PanelApp

Activity

Filter

Cancel
Date Panel Item Activity
3000 actions
Muscular dystrophy and myopathy_Paediatric v1.70 JPH1 Zornitza Stark Classified gene: JPH1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.70 JPH1 Zornitza Stark Gene: jph1 has been classified as Green List (High Evidence).
Mendeliome v1.1987 JPH1 Zornitza Stark Marked gene: JPH1 as ready
Mendeliome v1.1987 JPH1 Zornitza Stark Gene: jph1 has been classified as Green List (High Evidence).
Mendeliome v1.1987 JPH1 Zornitza Stark Classified gene: JPH1 as Green List (high evidence)
Mendeliome v1.1987 JPH1 Zornitza Stark Gene: jph1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.70 RFC4 Chirag Patel Classified gene: RFC4 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.70 RFC4 Chirag Patel Gene: rfc4 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.70 JPH1 Zornitza Stark Marked gene: JPH1 as ready
Muscular dystrophy and myopathy_Paediatric v1.70 JPH1 Zornitza Stark Gene: jph1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.70 JPH1 Zornitza Stark Classified gene: JPH1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.70 JPH1 Zornitza Stark Gene: jph1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6131 RFC4 Chirag Patel Classified gene: RFC4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6131 RFC4 Chirag Patel Gene: rfc4 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.198 RFC4 Chirag Patel Classified gene: RFC4 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.198 RFC4 Chirag Patel Gene: rfc4 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.69 RFC4 Chirag Patel Classified gene: RFC4 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.69 RFC4 Chirag Patel Gene: rfc4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6131 RFC4 Chirag Patel Classified gene: RFC4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6131 RFC4 Chirag Patel Gene: rfc4 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.198 RFC4 Chirag Patel Classified gene: RFC4 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.198 RFC4 Chirag Patel Gene: rfc4 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.69 RFC4 Chirag Patel Classified gene: RFC4 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.69 RFC4 Chirag Patel Gene: rfc4 has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v1.16 MED12 Zornitza Stark Marked gene: MED12 as ready
Congenital diaphragmatic hernia v1.16 MED12 Zornitza Stark Gene: med12 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6130 MED22 Zornitza Stark Marked gene: MED22 as ready
Intellectual disability syndromic and non-syndromic v0.6130 MED22 Zornitza Stark Gene: med22 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6130 MED22 Zornitza Stark Classified gene: MED22 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6130 MED22 Zornitza Stark Gene: med22 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1986 MED22 Zornitza Stark Marked gene: MED22 as ready
Mendeliome v1.1986 MED22 Zornitza Stark Gene: med22 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1986 MED22 Zornitza Stark Classified gene: MED22 as Amber List (moderate evidence)
Mendeliome v1.1986 MED22 Zornitza Stark Gene: med22 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6129 LARP1 Zornitza Stark Marked gene: LARP1 as ready
Intellectual disability syndromic and non-syndromic v0.6129 LARP1 Zornitza Stark Gene: larp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6129 LARP1 Zornitza Stark Classified gene: LARP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6129 LARP1 Zornitza Stark Gene: larp1 has been classified as Green List (High Evidence).
Mendeliome v1.1985 LARP1 Zornitza Stark Marked gene: LARP1 as ready
Mendeliome v1.1985 LARP1 Zornitza Stark Gene: larp1 has been classified as Green List (High Evidence).
Mendeliome v1.1985 LARP1 Zornitza Stark Classified gene: LARP1 as Green List (high evidence)
Mendeliome v1.1985 LARP1 Zornitza Stark Gene: larp1 has been classified as Green List (High Evidence).
Autism v0.199 LARP1 Zornitza Stark Marked gene: LARP1 as ready
Autism v0.199 LARP1 Zornitza Stark Gene: larp1 has been classified as Green List (High Evidence).
Autism v0.199 LARP1 Zornitza Stark Classified gene: LARP1 as Green List (high evidence)
Autism v0.199 LARP1 Zornitza Stark Gene: larp1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.83 PNPLA8 Zornitza Stark Marked gene: PNPLA8 as ready
Hereditary Spastic Paraplegia - paediatric v1.83 PNPLA8 Zornitza Stark Gene: pnpla8 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.83 PNPLA8 Zornitza Stark Phenotypes for gene: PNPLA8 were changed from PNPLA8-related neurological diseases to Complex neurodevelopmental disorder, MONDO:0100038, PNPLA8-related
Intellectual disability syndromic and non-syndromic v0.6128 PNPLA8 Zornitza Stark Marked gene: PNPLA8 as ready
Intellectual disability syndromic and non-syndromic v0.6128 PNPLA8 Zornitza Stark Gene: pnpla8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6128 PNPLA8 Zornitza Stark Phenotypes for gene: PNPLA8 were changed from PNPLA8-related neurological diseases to Complex neurodevelopmental disorder, MONDO:0100038, PNPLA8-related
Mitochondrial disease v0.929 PNPLA8 Zornitza Stark Phenotypes for gene: PNPLA8 were changed from Complex neurodevelopmental disorder, MONDO:0100038, PNPLA8-related; Mitochondrial myopathy with lactic acidosis (MIM#251950), AR to Complex neurodevelopmental disorder, MONDO:0100038, PNPLA8-related; Mitochondrial myopathy with lactic acidosis (MIM#251950), AR
Mitochondrial disease v0.928 PNPLA8 Zornitza Stark Phenotypes for gene: PNPLA8 were changed from Mitochondrial myopathy with lactic acidosis (MIM#251950), AR to Complex neurodevelopmental disorder, MONDO:0100038, PNPLA8-related; Mitochondrial myopathy with lactic acidosis (MIM#251950), AR
Genetic Epilepsy v1.53 PNPLA8 Zornitza Stark Marked gene: PNPLA8 as ready
Genetic Epilepsy v1.53 PNPLA8 Zornitza Stark Gene: pnpla8 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.53 PNPLA8 Zornitza Stark Phenotypes for gene: PNPLA8 were changed from Complex neurodevelopmental disorder, MONDO:0100038, PNPLA8-related to Complex neurodevelopmental disorder, MONDO:0100038, PNPLA8-related
Genetic Epilepsy v1.52 PNPLA8 Zornitza Stark Phenotypes for gene: PNPLA8 were changed from PNPLA8-related neurological diseases to Complex neurodevelopmental disorder, MONDO:0100038, PNPLA8-related
Cerebellar and Pontocerebellar Hypoplasia v1.70 RFC4 Chirag Patel Classified gene: RFC4 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.70 RFC4 Chirag Patel Gene: rfc4 has been classified as Green List (High Evidence).
Microcephaly v1.276 PNPLA8 Zornitza Stark Marked gene: PNPLA8 as ready
Microcephaly v1.276 PNPLA8 Zornitza Stark Gene: pnpla8 has been classified as Green List (High Evidence).
Microcephaly v1.276 PNPLA8 Zornitza Stark Phenotypes for gene: PNPLA8 were changed from PNPLA8-related neurological diseases to Complex neurodevelopmental disorder, MONDO:0100038, PNPLA8-related
Mendeliome v1.1984 PNPLA8 Zornitza Stark Phenotypes for gene: PNPLA8 were changed from Mitochondrial myopathy with lactic acidosis (MIM#251950), AR to Complex neurodevelopmental disorder, MONDO:0100038, PNPLA8-related; Mitochondrial myopathy with lactic acidosis (MIM#251950), AR
Cerebellar and Pontocerebellar Hypoplasia v1.69 PNPLA8 Zornitza Stark Marked gene: PNPLA8 as ready
Cerebellar and Pontocerebellar Hypoplasia v1.69 PNPLA8 Zornitza Stark Gene: pnpla8 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.69 PNPLA8 Zornitza Stark Phenotypes for gene: PNPLA8 were changed from Complex neurodevelopmental disorder, MONDO:0100038, PNPLA8-related to Complex neurodevelopmental disorder, MONDO:0100038, PNPLA8-related
Cerebellar and Pontocerebellar Hypoplasia v1.69 PNPLA8 Zornitza Stark Phenotypes for gene: PNPLA8 were changed from PNPLA8-related neurological diseases to Complex neurodevelopmental disorder, MONDO:0100038, PNPLA8-related
Dystonia - complex v0.238 PNPLA8 Zornitza Stark Marked gene: PNPLA8 as ready
Dystonia - complex v0.238 PNPLA8 Zornitza Stark Gene: pnpla8 has been classified as Green List (High Evidence).
Dystonia - complex v0.238 PNPLA8 Zornitza Stark Phenotypes for gene: PNPLA8 were changed from PNPLA8-related neurological diseases to Complex neurodevelopmental disorder, MONDO:0100038, PNPLA8-related
Cerebellar and Pontocerebellar Hypoplasia v1.68 RFC4 Chirag Patel gene: RFC4 was added
gene: RFC4 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature
Mode of inheritance for gene: RFC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RFC4 were set to PMID: 39106866
Phenotypes for gene: RFC4 were set to RFC4-related multisystem disorder
Review for gene: RFC4 was set to GREEN
gene: RFC4 was marked as current diagnostic
Added comment: 9 affected individuals (aged birth to 47yrs) from 8 unrelated families with a multisystem disorder. Clinical features included: muscle weakness/myopathy (9/9), motor incoordination/gait disturbance (8/8), delayed gross motor development (6/9), dysarthria (5/5), peripheral neuropathy (3/3 adults), bilateral sensorineural hearing impairment (6/9), decreased body weight (8/9), short stature (5/9), microcephaly (4/9), respiratory issues/insufficiency (6/9), cerebellar atrophy (4/9), pituitary hypoplasia (3/9).

