome v2.336 NCOA1 Zornitza Stark Gene: ncoa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.336 NCOA1 Zornitza Stark Classified gene: NCOA1 as Amber List (moderate evidence)
Mendeliome v2.336 NCOA1 Zornitza Stark Gene: ncoa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.335 NCOA1 Zornitza Stark gene: NCOA1 was added
gene: NCOA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NCOA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NCOA1 were set to 35137184; 30979869
Phenotypes for gene: NCOA1 were set to Inherited obesity, MONDO:0019182, NCOA1-related
Review for gene: NCOA1 was set to AMBER
Added comment: PMID 30979869 reports 16 individuals from 16 families and PMID 35137184 reports 47 individuals from 22 families with heterozygous NCOA1 missense variants presenting with severe early‑onset obesity (BMI SD > 3, onset < 10 y) often accompanied by hyperphagia, endocrine abnormalities (partial thyroid‑hormone resistance, menorrhagia) and bone fractures. Functional assays in PMID 30979869 demonstrate effects on STAT3‑POMC signalling, whereas PMID 35137184 provides a larger cohort lacking variant‑specific functional validation and includes several variants with population frequencies well above the monoallelic threshold. Many of the variants also lack segregation data.

Hence Amber rating.
Sources: Literature
Retinitis pigmentosa v1.10 FSD1L Zornitza Stark Marked gene: FSD1L as ready
Retinitis pigmentosa v1.10 FSD1L Zornitza Stark Gene: fsd1l has been classified as Green List (High Evidence).
Retinitis pigmentosa v1.10 FSD1L Zornitza Stark Phenotypes for gene: FSD1L were changed from Neurodevelopmental disorder with seizures, spastic tetraparesis, and vision impairment, MIM# 621643 to Retinitis pigmentosa 109, MIM# 621656
Retinitis pigmentosa v1.9 FSD1L Zornitza Stark changed review comment from: In 6 individuals from 4 families, the findings were isolated to RP, hence second OMIM# added.; to: In 6 individuals from 4 families, the findings were isolated to RP.
Retinitis pigmentosa v1.9 FSD1L Zornitza Stark Deleted their comment
Retinitis pigmentosa v1.9 FSD1L Zornitza Stark edited their review of gene: FSD1L: Changed phenotypes: Retinitis pigmentosa 109, MIM# 621656
Retinitis pigmentosa v1.9 Zornitza Stark Copied gene FSD1L from panel Mendeliome
Retinitis pigmentosa v1.9 FSD1L Zornitza Stark gene: FSD1L was added
gene: FSD1L was added to Retinitis pigmentosa. Sources: Expert Review Green,Other
Mode of inheritance for gene: FSD1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FSD1L were set to 41720098
Phenotypes for gene: FSD1L were set to Neurodevelopmental disorder with seizures, spastic tetraparesis, and vision impairment, MIM# 621643
Mendeliome v2.334 FSD1L Zornitza Stark edited their review of gene: FSD1L: Added comment: In 6 individuals from 4 families, the findings were isolated to RP, hence second OMIM# added.; Changed phenotypes: Neurodevelopmental disorder with seizures, spastic tetraparesis, and vision impairment, MIM# 621643, Retinitis pigmentosa 109, MIM# 621656
Intellectual disability syndromic and non-syndromic v2.53 Sangavi Sivagnanasundram Copied gene GRIPAP1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.53 GRIPAP1 Sangavi Sivagnanasundram gene: GRIPAP1 was added
gene: GRIPAP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: GRIPAP1 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: GRIPAP1 were set to 28285821
Phenotypes for gene: GRIPAP1 were set to GRIPAP1-related neurodevelopmental disorder MONDO:0001071
Mendeliome v2.334 GRIPAP1 Sangavi Sivagnanasundram Classified gene: GRIPAP1 as Amber List (moderate evidence)
Mendeliome v2.334 GRIPAP1 Sangavi Sivagnanasundram Gene: gripap1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.333 PPIL4 Sangavi Sivagnanasundram Classified gene: PPIL4 as Amber List (moderate evidence)
Mendeliome v2.333 PPIL4 Sangavi Sivagnanasundram Gene: ppil4 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v2.35 PLEKHA6 Sangavi Sivagnanasundram Classified gene: PLEKHA6 as Amber List (moderate evidence)
Infertility and Recurrent Pregnancy Loss v2.35 PLEKHA6 Sangavi Sivagnanasundram Gene: plekha6 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.332 PLEKHA6 Sangavi Sivagnanasundram Classified gene: PLEKHA6 as Amber List (moderate evidence)
Mendeliome v2.332 PLEKHA6 Sangavi Sivagnanasundram Gene: plekha6 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v2.34 Sangavi Sivagnanasundram Copied gene PLEKHA6 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v2.34 PLEKHA6 Sangavi Sivagnanasundram gene: PLEKHA6 was added
gene: PLEKHA6 was added to Infertility and Recurrent Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: PLEKHA6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLEKHA6 were set to 10.64898/2026.04.10.26349358
Phenotypes for gene: PLEKHA6 were set to idiopathic hypogonadotropic hypogonadism MONDO:0018555
Infertility and Recurrent Pregnancy Loss v2.33 Sangavi Sivagnanasundram Copied gene GPAT2 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v2.33 GPAT2 Sangavi Sivagnanasundram gene: GPAT2 was added
gene: GPAT2 was added to Infertility and Recurrent Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: GPAT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPAT2 were set to 39122675
Phenotypes for gene: GPAT2 were set to GPAT2-related non‑obstructive azoospermia/extreme oligozoospermia due to spermatogenic failure MONDO:0100459
Mendeliome v2.331 GPAT2 Sangavi Sivagnanasundram gene: GPAT2 was added
gene: GPAT2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPAT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPAT2 were set to 39122675
Phenotypes for gene: GPAT2 were set to GPAT2-related non‑obstructive azoospermia/extreme oligozoospermia due to spermatogenic failure MONDO:0100459
Review for gene: GPAT2 was set to AMBER
Added comment: PMID 39122675 reports 8 individuals from 8 families with biallelic GPAT2 variants presenting with non‑obstructive azoospermia, cryptozoospermia or extreme oligozoospermia (infertility disorder). Minigene splice assay for c.1156‑1G>A and immunohistochemistry show loss of GPAT2 protein in most testes.
6 different variants were reported however only 2 were rare enough for an AR gene, hence AMBER classification.
Sources: Literature
Mendeliome v2.330 ZC3H11A Lucy Spencer changed review comment from: PMID 40864167 identified 4 individuals from a large cohort of high myopia patients with missense in ZC3H11A. All were absent from gnomad except for one with 14 hets. A KO mouse recapitulated a myopic refraction shift and displayed IKBa downregulation. Overexpression of patient missense variants in also displayed significantly reduced IKBa expression.
Sources: Literature; to: PMID 40864167 identified 4 individuals from a large cohort of high myopia patients with missense in ZC3H11A. All were absent from gnomad except for one with 14 hets. A KO mouse recapitulated a myopic refraction shift and displayed IKBa downregulation. Overexpression of patient missense variants in also displayed significantly reduced IKBa expression.

No segregation or further functional studies on the variants were performed
Sources: Literature
Mendeliome v2.330 ZC3H11A Lucy Spencer Classified gene: ZC3H11A as Amber List (moderate evidence)
Mendeliome v2.330 ZC3H11A Lucy Spencer Gene: zc3h11a has been classified as Amber List (Moderate Evidence).
Mendeliome v2.329 ZC3H11A Lucy Spencer gene: ZC3H11A was added
gene: ZC3H11A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZC3H11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZC3H11A were set to 40864167
Phenotypes for gene: ZC3H11A were set to myopia MONDO:0001384, ZC3H11A-related
Review for gene: ZC3H11A was set to AMBER
Added comment: PMID 40864167 identified 4 individuals from a large cohort of high myopia patients with missense in ZC3H11A. All were absent from gnomad except for one with 14 hets. A KO mouse recapitulated a myopic refraction shift and displayed IKBa downregulation. Overexpression of patient missense variants in also displayed significantly reduced IKBa expression.
Sources: Literature
Mendeliome v2.328 GRIPAP1 Sangavi Sivagnanasundram gene: GRIPAP1 was added
gene: GRIPAP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GRIPAP1 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: GRIPAP1 were set to 28285821
Phenotypes for gene: GRIPAP1 were set to GRIPAP1-related neurodevelopmental disorder MONDO:0001071
Review for gene: GRIPAP1 was set to AMBER
Added comment: PMID 28285821 (reports gene alias GRASP1) reports three individuals (2 sibs) from two unrelated X‑linked families with severe intellectual disability. Mouse Grasp1 knockout recapitulates learning and memory deficits; wild‑type GRIPAP1 rescues spine loss, whereas the patient missense mutants fail to rescue, demonstrating loss‑of‑function.

Two missense vairants were identified. Both present in gnomAD v4.1
c.2465G>A R822Q- PopMax AF0.12% in AJ population but NFE PopMax AF is 0.0003368%, 1 hemozygote also reported.

c.218G>A S73N - too common for XLD condition, FAF 0.4%, 7 homs and 1263 hemizygotes
Sources: Literature
Intellectual disability syndromic and non-syndromic v2.52 Lucy Spencer Copied gene GAK from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.52 GAK Lucy Spencer gene: GAK was added
gene: GAK was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: GAK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GAK were set to 37056996
Phenotypes for gene: GAK were set to neurodevelopmental disorder MONDO:0700092, GAK-related
Mendeliome v2.327 GAK Lucy Spencer Classified gene: GAK as Amber List (moderate evidence)
Mendeliome v2.327 GAK Lucy Spencer Gene: gak has been classified as Amber List (Moderate Evidence).
Mendeliome v2.326 GAK Lucy Spencer gene: GAK was added
gene: GAK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GAK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GAK were set to 37056996
Phenotypes for gene: GAK were set to neurodevelopmental disorder MONDO:0700092, GAK-related
Review for gene: GAK was set to AMBER
Added comment: PMID 37056996 performed a systematic survey of de novo variants in genes encoding phosphatase catalytic subunits in rare disease patients in the 100000 genomes project. Table 2 lists says 3 missense were identified in GAK in individuals with developmental delay or macrocephaly however no variant information is provided. The supplemental data for this paper lists 5 missense variants in GAK, it is unclear which if any of these were observed in the above individuals. only 2 of these variants are absent from gnomad, the rest have over 10 hets each. The paper also mentions one de novo frameshift variant in GAK in DECIPHER in an individual with abnormality of the nervous an musculoskeletal systems. DECIPHER also had an addition de novo missense in an individual with a similar phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v2.51 Lucy Spencer Copied gene FIBCD1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.51 FIBCD1 Lucy Spencer gene: FIBCD1 was added
gene: FIBCD1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: FIBCD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FIBCD1 were set to 35916241
Phenotypes for gene: FIBCD1 were set to neurodevelopmental disorder MONDO:0700092, FIBCD1-related
Autism v1.13 Lucy Spencer Copied gene FIBCD1 from panel Mendeliome
Autism v1.13 FIBCD1 Lucy Spencer gene: FIBCD1 was added
gene: FIBCD1 was added to Autism. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: FIBCD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FIBCD1 were set to 35916241
Phenotypes for gene: FIBCD1 were set to neurodevelopmental disorder MONDO:0700092, FIBCD1-related
Mendeliome v2.325 FIBCD1 Lucy Spencer Classified gene: FIBCD1 as Amber List (moderate evidence)
Mendeliome v2.325 FIBCD1 Lucy Spencer Gene: fibcd1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.324 FIBCD1 Lucy Spencer gene: FIBCD1 was added
gene: FIBCD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FIBCD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FIBCD1 were set to 35916241
Phenotypes for gene: FIBCD1 were set to neurodevelopmental disorder MONDO:0700092, FIBCD1-related
Review for gene: FIBCD1 was set to AMBER
Added comment: PMID 35916241 reports 2 individual from 2 families with a neurodevelopmental disorder and biallelic missense in FIBCD1 (One compound het p.G29S and p.R406C, one homozygous due to UPD p.P456L). One individual also had a de novo missense in CSMD3 K522E which has an established BIallelic association with epilepsy. Features included severe NDD or ASD, dysmorphic features and in one individual MRI abnormalities.

knockdown studies in mice and drosophila recapitulated neurobehavioral deficits.
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.5 CHAF1A Lucy Spencer changed review comment from: PMID 39333427 reports 8 individuals from 6 families with oculoauriculovertebral spectrum and heterozygous variants in CHAF1A- 2 canonical splice and 4 PTC. 5 of the variants were de novo (1 of which was then inherited by the probands affected children) and 1 was inherited from a healthy father. all variants were absent from gnomad and the gene is constrained for LOF variants.

Cleft lip/plate was observed in one individual
Sources: Literature; to: PMID 39333427 reports 8 individuals from 6 families with oculoauriculovertebral spectrum and heterozygous variants in CHAF1A- 2 canonical splice and 4 PTC. 5 of the variants were de novo (1 of which was then inherited by the probands affected children) and 1 was inherited from a healthy father. all variants were absent from gnomad and the gene is constrained for LOF variants.

2 individuals had unilateral renal agenesis and vesicoureteral reflux or fused pelvic kidneys
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.5 Lucy Spencer Copied gene CHAF1A from panel Clefting disorders
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.5 CHAF1A Lucy Spencer gene: CHAF1A was added
gene: CHAF1A was added to Congenital anomalies of the kidney and urinary tract (CAKUT). Sources: Expert Review Amber,Literature,Literature
Mode of inheritance for gene: CHAF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHAF1A were set to 39333427
Phenotypes for gene: CHAF1A were set to oculoauriculovertebral spectrum with radial defects MONDO:0007712, CHAF1A-related
Growth failure v2.10 POLR3A chirag patel Marked gene: POLR3A as ready
Growth failure v2.10 POLR3A chirag patel Gene: polr3a has been classified as Green List (High Evidence).
Lipodystrophy_Lipoatrophy v2.5 POLR3A chirag patel Marked gene: POLR3A as ready
Lipodystrophy_Lipoatrophy v2.5 POLR3A chirag patel Gene: polr3a has been classified as Green List (High Evidence).
Mendeliome v2.323 chirag patel Added reviews for gene POLR3A from panel Skeletal dysplasia
Lipodystrophy_Lipoatrophy v2.5 chirag patel Copied gene POLR3A from panel Skeletal dysplasia
Lipodystrophy_Lipoatrophy v2.5 POLR3A chirag patel gene: POLR3A was added
gene: POLR3A was added to Lipodystrophy_Lipoatrophy. Sources: Expert Review Green,Literature
Mode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3A were set to 30414627, 30450527, 30323018, 21671373, 10607952
Phenotypes for gene: POLR3A were set to Wiedemann-Rautenstrauch syndrome, MONDO:0009910
Growth failure v2.10 chirag patel Copied gene POLR3A from panel Skeletal dysplasia
Growth failure v2.10 POLR3A chirag patel gene: POLR3A was added
gene: POLR3A was added to Growth failure. Sources: Expert Review Green,Literature
Mode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3A were set to 30414627, 30450527, 30323018, 21671373, 10607952
Phenotypes for gene: POLR3A were set to Wiedemann-Rautenstrauch syndrome, MONDO:0009910
Clefting disorders v1.2 CHAF1A Lucy Spencer changed review comment from: PMID 39333427 reports 8 individuals from 6 families with oculoauriculovertebral spectrum and heterozygous variants in CHAF1A- 2 canonical splice and 4 PTC. 5 of the variants were de novo (1 of which was then inherited by the probands affected children) and 1 was inherited from a healthy father. all variants were absent from gnomad and the gene is constrained for LOF variants.
Sources: Literature; to: PMID 39333427 reports 8 individuals from 6 families with oculoauriculovertebral spectrum and heterozygous variants in CHAF1A- 2 canonical splice and 4 PTC. 5 of the variants were de novo (1 of which was then inherited by the probands affected children) and 1 was inherited from a healthy father. all variants were absent from gnomad and the gene is constrained for LOF variants.

Cleft lip/plate was observed in one individual
Sources: Literature
Skeletal dysplasia v1.26 POLR3A chirag patel Classified gene: POLR3A as Green List (high evidence)
Skeletal dysplasia v1.26 POLR3A chirag patel Gene: polr3a has been classified as Green List (High Evidence).
Skeletal dysplasia v1.25 POLR3A chirag patel Marked gene: POLR3A as ready
Skeletal dysplasia v1.25 POLR3A chirag patel Gene: polr3a has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.25 POLR3A chirag patel gene: POLR3A was added
gene: POLR3A was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3A were set to 30414627, 30450527, 30323018, 21671373, 10607952
Phenotypes for gene: POLR3A were set to Wiedemann-Rautenstrauch syndrome, MONDO:0009910
Review for gene: POLR3A was set to GREEN
Added comment: Multiple families reported with biallelic variants in POLR3A and Wiedemann-Rautenstrauch syndrome (WDRTS). This is a rare autosomal recessive neonatal progeroid disorder characterized by intrauterine growth retardation, failure to thrive, short stature, a progeroid appearance, generalized lipoatrophy, various skeletal anomalies, hypotonia, and variable mental impairment.
Sources: Literature
Clefting disorders v1.2 CHAF1A Lucy Spencer Classified gene: CHAF1A as Amber List (moderate evidence)
Clefting disorders v1.2 CHAF1A Lucy Spencer Gene: chaf1a has been classified as Amber List (Moderate Evidence).
Ectodermal Dysplasia v1.6 Lucy Spencer Copied gene CHAF1A from panel Mendeliome
Ectodermal Dysplasia v1.6 CHAF1A Lucy Spencer gene: CHAF1A was added
gene: CHAF1A was added to Ectodermal Dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CHAF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHAF1A were set to 39333427
Phenotypes for gene: CHAF1A were set to oculoauriculovertebral spectrum with radial defects MONDO:0007712, CHAF1A-related
Clefting disorders v1.1 Lucy Spencer Copied gene CHAF1A from panel Mendeliome
Clefting disorders v1.1 CHAF1A Lucy Spencer gene: CHAF1A was added
gene: CHAF1A was added to Clefting disorders. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CHAF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHAF1A were set to 39333427
Phenotypes for gene: CHAF1A were set to oculoauriculovertebral spectrum with radial defects MONDO:0007712, CHAF1A-related
Mendeliome v2.322 CHAF1A Lucy Spencer Classified gene: CHAF1A as Green List (high evidence)
Mendeliome v2.322 CHAF1A Lucy Spencer Gene: chaf1a has been classified as Green List (High Evidence).
Mendeliome v2.321 CHAF1A Lucy Spencer gene: CHAF1A was added
gene: CHAF1A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CHAF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHAF1A were set to 39333427
Phenotypes for gene: CHAF1A were set to oculoauriculovertebral spectrum with radial defects MONDO:0007712, CHAF1A-related
Review for gene: CHAF1A was set to GREEN
Added comment: PMID 39333427 reports 8 individuals from 6 families with oculoauriculovertebral spectrum and heterozygous variants in CHAF1A- 2 canonical splice and 4 PTC. 5 of the variants were de novo (1 of which was then inherited by the probands affected children) and 1 was inherited from a healthy father. all variants were absent from gnomad and the gene is constrained for LOF variants.
Sources: Literature
Fetal anomalies v2.19 POLR3A chirag patel Deleted their review
Skeletal dysplasia v1.24 WLS chirag patel Marked gene: WLS as ready
Skeletal dysplasia v1.24 WLS chirag patel Gene: wls has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.24 WLS chirag patel gene: WLS was added
gene: WLS was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: WLS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WLS were set to 40618129; 34587386
Phenotypes for gene: WLS were set to Zaki syndrome, MONDO:0859209
Review for gene: WLS was set to GREEN
Added comment: PMID 34587386 reports 10 individuals from five families (three independent families with qualifying homozygous WLS missense variants) and PMID 40618129 reports 1 individual from a further independent family with compound heterozygous WLS variants, together defining Zaki syndrome – a multisystem congenital disorder featuring microcephaly, facial dysmorphism, foot syndactyly, renal agenesis/hydronephrosis, cardiac defects, short stature and developmental delay. Functional studies including protein loss, impaired Wnt secretion, knock‑in mouse models and rescue with the Wnt agonist CHIR99021 support a loss‑of‑function mechanism.

Skeletal anomalies included toe syndactyly, ectrodactyly, broad distal phalanges, long fingers, and hypoplasia of toe phalanges and toenails.
Sources: Literature
Mendeliome v2.320 PPIL4 Sangavi Sivagnanasundram gene: PPIL4 was added
gene: PPIL4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPIL4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPIL4 were set to 34887573
Phenotypes for gene: PPIL4 were set to PPIL4-related intracranial saccular aneurysm MONDO:0016483
Review for gene: PPIL4 was set to AMBER
Added comment: PMID 34887573 reports 5 unrelated families with 5 different heterozygous PPIL4 variants presenting with adult‑onset intracranial saccular aneurysm, a risk factor for subarachnoid haemorrhage.
The variants are present in gnomAD v4.1, two are a bit common for AD AF.
There are no pathogenic variants reported in ClinVar at this stage. The gene is not constraint for LoF however the authors of this are hypothesising haploinsufficiency as the mechanism of disease.
Rated AMBER given the uncertainty of the GDA and functional evidence.
Sources: Literature
Skeletal dysplasia v1.23 FGFR3 chirag patel Marked gene: FGFR3 as ready
Skeletal dysplasia v1.23 FGFR3 chirag patel Gene: fgfr3 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.23 FGFR3 chirag patel Phenotypes for gene: FGFR3 were changed from Crouzon syndrome with acanthosis nigricans 612247; Thanatophoric dysplasia, type II 187601; Thanatophoric dysplasia, type I 187600; SADDAN 616482; LADD syndrome 149730; Achondroplasia 100800; Hypochondroplasia 146000; Muenke syndrome 602849; CATSHL syndrome 610474 to achondroplasia MONDO:0007037; Thanatophoric dysplasia type 1 MONDO:0008546; Thanatophoric dysplasia type 2 MONDO:0008547; hypochondroplasia MONDO:0007793; Muenke syndrome MONDO:0011274; FGFR3-related chondrodysplasia MONDO:0019685; severe achondroplasia-developmental delay-acanthosis nigricans syndrome MONDO:0014658; Crouzon syndrome-acanthosis nigricans syndrome MONDO:0012833; camptodactyly-tall stature-scoliosis-hearing loss syndrome MONDO:0012504
Skeletal dysplasia v1.22 FGFR3 chirag patel Publications for gene: FGFR3 were set to
Skeletal dysplasia v1.21 FGFR2 chirag patel Marked gene: FGFR2 as ready
Skeletal dysplasia v1.21 FGFR2 chirag patel Gene: fgfr2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.21 FGFR2 chirag patel Publications for gene: FGFR2 were set to
Skeletal dysplasia v1.20 FGFR2 chirag patel Mode of inheritance for gene: FGFR2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.19 FGFR1 chirag patel Deleted their review
Skeletal dysplasia v1.19 CDK10 chirag patel Marked gene: CDK10 as ready
Skeletal dysplasia v1.19 CDK10 chirag patel Gene: cdk10 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.19 CDK10 chirag patel Classified gene: CDK10 as Green List (high evidence)
Skeletal dysplasia v1.19 CDK10 chirag patel Gene: cdk10 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.18 CDK10 chirag patel gene: CDK10 was added
gene: CDK10 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: CDK10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK10 were set to 41836559; 40960173; 36503922; 34369103; 28886341
Phenotypes for gene: CDK10 were set to Al Kaissi syndrome, MONDO:0044324
Review for gene: CDK10 was set to GREEN
Added comment: Multiple individuals from unrelated families reported with biallelic loss-of-function CDK10 variants (splice-site or frameshift) presenting with Al Kaissi syndrome. This is an autosomal recessive developmental disorder characterized by growth retardation, spine malformation particularly of the cervical spine (including clefting, segmentation anomalies, and improper fusion), dysmorphic facial features, and delayed psychomotor development with moderate to severe intellectual disability. Mouse osteoblast‑specific Cdk10 knockout recapitulates skeletal phenotype.
Sources: Literature
Fetal anomalies v2.19 TGFBR1 chirag patel Deleted their review
Skeletal dysplasia v1.17 TGFBR2 chirag patel Classified gene: TGFBR2 as Red List (low evidence)
Skeletal dysplasia v1.17 TGFBR2 chirag patel Gene: tgfbr2 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.16 SMAD3 chirag patel Classified gene: SMAD3 as Red List (low evidence)
Skeletal dysplasia v1.16 SMAD3 chirag patel Gene: smad3 has been classified as Red List (Low Evidence).
Mandibulofacial Acrofacial dysostosis v2.5 LMNA chirag patel Marked gene: LMNA as ready
Mandibulofacial Acrofacial dysostosis v2.5 LMNA chirag patel Gene: lmna has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v2.5 LMNA chirag patel Classified gene: LMNA as Green List (high evidence)
Mandibulofacial Acrofacial dysostosis v2.5 LMNA chirag patel Gene: lmna has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v2.4 LMNA chirag patel gene: LMNA was added
gene: LMNA was added to Mandibulofacial Acrofacial dysostosis. Sources: Literature
Mode of inheritance for gene: LMNA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LMNA were set to 12075506, 14627682, 12788894, 17848409
Phenotypes for gene: LMNA were set to Mandibuloacral dysplasia with type A lipodystrophy, MONDO:0009557
Review for gene: LMNA was set to GREEN
Added comment: Established association with multiple phenotypes.

Mandibuloacral dysplasia with type A lipodystrophy (MADA) is an autosomal recessive disorder characterized by growth retardation, craniofacial anomalies with mandibular hypoplasia, skeletal abnormalities with progressive osteolysis of the distal phalanges and clavicles, and pigmentary skin changes.
Sources: Literature
Skeletal dysplasia v1.15 LMNA chirag patel Marked gene: LMNA as ready
Skeletal dysplasia v1.15 LMNA chirag patel Gene: lmna has been classified as Green List (High Evidence).
Skeletal dysplasia v1.15 LMNA chirag patel Phenotypes for gene: LMNA were changed from Emery-Dreifuss muscular dystrophy 2, 181350; Heart-hand syndrome, Slovenian type 610140; Foundation Trust) Mandibuloacral dysplasia 248370; Muscular dystrophy, limb-girdle, type 1B 159001; Malouf syndrome 212112; 616516; Cardiomyopathy, dilated, 1A 115200; Lipodystrophy, familial partial, 2 151660; Emery-Dreifuss muscular dystrophy 3, 616516; Charcot-Marie-Tooth disease, type 2B1 605588; Mandibuloacral dysplasia 248370; Restrictive dermopathy, lethal 275210; Hutchinson-Gilford progeria 176670; Muscular dystrophy, congenital 613205 to Mandibuloacral dysplasia with type A lipodystrophy, MONDO:0009557; Hutchinson-Gilford progeria syndrome, MONDO:0008310; heart-hand syndrome, Slovenian type, MONDO:0012417
Skeletal dysplasia v1.14 LMNA chirag patel Publications for gene: LMNA were set to
Skeletal dysplasia v1.13 LMNA chirag patel reviewed gene: LMNA: Rating: GREEN; Mode of pathogenicity: None; Publications: 12075506, 14627682, 12788894, 17848409, 12714972, 12768443, 12702809, 18611980, 27723096; Phenotypes: Mandibuloacral dysplasia with type A lipodystrophy, MONDO:0009557, Hutchinson-Gilford progeria syndrome, MONDO:0008310, heart-hand syndrome, Slovenian type, MONDO:0012417; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v1.13 FIG4 chirag patel Marked gene: FIG4 as ready
Skeletal dysplasia v1.13 FIG4 chirag patel Gene: fig4 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.13 FIG4 chirag patel Phenotypes for gene: FIG4 were changed from Yunis-Varon syndrome 216340; Yunis-Varon syndrome 216340; Amyotrophic lateral sclerosis 11 612577 to Yunis-Varon syndrome, MONDO:0008995
Skeletal dysplasia v1.12 FIG4 chirag patel Publications for gene: FIG4 were set to
Skeletal dysplasia v1.11 FIG4 chirag patel reviewed gene: FIG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31094135, 24088667, 23623387, 39669591; Phenotypes: Yunis-Varon syndrome, MONDO:0008995; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.11 TGFBR2 chirag patel Classified gene: TGFBR2 as Red List (low evidence)
Skeletal dysplasia v1.11 TGFBR2 chirag patel Gene: tgfbr2 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.10 FBN1 chirag patel Phenotypes for gene: FBN1 were changed from Stiff skin syndrome 184900; Marfan syndrome 154700; Geleophysic dysplasia 2 614185; Weill-Marchesani syndrome 2, dominant 608328; Acromicric dysplasia 102370 to Acromicric dysplasia, MONDO:0007055; Geleophysic dysplasia 2, MONDO:0013612
Skeletal dysplasia v1.9 FBN1 chirag patel Marked gene: FBN1 as ready
Skeletal dysplasia v1.9 FBN1 chirag patel Gene: fbn1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.9 FBN1 chirag patel reviewed gene: FBN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21683322; Phenotypes: Acromicric dysplasia, MONDO:0007055, Geleophysic dysplasia 2, MONDO:0013612; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v1.11 RIPPLY3 Rylee Peters Marked gene: RIPPLY3 as ready
Congenital Heart Defect v1.11 RIPPLY3 Rylee Peters Gene: ripply3 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v1.11 Rylee Peters Copied gene RIPPLY3 from panel Mendeliome
Congenital Heart Defect v1.11 RIPPLY3 Rylee Peters gene: RIPPLY3 was added
gene: RIPPLY3 was added to Congenital Heart Defect. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: RIPPLY3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RIPPLY3 were set to 30241482; 21177346
Phenotypes for gene: RIPPLY3 were set to Congenital heart disease, MONDO:0005453, RIPPLY3-related
Mendeliome v2.319 RIPPLY3 Rylee Peters Marked gene: RIPPLY3 as ready
Mendeliome v2.319 RIPPLY3 Rylee Peters Gene: ripply3 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.319 RIPPLY3 Rylee Peters Classified gene: RIPPLY3 as Amber List (moderate evidence)
Mendeliome v2.319 RIPPLY3 Rylee Peters Gene: ripply3 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.318 RIPPLY3 Rylee Peters gene: RIPPLY3 was added
gene: RIPPLY3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RIPPLY3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RIPPLY3 were set to 30241482; 21177346
Phenotypes for gene: RIPPLY3 were set to Congenital heart disease, MONDO:0005453, RIPPLY3-related
Review for gene: RIPPLY3 was set to AMBER
Added comment: RIPPLY3 encodes a transcriptional corepressor that interacts with TBX1 to modulate cardiac outflow tract development.