WES or WGS identified biallelic loss-of-function variants in RFC4 (3 frameshift, 2 splice site, 1 single AA duplication, 2 single AA deletions, 2 missense), and almost all are likely to disrupt the C-terminal domain indispensable for Replication factor C (RFC) complex formation. All variants segregated with the disease.

The RFC complex (with 5 subunits) is central to process of regulation of DNA replication, and it loads proliferating cell nuclear antigen onto DNA to facilitate the recruitment of replication and repair proteins and enhance DNA polymerase processivity. RFC1 is associated with CANVAS but the contributions of RFC2-5 subunits on human Mendelian disorders is unknown.

Analysis of a previously determined cryo-EM structure of RFC bound to proliferating cell nuclear antigen suggested that the variants disrupt interactions within RFC4 and/or destabilize the RFC complex. Cellular studies using RFC4-deficient HeLa cells and primary fibroblasts demonstrated decreased RFC4 protein, compromised stability of the other RFC complex subunits, and perturbed RFC complex formation. Additionally, functional studies of the RFC4 variants affirmed diminished RFC complex formation, and cell cycle studies suggested perturbation of DNA replication and cell cycle progression.
Sources: Literature
Deafness_IsolatedAndComplex v1.197 RFC4 Chirag Patel gene: RFC4 was added
gene: RFC4 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: RFC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RFC4 were set to PMID: 39106866
Phenotypes for gene: RFC4 were set to RFC4-related multisystem disorder
Review for gene: RFC4 was set to GREEN
gene: RFC4 was marked as current diagnostic
Added comment: 9 affected individuals (aged birth to 47yrs) from 8 unrelated families with a multisystem disorder. Clinical features included: muscle weakness/myopathy (9/9), motor incoordination/gait disturbance (8/8), delayed gross motor development (6/9), dysarthria (5/5), peripheral neuropathy (3/3 adults), bilateral sensorineural hearing impairment (6/9), decreased body weight (8/9), short stature (5/9), microcephaly (4/9), respiratory issues/insufficiency (6/9), cerebellar atrophy (4/9), pituitary hypoplasia (3/9).

WES or WGS identified biallelic loss-of-function variants in RFC4 (3 frameshift, 2 splice site, 1 single AA duplication, 2 single AA deletions, 2 missense), and almost all are likely to disrupt the C-terminal domain indispensable for Replication factor C (RFC) complex formation. All variants segregated with the disease.

The RFC complex (with 5 subunits) is central to process of regulation of DNA replication, and it loads proliferating cell nuclear antigen onto DNA to facilitate the recruitment of replication and repair proteins and enhance DNA polymerase processivity. RFC1 is associated with CANVAS but the contributions of RFC2-5 subunits on human Mendelian disorders is unknown.

Analysis of a previously determined cryo-EM structure of RFC bound to proliferating cell nuclear antigen suggested that the variants disrupt interactions within RFC4 and/or destabilize the RFC complex. Cellular studies using RFC4-deficient HeLa cells and primary fibroblasts demonstrated decreased RFC4 protein, compromised stability of the other RFC complex subunits, and perturbed RFC complex formation. Additionally, functional studies of the RFC4 variants affirmed diminished RFC complex formation, and cell cycle studies suggested perturbation of DNA replication and cell cycle progression.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6127 RFC4 Chirag Patel gene: RFC4 was added
gene: RFC4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RFC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RFC4 were set to PMID: 39106866
Phenotypes for gene: RFC4 were set to RFC4-related multisystem disorder
Review for gene: RFC4 was set to GREEN
gene: RFC4 was marked as current diagnostic
Added comment: 9 affected individuals (aged birth to 47yrs) from 8 unrelated families with a multisystem disorder. Clinical features included: muscle weakness/myopathy (9/9), motor incoordination/gait disturbance (8/8), delayed gross motor development (6/9), dysarthria (5/5), peripheral neuropathy (3/3 adults), bilateral sensorineural hearing impairment (6/9), decreased body weight (8/9), short stature (5/9), microcephaly (4/9), respiratory issues/insufficiency (6/9), cerebellar atrophy (4/9), pituitary hypoplasia (3/9).

WES or WGS identified biallelic loss-of-function variants in RFC4 (3 frameshift, 2 splice site, 1 single AA duplication, 2 single AA deletions, 2 missense), and almost all are likely to disrupt the C-terminal domain indispensable for Replication factor C (RFC) complex formation. All variants segregated with the disease.

The RFC complex (with 5 subunits) is central to process of regulation of DNA replication, and it loads proliferating cell nuclear antigen onto DNA to facilitate the recruitment of replication and repair proteins and enhance DNA polymerase processivity. RFC1 is associated with CANVAS but the contributions of RFC2-5 subunits on human Mendelian disorders is unknown.

Analysis of a previously determined cryo-EM structure of RFC bound to proliferating cell nuclear antigen suggested that the variants disrupt interactions within RFC4 and/or destabilize the RFC complex. Cellular studies using RFC4-deficient HeLa cells and primary fibroblasts demonstrated decreased RFC4 protein, compromised stability of the other RFC complex subunits, and perturbed RFC complex formation. Additionally, functional studies of the RFC4 variants affirmed diminished RFC complex formation, and cell cycle studies suggested perturbation of DNA replication and cell cycle progression.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.68 RFC4 Chirag Patel gene: RFC4 was added
gene: RFC4 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: RFC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RFC4 were set to PMID: 39106866
Phenotypes for gene: RFC4 were set to RFC4-related multisystem disorder
Review for gene: RFC4 was set to GREEN
gene: RFC4 was marked as current diagnostic
Added comment: 9 affected individuals (aged birth to 47yrs) from 8 unrelated families with a multisystem disorder. Clinical features included: muscle weakness/myopathy (9/9), motor incoordination/gait disturbance (8/8), delayed gross motor development (6/9), dysarthria (5/5), peripheral neuropathy (3/3 adults), bilateral sensorineural hearing impairment (6/9), decreased body weight (8/9), short stature (5/9), microcephaly (4/9), respiratory issues/insufficiency (6/9), cerebellar atrophy (4/9), pituitary hypoplasia (3/9).

WES or WGS identified biallelic loss-of-function variants in RFC4 (3 frameshift, 2 splice site, 1 single AA duplication, 2 single AA deletions, 2 missense), and almost all are likely to disrupt the C-terminal domain indispensable for Replication factor C (RFC) complex formation. All variants segregated with the disease.

The RFC complex (with 5 subunits) is central to process of regulation of DNA replication, and it loads proliferating cell nuclear antigen onto DNA to facilitate the recruitment of replication and repair proteins and enhance DNA polymerase processivity. RFC1 is associated with CANVAS but the contributions of RFC2-5 subunits on human Mendelian disorders is unknown.

Analysis of a previously determined cryo-EM structure of RFC bound to proliferating cell nuclear antigen suggested that the variants disrupt interactions within RFC4 and/or destabilize the RFC complex. Cellular studies using RFC4-deficient HeLa cells and primary fibroblasts demonstrated decreased RFC4 protein, compromised stability of the other RFC complex subunits, and perturbed RFC complex formation. Additionally, functional studies of the RFC4 variants affirmed diminished RFC complex formation, and cell cycle studies suggested perturbation of DNA replication and cell cycle progression.
Sources: Literature
Mendeliome v1.1983 SPARCL1 Zornitza Stark Marked gene: SPARCL1 as ready
Mendeliome v1.1983 SPARCL1 Zornitza Stark Gene: sparcl1 has been classified as Red List (Low Evidence).
Mendeliome v1.1983 SPARCL1 Zornitza Stark gene: SPARCL1 was added
gene: SPARCL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPARCL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPARCL1 were set to 39169229
Phenotypes for gene: SPARCL1 were set to Corneal dystrophy, MONDO:0018102
Review for gene: SPARCL1 was set to RED
Added comment: 8 affected individuals with corneal dystrophy from 1 family (3 generations). Affected individuals had diffuse central stromal opacity, with reduced visual acuity in older family members. Histopathology of affected cornea tissue revealed mild stromal textural alterations with alcianophilic deposits.