PMID: 30241482 reports four individuals from four unrelated families with heterozygous missense RIPPLY3 variants presenting with conotruncal heart defects; these missense variants have 1-20hets in gnomAD v4. Luciferase reporter and co‑immunoprecipitation assays demonstrate reduced TBX1 repression. An earlier study demonstrated that Ripply3-deficient mice exhibit abnormal development of pharyngeal derivatives, including ectopic formation of the thymus and the parathyroid gland, as well as cardiovascular malformation (PMID: 21177346).
Sources: Literature
Skeletal dysplasia v1.9 DOLPP1 chirag patel reviewed gene: DOLPP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v1.9 HDAC5 chirag patel changed review comment from: Not skeletal dysplasia gene; to: Not evidence for associated with skeletal dysplasia
Skeletal dysplasia v1.9 HDAC5 chirag patel reviewed gene: HDAC5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v1.9 PIN1 chirag patel reviewed gene: PIN1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v1.9 USH2A chirag patel reviewed gene: USH2A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v1.9 USH1G chirag patel reviewed gene: USH1G: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v1.9 USH1C chirag patel reviewed gene: USH1C: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v1.9 TSC2 chirag patel reviewed gene: TSC2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v1.9 TSC1 chirag patel reviewed gene: TSC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v1.9 VHL chirag patel reviewed gene: VHL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v1.9 PLEKHM1 chirag patel Marked gene: PLEKHM1 as ready
Skeletal dysplasia v1.9 PLEKHM1 chirag patel Gene: plekhm1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.9 PLEKHM1 chirag patel Classified gene: PLEKHM1 as Green List (high evidence)
Skeletal dysplasia v1.9 PLEKHM1 chirag patel Gene: plekhm1 has been classified as Green List (High Evidence).
Fetal anomalies v2.19 INTU chirag patel Phenotypes for gene: INTU were changed from Orofaciodigital syndrome XVII MIM#617926; Short-rib thoracic dysplasia 20 with polydactyly MIM#617925 to INTU-related skeletal ciliopathy, MONDO:1060154
Fetal anomalies v2.18 INTU chirag patel Publications for gene: INTU were set to 28289185; 29451301; 30266093; 34623732; 27158779
Skeletal dysplasia v1.8 INTU chirag patel Marked gene: INTU as ready
Skeletal dysplasia v1.8 INTU chirag patel Gene: intu has been classified as Green List (High Evidence).
Skeletal Ciliopathies v2.1 INTU chirag patel Marked gene: INTU as ready
Skeletal Ciliopathies v2.1 INTU chirag patel Gene: intu has been classified as Green List (High Evidence).
Ciliopathies v2.4 INTU chirag patel Publications for gene: INTU were set to PMID: 27158779; 29451301; 20067783
Ciliopathies v2.3 INTU chirag patel Phenotypes for gene: INTU were changed from ?Orofaciodigital syndrome XVII MIM#617926; ?Short-rib thoracic dysplasia 20 with polydactyly MIM#617925 to INTU-related skeletal ciliopathy, MONDO:1060154
Ciliopathies v2.2 chirag patel Added reviews for gene INTU from panel Mendeliome
Skeletal dysplasia v1.8 chirag patel Copied gene INTU from panel Mendeliome
Skeletal dysplasia v1.8 INTU chirag patel gene: INTU was added
gene: INTU was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: INTU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTU were set to 27158779; 29451301; 20067783; 34623732; 20067783; 22935613; 25774014
Phenotypes for gene: INTU were set to INTU-related skeletal ciliopathy, MONDO:1060154
Skeletal Ciliopathies v2.1 chirag patel Copied gene INTU from panel Mendeliome
Skeletal Ciliopathies v2.1 INTU chirag patel gene: INTU was added
gene: INTU was added to Skeletal Ciliopathies. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: INTU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTU were set to 27158779; 29451301; 20067783; 34623732; 20067783; 22935613; 25774014
Phenotypes for gene: INTU were set to INTU-related skeletal ciliopathy, MONDO:1060154
Fetal anomalies v2.17 chirag patel Added reviews for gene INTU from panel Mendeliome
Mendeliome v2.317 INTU chirag patel Publications for gene: INTU were set to 27158779; 29451301; 20067783
Mendeliome v2.316 INTU chirag patel Phenotypes for gene: INTU were changed from INTU-related skeletal ciliopathy, MONDO:1060154 to INTU-related skeletal ciliopathy, MONDO:1060154
Mendeliome v2.316 INTU chirag patel Phenotypes for gene: INTU were changed from ?Orofaciodigital syndrome XVII MIM#617926; ?Short-rib thoracic dysplasia 20 with polydactyly to INTU-related skeletal ciliopathy, MONDO:1060154
Mendeliome v2.315 INTU chirag patel reviewed gene: INTU: Rating: GREEN; Mode of pathogenicity: None; Publications: 27158779, 29451301, 34623732, 20067783, 22935613, 25774014; Phenotypes: INTU-related skeletal ciliopathy, MONDO:1060154; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.315 PLEKHA6 Sangavi Sivagnanasundram gene: PLEKHA6 was added
gene: PLEKHA6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLEKHA6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLEKHA6 were set to 10.64898/2026.04.10.26349358
Phenotypes for gene: PLEKHA6 were set to idiopathic hypogonadotropic hypogonadism MONDO:0018555
Review for gene: PLEKHA6 was set to AMBER
Added comment: Preprint publication Topaloglu et al 2026

The publication reports > 5 unrelated families with missense PLEKHA6 variants presenting with idiopathic hypogonadotropic hypogonadism (IHH).
Some of the reported missense variants are present in gnomAD with a high AF for AD GDA however there are rare variants reported as well.
The authors report one homozygous proband which appears to segregate in the family as homozygous as well however there is no pedigree available or mention of consanguinity. There are no other reports of AR association for this gene.

There are no pathogenic variants reported in ClinVar and the gene is not constrained for missense either.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v2.32 SPOCD1 chirag patel Marked gene: SPOCD1 as ready
Infertility and Recurrent Pregnancy Loss v2.32 SPOCD1 chirag patel Gene: spocd1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v2.32 chirag patel Copied gene SPOCD1 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v2.32 SPOCD1 chirag patel gene: SPOCD1 was added
gene: SPOCD1 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: SPOCD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPOCD1 were set to 38359823
Phenotypes for gene: SPOCD1 were set to Azoospermia, MONDO:0100459
Mendeliome v2.314 SPOCD1 chirag patel Marked gene: SPOCD1 as ready
Mendeliome v2.314 SPOCD1 chirag patel Gene: spocd1 has been classified as Green List (High Evidence).
Mendeliome v2.314 SPOCD1 chirag patel Classified gene: SPOCD1 as Green List (high evidence)
Mendeliome v2.314 SPOCD1 chirag patel Gene: spocd1 has been classified as Green List (High Evidence).
Mendeliome v2.313 SPOCD1 chirag patel gene: SPOCD1 was added
gene: SPOCD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPOCD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPOCD1 were set to 38359823
Phenotypes for gene: SPOCD1 were set to Azoospermia, MONDO:0100459
Review for gene: SPOCD1 was set to GREEN
Added comment: PMID 38359823 reports 3 males from 3 unrelated families (2 consanguineous) presenting with non‑obstructive azoospermia (male infertility). They found 3 rare homozygous SPOCD1 variants (p.(Leu971Arg), p.(Gln1119Thrfs*66), p.(Arg664Glnfs*57). Segregation in one family showed the parents and an unaffected brother were heterozygous for the variant. Testicular histology showed Sertoli‑cell‑only or meiotic arrest, and residual germ cells exhibited LINE‑1 de‑repression. SPOCD1 is a guardian of human male fertility and is required for transposon silencing. Protein‑expression assays show missense L971R disrupts SPOC‑domain folding, and the frameshift alleles truncated the protein, supporting loss‑of‑function as the disease mechanism.
Sources: Literature
Disorders of immune dysregulation v2.4 PPL chirag patel Marked gene: PPL as ready
Disorders of immune dysregulation v2.4 PPL chirag patel Gene: ppl has been classified as Green List (High Evidence).
Disorders of immune dysregulation v2.4 chirag patel Copied gene PPL from panel Mendeliome
Disorders of immune dysregulation v2.4 PPL chirag patel gene: PPL was added
gene: PPL was added to Disorders of immune dysregulation. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PPL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPL were set to 34815391
Phenotypes for gene: PPL were set to Eosinophilic esophagitis, MONDO:0005361
Mendeliome v2.312 PPL chirag patel Marked gene: PPL as ready
Mendeliome v2.312 PPL chirag patel Gene: ppl has been classified as Green List (High Evidence).
Mendeliome v2.312 PPL chirag patel Classified gene: PPL as Green List (high evidence)
Mendeliome v2.312 PPL chirag patel Gene: ppl has been classified as Green List (High Evidence).
Mendeliome v2.311 PPL chirag patel gene: PPL was added
gene: PPL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPL were set to 34815391
Phenotypes for gene: PPL were set to Eosinophilic esophagitis, MONDO:0005361
Review for gene: PPL was set to GREEN
Added comment: PMID 34815391 reports 17 affected individuals from 7 families with eosinophilic oesophagitis and 6 different heterozygous missense PPL variants. Most variants are rare but 2 are seen in 140 hets (p.Val1377Glu) and 159 hets (p.Glu632Lys) in gnomAD v4. The variants segregated with affected siblings/relatives in 6/7 families, and parental testing was only done in 2/7 families with reduced penetrance noted in those families. One large family also had a DSP (desmoplakin variant segregating with disease). Periplakin (PPL) is a member of the plakin protein family that localize to desmosomes and is highly expressed in the esophagus. PPL knockout EPC2 cells (human esophageal cell lines) demonstrated acantholysis and significantly decreased barrier function. EPC2 cells transduced with PPL variants showed impaired epithelial barrier integrity and reduced barrier function. A wound healing assay showed mutant PPL increased wound‑healing speed, reduced active RhoA, and increased susceptibility to CAPN14‑mediated degradation.
Sources: Literature
Mendeliome v2.310 YBX3 Sangavi Sivagnanasundram gene: YBX3 was added
gene: YBX3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: YBX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: YBX3 were set to 39423228; 38260399
Phenotypes for gene: YBX3 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: YBX3 was set to RED
Added comment: PMID 39423228 reports 3 individuals with a heterozygous missense variant p.Asn127Tyr in YBX3.
Two of the individuals were reported to have a neurological phenotype including ID, DD and seizures whilst the third individual presented with a complex metabolic phenotype with no neurological phenotype.

p.Asn127Tyr is a rare variant (absent in gnomADv4.1) however there are no pathogenic reported variants in this gene in ClinVar and no Morbid entry.
The gene is not constrained for missense variants or LoF.
Both GDA are red given only one rare variant was reported in all three individuals.
Sources: Literature
Mendeliome v2.309 MATN2 chirag patel Marked gene: MATN2 as ready
Mendeliome v2.309 MATN2 chirag patel Gene: matn2 has been classified as Red List (Low Evidence).
Mendeliome v2.309 MATN2 chirag patel Marked gene: MATN2 as ready
Mendeliome v2.309 MATN2 chirag patel Gene: matn2 has been classified as Red List (Low Evidence).
Mendeliome v2.309 MATN2 chirag patel gene: MATN2 was added
gene: MATN2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MATN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MATN2 were set to 35584218
Phenotypes for gene: MATN2 were set to Syndromic disease, MONDO:0002254
Review for gene: MATN2 was set to RED
Added comment: PMID 35584218 reports 3 individuals from 3 families presenting with non-specific or consistent multisystem issues (limited clinical information in paper). They identified biallelic variants in MATN2 which is a basement membrane gene (compound HTZ p.Cys249Ser missense and c.1450+1G>A splice variants; homozygous p.Cys529Valfs*13 frameshift variant; and homozygous c.1081+3_1081+6del splice variant). Functional assays in podocytes demonstrate defective secretion or translation of the mutant proteins, supporting loss‑of‑function. CRISPR-Cas9 knockdown of MATN2 nearly abolished the ECM fraction of MATN2, which was rescued by over expression of wild-type V5-tagged MATN2. Overexpression of the MATN2 p.Cys249Ser-V5 missense variant resulted in MATN2 accumulation in the cellular fraction, suggesting a defect in secretion. Minigene splicing assay confirmed aberrant splicing and the introduction of a premature stop codon for the predicted splicing variant (c.1081+3-1081+6del). Podocyte-derived matrix by proteomics showed decreased levels of core basement membrane components (nidogen and collagen IV).
Sources: Literature
Pulmonary Arterial Hypertension v2.1 MUC6 chirag patel Marked gene: MUC6 as ready
Pulmonary Arterial Hypertension v2.1 MUC6 chirag patel Gene: muc6 has been classified as Red List (Low Evidence).
Pulmonary Arterial Hypertension v2.1 chirag patel Copied gene MUC6 from panel Mendeliome
Pulmonary Arterial Hypertension v2.1 MUC6 chirag patel gene: MUC6 was added
gene: MUC6 was added to Pulmonary Arterial Hypertension. Sources: Expert Review Red,Literature
Mode of inheritance for gene: MUC6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MUC6 were set to 30047301
Phenotypes for gene: MUC6 were set to Pulmonary arterial hypertension, MONDO:0015924
Mendeliome v2.308 MUC6 chirag patel Marked gene: MUC6 as ready
Mendeliome v2.308 MUC6 chirag patel Gene: muc6 has been classified as Red List (Low Evidence).
Mendeliome v2.308 MUC6 chirag patel gene: MUC6 was added
gene: MUC6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MUC6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MUC6 were set to 30047301
Phenotypes for gene: MUC6 were set to Pulmonary arterial hypertension, MONDO:0015924
Review for gene: MUC6 was set to RED
Added comment: PMID 30047301 reports 4 individuals from 2 unrelated Chinese families with pulmonary arterial hypertension, with the same heterozygous missense variant (p.Pro1716Ser) in MUC6 gene. This was validated with Sanger sequencing, and the same variant was also observed in a cohort of 20/30 individuals with idiopathic PAH. The variant is absent in gnomAD v4 and lies in the variable tandem repeat domain. No functional studies were performed.
Sources: Literature
Colorectal Cancer and Polyposis v2.1 HIC1 chirag patel Marked gene: HIC1 as ready
Colorectal Cancer and Polyposis v2.1 HIC1 chirag patel Gene: hic1 has been classified as Amber List (Moderate Evidence).
Colorectal Cancer and Polyposis v2.1 chirag patel Copied gene HIC1 from panel Mendeliome
Colorectal Cancer and Polyposis v2.1 HIC1 chirag patel gene: HIC1 was added
gene: HIC1 was added to Colorectal Cancer and Polyposis. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: HIC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIC1 were set to 40444741; 33672345
Phenotypes for gene: HIC1 were set to Sessile serrated polyposis cancer syndrome, MONDO:0014919
Mendeliome v2.307 HIC1 chirag patel changed review comment from: PMID 40444741 reports 5 individuals from 3 families and PMID 33672345 reports 2 individuals from 1 family with heterozygous missense HIC1 variants (p.Ala37Val, p.Gln432Arg x 2, p.Gly471Arg) causing serrated polyposis syndrome (adult‑onset). Clinical features include multiple serrated colonic polyps and increased colorectal cancer risk. HIC1 is a tumor suppressor gene which encodes a transcriptional repressor involved in the DNA damage response. Hic1 inactivation in mice cells is known to lead to cell cycle arrest, premature senescence, and chromosomal instability. PMID 40444741 reported functional assays in cell lines which showed loss‑of‑function of HIC1 transcriptional repression (increased γ‑H2AX - marker of DNA damage, and reduced SIRT1 promoter activity).
Sources: Literature; to: PMID 40444741 reports 5 individuals from 3 families and PMID 33672345 reports 2 individuals from 1 family with multiple serrated colonic polyps and serrated polyposis syndrome (adult‑onset). They identified heterozygous missense HIC1 variants (p.Ala37Val - 134 hets/5 homs, v4; p.Gln432Arg x 2 - 1 het, v4; p.Gly471Arg - 57 hets, v4). HIC1 is a tumor suppressor gene which encodes a transcriptional repressor involved in the DNA damage response. Hic1 inactivation in mice cells is known to lead to cell cycle arrest, premature senescence, and chromosomal instability. PMID 40444741 reported functional assays in cell lines which showed loss‑of‑function of HIC1 transcriptional repression (increased γ‑H2AX - marker of DNA damage, and reduced SIRT1 promoter activity).
Sources: Literature
Mendeliome v2.307 HIC1 chirag patel Marked gene: HIC1 as ready
Mendeliome v2.307 HIC1 chirag patel Gene: hic1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.307 HIC1 chirag patel Classified gene: HIC1 as Amber List (moderate evidence)
Mendeliome v2.307 HIC1 chirag patel Gene: hic1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.306 HIC1 chirag patel gene: HIC1 was added
gene: HIC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HIC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIC1 were set to 40444741; 33672345
Phenotypes for gene: HIC1 were set to Sessile serrated polyposis cancer syndrome, MONDO:0014919
Review for gene: HIC1 was set to AMBER
Added comment: PMID 40444741 reports 5 individuals from 3 families and PMID 33672345 reports 2 individuals from 1 family with heterozygous missense HIC1 variants (p.Ala37Val, p.Gln432Arg x 2, p.Gly471Arg) causing serrated polyposis syndrome (adult‑onset). Clinical features include multiple serrated colonic polyps and increased colorectal cancer risk. HIC1 is a tumor suppressor gene which encodes a transcriptional repressor involved in the DNA damage response. Hic1 inactivation in mice cells is known to lead to cell cycle arrest, premature senescence, and chromosomal instability. PMID 40444741 reported functional assays in cell lines which showed loss‑of‑function of HIC1 transcriptional repression (increased γ‑H2AX - marker of DNA damage, and reduced SIRT1 promoter activity).
Sources: Literature
Mendeliome v2.305 NPTN Achchuthan Shanmugasundram gene: NPTN was added
gene: NPTN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NPTN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NPTN were set to 42387534
Phenotypes for gene: NPTN were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: NPTN was set to GREEN
Added comment: PMID:42387534 (2026) reported a cohort of eight individuals with seven different heterozygous variants in NPTN, seven of which are of de novo origin. The patients presented with an overlapping, but unspecific phenotype, All eight individuals presented with developmental delay (DD) and/or intellectual disability (ID) ranging from mild to severe (severe in four, moderate in two and mild in two). Seven individuals were diagnosed with autism spectrum disorder and six were reported with subtle dysmorphic facial features.