WGS from 4 affected individuals in family identified a novel heterozygous missense variant in exon 4 of SPARCL1 (c.334G > A; p.(Glu112Lys)) which segregated with disease.

SPARC-like protein 1 (SPARCL1) is a secreted matricellular protein involved in cell migration, cell adhesion, tissue repair, and remodelling. SPARCL1 has been shown to regulate decorin. Heterozygous variants in DCN, encoding decorin, cause autosomal dominant congenital stromal corneal dystrophy, suggesting a common pathogenic pathway. Immunohistochemistry showed the level of decorin was significantly decreased in the corneal stroma of the affected tissue, and SPARCL1 appeared to be retained in the epithelium.
Sources: Literature
Corneal Dystrophy v1.11 SPARCL1 Zornitza Stark Marked gene: SPARCL1 as ready
Corneal Dystrophy v1.11 SPARCL1 Zornitza Stark Gene: sparcl1 has been classified as Red List (Low Evidence).
Optic Atrophy v1.37 NDUFA7 Zornitza Stark Classified gene: NDUFA7 as Red List (low evidence)
Optic Atrophy v1.37 NDUFA7 Zornitza Stark Gene: ndufa7 has been classified as Red List (Low Evidence).
Mendeliome v1.1982 NDUFA7 Zornitza Stark Phenotypes for gene: NDUFA7 were changed from to Optic atrophy, MONDO:0003608, NDUFA7-related
Optic Atrophy v1.36 NDUFA7 Zornitza Stark Classified gene: NDUFA7 as Red List (low evidence)
Optic Atrophy v1.36 NDUFA7 Zornitza Stark Gene: ndufa7 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.262 CPT1A Cassandra Muller reviewed gene: CPT1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 12189492, 25778941, 23430932; Phenotypes: CPT deficiency, hepatic, type IA, 255120 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1981 NDUFA7 Zornitza Stark Mode of inheritance for gene: NDUFA7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Optic Atrophy v1.35 NDUFA7 Zornitza Stark reviewed gene: NDUFA7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Optic atrophy, MONDO:0003608, NDUFA7-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1980 NDUFA7 Zornitza Stark edited their review of gene: NDUFA7: Changed rating: RED
Mendeliome v1.1980 NDUFA7 Zornitza Stark reviewed gene: NDUFA7: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Optic atrophy, MONDO:0003608, NDUFA7-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic Atrophy v1.35 NDUFA7 Zornitza Stark Marked gene: NDUFA7 as ready
Optic Atrophy v1.35 NDUFA7 Zornitza Stark Gene: ndufa7 has been classified as Amber List (Moderate Evidence).
Optic Atrophy v1.35 NDUFA7 Zornitza Stark Phenotypes for gene: NDUFA7 were changed from Leber Hereditary Optic Neuropathy, MIM#619382 to Optic atrophy, MONDO:0003608, NDUFA7-related
Optic Atrophy v1.34 NDUFA7 Zornitza Stark Classified gene: NDUFA7 as Amber List (moderate evidence)
Optic Atrophy v1.34 NDUFA7 Zornitza Stark Gene: ndufa7 has been classified as Amber List (Moderate Evidence).
Optic Atrophy v1.33 NDUFA7 Zornitza Stark Classified gene: NDUFA7 as Amber List (moderate evidence)
Optic Atrophy v1.33 NDUFA7 Zornitza Stark Gene: ndufa7 has been classified as Amber List (Moderate Evidence).
Hyperinsulinism v1.30 MAGEL2 Zornitza Stark Marked gene: MAGEL2 as ready
Hyperinsulinism v1.30 MAGEL2 Zornitza Stark Gene: magel2 has been classified as Green List (High Evidence).
Hyperinsulinism v1.30 MAGEL2 Zornitza Stark Classified gene: MAGEL2 as Green List (high evidence)
Hyperinsulinism v1.30 MAGEL2 Zornitza Stark Gene: magel2 has been classified as Green List (High Evidence).
Hyperinsulinism v1.29 MAGEL2 Zornitza Stark gene: MAGEL2 was added
gene: MAGEL2 was added to Hyperinsulinism. Sources: Expert list
Mode of inheritance for gene: MAGEL2 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for gene: MAGEL2 were set to 25473036; 29599419; 31397880
Phenotypes for gene: MAGEL2 were set to Schaaf-Yang syndrome, MIM# 615547
Review for gene: MAGEL2 was set to GREEN
Added comment: MAGEL2 is a maternally imprinted gene, paternally expressed, located on chromosome 15q11, within the critical region of Prader Willi syndrome. Congenital hyperinsulinism due to pathogenic variants on the paternal allele of MAGEL2 have been reported in 3 patients from 2 families with a diagnosis of persistent congenital hyperinsulinism and extra pancreatic features (ptosis, exotropia, high palate, smooth philtrum, inverted nipples, skeletal anomalies, hypotonia, low muscle mass and increased central distribution of body fat) (Soden et al Sci Transl Med 2014 PMID:25473036). Hypoglycaemia has been reported in a further 13 cases (Jobling et al J Med Genet 2018 PMID: 29599419, Patak et al 2019, Clin Genet PMID: 31397880).
Sources: Expert list
Hyperinsulinism v1.28 CACNA1C Zornitza Stark Marked gene: CACNA1C as ready
Hyperinsulinism v1.28 CACNA1C Zornitza Stark Gene: cacna1c has been classified as Amber List (Moderate Evidence).
Hyperinsulinism v1.28 CACNA1C Zornitza Stark Classified gene: CACNA1C as Amber List (moderate evidence)
Hyperinsulinism v1.28 CACNA1C Zornitza Stark Gene: cacna1c has been classified as Amber List (Moderate Evidence).
Hyperinsulinism v1.27 CACNA1C Zornitza Stark gene: CACNA1C was added
gene: CACNA1C was added to Hyperinsulinism. Sources: Expert list
Mode of inheritance for gene: CACNA1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1C were set to 35897673
Phenotypes for gene: CACNA1C were set to Hyperinsulinism, MONDO:0002177, CACNA1C-related; Timothy syndrome, MIM# 601005
Review for gene: CACNA1C was set to AMBER
Added comment: PMID: 35897673 reports novel heterozygous CACNA1C variant in a patient with congenital hyperinsulinism (CHI), which appears to have gain-of-function and loss-of-function effects at the electrophysiological level, explaining the hyperinsulinism and resulting hypoglycemia in the patient reported. It appeared that c.1679T>C, p.L566P (NM_000719.6) reported in this patient has a minor effects on the cardiac action potential in an in silico model, in contrast to c.1216G>T, p.G406R (NM_000719.6) which is associated with the Long QT in Timothy syndrome (OMIM:601005). Therefore the authors conclude that this represents a novel congeital non-syndromic hyperinsulinism.
Hypoglycemia is also seen in Timothy syndrome patients with c.1216G>T, p.G406R (Table S3, PMID: 35897673).
Sources: Expert list
Hyperinsulinism v1.26 GPC3 Zornitza Stark Marked gene: GPC3 as ready
Hyperinsulinism v1.26 GPC3 Zornitza Stark Gene: gpc3 has been classified as Red List (Low Evidence).
Hyperinsulinism v1.26 AKT2 Zornitza Stark Marked gene: AKT2 as ready
Hyperinsulinism v1.26 AKT2 Zornitza Stark Gene: akt2 has been classified as Red List (Low Evidence).
Hyperinsulinism v1.26 PGM1 Zornitza Stark Marked gene: PGM1 as ready
Hyperinsulinism v1.26 PGM1 Zornitza Stark Gene: pgm1 has been classified as Green List (High Evidence).
Hyperinsulinism v1.26 PGM1 Zornitza Stark Publications for gene: PGM1 were set to PMID: 24499211, 27206562
Hyperinsulinism v1.25 MAFA Zornitza Stark Marked gene: MAFA as ready
Hyperinsulinism v1.25 MAFA Zornitza Stark Gene: mafa has been classified as Green List (High Evidence).
Hyperinsulinism v1.25 EP300 Zornitza Stark Marked gene: EP300 as ready
Hyperinsulinism v1.25 EP300 Zornitza Stark Gene: ep300 has been classified as Green List (High Evidence).
Hyperinsulinism v1.25 EP300 Zornitza Stark Publications for gene: EP300 were set to PMID: 31137009, 33442921, 2240025, 31414570, 33043588
Hyperinsulinism v1.24 CREBBP Zornitza Stark Marked gene: CREBBP as ready
Hyperinsulinism v1.24 CREBBP Zornitza Stark Gene: crebbp has been classified as Green List (High Evidence).
Hyperinsulinism v1.24 CREBBP Zornitza Stark Publications for gene: CREBBP were set to PMID: 31137009, 33442921, 2240025, 31414570, 33043588
Genetic Epilepsy v1.51 KMT2C Zornitza Stark Marked gene: KMT2C as ready
Genetic Epilepsy v1.51 KMT2C Zornitza Stark Gene: kmt2c has been classified as Green List (High Evidence).
Genetic Epilepsy v1.51 KMT2C Zornitza Stark Classified gene: KMT2C as Green List (high evidence)
Genetic Epilepsy v1.51 KMT2C Zornitza Stark Gene: kmt2c has been classified as Green List (High Evidence).
Genetic Epilepsy v1.50 KMT2C Zornitza Stark Classified gene: KMT2C as Green List (high evidence)
Genetic Epilepsy v1.50 KMT2C Zornitza Stark Gene: kmt2c has been classified as Green List (High Evidence).
Genetic Epilepsy v1.49 KMT2C Zornitza Stark gene: KMT2C was added
gene: KMT2C was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KMT2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KMT2C were set to 39013459
Phenotypes for gene: KMT2C were set to Kleefstra syndrome 2, MIM# 617768
Review for gene: KMT2C was set to GREEN
Added comment: Large cohort of 98 individuals reported. Seizures are part of the phenotype.
Sources: Literature
Mendeliome v1.1980 ABL1 Sangavi Sivagnanasundram reviewed gene: ABL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 39155385, 38743093; Phenotypes: Human ABL1 Deficiency Syndrome (HADS); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1980 GMPPB Sangavi Sivagnanasundram reviewed gene: GMPPB: Rating: GREEN; Mode of pathogenicity: None; Publications: 27147698; Phenotypes: myopathy caused by variation in GMPPB MONDO:0700084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.262 LMNA Zornitza Stark Phenotypes for gene: LMNA were changed from Restrictive dermopathy, lethal, 275210 (3) to Mandibuloacral dysplasia, MIM# 248370
Prepair 1000+ v1.261 LMNA Zornitza Stark edited their review of gene: LMNA: Changed phenotypes: Mandibuloacral dysplasia, MIM# 248370
Prepair 1000+ v1.261 GNE Zornitza Stark Marked gene: GNE as ready
Prepair 1000+ v1.261 GNE Zornitza Stark Gene: gne has been classified as Green List (High Evidence).
Prepair 1000+ v1.261 GNE Zornitza Stark Phenotypes for gene: GNE were changed from Inclusion body myopathy, autosomal recessive, 600737 (3) to Nonaka myopathy MIM#605820; Thrombocytopenia 12 with or without myopathy MIM#620757
Prepair 1000+ v1.260 GNE Zornitza Stark Publications for gene: GNE were set to
Prepair 1000+ v1.259 GNE Zornitza Stark Tag for review tag was added to gene: GNE.
Prepair 1000+ v1.259 GNE Zornitza Stark reviewed gene: GNE: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Nonaka myopathy MIM#605820, Thrombocytopenia 12 with or without myopathy MIM#620757; Mode of inheritance: None
Prepair 1000+ v1.259 B9D1 Lilian Downie Marked gene: B9D1 as ready
Prepair 1000+ v1.259 B9D1 Lilian Downie Added comment: Comment when marking as ready: Promote to green when final list confirmed
Prepair 1000+ v1.259 B9D1 Lilian Downie Gene: b9d1 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.259 B9D1 Lilian Downie Publications for gene: B9D1 were set to 21493627; 24886560; 25920555
Prepair 1000+ v1.258 B9D1 Lilian Downie reviewed gene: B9D1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21493627, 24886560, 25920555, 32622957; Phenotypes: Joubert syndrome 27, MIM# 617120, Meckel syndrome 9, MIM# 614209; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic Atrophy v1.32 NDUFA7 Mark Cleghorn gene: NDUFA7 was added
gene: NDUFA7 was added to Optic Atrophy. Sources: Other
Mode of inheritance for gene: NDUFA7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFA7 were set to Leber Hereditary Optic Neuropathy, MIM#619382
Penetrance for gene: NDUFA7 were set to unknown
Review for gene: NDUFA7 was set to AMBER
Added comment: NDUFA7
ESHG talk 2/6/24, unpublished
Christine Michaela Neuhofer, Technische Universitat Munchen

Biallelic LoF with Leber Hereditary optic neuropathy (LHON)

Only 1 case, with LHON and homozygous NDUFA7:c.51+1dup
NDUFA7 protein interacts w DNAJC30 – known nuclear LHON gene

Analysis on patient fibroblasts supports disruption to complex I activity via DNAJC30
Sources: Other
Corneal Dystrophy v1.11 SPARCL1 Chirag Patel gene: SPARCL1 was added
gene: SPARCL1 was added to Corneal Dystrophy. Sources: Literature
Mode of inheritance for gene: SPARCL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPARCL1 were set to PMID: 39169229
Phenotypes for gene: SPARCL1 were set to Corneal dystrophy, MONDO:0018102
Review for gene: SPARCL1 was set to RED
Added comment: 8 affected individuals with corneal dystrophy from 1 family (3 generations). Affected individuals had diffuse central stromal opacity, with reduced visual acuity in older family members. Histopathology of affected cornea tissue revealed mild stromal textural alterations with alcianophilic deposits.

WGS from 4 affected individuals in family identified a novel heterozygous missense variant in exon 4 of SPARCL1 (c.334G > A; p.(Glu112Lys)) which segregated with disease.

SPARC-like protein 1 (SPARCL1) is a secreted matricellular protein involved in cell migration, cell adhesion, tissue repair, and remodelling. SPARCL1 has been shown to regulate decorin. Heterozygous variants in DCN, encoding decorin, cause autosomal dominant congenital stromal corneal dystrophy, suggesting a common pathogenic pathway. Immunohistochemistry showed the level of decorin was significantly decreased in the corneal stroma of the affected tissue, and SPARCL1 appeared to be retained in the epithelium.
Sources: Literature
Dystonia - complex v0.237 PNPLA8 Chirag Patel Classified gene: PNPLA8 as Green List (high evidence)
Dystonia - complex v0.237 PNPLA8 Chirag Patel Gene: pnpla8 has been classified as Green List (High Evidence).
Dystonia - complex v0.236 PNPLA8 Chirag Patel gene: PNPLA8 was added
gene: PNPLA8 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA8 were set to PMID: 39082157
Phenotypes for gene: PNPLA8 were set to PNPLA8-related neurological diseases
Review for gene: PNPLA8 was set to GREEN
gene: PNPLA8 was marked as current diagnostic
Added comment: Cohort analysis of clinical features of new and previously reported individuals with biallelic PNPLA8 variants (25 affected individuals across 20 families). They showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. Complete loss of PNPLA8 was associated with the more profound end of the spectrum. 11/15 individuals (info available) had dystonia (onset in childhood).

Using cerebral organoids generated from human induced pluripotent stem cells, they found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. They show that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development.
Sources: Literature
Hereditary Spastic Paraplegia - paediatric v1.82 PNPLA8 Chirag Patel Classified gene: PNPLA8 as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v1.82 PNPLA8 Chirag Patel Gene: pnpla8 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.67 PNPLA8 Chirag Patel Classified gene: PNPLA8 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.67 PNPLA8 Chirag Patel Gene: pnpla8 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.81 PNPLA8 Chirag Patel gene: PNPLA8 was added
gene: PNPLA8 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA8 were set to PMID: 39082157
Phenotypes for gene: PNPLA8 were set to PNPLA8-related neurological diseases
Review for gene: PNPLA8 was set to GREEN
gene: PNPLA8 was marked as current diagnostic
Added comment: Cohort analysis of clinical features of new and previously reported individuals with biallelic PNPLA8 variants (25 affected individuals across 20 families). They showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. Complete loss of PNPLA8 was associated with the more profound end of the spectrum. 15/23 individuals (info available) had spasticity (onset in early childhood).