Four individuals had variants (three variants) affecting the two hNp isoforms, hNp55 and hNp65 and other four variants affect only the neuron-specific hNp65 isoform. It was observed that the severity of ID/DD and other clinical findings correlate with the impact on both hNp isoforms (severe) or only on the hNp65 isoform (mild/moderate).

Functional evidence from human cell line, cultured primary rodent neurons, and in vivo in Drosophila melanogaster showed that the missense variants are inefficiently expressed and inefficiently support PMCA levels, resulting in failed cytosolic Ca(2+) regulation. Haploinsuffient Nptn+/− mice expressed reduced amounts of both Np and PMCA. In a social behavior test, Nptn+/− mice displayed loss of preference for a novel mouse representing an endophenotype analog to social deficits that characterize autism.

This gene has not yet been associated with relevant phenotypes in OMIM, Gene2Phenotype or ClinGen (last accessed 29 July 2026).
Sources: Literature
Mendeliome v2.305 TES Rylee Peters Marked gene: TES as ready
Mendeliome v2.305 TES Rylee Peters Gene: tes has been classified as Red List (Low Evidence).
Mendeliome v2.305 TES Rylee Peters gene: TES was added
gene: TES was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TES was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TES were set to 33092471
Phenotypes for gene: TES were set to Thoracic aortic aneurysm, MONDO:0005396,TES-related
Review for gene: TES was set to RED
Added comment: PMID: 33092471 reports four individuals from four unrelated families with heterozygous missense TES variants (c.751T>C p.Y251H in three families however has 20 hets in gnomAD and c.838T>C p.Y280H in one family) presenting with early‑onset isolated thoracic aortic aneurysm (<50 years). Functional studies with homozygous mouse knock‑in of the orthologous p.Y251H and Tes‑/‑ knockout showed that the thoracic aorta was spontaneously dilated showed reduced Tes expression.
Sources: Literature
Mendeliome v2.304 ATP8B2 Lucy Spencer Classified gene: ATP8B2 as Amber List (moderate evidence)
Mendeliome v2.304 ATP8B2 Lucy Spencer Gene: atp8b2 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.303 ATP8B2 Lucy Spencer gene: ATP8B2 was added
gene: ATP8B2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP8B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP8B2 were set to 39219493
Phenotypes for gene: ATP8B2 were set to Neurodevelopmental disorder MONDO:0700092, ATP8B2-related
Review for gene: ATP8B2 was set to AMBER
Added comment: PMID 39219493 3 individuals with ID and de novo missense in ATP8B2 Asn817Ser, Arg549Gln and Gly759Ser. 2 of the variants are absent from gnomad or only have 1 het but Arg549Gln has 7 hets in gnomad. In transfected cells Asn817Ser and Gly759Ser almost abolished PC-flipping activity while Arg549Gln had no significant impact. 2 compelling variants, limited phenotype information. Amber
Sources: Literature
Incidentalome v1.8 SFPQ Zornitza Stark Marked gene: SFPQ as ready
Incidentalome v1.8 SFPQ Zornitza Stark Gene: sfpq has been classified as Red List (Low Evidence).
Incidentalome v1.8 SFPQ Zornitza Stark gene: SFPQ was added
gene: SFPQ was added to Incidentalome. Sources: Literature
Mode of inheritance for gene: SFPQ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SFPQ were set to 28392072
Phenotypes for gene: SFPQ were set to Amyotrophic lateral sclerosis, MONDO:0004976, SFPQ-related
Review for gene: SFPQ was set to RED
Added comment: Reports two individuals from unrelated families with heterozygous missense SFPQ variants (NM_005066:c.1597A>C and NM_005066:c.1600C>A) presenting with familial amyotrophic lateral sclerosis (ALS). Variants are present at low levels in gnomAD. Each variant was tested in a zebrafish null‑mutant rescue assay, showing reduced axonal SFPQ localisation and abnormal motor‑axon morphology, while wild‑type SFPQ fully rescues. No segregation data were available.

RED rating due to lack of segregation and pop frequency. Not replicated over time so far.
Sources: Literature
Motor Neurone Disease v2.11 SFPQ Zornitza Stark Marked gene: SFPQ as ready
Motor Neurone Disease v2.11 SFPQ Zornitza Stark Gene: sfpq has been classified as Red List (Low Evidence).
Motor Neurone Disease v2.11 SFPQ Zornitza Stark gene: SFPQ was added
gene: SFPQ was added to Motor Neurone Disease. Sources: Literature
Mode of inheritance for gene: SFPQ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SFPQ were set to 28392072
Phenotypes for gene: SFPQ were set to Amyotrophic lateral sclerosis, MONDO:0004976, SFPQ-related
Review for gene: SFPQ was set to RED
Added comment: Reports two individuals from unrelated families with heterozygous missense SFPQ variants (NM_005066:c.1597A>C and NM_005066:c.1600C>A) presenting with familial amyotrophic lateral sclerosis (ALS). Variants are present at low levels in gnomAD. Each variant was tested in a zebrafish null‑mutant rescue assay, showing reduced axonal SFPQ localisation and abnormal motor‑axon morphology, while wild‑type SFPQ fully rescues. No segregation data were available.

RED rating due to lack of segregation and pop frequency. Not replicated over time so far.
Sources: Literature
Mendeliome v2.302 KCNH7 Zornitza Stark Classified gene: KCNH7 as Amber List (moderate evidence)
Mendeliome v2.302 KCNH7 Zornitza Stark Gene: kcnh7 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.301 KCNH7 Zornitza Stark edited their review of gene: KCNH7: Changed rating: AMBER
Genetic Epilepsy v2.28 KCNH7 Zornitza Stark Classified gene: KCNH7 as Amber List (moderate evidence)
Genetic Epilepsy v2.28 KCNH7 Zornitza Stark Gene: kcnh7 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v2.27 KCNH7 Zornitza Stark edited their review of gene: KCNH7: Changed rating: AMBER
Genetic Epilepsy v2.27 KCNH7 Zornitza Stark Marked gene: KCNH7 as ready
Genetic Epilepsy v2.27 KCNH7 Zornitza Stark Gene: kcnh7 has been classified as Green List (High Evidence).
Genetic Epilepsy v2.27 KCNH7 Zornitza Stark Classified gene: KCNH7 as Green List (high evidence)
Genetic Epilepsy v2.27 KCNH7 Zornitza Stark Gene: kcnh7 has been classified as Green List (High Evidence).
Genetic Epilepsy v2.26 KCNH7 Zornitza Stark gene: KCNH7 was added
gene: KCNH7 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KCNH7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNH7 were set to 39634124
Phenotypes for gene: KCNH7 were set to Epilepsy, MONDO:0005027, KCNH7-related
Review for gene: KCNH7 was set to GREEN
Added comment: PMID 39634124 reports three individuals from three families with de novo heterozygous KCNH7 variants (c.83A>G p.K28R, c.1919A>G p.E640G, c.1324C>T p.R442X) presenting with early‑onset epilepsy (generalized tonic‑clonic seizures, focal motor seizures, West syndrome). Functional evidence is limited to a mouse ERG3 knockdown model and protein structural modelling. One of the variants, p.R442X, is present in 4 hets in gnomAD.
Sources: Literature
Mendeliome v2.301 KCNH7 Zornitza Stark Marked gene: KCNH7 as ready
Mendeliome v2.301 KCNH7 Zornitza Stark Gene: kcnh7 has been classified as Green List (High Evidence).
Mendeliome v2.301 KCNH7 Zornitza Stark Classified gene: KCNH7 as Green List (high evidence)
Mendeliome v2.301 KCNH7 Zornitza Stark Gene: kcnh7 has been classified as Green List (High Evidence).
Mendeliome v2.300 KCNH7 Zornitza Stark gene: KCNH7 was added
gene: KCNH7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KCNH7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNH7 were set to 39634124
Phenotypes for gene: KCNH7 were set to Epilepsy, MONDO:0005027, KCNH7-related
Review for gene: KCNH7 was set to GREEN
Added comment: PMID 39634124 reports three individuals from three families with de novo heterozygous KCNH7 variants (c.83A>G p.K28R, c.1919A>G p.E640G, c.1324C>T p.R442X) presenting with early‑onset epilepsy (generalized tonic‑clonic seizures, focal motor seizures, West syndrome). Functional evidence is limited to a mouse ERG3 knockdown model and protein structural modelling. One of the variants, p.R442X, is present in 4 hets in gnomAD.
Sources: Literature
Mendeliome v2.299 CCDC201 Sangavi Sivagnanasundram gene: CCDC201 was added
gene: CCDC201 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC201 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC201 were set to 39192094
Phenotypes for gene: CCDC201 were set to Infertility disorder, MONDO:0005047
Review for gene: CCDC201 was set to RED
Added comment: PMID 39192094
This publication reports 27 individuals from 27 families presenting with primary ovarian insufficiency (menopause <40 y) and early menopause (menopause <45 y).
One variant was reported in all the reported individuals p.Arg162Ter. The FAF of the reported variant is 0.5037% and there have been 2 homozygotes reported in gnomAD v4.1.
The publication is based off population screening, therefore the GDA to remain as RED until further supportive evidence is published.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v2.31 CCER1 Zornitza Stark Marked gene: CCER1 as ready
Infertility and Recurrent Pregnancy Loss v2.31 CCER1 Zornitza Stark Gene: ccer1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v2.31 CCER1 Zornitza Stark Classified gene: CCER1 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v2.31 CCER1 Zornitza Stark Gene: ccer1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v2.30 CCER1 Zornitza Stark gene: CCER1 was added
gene: CCER1 was added to Infertility and Recurrent Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: CCER1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCER1 were set to 38081819
Phenotypes for gene: CCER1 were set to Infertility disorder, MONDO:0005047
Review for gene: CCER1 was set to GREEN
Added comment: PMID 38081819 reports 5 individuals from 5 families with heterozygous loss-of-function CCER1 variants presenting with nonobstructive azoospermia (NOA). Mouse knockout recapitulates male infertility and patient-derived mutant proteins lack phase‑separated nuclear condensates, supporting a loss‑of‑function (haploinsufficiency) mechanism.
Sources: Literature
Mendeliome v2.298 CCER1 Zornitza Stark Marked gene: CCER1 as ready
Mendeliome v2.298 CCER1 Zornitza Stark Gene: ccer1 has been classified as Green List (High Evidence).
Mendeliome v2.298 CCER1 Zornitza Stark Phenotypes for gene: CCER1 were changed from Infertility disorder, MONDO:0005047 to Infertility disorder, MONDO:0005047, CCER1-related
Mendeliome v2.297 CCER1 Zornitza Stark Classified gene: CCER1 as Green List (high evidence)
Mendeliome v2.297 CCER1 Zornitza Stark Gene: ccer1 has been classified as Green List (High Evidence).
Mendeliome v2.296 CCER1 Zornitza Stark gene: CCER1 was added
gene: CCER1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCER1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCER1 were set to 38081819
Phenotypes for gene: CCER1 were set to Infertility disorder, MONDO:0005047
Review for gene: CCER1 was set to GREEN
Added comment: PMID 38081819 reports 5 individuals from 5 families with heterozygous loss-of-function CCER1 variants presenting with nonobstructive azoospermia (NOA). Mouse knockout recapitulates male infertility and patient-derived mutant proteins lack phase‑separated nuclear condensates, supporting a loss‑of‑function (haploinsufficiency) mechanism.
Sources: Literature
Dystonia and Chorea v1.7 CAMK4 Zornitza Stark Phenotypes for gene: CAMK4 were changed from Intellectual disability; Autism; Behavioral abnormality; Abnormality of movement; Dystonia; Ataxia; Chorea; Myoclonus to Neurodevelopmental disorder, MONDO:0700092, CAMK4-related
Dystonia and Chorea v1.6 CAMK4 Zornitza Stark Publications for gene: CAMK4 were set to 30262571; 33098801; 33211350
Dystonia and Chorea v1.5 CAMK4 Zornitza Stark edited their review of gene: CAMK4: Added comment: Two additional individuals with de novo missense variants reported in PMIDs 37070062 and 37644014. MODERATE by ClinGen.; Changed publications: 30262571, 33098801, 33211350, 37070062, 37644014; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, CAMK4-related
Intellectual disability syndromic and non-syndromic v2.50 CAMK4 Zornitza Stark Phenotypes for gene: CAMK4 were changed from Global developmental delay; Intellectual disability; Autism; Behavioral abnormality; Abnormality of movement; Dystonia; Ataxia; Chorea; Myoclonus to Neurodevelopmental disorder, MONDO:0700092, CAMK4-related
Intellectual disability syndromic and non-syndromic v2.49 CAMK4 Zornitza Stark Publications for gene: CAMK4 were set to 30262571; 33098801; 33211350
Intellectual disability syndromic and non-syndromic v2.48 CAMK4 Zornitza Stark reviewed gene: CAMK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 37070062, 37644014; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CAMK4-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v2.295 CAMK4 Zornitza Stark Phenotypes for gene: CAMK4 were changed from Intellectual disability; Autism; Behavioral abnormality; Abnormality of movement; Dystonia; Ataxia; Chorea; Myoclonus to Neurodevelopmental disorder, MONDO:0700092, CAMK4-related
Mendeliome v2.294 CAMK4 Zornitza Stark Publications for gene: CAMK4 were set to 30262571; 33098801; 33211350
Mendeliome v2.293 CAMK4 Zornitza Stark edited their review of gene: CAMK4: Added comment: Two additional individuals with de novo missense variants reported in PMIDs 37070062 and 37644014. MODERATE by ClinGen.; Changed publications: 30262571, 33098801, 33211350, 37070062, 37644014; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, CAMK4-related
Mendeliome v2.293 SLC13A1 Zornitza Stark Phenotypes for gene: SLC13A1 were changed from sulfation-related bone disorder MONDO:0019688, SLC13A1-related to Hyposulfataemia with skeletal dysplasia, MIM# 621654
Mendeliome v2.292 SLC13A1 Zornitza Stark reviewed gene: SLC13A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 39925707, 36175384; Phenotypes: Hyposulfataemia with skeletal dysplasia, MIM# 621654; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.6 SLC13A1 Zornitza Stark Phenotypes for gene: SLC13A1 were changed from sulfation-related bone disorder MONDO:0019688, SLC13A1-related to Hyposulfataemia with skeletal dysplasia, MIM# 621654
Skeletal dysplasia v1.5 SLC13A1 Zornitza Stark Publications for gene: SLC13A1 were set to 36175384; 39925707
Skeletal dysplasia v1.4 SLC13A1 Zornitza Stark edited their review of gene: SLC13A1: Added comment: PMID 36175384: additional report of an affected individual homozygous for the p.(Arg12*) variant, which has 7 homs in gnomAD v4.; Changed publications: 39925707, 36175384; Changed phenotypes: Hyposulfatemia with skeletal dysplasia, MIM# 621654
Mendeliome v2.292 PTPN18 Bryony Thompson Marked gene: PTPN18 as ready
Mendeliome v2.292 PTPN18 Bryony Thompson Gene: ptpn18 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.292 PTPN18 Bryony Thompson Classified gene: PTPN18 as Amber List (moderate evidence)
Mendeliome v2.292 PTPN18 Bryony Thompson Gene: ptpn18 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.291 PTPN18 Bryony Thompson gene: PTPN18 was added
gene: PTPN18 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTPN18 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN18 were set to 37056996
Phenotypes for gene: PTPN18 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: PTPN18 was set to AMBER
Added comment: PMID 37056996 reports 4 individuals from 4 families with de novo heterozygous splice‑region and missense variants presenting with a neurodevelopmental disorder characterised by autistic behaviour, delayed speech and intellectual disability. No variant‑specific functional validation was performed. One of the missense (Gln371Arg) has 7 hets in gnomAD v4, 2 hets in the South Asian population. This is higher than expected for an AD neurodevelopmental disorder.
Sources: Literature
Intellectual disability syndromic and non-syndromic v2.48 Bryony Thompson Copied gene LGALS3BP from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.48 LGALS3BP Bryony Thompson gene: LGALS3BP was added
gene: LGALS3BP was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: LGALS3BP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LGALS3BP were set to 37205765; 34728600
Phenotypes for gene: LGALS3BP were set to Neurodevelopmental disorder, MONDO:0700092
Mendeliome v2.290 LGALS3BP Bryony Thompson Classified gene: LGALS3BP as Amber List (moderate evidence)
Mendeliome v2.290 LGALS3BP Bryony Thompson Gene: lgals3bp has been classified as Amber List (Moderate Evidence).
Mendeliome v2.289 LGALS3BP Bryony Thompson gene: LGALS3BP was added
gene: LGALS3BP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LGALS3BP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LGALS3BP were set to 37205765; 34728600
Phenotypes for gene: LGALS3BP were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: LGALS3BP was set to AMBER
Added comment: PMID 34728600 reports 3 individuals from 3 families with de novo heterozygous missense LGALS3BP variants presenting with cortical malformations (periventricular heterotopia, microcephaly, abnormal gyrification), developmental delay and seizures; functional studies in CRISPR‑edited organoids and mouse models demonstrate loss‑of‑function rescued by wild‑type LGALS3BP. PMID 37205765 describes cerebral organoids from a carrier of E370K reported in a previous family from PMID 34728600. This variant is present in 28 hets in gnomAD v4, which is more common than expected for an AD condition.
Sources: Literature
Intellectual disability syndromic and non-syndromic v2.47 Bryony Thompson Copied gene KDM8 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.47 KDM8 Bryony Thompson gene: KDM8 was added
gene: KDM8 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: KDM8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KDM8 were set to 36795492
Phenotypes for gene: KDM8 were set to Neurodevelopmental disorder, MONDO:0700092
Mendeliome v2.288 KDM8 Bryony Thompson Marked gene: KDM8 as ready
Mendeliome v2.288 KDM8 Bryony Thompson Gene: kdm8 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.288 KDM8 Bryony Thompson Classified gene: KDM8 as Amber List (moderate evidence)
Mendeliome v2.288 KDM8 Bryony Thompson Gene: kdm8 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.287 KDM8 Bryony Thompson gene: KDM8 was added
gene: KDM8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KDM8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KDM8 were set to 36795492
Phenotypes for gene: KDM8 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: KDM8 was set to AMBER
Added comment: Fletcher2023 reports 3 individuals from 2 families with biallelic loss-of-function KDM8 variants presenting with a severe neurodevelopmental disorder characterised by intra‑uterine and post‑natal growth failure, intellectual disability, facial dysmorphism, relative macrocephaly and growth delay. Patient fibroblast assays reveal replication‑stress phenotypes that are rescued by wild‑type KDM8.
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v1.3 Bryony Thompson Copied gene DIS3 from panel Mendeliome
Primary Ovarian Insufficiency_Premature Ovarian Failure v1.3 DIS3 Bryony Thompson gene: DIS3 was added
gene: DIS3 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: DIS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DIS3 were set to 39400047; 36869713
Phenotypes for gene: DIS3 were set to Infertility disorder, MONDO:0005047
Infertility and Recurrent Pregnancy Loss v2.29 Bryony Thompson Copied gene DIS3 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v2.29 DIS3 Bryony Thompson gene: DIS3 was added
gene: DIS3 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: DIS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DIS3 were set to 39400047; 36869713
Phenotypes for gene: DIS3 were set to Infertility disorder, MONDO:0005047
Mendeliome v2.286 DIS3 Bryony Thompson Marked gene: DIS3 as ready
Mendeliome v2.286 DIS3 Bryony Thompson Gene: dis3 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.286 DIS3 Bryony Thompson Classified gene: DIS3 as Amber List (moderate evidence)
Mendeliome v2.286 DIS3 Bryony Thompson Gene: dis3 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.285 DIS3 Bryony Thompson gene: DIS3 was added
gene: DIS3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DIS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DIS3 were set to 39400047; 36869713
Phenotypes for gene: DIS3 were set to Infertility disorder, MONDO:0005047
Review for gene: DIS3 was set to AMBER
Added comment: PMID 39400047 reports 1 individual from a consanguineous family and PMID 36869713 reports 2 individuals with primary ovarian insufficiency (amenorrhea, elevated FSH, atrophic ovaries) with adolescent onset, occasionally accompanied by short stature from a sibling pair with biallelic DIS3 variants. Functional studies, including a Drosophila rescue assay that demonstrates a hypomorphic allele fails to rescue ovarian development, support loss‑of‑function as the disease mechanism.
Sources: Literature
Mendeliome v2.284 CABLES1 Bryony Thompson Marked gene: CABLES1 as ready
Mendeliome v2.284 CABLES1 Bryony Thompson Gene: cables1 has been classified as Red List (Low Evidence).
Mendeliome v2.284 CABLES1 Bryony Thompson gene: CABLES1 was added
gene: CABLES1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CABLES1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CABLES1 were set to 28533356
Phenotypes for gene: CABLES1 were set to ACTH-dependent Cushing syndrome MONDO:0020528
Review for gene: CABLES1 was set to RED
Added comment: PMID 28533356 reports four individuals from four families with heterozygous missense CABLES1 variants presenting with Cushing's disease (ACTH‑secreting pituitary macroadenoma); functional assays in AtT‑20 cells demonstrate mutant proteins lose their growth inhibition activity. It is not clear if this would be a mechanism for pathogenicity. One variant was inherited from an unaffected father, while parental status was unknown for the remaining cases. Two variants are too common in gnomAD than would be expected for a dominant inheritance pattern.
Sources: Literature
Ataxia v2.7 OGDH Bryony Thompson Marked gene: OGDH as ready
Ataxia v2.7 OGDH Bryony Thompson Gene: ogdh has been classified as Amber List (Moderate Evidence).
Ataxia v2.7 OGDH Bryony Thompson Phenotypes for gene: OGDH were changed from Oxoglutarate dehydrogenase deficiency, MIM# 203740; Developmental delay; ataxia; seizure; raised lactate to Hereditary ataxia MONDO:0100309
Ataxia v2.6 OGDH Bryony Thompson Publications for gene: OGDH were set to 32383294; 36520152; 42266417
Ataxia v2.5 OGDH Bryony Thompson Mode of pathogenicity for gene: OGDH was changed from None to Other
Ataxia v2.4 OGDH Bryony Thompson Mode of inheritance for gene: OGDH was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia v2.3 OGDH Bryony Thompson Classified gene: OGDH as Amber List (moderate evidence)
Ataxia v2.3 OGDH Bryony Thompson Gene: ogdh has been classified as Amber List (Moderate Evidence).
Ataxia v2.2 Bryony Thompson Copied gene OGDH from panel Mendeliome
Ataxia v2.2 OGDH Bryony Thompson gene: OGDH was added
gene: OGDH was added to Ataxia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: OGDH was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: OGDH were set to 32383294; 36520152; 42266417
Phenotypes for gene: OGDH were set to Oxoglutarate dehydrogenase deficiency, MIM# 203740; Developmental delay; ataxia; seizure; raised lactate
Mendeliome v2.283 OGDH Bryony Thompson Publications for gene: OGDH were set to 32383294; 36520152
Mendeliome v2.282 OGDH Bryony Thompson Mode of inheritance for gene: OGDH was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v2.281 OGDH Bryony Thompson reviewed gene: OGDH: Rating: AMBER; Mode of pathogenicity: Other; Publications: 42266417; Phenotypes: Hereditary ataxia MONDO:0100309; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v2.281 SARDH Bryony Thompson Publications for gene: SARDH were set to 22825317; 27604308
Growth failure v2.9 ARCN1 Boris Keren gene: ARCN1 was added
gene: ARCN1 was added to Growth failure. Sources: Literature
Mode of inheritance for gene: ARCN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARCN1 were set to 35300924
Phenotypes for gene: ARCN1 were set to small stature; IUGR; cleft; genitourinary malformations; microcephaly; transient liver dysfunction; giant cell hepatitis; hepatoblastoma; cataracts; lethal skeletal manifestations
Penetrance for gene: ARCN1 were set to Complete
Review for gene: ARCN1 was set to GREEN
gene: ARCN1 was marked as current diagnostic
Added comment: 14 cases all with micrognathia, short stature and IUGR.
Other common features : developmental delay (10/14, 71.4%), genitourinary malformations in males (6/8, 75%), microcephaly (12/15, 80%). Developmental delay 73% of patients, but only 3/14 patients had intellectual disability.
Possible signs : transient liver dysfunction and specific glycosylation abnormalities during illness, giant cell hepatitis, hepatoblastoma, cataracts, and lethal skeletal manifestations
Sources: Literature
Miscellaneous Metabolic Disorders v2.1 Bryony Thompson Added reviews for gene SARDH from panel Mendeliome
Early-onset Dementia v2.11 Bryony Thompson Copied gene SARDH from panel Mendeliome
Early-onset Dementia v2.11 SARDH Bryony Thompson gene: SARDH was added
gene: SARDH was added to Early-onset Dementia. Sources: Expert Review Amber,Expert Review Amber,Literature,Victorian Clinical Genetics Services
Mode of inheritance for gene: SARDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARDH were set to 22825317; 27604308
Phenotypes for gene: SARDH were set to Sarcosinemia MIM#268900; Disorders of serine, glycine or glycerate metabolism
Mendeliome v2.280 SARDH Bryony Thompson edited their review of gene: SARDH: Added comment: Variable phenotype including normal individuals - assigning to amber
**New evidence**: PMID 31815201 reports 11 cases with sarcosinemia and cognitive decline homozygous for three distinct loss‑of‑function SARDH variants (c.1553G>T, c.1540C>T, c.860C>T) and demonstrates markedly reduced blood SARDH activity and low urinary formaldehyde. Unsure if cases are related. PMID 42337718 adds one further case with compound heterozygous SARDH variants (c.293G>C missense and c.679C>T nonsense) presenting with acute childhood leukoencephalopathy and cytotoxic white‑matter edema.
**Prior evidence**: PMID 22825317 reports 3 consanguineous and 1 UPD case with homozygous variants and variable clinical features, including normal phenotype (in 2 individuals), cardiomyopathy, and developmental delay.; Changed rating: AMBER; Changed publications: 42337718, 31815201, 22825317; Changed phenotypes: sarcosinemia, MONDO:0010008
Genomic newborn screening: BabyScreen+ v2.0 PJVK TRAIL SCHN commented on gene: PJVK
Fetal anomalies v2.16 ASTN1 Zornitza Stark Phenotypes for gene: ASTN1 were changed from Polymicrogyria; hypoplastic corpus callosum to Neurodevelopmental disorder (MONDO:0700092), ASTN1-related
Fetal anomalies v2.15 ASTN1 Zornitza Stark Publications for gene: ASTN1 were set to 27431290; 26539891; 29706646; 11861479
Fetal anomalies v2.14 ASTN1 Zornitza Stark Classified gene: ASTN1 as Green List (high evidence)
Fetal anomalies v2.14 ASTN1 Zornitza Stark Gene: astn1 has been classified as Green List (High Evidence).
Fetal anomalies v2.13 ASTN1 Zornitza Stark reviewed gene: ASTN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41544630; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), ASTN1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v2.46 ASTN1 Zornitza Stark Phenotypes for gene: ASTN1 were changed from to Neurodevelopmental disorder (MONDO:0700092), ASTN1-related
Intellectual disability syndromic and non-syndromic v2.45 ASTN1 Zornitza Stark Publications for gene: ASTN1 were set to 29706646; 27431290; 26539891
Intellectual disability syndromic and non-syndromic v2.44 ASTN1 Zornitza Stark edited their review of gene: ASTN1: Added comment: PMID 41544630 reports 18 individuals with NDDs from 12 unrelated families with bi-allelic, ultra-rare, predicted damaging variants in ASTN1. Clinical features ranged from mild to profound developmental delay or intellectual disability +/- autism, ADHD, and epilepsy. Other recurrent abnormalities included dysmorphic facial features, hypotonia, spasticity, and ataxia. The neuroradiographic phenotype ranged from normal to mild (a thin corpus callosum and cerebellar dysgenesis), to severe (polymicrogyria and lissencephaly).; Changed publications: 41544630, 29706646, 27431290, 26539891; Changed phenotypes: Neurodevelopmental disorder (MONDO:0700092), ASTN1-related
Polymicrogyria and Schizencephaly v1.3 ASTN1 Zornitza Stark Phenotypes for gene: ASTN1 were changed from Polymicrogyria; hypoplastic corpus callosum to Neurodevelopmental disorder (MONDO:0700092), ASTN1-related
Polymicrogyria and Schizencephaly v1.2 ASTN1 Zornitza Stark Publications for gene: ASTN1 were set to 29706646
Polymicrogyria and Schizencephaly v1.1 ASTN1 Zornitza Stark Classified gene: ASTN1 as Green List (high evidence)
Polymicrogyria and Schizencephaly v1.1 ASTN1 Zornitza Stark Gene: astn1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v1.0 ASTN1 Zornitza Stark reviewed gene: ASTN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41544630; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), ASTN1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v1.6 ASTN1 Zornitza Stark Marked gene: ASTN1 as ready
Callosome v1.6 ASTN1 Zornitza Stark Gene: astn1 has been classified as Green List (High Evidence).
Callosome v1.6 ASTN1 Zornitza Stark Phenotypes for gene: ASTN1 were changed from to Neurodevelopmental disorder (MONDO:0700092), ASTN1-related
Callosome v1.5 ASTN1 Zornitza Stark Publications for gene: ASTN1 were set to
Callosome v1.4 ASTN1 Zornitza Stark Mode of inheritance for gene: ASTN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Callosome v1.3 ASTN1 Zornitza Stark edited their review of gene: ASTN1: Added comment: PMID 41544630 reports 18 individuals with NDDs from 12 unrelated families with bi-allelic, ultra-rare, predicted damaging variants in ASTN1. Clinical features ranged from mild to profound developmental delay or intellectual disability +/- autism, ADHD, and epilepsy. Other recurrent abnormalities included dysmorphic facial features, hypotonia, spasticity, and ataxia. The neuroradiographic phenotype ranged from normal to mild (a thin corpus callosum and cerebellar dysgenesis), to severe (polymicrogyria and lissencephaly).; Changed publications: 29706646, 27431290, 26539891, 41544630; Changed phenotypes: Neurodevelopmental disorder (MONDO:0700092), ASTN1-related
Mendeliome v2.280 ASTN1 Zornitza Stark Phenotypes for gene: ASTN1 were changed from Cerebral malformation, MONDO:0016054, ASTN1-related to Neurodevelopmental disorder (MONDO:0700092), ASTN1-related
Mendeliome v2.279 ASTN1 Zornitza Stark Publications for gene: ASTN1 were set to 29706646; 27431290; 26539891
Genetic Epilepsy v2.25 ASTN1 Zornitza Stark Phenotypes for gene: ASTN1 were changed from Intellectual disability; epilepsy; structural brain malformations to Neurodevelopmental disorder (MONDO:0700092), ASTN1-related
Genetic Epilepsy v2.24 ASTN1 Zornitza Stark Publications for gene: ASTN1 were set to 29706646; 27431290; 26539891
Genetic Epilepsy v2.23 ASTN1 Zornitza Stark edited their review of gene: ASTN1: Added comment: PMID 41544630 reports 18 individuals with NDDs from 12 unrelated families with bi-allelic, ultra-rare, predicted damaging variants in ASTN1. Clinical features ranged from mild to profound developmental delay or intellectual disability +/- autism, ADHD, and epilepsy. Other recurrent abnormalities included dysmorphic facial features, hypotonia, spasticity, and ataxia. The neuroradiographic phenotype ranged from normal to mild (a thin corpus callosum and cerebellar dysgenesis), to severe (polymicrogyria and lissencephaly).; Changed publications: 29706646, 27431290, 26539891, 41544630; Changed phenotypes: Neurodevelopmental disorder (MONDO:0700092), ASTN1-related
Mendeliome v2.278 ASTN1 Zornitza Stark edited their review of gene: ASTN1: Added comment: PMID 41544630 reports 18 individuals with NDDs from 12 unrelated families with bi-allelic, ultra-rare, predicted damaging variants in ASTN1. Clinical features ranged from mild to profound developmental delay or intellectual disability +/- autism, ADHD, and epilepsy. Other recurrent abnormalities included dysmorphic facial features, hypotonia, spasticity, and ataxia. The neuroradiographic phenotype ranged from normal to mild (a thin corpus callosum and cerebellar dysgenesis), to severe (polymicrogyria and lissencephaly).; Changed publications: 29706646, 27431290, 26539891, 41544630; Changed phenotypes: Neurodevelopmental disorder (MONDO:0700092), ASTN1-relatedrd
Mendeliome v2.278 POLR3A Achchuthan Shanmugasundram reviewed gene: POLR3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 42260910; Phenotypes: Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM:607694, leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, MONDO:0011897, peripheral neuropathy, MONDO:0005244; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v2.28 CNTD1 Rylee Peters Marked gene: CNTD1 as ready
Infertility and Recurrent Pregnancy Loss v2.28 CNTD1 Rylee Peters Gene: cntd1 has been classified as Red List (Low Evidence).
Infertility and Recurrent Pregnancy Loss v2.28 Rylee Peters Copied gene CNTD1 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v2.28 CNTD1 Rylee Peters gene: CNTD1 was added
gene: CNTD1 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Red,Literature
Mode of inheritance for gene: CNTD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNTD1 were set to 42339205; 42221552
Phenotypes for gene: CNTD1 were set to Infertility disorder, MONDO:0005047, CNTD1-related
Mendeliome v2.278 CNTD1 Rylee Peters Marked gene: CNTD1 as ready
Mendeliome v2.278 CNTD1 Rylee Peters Gene: cntd1 has been classified as Red List (Low Evidence).
Mendeliome v2.278 CNTD1 Rylee Peters changed review comment from: PMID: 42339205 reports a single individual with autosomal recessive diminished ovarian reserve (low AMH, low AFC, infertility) caused by a homozygous splice‑site loss‑of‑function CNTD1 variant; detailed hormonal profiling and a Cntd1 knockout mouse model support the association.