Using cerebral organoids generated from human induced pluripotent stem cells, they found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. They show that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development.
Sources: Literature
Cerebellar and Pontocerebellar Hypoplasia v1.66 PNPLA8 Chirag Patel gene: PNPLA8 was added
gene: PNPLA8 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature
Mode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA8 were set to PMID: 39082157
Phenotypes for gene: PNPLA8 were set to PNPLA8-related neurological diseases
Review for gene: PNPLA8 was set to GREEN
gene: PNPLA8 was marked as current diagnostic
Added comment: Cohort analysis of clinical features of new and previously reported individuals with biallelic PNPLA8 variants (25 affected individuals across 20 families). They showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. Complete loss of PNPLA8 was associated with the more profound end of the spectrum. 20/21 individuals (info available) had cerebellar atrophy with/without pontocerebellar hypoplasia.

Using cerebral organoids generated from human induced pluripotent stem cells, they found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. They show that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development.
Sources: Literature
Genetic Epilepsy v1.48 PNPLA8 Chirag Patel Classified gene: PNPLA8 as Green List (high evidence)
Genetic Epilepsy v1.48 PNPLA8 Chirag Patel Gene: pnpla8 has been classified as Green List (High Evidence).
Autism v0.198 LARP1 Sangavi Sivagnanasundram gene: LARP1 was added
gene: LARP1 was added to Autism. Sources: Other
Mode of inheritance for gene: LARP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LARP1 were set to 39182167
Phenotypes for gene: LARP1 were set to Neurodevelopmental disorder; MONDO:0700092
Review for gene: LARP1 was set to GREEN
Added comment: Seven unrelated probands (6 males and 1 female) with ASD or another variable NDD phenotype (ID, hypotonia, motor delay and/or ASD). Variants were showed to be de novo null variants or missense variants that resulted in haploinsufficiency.

Ex vivo (knockout CRISPR-Cas9) functional assay using lymphoblasts that was collected and immortilised from one proband was conducted to assess the functional impact of the LARP1 variant. The results showed a reduction in protein compared to WT causing reduced rates of aerobic respiration and glycolysis.
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6126 LARP1 Sangavi Sivagnanasundram gene: LARP1 was added
gene: LARP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: LARP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LARP1 were set to 39182167
Phenotypes for gene: LARP1 were set to Neurodevelopmental disorder; MONDO:0700092
Review for gene: LARP1 was set to GREEN
Added comment: Seven unrelated probands (6 males and 1 female) with ASD or another variable NDD phenotype (ID, hypotonia, motor delay and/or ASD). Variants were showed to be de novo null variants or missense variants that resulted in haploinsufficiency.

Ex vivo (knockout CRISPR-Cas9) functional assay using lymphoblasts that was collected and immortilised from one proband was conducted to assess the functional impact of the LARP1 variant. The results showed a reduction in protein compared to WT causing reduced rates of aerobic respiration and glycolysis
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6126 PNPLA8 Chirag Patel Classified gene: PNPLA8 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6126 PNPLA8 Chirag Patel Gene: pnpla8 has been classified as Green List (High Evidence).
Mendeliome v1.1980 LARP1 Sangavi Sivagnanasundram gene: LARP1 was added
gene: LARP1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: LARP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LARP1 were set to 39182167
Phenotypes for gene: LARP1 were set to Neurodevelopmental disorder; MONDO:0700092
Review for gene: LARP1 was set to GREEN
Added comment: Seven unrelated probands (6 males and 1 female) with ASD or another variable NDD phenotype (ID, hypotonia, motor delay and/or ASD). Variants were showed to be de novo null variants or missense variants that resulted in haploinsufficiency.

Ex vivo (knockout CRISPR-Cas9) functional assay using lymphoblasts that was collected and immortilised from one proband was conducted to assess the functional impact of the LARP1 variant. The results showed a reduction in protein compared to WT causing reduced rates of aerobic respiration and glycolysis.
Sources: Other
Genetic Epilepsy v1.47 PNPLA8 Chirag Patel gene: PNPLA8 was added
gene: PNPLA8 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA8 were set to PMID: 39082157
Phenotypes for gene: PNPLA8 were set to PNPLA8-related neurological diseases
Review for gene: PNPLA8 was set to GREEN
gene: PNPLA8 was marked as current diagnostic
Added comment: Cohort analysis of clinical features of new and previously reported individuals with biallelic PNPLA8 variants (25 affected individuals across 20 families). They showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. Complete loss of PNPLA8 was associated with the more profound end of the spectrum. 19/25 individuals had seizures (onset 1 day to 31 years).

Using cerebral organoids generated from human induced pluripotent stem cells, they found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. They show that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6125 PNPLA8 Chirag Patel Classified gene: PNPLA8 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6125 PNPLA8 Chirag Patel Gene: pnpla8 has been classified as Green List (High Evidence).
Mendeliome v1.1980 PNPLA8 Chirag Patel edited their review of gene: PNPLA8: Added comment: Cohort analysis of clinical features of new and previously reported individuals with biallelic PNPLA8 variants (25 affected individuals across 20 families). They showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. Complete loss of PNPLA8 was associated with the more profound end of the spectrum.

Using cerebral organoids generated from human induced pluripotent stem cells, they found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. They show that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development.; Set current diagnostic: yes
Mendeliome v1.1980 PNPLA8 Chirag Patel reviewed gene: PNPLA8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 39082157; Phenotypes: PNPLA8-related neurological diseases; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6124 PNPLA8 Chirag Patel gene: PNPLA8 was added
gene: PNPLA8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA8 were set to PMID: 39082157
Phenotypes for gene: PNPLA8 were set to PNPLA8-related neurological diseases
Review for gene: PNPLA8 was set to GREEN
gene: PNPLA8 was marked as current diagnostic
Added comment: Cohort analysis of clinical features of new and previously reported individuals with biallelic PNPLA8 variants (25 affected individuals across 20 families). They showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. Complete loss of PNPLA8 was associated with the more profound end of the spectrum. 13/19 individuals (info available) had developmental delay and/or severe intellectual disability.

Using cerebral organoids generated from human induced pluripotent stem cells, they found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. They show that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development.
Sources: Literature
Microcephaly v1.275 PNPLA8 Chirag Patel Phenotypes for gene: PNPLA8 were changed from PNPLA8-related neurological diseases; Mitochondrial myopathy with lactic acidosis, OMIM # 251950 to PNPLA8-related neurological diseases
Microcephaly v1.274 PNPLA8 Chirag Patel Classified gene: PNPLA8 as Green List (high evidence)
Microcephaly v1.274 PNPLA8 Chirag Patel Gene: pnpla8 has been classified as Green List (High Evidence).
Microcephaly v1.273 PNPLA8 Chirag Patel gene: PNPLA8 was added
gene: PNPLA8 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA8 were set to PMID: 39082157
Phenotypes for gene: PNPLA8 were set to PNPLA8-related neurological diseases; Mitochondrial myopathy with lactic acidosis, OMIM # 251950
Review for gene: PNPLA8 was set to GREEN
gene: PNPLA8 was marked as current diagnostic
Added comment: Cohort analysis of clinical features of new and previously reported individuals with biallelic PNPLA8 variants (25 affected individuals across 20 families). They showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. Complete loss of PNPLA8 was associated with the more profound end of the spectrum. 17/25 individuals had congenital and/or progressive microcephaly.

Using cerebral organoids generated from human induced pluripotent stem cells, they found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. They show that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development.
Sources: Literature
Mendeliome v1.1980 MED22 Mark Cleghorn gene: MED22 was added
gene: MED22 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: MED22 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MED22 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: MED22 were set to unknown
Review for gene: MED22 was set to AMBER
Added comment: ESHG talk 2/6/24, unpublished
Elisa Cali, UCL

Recurrent homozygous MED22:c.397_399del (p.Glu133del) inframe variant in 8 individuals from 6 families w progressive NDD, microcepahly, cerebellar atrophy, dystonia, seizures

Rare in gnomad v4.1 (9 het alleles, no homozygotes)

Functional work on patient fibroblasts: quantity of protein comparable to controls, did not mentioned assays of protein function (?mechanism proposed)
Drosophilia heterozygous model with equivalent of p.Glu133del variant: structural anomalies, less movements, all died prior to pupae stage
Zebrafish: MED22 mutants less mobile, died prior to adulthood, reduced brain size
Sources: Other
Ciliopathies v1.59 TMEM216 Zornitza Stark Publications for gene: TMEM216 were set to 20036350; 20512146
Intellectual disability syndromic and non-syndromic v0.6123 MED22 Mark Cleghorn gene: MED22 was added
gene: MED22 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: MED22 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MED22 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: MED22 were set to unknown
Review for gene: MED22 was set to AMBER
Added comment: ESHG talk 2/6/24, unpublished
Elisa Cali, UCL

Recurrent homozygous MED22:c.397_399del (p.Glu133del) inframe variant in 8 individuals from 6 families w progressive NDD, microcepahly, cerebellar atrophy, dystonia, seizures

Rare in gnomad v4.1 (9 het alleles, no homozygotes)

Functional work on patient fibroblasts: quantity of protein comparable to controls, did not mentioned assays of protein function (?mechanism proposed)
Drosophilia heterozygous model with equivalent of p.Glu133del variant: structural anomalies, less movements, all died prior to pupae stage
Zebrafish: MED22 mutants less mobile, died prior to adulthood, reduced brain size
Sources: Other
Ciliopathies v1.58 TMEM216 Zornitza Stark Tag UTR tag was added to gene: TMEM216.
Ciliopathies v1.58 TMEM216 Zornitza Stark edited their review of gene: TMEM216: Added comment: PMID 39191256: Two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]) found in individuals of South Asian and African ancestry, respectively.

This included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations.

Clinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation with night blindness in the first decade and progressive peripheral field loss thereafter. No evident systemic ciliopathy features were noted.

Functional characterization of these variants by luciferase reporter gene assay showed reduced promotor activity.; Changed publications: 20036350, 20512146, 39191256; Changed phenotypes: Joubert syndrome 2, MIM# 608091, Meckel syndrome 2, MIM# 603194, Retinitis pigmentosa, MONDO:0019200, TMEM216-related
Mendeliome v1.1980 TMEM216 Zornitza Stark Phenotypes for gene: TMEM216 were changed from Joubert syndrome 2, MIM# 608091; MONDO:0011963; Meckel syndrome 2, MIM# 603194; MONDO:0011296 to Joubert syndrome 2, MIM# 608091; MONDO:0011963; Meckel syndrome 2, MIM# 603194; MONDO:0011296; Retinitis pigmentosa, MONDO:0019200, TMEM216-related
Mendeliome v1.1979 TMEM216 Zornitza Stark Publications for gene: TMEM216 were set to 20036350; 20512146
Mendeliome v1.1978 TMEM216 Zornitza Stark Tag founder tag was added to gene: TMEM216.
Tag UTR tag was added to gene: TMEM216.
Mendeliome v1.1978 TMEM216 Zornitza Stark edited their review of gene: TMEM216: Added comment: PMID 39191256: Two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]) found in individuals of South Asian and African ancestry, respectively.

This included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations.

Clinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation with night blindness in the first decade and progressive peripheral field loss thereafter. No evident systemic ciliopathy features were noted.

Functional characterization of these variants by luciferase reporter gene assay showed reduced promotor activity.; Changed publications: 20036350, 20512146, 39191256; Changed phenotypes: Joubert syndrome 2, MIM# 608091, MONDO:0011963, Meckel syndrome 2, MIM# 603194, MONDO:0011296, Retinitis pigmentosa, MONDO:0019200, TMEM216-related
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.152 TMEM216 Zornitza Stark Publications for gene: TMEM216 were set to
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.151 TMEM216 Zornitza Stark edited their review of gene: TMEM216: Changed publications: 39191256
Congenital diaphragmatic hernia v1.16 MED12 Chirag Patel Classified gene: MED12 as Green List (high evidence)
Congenital diaphragmatic hernia v1.16 MED12 Chirag Patel Gene: med12 has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v1.15 MED12 Chirag Patel gene: MED12 was added
gene: MED12 was added to Congenital diaphragmatic hernia. Sources: Literature
Mode of inheritance for gene: MED12 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: MED12 were set to PMID: 39215511
Phenotypes for gene: MED12 were set to MED12-related disorders; Hardikar syndrome, OMIM # 301068
Review for gene: MED12 was set to GREEN
gene: MED12 was marked as current diagnostic
Added comment: MED12-related disorders include:
1) X-linked recessive Opitz-Kaveggia syndrome, Lujan-Fryns syndrome, Ohdo syndrome, and nonspecific intellectual disability in males predominantly carrying missense variants
2) X-linked dominant Hardikar syndrome and nonspecific intellectual disability in females known to predominantly carry de novo nonsense/frameshift and nonsense/missense variants, respectively.

Paper reviews occurrence of congenital diaphragmatic hernia in 18 individuals with molecularly confirmed MED12 mutation on WES/WGS. They report CDH in 3/7 females with Hardikar syndrome or nonspecific intellectual disability, but no CDH in 11 males with MED12-related disorders.
Sources: Literature
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.151 TMEM216 Zornitza Stark Marked gene: TMEM216 as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.151 TMEM216 Zornitza Stark Gene: tmem216 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.151 TMEM216 Zornitza Stark Classified gene: TMEM216 as Green List (high evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.151 TMEM216 Zornitza Stark Gene: tmem216 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.150 TMEM216 Zornitza Stark gene: TMEM216 was added
gene: TMEM216 was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: Literature
UTR tags were added to gene: TMEM216.
Mode of inheritance for gene: TMEM216 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM216 were set to Retinitis pigmentosa, MONDO:0019200, TMEM216-related
Review for gene: TMEM216 was set to GREEN
Added comment: Two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]) found in individuals of South Asian and African ancestry, respectively.

This included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations.

Clinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation with night blindness in the first decade and progressive peripheral field loss thereafter. No evident systemic ciliopathy features were noted.

Functional characterization of these variants by luciferase reporter gene assay showed reduced promotor activity.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.67 JPH1 Sangavi Sivagnanasundram gene: JPH1 was added
gene: JPH1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Other
Mode of inheritance for gene: JPH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JPH1 were set to 39209426
Phenotypes for gene: JPH1 were set to Congenital myopathy MONDO:0019952
Review for gene: JPH1 was set to GREEN
Added comment: 4 unrelated probands presented with congenital myopathy with facial weakness and ocular involvement. All individuals had presence of 4 different LoF variants identified in JPH1.

p.(Asp125Thrfs*30), p.(Tyr118*), p.(Leu580Trpfs*16) and p.(Glu504Serfs*3) - all variants were absent from gnomADv4.1
Sources: Other
Mendeliome v1.1978 JPH1 Sangavi Sivagnanasundram changed review comment from: 4 unrelated probands presented with congenital myopathy with prominent facial and ocular involvement. All individuals had presence of 4 different LoF variants identified in JPH1.

p.(Asp125Thrfs*30), p.(Tyr118*), p.(Leu580Trpfs*16) and p.(Glu504Serfs*3) - all variants were absent from gnomADv4.1
Sources: Other; to: 4 unrelated probands presented with congenital myopathy with facial weakness and ocular involvement. All individuals had presence of 4 different LoF variants identified in JPH1.

p.(Asp125Thrfs*30), p.(Tyr118*), p.(Leu580Trpfs*16) and p.(Glu504Serfs*3) - all variants were absent from gnomADv4.1
Sources: Other
Mendeliome v1.1978 JPH1 Sangavi Sivagnanasundram gene: JPH1 was added
gene: JPH1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: JPH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JPH1 were set to 39209426
Phenotypes for gene: JPH1 were set to Congenital myopathy MONDO:0019952
Review for gene: JPH1 was set to GREEN
Added comment: 4 unrelated probands presented with congenital myopathy with prominent facial and ocular involvement. All individuals had presence of 4 different LoF variants identified in JPH1.