PMID: 42221552 reports one individual from a second family with autosomal recessive recurrent good‑quality cleavage‑stage blastulation failure linked to a homozygous missense CNTD1 variant, but functional data is lacking.
Sources: Literature; to: PMID: 42339205 reports a single individual with autosomal recessive diminished ovarian reserve (low AMH, low AFC, infertility) caused by a homozygous splice‑site loss‑of‑function CNTD1 variant; detailed hormonal profiling and a Cntd1 knockout mouse model support the association.

PMID: 42221552 reports one individual from a second family with autosomal recessive recurrent good‑quality cleavage‑stage blastulation failure linked to a homozygous missense CNTD1 variant, but functional data is absent.
Sources: Literature
Mendeliome v2.278 CNTD1 Rylee Peters gene: CNTD1 was added
gene: CNTD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CNTD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNTD1 were set to 42339205; 42221552
Phenotypes for gene: CNTD1 were set to Infertility disorder, MONDO:0005047, CNTD1-related
Review for gene: CNTD1 was set to RED
Added comment: PMID: 42339205 reports a single individual with autosomal recessive diminished ovarian reserve (low AMH, low AFC, infertility) caused by a homozygous splice‑site loss‑of‑function CNTD1 variant; detailed hormonal profiling and a Cntd1 knockout mouse model support the association.

PMID: 42221552 reports one individual from a second family with autosomal recessive recurrent good‑quality cleavage‑stage blastulation failure linked to a homozygous missense CNTD1 variant, but functional data is lacking.
Sources: Literature
Cholestasis v2.2 PTK2B Rylee Peters Marked gene: PTK2B as ready
Cholestasis v2.2 PTK2B Rylee Peters Gene: ptk2b has been classified as Red List (Low Evidence).
Cholestasis v2.2 Rylee Peters Copied gene PTK2B from panel Mendeliome
Cholestasis v2.2 PTK2B Rylee Peters gene: PTK2B was added
gene: PTK2B was added to Cholestasis. Sources: Expert Review Red,Literature
Mode of inheritance for gene: PTK2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTK2B were set to 42252453
Phenotypes for gene: PTK2B were set to Inborn error of immunity, MONDO:0003778, PTK2B-related
Mendeliome v2.277 PTK2B Rylee Peters Marked gene: PTK2B as ready
Mendeliome v2.277 PTK2B Rylee Peters Gene: ptk2b has been classified as Red List (Low Evidence).
Mendeliome v2.277 PTK2B Rylee Peters gene: PTK2B was added
gene: PTK2B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTK2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTK2B were set to 42252453
Phenotypes for gene: PTK2B were set to Inborn error of immunity, MONDO:0003778, PTK2B-related
Review for gene: PTK2B was set to RED
Added comment: PMID: 42252453 reports three affected individuals from one Chinese Han family with a heterozygous missense PTK2B c.1679C>G (p.Pro560Arg) variant presenting with adult‑onset primary biliary cholangitis (PBC). Homozygous knock‑in mice recapitulate PBC‑like autoimmune features, whereas heterozygous mice are phenotypically normal.
Sources: Literature
Intellectual disability syndromic and non-syndromic v2.44 KIF6 Rylee Peters Marked gene: KIF6 as ready
Intellectual disability syndromic and non-syndromic v2.44 KIF6 Rylee Peters Gene: kif6 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v2.44 KIF6 Rylee Peters gene: KIF6 was added
gene: KIF6 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: KIF6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF6 were set to 30475797
Phenotypes for gene: KIF6 were set to Neurodevelopmental disorder, MONDO:0700092, KIF6-related
Review for gene: KIF6 was set to RED
Added comment: PMID: 30475797 describes a consanguineous family homozygous for a frameshift KIF6 variant (p.L398fsX2) presenting with macrocephaly, intellectual disability and developmental delay. Knock-in homozygous mouse model with analogous variant displayed severe, postnatal-onset hydrocephalus.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v2.27 KIF6 Rylee Peters Marked gene: KIF6 as ready
Infertility and Recurrent Pregnancy Loss v2.27 KIF6 Rylee Peters Gene: kif6 has been classified as Red List (Low Evidence).
Infertility and Recurrent Pregnancy Loss v2.27 KIF6 Rylee Peters Publications for gene: KIF6 were set to 42348434; 30475797
Infertility and Recurrent Pregnancy Loss v2.26 KIF6 Rylee Peters changed review comment from: PMID: 42348434 reports two unrelated families with homozygous KIF6 variants (p.T442Sfs*3; p.E474K) causing severe asthenozoospermia with complete sperm immotility. Knock-in mouse models carrying the patient variants recapitulated the human infertility phenotypes. Hydrocephalus also observed in the mouse model for the frameshift variant. The missense variant, p.E474K has 182 hets, 1 hom in v4.
Sources: Literature; to: PMID: 42348434 reports two unrelated families with homozygous KIF6 variants (p.T442Sfs*3; p.E474K) causing severe asthenozoospermia with complete sperm immotility. Knock-in mouse models carrying the patient variants recapitulated the human infertility phenotypes. Hydrocephalus also observed in the mouse model for the frameshift variant. The missense variant, p.E474K has 182 hets, 1 hom in v4.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v2.26 KIF6 Rylee Peters gene: KIF6 was added
gene: KIF6 was added to Infertility and Recurrent Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: KIF6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF6 were set to 42348434; 30475797
Phenotypes for gene: KIF6 were set to Infertility disorder, MONDO:0005047, KIF6-related
Review for gene: KIF6 was set to RED
Added comment: PMID: 42348434 reports two unrelated families with homozygous KIF6 variants (p.T442Sfs*3; p.E474K) causing severe asthenozoospermia with complete sperm immotility. Knock-in mouse models carrying the patient variants recapitulated the human infertility phenotypes. Hydrocephalus also observed in the mouse model for the frameshift variant. The missense variant, p.E474K has 182 hets, 1 hom in v4.
Sources: Literature
Mendeliome v2.276 KIF6 Rylee Peters Marked gene: KIF6 as ready
Mendeliome v2.276 KIF6 Rylee Peters Gene: kif6 has been classified as Red List (Low Evidence).
Mendeliome v2.276 KIF6 Rylee Peters gene: KIF6 was added
gene: KIF6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF6 were set to 42348434; 30475797
Phenotypes for gene: KIF6 were set to Infertility disorder, MONDO:0005047, KIF6-related; Neurodevelopmental disorder, MONDO:0700092, KIF6-related
Review for gene: KIF6 was set to RED
Added comment: KIF6 encodes an 814‑amino‑acid kinesin involved in intracellular mRNA transport.

PMID: 42348434 reports two unrelated families with homozygous KIF6 variants (p.T442Sfs*3; p.E474K) causing severe asthenozoospermia with complete sperm immotility. Knock-in mouse models carrying the patient variants recapitulated the human infertility phenotypes. Hydrocephalus also observed in the mouse model for the frameshift variant. The missense variant, p.E474K has 182 hets, 1 hom in v4.

PMID: 30475797 describes a consanguineous family homozygous for a frameshift KIF6 variant (p.L398fsX2) presenting with macrocephaly, intellectual disability and developmental delay. Knock-in homozygous mouse model with analogous variant displayed severe, postnatal-onset hydrocephalus.
Sources: Literature
Dystonia and Chorea v1.5 PCDHGB1 Shekeeb S gene: PCDHGB1 was added
gene: PCDHGB1 was added to Dystonia and Chorea. Sources: Literature
Mode of inheritance for gene: PCDHGB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PCDHGB1 were set to 42482420; 35229923
Phenotypes for gene: PCDHGB1 were set to Dystonia (HP:0001332); Cervical dystonia (HP:0002481); Blepharospasm (HP:0000617); Oromandibular dystonia (HP:0007291); Laryngeal dystonia (HP:0001593); Focal dystonia (HP:0002515); Segmental dystonia (HP:0007328); Generalized dystonia (HP:0007329); Myoclonus (HP:0001336); Parkinsonism (HP:0001300); Ataxia (HP:0001251); External ophthalmoplegia (HP:0000605); Sensorineural hearing impairment (HP:0000407); Abnormal gait (HP:0001288); Tremor (HP:0001337); Adult onset (HP:0003581); Childhood onset (HP:0011463); Family history of dystonia (HP:0032371); Autosomal dominant inheritance (HP:0000006)
Penetrance for gene: PCDHGB1 were set to unknown
Review for gene: PCDHGB1 was set to GREEN
gene: PCDHGB1 was marked as current diagnostic
Added comment: Sources: Literature
Genomic newborn screening: BabyScreen+ v2.0 SUFU TRAIL SCHN commented on gene: SUFU
Genomic newborn screening: BabyScreen+ v2.0 THRB TRAIL SCHN commented on gene: THRB
Genomic newborn screening: BabyScreen+ v2.0 SDHD TRAIL SCHN commented on gene: SDHD
Genomic newborn screening: BabyScreen+ v2.0 ALK TRAIL SCHN commented on gene: ALK
Genomic newborn screening: BabyScreen+ v2.0 PHOX2B TRAIL SCHN commented on gene: PHOX2B
Genomic newborn screening: BabyScreen+ v2.0 APOB TRAIL SCHN changed review comment from: "Please tag as ""TRAIL Study""
Rationale: Clinician supported inclusion"; to: Please tag as "TRAIL Study"
Rationale: Clinician supported inclusion
Genomic newborn screening: BabyScreen+ v2.0 CASQ2 TRAIL SCHN changed review comment from: "Please tag as ""TRAIL Study""
Rationale: Clinician supported inclusion"; to: Please tag as "TRAIL Study"
Rationale: Clinician supported inclusion
Genomic newborn screening: BabyScreen+ v2.0 STRC TRAIL SCHN changed review comment from: "Please tag as ""TRAIL Study""
Rationale: Clinician supported inclusion"; to: Please tag as "TRAIL Study"
Rationale: Clinician supported inclusion
Genomic newborn screening: BabyScreen+ v2.0 APOB TRAIL SCHN commented on gene: APOB
Genomic newborn screening: BabyScreen+ v2.0 CASQ2 TRAIL SCHN commented on gene: CASQ2
Genomic newborn screening: BabyScreen+ v2.0 STRC TRAIL SCHN commented on gene: STRC
Genomic newborn screening: BabyScreen+ v2.0 SDHAF2 TRAIL SCHN commented on gene: SDHAF2
Genomic newborn screening: BabyScreen+ v2.0 SDHB TRAIL SCHN commented on gene: SDHB
Genomic newborn screening: BabyScreen+ v2.0 SDHC TRAIL SCHN commented on gene: SDHC
Genomic newborn screening: BabyScreen+ v2.0 PMS2 TRAIL SCHN commented on gene: PMS2
Genomic newborn screening: BabyScreen+ v2.0 SLC37A4 TRAIL SCHN changed review comment from: Included in Trail Study for: Glycogen storage disease type 1b (GSD1b) AND Glycogen storage disease Ic.
Not included in TRAIL Study for: Congenital disorder of glycosylation, type IIw. (Rationale: Not for cohort 5, no specific treatment); to: Included in Trail Study for: Glycogen storage disease type 1b (GSD1b) and Glycogen storage disease Ic.

Not included in TRAIL Study for: Congenital disorder of glycosylation, type IIw. (Rationale: Not for cohort 5, no specific treatment)
Genomic newborn screening: BabyScreen+ v2.0 SLC26A4 TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"; to: Please tag as "TRAIL Study"

Included for all: Deafness, autosomal recessive 4, with enlarged vestibular aqueduct and Pendred syndrome
Genomic newborn screening: BabyScreen+ v2.0 RAG2 TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"; to: Please tag as "TRAIL Study"

Included for all: Severe combined immunodeficiency (SCID), B cell-negative and Omenn Syndrome and Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity
Genomic newborn screening: BabyScreen+ v2.0 RAG1 TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"; to: Please tag as "TRAIL Study"

Included for all: Severe combined immunodeficiency (SCID), B cell-negative and Omenn Syndrome and Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity
Genomic newborn screening: BabyScreen+ v2.0 PTPRQ TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"; to: Please tag as "TRAIL Study"

Included for both: Deafness, autosomal recessive 84A and Deafness, autosomal dominant 73
Genomic newborn screening: BabyScreen+ v2.0 PTCH1 TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"; to: Please tag as "TRAIL Study"

Include for both: Gorlin Syndrome AND Basal cell nevus syndrome
Genomic newborn screening: BabyScreen+ v2.0 PHKB TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"; to: Please tag as "TRAIL Study"

Included for both: Glycogen storage disease IXb and Phosphorylase kinase deficiency of liver and muscle, autosomal recessive
Genomic newborn screening: BabyScreen+ v2.0 PHKA2 TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"; to: Please tag as "TRAIL Study"

Included for both: Glycogen storage disease IXa1 and Glycogen storage disease IXa2
Genomic newborn screening: BabyScreen+ v2.0 KCNQ1 TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"; to: Please tag as "TRAIL Study"

Included for both: Jervell and Lange-Nielsen syndrome and Long QT syndrome 1
Genomic newborn screening: BabyScreen+ v2.0 GCH1 TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"; to: Please tag as "TRAIL Study"

Included for both: Hyperphenylalaninemia, BH4-deficient, B and
Dystonia, DOPA-responsive, with or without hyperphenylalaninemia
Genomic newborn screening: BabyScreen+ v2.0 G6PC3 TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"; to: Please tag as "TRAIL Study"

Note: Have tagged G6PC1 and G6PC3, Included for both: Neutropenia (congenital) AND Glycogen storage disease Ia
Genomic newborn screening: BabyScreen+ v2.0 G6PC1 TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"; to: Please tag as "TRAIL Study"

Note: Have tagged G6PC1 and G6PC3, Included for both: Neutropenia (congenital) AND Glycogen storage disease Ia
Genomic newborn screening: BabyScreen+ v2.0 CPT2 TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"; to: Please tag as "TRAIL Study"

Included for all: Carnitine palmitoyltransferase II (CPT II) deficiency, infantile and Carnitine palmitoyltransferase II (CPT II) deficiency, lethal neonatal and Carnitine palmitoyltransferase II (CPT II) deficiency, myopathic, stress-induced
Genomic newborn screening: BabyScreen+ v2.0 ACAT1 TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"

Included for both: Alpha-methylacetoacetic aciduria AND Beta-ketothiolase deficiency ; to: Please tag as "TRAIL Study"

Included for both: Alpha-methylacetoacetic aciduria and Beta-ketothiolase deficiency
Genomic newborn screening: BabyScreen+ v2.0 ACAT1 TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"; to: Please tag as "TRAIL Study"

Included for both: Alpha-methylacetoacetic aciduria AND Beta-ketothiolase deficiency
Genomic newborn screening: BabyScreen+ v2.0 SLC2A1 TRAIL SCHN commented on gene: SLC2A1: Please tag as "TRAIL Study" for GLUT1 deficiency syndrome 1, infantile onset, severe AND GLUT1 deficiency syndrome 2, childhood onset.