p.(Asp125Thrfs*30), p.(Tyr118*), p.(Leu580Trpfs*16) and p.(Glu504Serfs*3) - all variants were absent from gnomADv4.1
Sources: Other
Mendeliome v1.1978 PLEC Zornitza Stark Phenotypes for gene: PLEC were changed from ?Epidermolysis bullosa simplex with nail dystrophy, MIM# 616487; Epidermolysis bullosa simplex with muscular dystrophy, MIM# 226670; Epidermolysis bullosa simplex with pyloric atresia, MIM# 612138; Epidermolysis bullosa simplex, Ogna type MIM#131950; Muscular dystrophy, limb-girdle, autosomal recessive 17, MIM# 613723 to Epidermolysis bullosa simplex with nail dystrophy, MIM# 616487; Epidermolysis bullosa simplex with muscular dystrophy, MIM# 226670; Epidermolysis bullosa simplex with pyloric atresia, MIM# 612138; Epidermolysis bullosa simplex, Ogna type MIM#131950; Muscular dystrophy, limb-girdle, autosomal recessive 17, MIM# 613723; Progressive familial intrahepatic cholestasis, MONDO:0015762, PLEC-related
Mendeliome v1.1977 PLEC Zornitza Stark Publications for gene: PLEC were set to 22144912
Mendeliome v1.1976 PLEC Zornitza Stark reviewed gene: PLEC: Rating: AMBER; Mode of pathogenicity: None; Publications: 39168815; Phenotypes: Progressive familial intrahepatic cholestasis, MONDO:0015762, PLEC-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.244 PLEC Zornitza Stark Marked gene: PLEC as ready
Cholestasis v0.244 PLEC Zornitza Stark Gene: plec has been classified as Amber List (Moderate Evidence).
Cholestasis v0.244 PLEC Zornitza Stark Classified gene: PLEC as Amber List (moderate evidence)
Cholestasis v0.244 PLEC Zornitza Stark Gene: plec has been classified as Amber List (Moderate Evidence).
Cholestasis v0.243 PLEC Zornitza Stark gene: PLEC was added
gene: PLEC was added to Cholestasis. Sources: Literature
Mode of inheritance for gene: PLEC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLEC were set to 39168815
Phenotypes for gene: PLEC were set to Progressive familial intrahepatic cholestasis, MONDO:0015762, PLEC-related
Review for gene: PLEC was set to AMBER
Added comment: Four individuals reported with PFIC and bi-allelic variants in PLEC (one pair of sibs, and two other unrelated infants). However, limited functional data and several of the variants are missense.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6123 BICRA Mark Cleghorn reviewed gene: BICRA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coffin-Siris syndrome-12, MIM#619325; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1976 SF3B1 Mark Cleghorn gene: SF3B1 was added
gene: SF3B1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: SF3B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SF3B1 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: SF3B1 were set to unknown
Review for gene: SF3B1 was set to AMBER
Added comment: SF3B1
Delphine Bernard, University of Brest
ESHG talk 2/6/24, unpublished

De novo germline SF3B1 variants, proposed spliceosomopathy/NDD gene

SF3B1 is an RNA binding protein that stabilizes the U2 snRNP complex at branchpoint sequences
Somatic SF3B1 missense commonly occur in haematological malignancy (K700E recurrent)

25 patients with syndromic NDD + de novo heterozygous rare SF3B1 variants identified on WES, genematcher
13 missense (incl recurrent xxx and xxx) within HEAT domain
5 nonsense
4 splicing
1 frameshift

Patients w missense variants may have more severe phenotype incl mircocepahly, palate anomalies, cerebral anomalies, GI/cardiac anomalies

Cellular models of missense variants: erythroleukaemia K562, HEK293T
Suggest missense variants do not cause loss of function, but increase exon skipping and alternative 3’ splice site use
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6123 SF3B1 Mark Cleghorn gene: SF3B1 was added
gene: SF3B1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: SF3B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SF3B1 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: SF3B1 were set to unknown
Review for gene: SF3B1 was set to AMBER
Added comment: SF3B1
Delphine Bernard, University of Brest
ESHG talk 2/6/24, unpublished

De novo germline SF3B1 variants, proposed spliceosomopathy/NDD gene

SF3B1 is an RNA binding protein that stabilizes the U2 snRNP complex at branchpoint sequences
Somatic SF3B1 missense commonly occur in haematological malignancy (K700E recurrent)

25 patients with syndromic NDD + de novo heterozygous rare SF3B1 variants identified on WES, genematcher
13 missense (incl recurrent xxx and xxx) within HEAT domain
5 nonsense
4 splicing
1 frameshift

Patients w missense variants may have more severe phenotype incl mircocepahly, palate anomalies, cerebral anomalies, GI/cardiac anomalies

Cellular models of missense variants: erythroluekaemia K562, HEK293T
Suggest missense variants do not cause loss of function, but increase exon skipping and alternative 3’ splice sites
Sources: Other
Cataract v0.369 GBF1 Ain Roesley Marked gene: GBF1 as ready
Cataract v0.369 GBF1 Ain Roesley Gene: gbf1 has been classified as Red List (Low Evidence).
Cataract v0.369 GBF1 Ain Roesley gene: GBF1 was added
gene: GBF1 was added to Cataract. Sources: Literature
Mode of inheritance for gene: GBF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GBF1 were set to 39110251
Phenotypes for gene: GBF1 were set to autosomal dominant cataract MONDO:0022672, GBF1-related
Penetrance for gene: GBF1 were set to Complete
Review for gene: GBF1 was set to RED
gene: GBF1 was marked as current diagnostic
Added comment: 1 missense in a multi-generational family.

however, this variant has 98 hets on gnomad v4 and low conservation (changes in 2 mammals and reptiles).

Using the human lens epithelium (HLE) cell line, we found that the p.T1287I mutation reduced GBF1 protein levels. Knockdown of endogenous GBF1 activated the unfolded protein response and enhanced autophagy, as well as increasing XBP1s protein levels and decreasing p-JNK1 protein levels. Heterozygous Gbf1 knockout (Gbf1+/-) mice also exhibited cataract malformation, while their littermate wild-type (Gbf1+/+) mice did not.
Sources: Literature
Mendeliome v1.1976 GBF1 Ain Roesley reviewed gene: GBF1: Rating: RED; Mode of pathogenicity: None; Publications: 39110251; Phenotypes: autosomal dominant cataract MONDO:0022672, GBF1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.1976 TLN1 Ain Roesley reviewed gene: TLN1: Rating: AMBER; Mode of pathogenicity: None; Publications: 39163585; Phenotypes: idiopathic spontaneous coronary artery dissection MONDO:0007385; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Prepair 1000+ v1.258 LGI4 Andrew Coventry reviewed gene: LGI4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28318499 16341215 31513940; Phenotypes: Arthrogryposis multiplex congenita 1, neurogenic, with myelin defect MIM#617468; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.149 COQ8B Bryony Thompson Marked gene: COQ8B as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.149 COQ8B Bryony Thompson Gene: coq8b has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.149 COQ8B Bryony Thompson Classified gene: COQ8B as Green List (high evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.149 COQ8B Bryony Thompson Gene: coq8b has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.148 COQ8B Bryony Thompson gene: COQ8B was added
gene: COQ8B was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: Literature
Mode of inheritance for gene: COQ8B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ8B were set to 39226897; 25967120
Phenotypes for gene: COQ8B were set to Retinitis pigmentosa MONDO:0019200
Review for gene: COQ8B was set to GREEN
gene: COQ8B was marked as current diagnostic
Added comment: PMID: 39226897 - 5 individuals from 4 unrelated families with non-syndromic RP (normal renal function) and COQ8B chet variants (5 different variants). In vitro functional assays of the variant demonstrated a significant decrease in ligand-protein interaction compared to the wild type.
PMID: 25967120 - 1 case with a homozygous truncating variant reported with FSGS and RP
Sources: Literature
Mendeliome v1.1976 COQ8B Bryony Thompson reviewed gene: COQ8B: Rating: GREEN; Mode of pathogenicity: None; Publications: 39226897, 25967120; Phenotypes: Retinitis pigmentosa MONDO:0019200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.258 LAMB1 Andrew Coventry reviewed gene: LAMB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23472759 25925986 29888467 25925986 32548278 34606115 32548278 34606115; Phenotypes: Lissencephaly 5 MIM#615191; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.258 KRT85 Andrew Coventry reviewed gene: KRT85: Rating: AMBER; Mode of pathogenicity: None; Publications: 16525032 19865094 31273852 37178037; Phenotypes: Ectodermal dysplasia 4, hair/nail type MIM#602032; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.258 JAK3 Andrew Coventry reviewed gene: JAK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 14615376 11668610 7481767 7481769 9354668 7659163 7481768 30032486 9753072; Phenotypes: Severe combined immunodeficiency, autosomal recessive, T-negative/B-positive type MIM#600802; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.258 ITGB2 Andrew Coventry reviewed gene: ITGB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 1968911 1694220 33957747 32279896 31374327; Phenotypes: Leukocyte adhesion deficiency MIM#116920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.258 ICOS Andrew Coventry reviewed gene: ICOS: Rating: GREEN; Mode of pathogenicity: None; Publications: 12577056 15507387 19380800 28861081 31858365 11343122 16982935 8438047; Phenotypes: Immunodeficiency, common variable, 1 MIM#607594; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.258 COL4A4 Kate Scarff reviewed gene: COL4A4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301386; Phenotypes: Alport syndrome 2, autosomal recessive MIM# 203780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1976 C12orf66 Mark Cleghorn gene: C12orf66 was added
gene: C12orf66 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: C12orf66 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: C12orf66 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: C12orf66 were set to unknown
Review for gene: C12orf66 was set to AMBER
Added comment: KICS2 (previously known as C12ORF66)
Rebecca Buchert, Universitatklinikum Tubingen
ESHG talk 2/6/24, unpublished