Not included in TRAIL Study for: Epilepsy, idiopathic generalized, susceptibility to, 12.
Genomic newborn screening: BabyScreen+ v2.0 TECTA TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"; to: Please tag as "TRAIL Study"
Included for both: Deafness, autosomal recessive 21 AND Deafness, autosomal dominant 8/12
Genomic newborn screening: BabyScreen+ v2.0 STAT3 TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"; to: Please tag as "TRAIL Study"
Included for: Autoimmune disease, multisystem, infantile-onset, 1 AND Hyper-IgE syndrome 1
Genomic newborn screening: BabyScreen+ v2.0 SLC37A4 TRAIL SCHN commented on gene: SLC37A4
Autoinflammatory Disorders v3.11 DNAJC17 Peter McNaughton gene: DNAJC17 was added
gene: DNAJC17 was added to Autoinflammatory Disorders. Sources: Literature
Mode of inheritance for gene: DNAJC17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC17 were set to PMID: 42495638
Phenotypes for gene: DNAJC17 were set to Combined Immune deficiency; retinopathy; autoinflammation
Review for gene: DNAJC17 was set to GREEN
Added comment: 3 patients from 2x unrelated families with homozygous variant (c.681G>A; p.Ala227=) with molecular characterisation suggesting exon skipping and reduced but not absent DNAJC17
mRNA and protein expression supporting the hypothesis of hypomorphic
rather than null function.
Sources: Literature
Ataxia v2.1 ESRRG Zornitza Stark Phenotypes for gene: ESRRG were changed from Movement disorder, MONDO:0005395, ESRRG-related to Movement disorder, congenital nonprogressive, with ataxia and eye movement abnormalities, MIM# 621639
Ataxia v2.0 ESRRG Zornitza Stark edited their review of gene: ESRRG: Changed phenotypes: Movement disorder, congenital nonprogressive, with ataxia and eye movement abnormalities, MIM# 621639
Intellectual disability syndromic and non-syndromic v2.43 ESRRG Zornitza Stark Phenotypes for gene: ESRRG were changed from Movement disorder, MONDO:0005395, ESRRG-related to Movement disorder, congenital nonprogressive, with ataxia and eye movement abnormalities, MIM# 621639
Intellectual disability syndromic and non-syndromic v2.42 ESRRG Zornitza Stark edited their review of gene: ESRRG: Changed phenotypes: Movement disorder, congenital nonprogressive, with ataxia and eye movement abnormalities, MIM# 621639
Mendeliome v2.275 ESRRG Zornitza Stark Phenotypes for gene: ESRRG were changed from Movement disorder, MONDO:0005395, ESRRG-related to Movement disorder, congenital nonprogressive, with ataxia and eye movement abnormalities, MIM# 621639
Mendeliome v2.274 ESRRG Zornitza Stark edited their review of gene: ESRRG: Changed phenotypes: Movement disorder, congenital nonprogressive, with ataxia and eye movement abnormalities, MIM# 621639
Ectodermal Dysplasia v1.5 FAM210A Zornitza Stark Marked gene: FAM210A as ready
Ectodermal Dysplasia v1.5 FAM210A Zornitza Stark Gene: fam210a has been classified as Green List (High Evidence).
Skeletal dysplasia v1.4 FAM210A Zornitza Stark Marked gene: FAM210A as ready
Skeletal dysplasia v1.4 FAM210A Zornitza Stark Gene: fam210a has been classified as Green List (High Evidence).
Skeletal dysplasia v1.4 Zornitza Stark Copied gene FAM210A from panel Mendeliome
Skeletal dysplasia v1.4 FAM210A Zornitza Stark gene: FAM210A was added
gene: FAM210A was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: FAM210A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM210A were set to 42410297
Phenotypes for gene: FAM210A were set to Spondyloepimetaphyseal dysplasia with tracheal stenosis and ectodermal dysplasia, OMIM:621650
Ectodermal Dysplasia v1.5 Zornitza Stark Copied gene FAM210A from panel Mendeliome
Ectodermal Dysplasia v1.5 FAM210A Zornitza Stark gene: FAM210A was added
gene: FAM210A was added to Ectodermal Dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: FAM210A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM210A were set to 42410297
Phenotypes for gene: FAM210A were set to Spondyloepimetaphyseal dysplasia with tracheal stenosis and ectodermal dysplasia, OMIM:621650
Mendeliome v2.274 FAM210A Zornitza Stark Marked gene: FAM210A as ready
Mendeliome v2.274 FAM210A Zornitza Stark Gene: fam210a has been classified as Green List (High Evidence).
Mendeliome v2.274 FAM210A Zornitza Stark Classified gene: FAM210A as Green List (high evidence)
Mendeliome v2.274 FAM210A Zornitza Stark Gene: fam210a has been classified as Green List (High Evidence).
Mendeliome v2.273 ATOH1 Zornitza Stark reviewed gene: ATOH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41592563; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Leukodystrophy v1.1 BLOC1S1 Zornitza Stark Publications for gene: BLOC1S1 were set to https://www.medrxiv.org/content/10.1101/2025.07.17.25331211v1
Leukodystrophy v1.0 BLOC1S1 Zornitza Stark edited their review of gene: BLOC1S1: Added comment: Now published in PMID 41887224: 11 individuals from seven families.; Changed publications: 33875846, 41887224
Intellectual disability syndromic and non-syndromic v2.42 BLOC1S1 Zornitza Stark Publications for gene: BLOC1S1 were set to 33875846
Intellectual disability syndromic and non-syndromic v2.41 BLOC1S1 Zornitza Stark edited their review of gene: BLOC1S1: Added comment: Now published in PMID 41887224: 11 individuals from seven families.; Changed publications: 33875846, 41887224
Genetic Epilepsy v2.23 BLOC1S1 Zornitza Stark Publications for gene: BLOC1S1 were set to 33875846; https://www.medrxiv.org/content/10.1101/2025.07.17.25331211v1
Genetic Epilepsy v2.22 BLOC1S1 Zornitza Stark edited their review of gene: BLOC1S1: Added comment: Now published in PMID 41887224: 11 individuals from seven families.; Changed publications: 33875846, 41887224
Optic Atrophy v2.1 BLOC1S1 Zornitza Stark Publications for gene: BLOC1S1 were set to 33875846; https://www.medrxiv.org/content/10.1101/2025.07.17.25331211v1
Optic Atrophy v2.0 BLOC1S1 Zornitza Stark edited their review of gene: BLOC1S1: Added comment: Now published in 41887224: 11 individuals from 7 families.; Changed publications: 33875846, 41887224
Mendeliome v2.273 BLOC1S1 Zornitza Stark Publications for gene: BLOC1S1 were set to 33875846
Mendeliome v2.272 BLOC1S1 Zornitza Stark edited their review of gene: BLOC1S1: Added comment: Now published: 11 individuals from seven unrelated families.; Changed publications: 33875846, 41887224
Infertility and Recurrent Pregnancy Loss v2.25 RHOXF1 Zornitza Stark Marked gene: RHOXF1 as ready
Infertility and Recurrent Pregnancy Loss v2.25 RHOXF1 Zornitza Stark Gene: rhoxf1 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v2.25 Zornitza Stark Copied gene RHOXF1 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v2.25 RHOXF1 Zornitza Stark gene: RHOXF1 was added
gene: RHOXF1 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: RHOXF1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RHOXF1 were set to 38258527; 42379029; 28171600
Phenotypes for gene: RHOXF1 were set to Spermatogenic failure, MONDO:0004983, RHOXF1-related
Mendeliome v2.272 RHOXF1 Zornitza Stark Publications for gene: RHOXF1 were set to PMID: 38258527
Mendeliome v2.271 RHOXF1 Zornitza Stark reviewed gene: RHOXF1: Rating: AMBER; Mode of pathogenicity: None; Publications: 42379029; Phenotypes: Spermatogenic failure, MONDO:0004983, RHOXF1-related; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Infertility and Recurrent Pregnancy Loss v2.24 AGTPBP1 Zornitza Stark Marked gene: AGTPBP1 as ready
Infertility and Recurrent Pregnancy Loss v2.24 AGTPBP1 Zornitza Stark Gene: agtpbp1 has been classified as Red List (Low Evidence).
Infertility and Recurrent Pregnancy Loss v2.24 AGTPBP1 Zornitza Stark Phenotypes for gene: AGTPBP1 were changed from Neurodegeneration, childhood-onset, with cerebellar atrophy, MONDO:0032650 to Infertility disorder, MONDO:0005047, AGTPBP1-related
Infertility and Recurrent Pregnancy Loss v2.23 AGTPBP1 Zornitza Stark Publications for gene: AGTPBP1 were set to 42358771; 41160201; 38587696; 38153683; 37937809; 34324503; 33909173; 33624935; 31102495; 30976113; 30237576
Infertility and Recurrent Pregnancy Loss v2.22 AGTPBP1 Zornitza Stark Mode of inheritance for gene: AGTPBP1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Infertility and Recurrent Pregnancy Loss v2.21 AGTPBP1 Zornitza Stark Classified gene: AGTPBP1 as Red List (low evidence)
Infertility and Recurrent Pregnancy Loss v2.21 AGTPBP1 Zornitza Stark Gene: agtpbp1 has been classified as Red List (Low Evidence).
Infertility and Recurrent Pregnancy Loss v2.20 AGTPBP1 Zornitza Stark edited their review of gene: AGTPBP1: Changed rating: RED
Infertility and Recurrent Pregnancy Loss v2.20 AGTPBP1 Zornitza Stark changed review comment from: Newly reported association with teratozoospermia (monoallelic): the heterozygous p.Arg811His missense variant is identified in two unrelated families (PMID 41160201, PMID 37937809). A CRISPR‑engineered mouse knock‑in recapitulates the sperm head‑ and tail‑defect phenotype, providing variant‑specific functional evidence.

RED for the mono-allelic association as it appears confined to this single missense variant, further reports needed.; to: The heterozygous p.Arg811His missense variant is identified in two unrelated families (PMID 41160201, PMID 37937809). A CRISPR‑engineered mouse knock‑in recapitulates the sperm head‑ and tail‑defect phenotype, providing variant‑specific functional evidence.

RED for this association as it appears confined to this single missense variant, further reports needed.
Infertility and Recurrent Pregnancy Loss v2.20 AGTPBP1 Zornitza Stark Deleted their comment
Infertility and Recurrent Pregnancy Loss v2.20 AGTPBP1 Zornitza Stark edited their review of gene: AGTPBP1: Changed publications: 41160201, 37937809; Changed phenotypes: Infertility disorder, MONDO:0005047, AGTPBP1-related; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Infertility and Recurrent Pregnancy Loss v2.20 Zornitza Stark Copied gene AGTPBP1 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v2.20 AGTPBP1 Zornitza Stark gene: AGTPBP1 was added
gene: AGTPBP1 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: AGTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGTPBP1 were set to 42358771; 41160201; 38587696; 38153683; 37937809; 34324503; 33909173; 33624935; 31102495; 30976113; 30237576
Phenotypes for gene: AGTPBP1 were set to Neurodegeneration, childhood-onset, with cerebellar atrophy, MONDO:0032650
Mendeliome v2.271 AGTPBP1 Zornitza Stark Publications for gene: AGTPBP1 were set to 30420557, 28600779, 30976113, 38153683, 28325758
Mendeliome v2.270 AGTPBP1 Zornitza Stark edited their review of gene: AGTPBP1: Added comment: Newly reported association with teratozoospermia (monoallelic): the heterozygous p.Arg811His missense variant is identified in two unrelated families (PMID 41160201, PMID 37937809). A CRISPR‑engineered mouse knock‑in recapitulates the sperm head‑ and tail‑defect phenotype, providing variant‑specific functional evidence.

RED for the mono-allelic association as it appears confined to this single missense variant, further reports needed.; Changed publications: 42358771, 41160201, 38587696, 38153683, 37937809, 34324503, 33909173, 33624935, 31102495, 30976113, 30237576; Changed phenotypes: Neurodegeneration, childhood-onset, with cerebellar atrophy, MONDO:0032650, Infertility disorder, MONDO:0005047
Infertility and Recurrent Pregnancy Loss v2.19 SPO11 Zornitza Stark Marked gene: SPO11 as ready
Infertility and Recurrent Pregnancy Loss v2.19 SPO11 Zornitza Stark Gene: spo11 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v2.19 Zornitza Stark Copied gene SPO11 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v2.19 SPO11 Zornitza Stark gene: SPO11 was added
gene: SPO11 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: SPO11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPO11 were set to 42221552; 39932629; 29790874
Phenotypes for gene: SPO11 were set to Infertility disorder, MONDO:0005047, SPO11-related
Mendeliome v2.270 SPO11 Zornitza Stark Marked gene: SPO11 as ready
Mendeliome v2.270 SPO11 Zornitza Stark Gene: spo11 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.270 SPO11 Zornitza Stark Classified gene: SPO11 as Amber List (moderate evidence)
Mendeliome v2.270 SPO11 Zornitza Stark Gene: spo11 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.269 SPO11 Zornitza Stark gene: SPO11 was added
gene: SPO11 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPO11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPO11 were set to 42221552; 39932629; 29790874
Phenotypes for gene: SPO11 were set to Infertility disorder, MONDO:0005047, SPO11-related
Review for gene: SPO11 was set to AMBER
Added comment: PMID 39932629 reports 2 individuals from a single family with biallelic loss-of-function SPO11 variants causing non‑obstructive azoospermia (NOA) and meiotic arrest; PMID 29790874 reports 2 brothers from a second family with a homozygous missense SPO11 variant also presenting with NOA. PMID 42221552 reports 2 individuals from 2 families with biallelic SPO11 variants (one frameshift, one missense) manifesting as recurrent good‑quality cleavage‑stage blastulation failure, characterised by normal early cleavage but arrest at the morula/blastocyst stage and complex embryonic aneuploidy.
Sources: Literature
Mendeliome v2.268 FAM210A Achchuthan Shanmugasundram gene: FAM210A was added
gene: FAM210A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FAM210A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM210A were set to 42410297
Phenotypes for gene: FAM210A were set to Spondyloepimetaphyseal dysplasia with tracheal stenosis and ectodermal dysplasia, OMIM:621650
Review for gene: FAM210A was set to GREEN
Added comment: PMID:42410297 (2026) reported five patients from four unrelated families with skeletal dysplasia phenotype characterised by spondyloepimetaphyseal dysplasiachondrodysplasia with short stature (all patents), tracheal stenosis (all patients), conical teeth and/or early tooth decay, and sparse hair suggestive of ectodermal dysplasia (in three unrelated patients).

They were identified with biallelic variants in FAM210A gene (new gene name - MIMS1) - homozygous missense variants in three families and compound heterozygous nonsense variants in the first family with two siblings.

This gene has been associated with relevant phenotype in OMIM (MIM #621650, last accessed 24 July 2026).
Sources: Literature
Congenital Heart Defect v1.10 PRMT9 Zornitza Stark reviewed gene: PRMT9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 85, MIM# 621649; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.268 PTPRU Sarah Milton Deleted their review
Mendeliome v2.268 PTPRU Sarah Milton gene: PTPRU was added
gene: PTPRU was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTPRU was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPRU were set to 37056996
Phenotypes for gene: PTPRU were set to Neurodevelopmental disorder, MONDO:0700092, PTPRU-related
Review for gene: PTPRU was set to RED
Added comment: PMID 37056996 reports candidate neurodevelopmental genes and notes 3 individuals from 3 families with de novo heterozygous missense variants in PTPRU.

The individuals presented with intellectual disability. No variant‑specific functional assays were performed and all variants are absent from or extremely rare in population databases. Further research is required to establish this gene disease association.
Sources: Literature
Cardiomyopathy_Paediatric v1.51 QRSL1 Sarah Milton Classified gene: QRSL1 as Green List (high evidence)
Cardiomyopathy_Paediatric v1.51 QRSL1 Sarah Milton Gene: qrsl1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.50 QRSL1 Sarah Milton gene: QRSL1 was added
gene: QRSL1 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: QRSL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: QRSL1 were set to 35894854; 30283131; 29440775
Phenotypes for gene: QRSL1 were set to Combined oxidative phosphorylation deficiency 40, MIM#618835
Review for gene: QRSL1 was set to GREEN
Added comment: PMID 29440775, PMID 30283131 and PMID 35894854 report a number of individuals with biallelic loss-of-function QRSL1 variants resulting in combined oxidative phosphorylation deficiency 40, characterised by a multisystem mitochondrial disease featuring early‑onset (prenatal/neonatal) hypertrophic cardiomyopathy.
Sources: Literature
Intellectual disability syndromic and non-syndromic v2.41 Sarah Milton Copied gene NDUFA5 from panel Mitochondrial disease
Intellectual disability syndromic and non-syndromic v2.41 NDUFA5 Sarah Milton gene: NDUFA5 was added
gene: NDUFA5 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NDUFA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFA5 were set to 41916321
Phenotypes for gene: NDUFA5 were set to Mitochondrial disease, MONDO:0044970, NDUFA5-related
Penetrance for gene: NDUFA5 were set to Complete
Infertility and Recurrent Pregnancy Loss v2.18 CEP131 Zornitza Stark Marked gene: CEP131 as ready
Infertility and Recurrent Pregnancy Loss v2.18 CEP131 Zornitza Stark Gene: cep131 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v2.18 Zornitza Stark Copied gene CEP131 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v2.18 CEP131 Zornitza Stark gene: CEP131 was added
gene: CEP131 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CEP131 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP131 were set to 42299473
Phenotypes for gene: CEP131 were set to Infertility disorder, MONDO:0005047, CEP131-related
Mendeliome v2.267 CEP131 Zornitza Stark Marked gene: CEP131 as ready
Mendeliome v2.267 CEP131 Zornitza Stark Gene: cep131 has been classified as Green List (High Evidence).
Mendeliome v2.267 CEP131 Zornitza Stark Classified gene: CEP131 as Green List (high evidence)
Mendeliome v2.267 CEP131 Zornitza Stark Gene: cep131 has been classified as Green List (High Evidence).
Mendeliome v2.266 CEP131 Zornitza Stark gene: CEP131 was added
gene: CEP131 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CEP131 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP131 were set to 42299473
Phenotypes for gene: CEP131 were set to Infertility disorder, MONDO:0005047, CEP131-related
Review for gene: CEP131 was set to GREEN
Added comment: PMID 42299473 reports four individuals from four families with biallelic missense CEP131 variants presenting with multiple morphological abnormalities of the sperm flagellum (MMAF) and adult‑onset male infertility. Segregation analysis shows heterozygous carrier parents and unaffected siblings, confirming recessive inheritance. Functional studies reveal disrupted CEP131 localisation and loss of CEP131‑CEP290 interaction.
Sources: Literature
Complement Deficiencies v2.4 C1R Zornitza Stark Marked gene: C1R as ready
Complement Deficiencies v2.4 C1R Zornitza Stark Gene: c1r has been classified as Green List (High Evidence).
Complement Deficiencies v2.4 C1R Zornitza Stark Phenotypes for gene: C1R were changed from to Ehlers-Danlos syndrome, periodontal type 1, MONDO:0020684; Inborn error of immunity, MONDO:0003778
Complement Deficiencies v2.3 C1R Zornitza Stark Publications for gene: C1R were set to
Complement Deficiencies v2.2 C1R Zornitza Stark Mode of inheritance for gene: C1R was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Complement Deficiencies v2.1 Zornitza Stark Added reviews for gene C1R from panel Mendeliome
Mendeliome v2.265 C1R Zornitza Stark Phenotypes for gene: C1R were changed from Ehlers-Danlos syndrome, periodontal type, 1 MIM# 130080 Current Edit to Ehlers-Danlos syndrome, periodontal type, 1 MIM# 130080; Inborn error of immunity, MONDO:0003778
Mendeliome v2.264 C1R Zornitza Stark Publications for gene: C1R were set to 27745832; 28306229
Mendeliome v2.263 C1R Zornitza Stark Mode of inheritance for gene: C1R was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v2.262 C1R Zornitza Stark reviewed gene: C1R: Rating: GREEN; Mode of pathogenicity: None; Publications: 42251732, 38923752, 37323685, 36960056, 36348983, 35571048, 35365885, 33890303, 33005042, 31749804, 31440263, 30535813, 30025171, 28544690, 27745832; Phenotypes: Ehlers-Danlos syndrome, periodontal type 1, MONDO:0020684, Inborn error of immunity, MONDO:0003778; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinitis pigmentosa v1.8 CRB1 Zornitza Stark Phenotypes for gene: CRB1 were changed from Leber congenital amaurosis 8, 613835; Retinitis pigmentosa-12, autosomal recessive, 600105 to Leber congenital amaurosis 8 MIM#613835; Pigmented paravenous chorioretinal atrophy MIM#172870; Retinitis pigmentosa-12 MIM#600105
Retinitis pigmentosa v1.7 CRB1 Zornitza Stark Publications for gene: CRB1 were set to 11231775; 11389483; 16543197
Retinitis pigmentosa v1.6 CRB1 Zornitza Stark Mode of inheritance for gene: CRB1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinitis pigmentosa v1.5 CRB1 Zornitza Stark reviewed gene: CRB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 42376998, 41626423, 34130719, 33921607, 28800606, 30285347, 32922261, 31884620, 15459956, 15623792; Phenotypes: Leber congenital amaurosis 8 MIM#613835, Pigmented paravenous chorioretinal atrophy MIM#172870, Retinitis pigmentosa-12 MIM#600105; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v2.262 CRB1 Zornitza Stark Publications for gene: CRB1 were set to 30285347; 32922261; 31884620; 15459956; 15623792
Mendeliome v2.261 CRB1 Zornitza Stark Mode of inheritance for gene: CRB1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v2.260 CRB1 Zornitza Stark reviewed gene: CRB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 42376998, 41626423, 34130719, 33921607, 28800606; Phenotypes: Leber congenital amaurosis 8, MONDO:0013453, hereditary macular dystrophy, MONDO:0020242, inherited retinal dystrophy, MONDO:0019118, retinitis pigmentosa 12, MONDO:0010818; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.4 FREM1 Zornitza Stark Marked gene: FREM1 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.4 FREM1 Zornitza Stark Gene: frem1 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.4 FREM1 Zornitza Stark Phenotypes for gene: FREM1 were changed from to Manitoba oculotrichoanal syndrome 248450; Bifid nose with or without anorectal and renal anomalies, MIM# 608980
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.3 FREM1 Zornitza Stark Publications for gene: FREM1 were set to
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.2 FREM1 Zornitza Stark Mode of inheritance for gene: FREM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.1 FREM1 Zornitza Stark changed review comment from: Bi-allelic variants are associated with multiple congenital anomaly syndromes (MOTA and BNAR), which likely represent a spectrum. Multiple families reported.

Three families reported with trigonocephaly and single missense variants.; to: Bi-allelic variants are associated with multiple congenital anomaly syndromes (MOTA and BNAR), which likely represent a spectrum. Multiple families reported.

Three families reported with trigonocephaly and single missense variants: DISPUTED and not relevant to this panel.
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.1 FREM1 Zornitza Stark edited their review of gene: FREM1: Changed phenotypes: Manitoba oculotrichoanal syndrome 248450, Bifid nose with or without anorectal and renal anomalies, MIM# 608980; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v2.17 CFAP119 Zornitza Stark Publications for gene: CFAP119 were set to 40759592
Infertility and Recurrent Pregnancy Loss v2.16 CFAP119 Zornitza Stark Classified gene: CFAP119 as Amber List (moderate evidence)
Infertility and Recurrent Pregnancy Loss v2.16 CFAP119 Zornitza Stark Gene: cfap119 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v2.15 CFAP119 Zornitza Stark edited their review of gene: CFAP119: Added comment: PMID 42290102 reports two families with homozygous CFAP119 variants (c.709_711del frameshift and c.898C>T missense) presenting with severe oligoasthenoteratozoospermia (low count, poor motility, abnormal head/tail morphology). PMID 40759592 reports an additional consanguineous family harbouring the same homozygous missense c.898C>T variant. Functional studies demonstrate markedly reduced CFAP119 mRNA and protein levels, loss of CABCOCO1 interaction and flagellar structural defects, but no rescue experiments or animal‑model validation. Amber rating as two of the families have the same homozygous missense variant.; Changed rating: AMBER; Changed publications: 40759592, 42290102; Changed phenotypes: Spermatogenic failure, MONDO:0004983, CFAP119-related
Mendeliome v2.260 CFAP119 Zornitza Stark Phenotypes for gene: CFAP119 were changed from Spermatogenic failure, MONDO:0004983, CCDC189-related to Spermatogenic failure, MONDO:0004983, CFAP119-related
Mendeliome v2.259 CFAP119 Zornitza Stark Publications for gene: CFAP119 were set to 40759592
Mendeliome v2.258 CFAP119 Zornitza Stark Classified gene: CFAP119 as Amber List (moderate evidence)
Mendeliome v2.258 CFAP119 Zornitza Stark Gene: cfap119 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.257 CFAP119 Zornitza Stark edited their review of gene: CFAP119: Added comment: PMID 42290102 reports two families with homozygous CFAP119 variants (c.709_711del frameshift and c.898C>T missense) presenting with severe oligoasthenoteratozoospermia (low count, poor motility, abnormal head/tail morphology). PMID 40759592 reports an additional consanguineous family harbouring the same homozygous missense c.898C>T variant. Functional studies demonstrate markedly reduced CFAP119 mRNA and protein levels, loss of CABCOCO1 interaction and flagellar structural defects, but no rescue experiments or animal‑model validation.

Amber rating as two of the families have the same homozygous missense variant.; Changed rating: AMBER; Changed publications: 42290102, 42290102, 40759592; Changed phenotypes: Infertility disorder, MONDO:0005047
Mendeliome v2.257 REL Zornitza Stark Publications for gene: REL were set to 31103457; 34623332
Combined Immunodeficiency v2.4 REL Zornitza Stark Publications for gene: REL were set to 31103457; 34623332
Combined Immunodeficiency v2.3 REL Zornitza Stark edited their review of gene: REL: Changed publications: 42117340
Combined Immunodeficiency v2.3 REL Zornitza Stark Classified gene: REL as Green List (high evidence)
Combined Immunodeficiency v2.3 REL Zornitza Stark Gene: rel has been classified as Green List (High Evidence).
Combined Immunodeficiency v2.2 REL Zornitza Stark edited their review of gene: REL: Added comment: PMID 42117340 reports a novel biallelic REL frameshift variant (c.24del, p.Tyr9Ilefs*2) in a Moroccan child with immunodeficiency‑92, adding a third independent family. The child presented with combined immunodeficiency, severe hypogammaglobulinaemia, recurrent bacterial, viral and fungal infections, chronic diarrhoea, BCGitis, craniosynostosis, epilepsy and language delay. It is unclear whether the non-immune features are part of the phenotype for this condition as these were not observed in the two previous reported families.; Changed rating: GREEN; Changed publications: 31103457, 34623332, 42117340
Mendeliome v2.256 REL Zornitza Stark Classified gene: REL as Green List (high evidence)
Mendeliome v2.256 REL Zornitza Stark Gene: rel has been classified as Green List (High Evidence).
Mendeliome v2.255 REL Zornitza Stark edited their review of gene: REL: Added comment: PMID 42117340 reports a novel biallelic REL frameshift variant (c.24del, p.Tyr9Ilefs*2) in a Moroccan child with immunodeficiency‑92, adding a third independent family. The child presented with combined immunodeficiency, severe hypogammaglobulinaemia, recurrent bacterial, viral and fungal infections, chronic diarrhoea, BCGitis, craniosynostosis, epilepsy and language delay. It is unclear whether the non-immune features are part of the phenotype for this condition as these were not observed in the two previous reported families.; Changed rating: GREEN; Changed publications: 42117340, 34623332, 31103457; Changed phenotypes: immunodeficiency 92, MONDO:0030498
Intellectual disability syndromic and non-syndromic v2.40 GIGYF2 Zornitza Stark Marked gene: GIGYF2 as ready
Intellectual disability syndromic and non-syndromic v2.40 GIGYF2 Zornitza Stark Gene: gigyf2 has been classified as Green List (High Evidence).
Autism v1.12 GIGYF2 Zornitza Stark Marked gene: GIGYF2 as ready
Autism v1.12 GIGYF2 Zornitza Stark Gene: gigyf2 has been classified as Green List (High Evidence).
Autism v1.12 GIGYF2 Zornitza Stark Phenotypes for gene: GIGYF2 were changed from to Neurodevelopmental disorder, MONDO:0700092, GIGYF2-related
Autism v1.11 GIGYF2 Zornitza Stark Publications for gene: GIGYF2 were set to
Autism v1.10 GIGYF2 Zornitza Stark Mode of inheritance for gene: GIGYF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v1.9 GIGYF2 Zornitza Stark Classified gene: GIGYF2 as Green List (high evidence)
Autism v1.9 GIGYF2 Zornitza Stark Gene: gigyf2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.40 Zornitza Stark Copied gene GIGYF2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.40 GIGYF2 Zornitza Stark gene: GIGYF2 was added
gene: GIGYF2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GIGYF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GIGYF2 were set to 42297935; 18358451; 33239198; 25279164; 20060621; 19250854; 26152800; 19449032
Phenotypes for gene: GIGYF2 were set to Neurodevelopmental disorder, MONDO:0700092, GIGYF2-related
Autism v1.8 Zornitza Stark Added reviews for gene GIGYF2 from panel Mendeliome
Mendeliome v2.255 GIGYF2 Zornitza Stark Phenotypes for gene: GIGYF2 were changed from {Parkinson disease 11} MIM#607688 to Neurodevelopmental disorder, MONDO:0700092, GIGYF2-related
Mendeliome v2.254 GIGYF2 Zornitza Stark Publications for gene: GIGYF2 were set to 18358451; 33239198; 25279164; 20060621; 19250854; 26152800; 19449032
Mendeliome v2.253 GIGYF2 Zornitza Stark Classified gene: GIGYF2 as Green List (high evidence)
Mendeliome v2.253 GIGYF2 Zornitza Stark Gene: gigyf2 has been classified as Green List (High Evidence).