Proposed ID + epilepsy gene

8 families w 11 affected individuals
Phenotypes: 11/11 ID, 9/11 epilepsy, 3/11 hearing impairment
3/8 homozygous missense variants (p.Asp296Glu, p.Tyr393Cys, p.Tyr393Cys), all highly conserved
1/8 compound het PTC (p.Lys262*) with 1.1Mb deletion
4/8 homozygous PTC (p.Glu3*, p.Gly79Valfs*18, p.Gly79Valfs*18, p.Lys260Asnfs*18)

Gene appears to be involved in mTOR pathway, and cilia function
mTORC1 activity in CRISPR-HEK293T cells – reduced activity in cells w variants above

Zebrafish model: otolith defects, ciliary dysfunction
?not clear that this truly mimics phenotype observed in patient cohort described
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6123 C12orf66 Mark Cleghorn gene: C12orf66 was added
gene: C12orf66 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: C12orf66 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: C12orf66 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: C12orf66 were set to unknown
Review for gene: C12orf66 was set to AMBER
Added comment: KICS2 (previously known as C12ORF66)
Rebecca Buchert, Universitatklinikum Tubingen
ESHG talk 2/6/24, unpublished

Proposed ID + epilepsy gene

8 families w 11 affected individuals
Phenotypes: 11/11 ID, 9/11 epilepsy, 3/11 hearing impairment
3/8 homozygous missense variants (p.Asp296Glu, p.Tyr393Cys, p.Tyr393Cys), all highly conserved
1/8 compound het PTC (p.Lys262*) with 1.1Mb deletion
4/8 homozygous PTC (p.Glu3*, p.Gly79Valfs*18, p.Gly79Valfs*18, p.Lys260Asnfs*18)

Gene appears to be involved in mTOR pathway, and cilia function
mTORC1 activity in CRISPR-HEK293T cells – reduced activity in cells w variants above

Zebrafish model: otolith defects, ciliary dysfunction
?not clear if truly mimics phenotype observed in patient cohort described
Sources: Other
Prepair 1000+ v1.258 EPM2A Lilian Downie Marked gene: EPM2A as ready
Prepair 1000+ v1.258 EPM2A Lilian Downie Gene: epm2a has been classified as Green List (High Evidence).
Mendeliome v1.1976 MYBBP1A Zornitza Stark Marked gene: MYBBP1A as ready
Mendeliome v1.1976 MYBBP1A Zornitza Stark Gene: mybbp1a has been classified as Green List (High Evidence).
Mendeliome v1.1976 MYBBP1A Zornitza Stark Classified gene: MYBBP1A as Green List (high evidence)
Mendeliome v1.1976 MYBBP1A Zornitza Stark Gene: mybbp1a has been classified as Green List (High Evidence).
Mendeliome v1.1975 MYBBP1A Zornitza Stark gene: MYBBP1A was added
gene: MYBBP1A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MYBBP1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYBBP1A were set to 39191491; 28425981
Phenotypes for gene: MYBBP1A were set to Hydrops fetalis, MONDO:0015193, MYBBP1A-related
Review for gene: MYBBP1A was set to GREEN
Added comment: Three unrelated fetuses with bi-allelic variants in this gene and severe hydrops.
Sources: Literature
Fetal anomalies v1.267 MYBBP1A Zornitza Stark Marked gene: MYBBP1A as ready
Fetal anomalies v1.267 MYBBP1A Zornitza Stark Gene: mybbp1a has been classified as Green List (High Evidence).
Fetal anomalies v1.267 MYBBP1A Zornitza Stark Classified gene: MYBBP1A as Green List (high evidence)
Fetal anomalies v1.267 MYBBP1A Zornitza Stark Gene: mybbp1a has been classified as Green List (High Evidence).
Prepair 1000+ v1.258 EPM2A Lilian Downie Publications for gene: EPM2A were set to 9771710 9931343 11175283 12019207 12560877 14722920; 30947044; 22036712; 16311711; 28818698
Fetal anomalies v1.266 MYBBP1A Zornitza Stark gene: MYBBP1A was added
gene: MYBBP1A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MYBBP1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYBBP1A were set to 39191491; 28425981
Phenotypes for gene: MYBBP1A were set to Hydrops fetalis, MONDO:0015193, MYBBP1A-related
Review for gene: MYBBP1A was set to GREEN
Added comment: Three unrelated fetuses with bi-allelic variants in this gene and severe hydrops.
Sources: Literature
Hydrops fetalis v0.320 MYBBP1A Zornitza Stark Marked gene: MYBBP1A as ready
Hydrops fetalis v0.320 MYBBP1A Zornitza Stark Gene: mybbp1a has been classified as Green List (High Evidence).
Hydrops fetalis v0.320 MYBBP1A Zornitza Stark Classified gene: MYBBP1A as Green List (high evidence)
Hydrops fetalis v0.320 MYBBP1A Zornitza Stark Gene: mybbp1a has been classified as Green List (High Evidence).
Prepair 1000+ v1.257 EPM2A Lilian Downie Publications for gene: EPM2A were set to
Hydrops fetalis v0.319 MYBBP1A Zornitza Stark Classified gene: MYBBP1A as Green List (high evidence)
Hydrops fetalis v0.319 MYBBP1A Zornitza Stark Gene: mybbp1a has been classified as Green List (High Evidence).
Prepair 1000+ v1.256 FREM1 Lilian Downie Marked gene: FREM1 as ready
Prepair 1000+ v1.256 FREM1 Lilian Downie Added comment: Comment when marking as ready: 2 AR phenotypes with this gene - have not been assessed by ClinGen yet but appear to be spectrum of the same condition.
Prepair 1000+ v1.256 FREM1 Lilian Downie Gene: frem1 has been classified as Green List (High Evidence).
Hydrops fetalis v0.318 MYBBP1A Zornitza Stark gene: MYBBP1A was added
gene: MYBBP1A was added to Hydrops fetalis. Sources: Literature
Mode of inheritance for gene: MYBBP1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYBBP1A were set to 39191491; 28425981
Phenotypes for gene: MYBBP1A were set to Hydrops fetalis, MONDO:0015193, MYBBP1A-related
Review for gene: MYBBP1A was set to GREEN
Added comment: Three unrelated fetuses with bi-allelic variants in this gene and severe hydrops.
Sources: Literature
Prepair 1000+ v1.256 FREM1 Lilian Downie Phenotypes for gene: FREM1 were changed from Bifid nose with or without anorectal and renal anomalies, 608980 (3) to Manitoba oculotrichoanal syndrome MIM# 248450; Bifid nose with or without anorectal and renal anomalies, MIM# 608980
Prepair 1000+ v1.255 FREM1 Lilian Downie Publications for gene: FREM1 were set to 32016392; 21931569; 21507892; 19732862; 20301721; 28111185; 19732862
Prepair 1000+ v1.254 FREM1 Lilian Downie Publications for gene: FREM1 were set to
Polymicrogyria and Schizencephaly v0.192 CEP83 Zornitza Stark Marked gene: CEP83 as ready
Polymicrogyria and Schizencephaly v0.192 CEP83 Zornitza Stark Gene: cep83 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.253 FTO Lilian Downie Marked gene: FTO as ready
Prepair 1000+ v1.253 FTO Lilian Downie Added comment: Comment when marking as ready: Growth retardation, developmental delay, and facial dysmorphism (GDFD) is an autosomal recessive multiple congenital anomaly syndrome characterized by severe psychomotor retardation, poor overall growth, and dysmorphic facial features. Additional features may include cardiac malformations and deafness
Prepair 1000+ v1.253 FTO Lilian Downie Gene: fto has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.192 CEP83 Zornitza Stark gene: CEP83 was added
gene: CEP83 was added to Polymicrogyria and Schizencephaly. Sources: Literature
Mode of inheritance for gene: CEP83 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP83 were set to 39219159
Phenotypes for gene: CEP83 were set to Nephronophthisis 18, MIM# 615862
Review for gene: CEP83 was set to RED
Added comment: Single individual reported with nephronophthisis and PMG and ID. Compound het variants in CEP83.
Sources: Literature
Prepair 1000+ v1.253 FTO Lilian Downie Publications for gene: FTO were set to
Prepair 1000+ v1.252 KCNJ11 Shakira Heerah reviewed gene: KCNJ11: Rating: GREEN; Mode of pathogenicity: None; Publications: 23345197, 32252216, 9356020; Phenotypes: Hyperinsulinemic hypoglycemia, familial, 2, 601820 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.252 FTO Lilian Downie Phenotypes for gene: FTO were changed from Growth retardation, developmental delay, coarse facies, and early death, 612938 (3) to Growth retardation, developmental delay, facial dysmorphism MIM#612938
Prepair 1000+ v1.251 COL17A1 Lilian Downie Marked gene: COL17A1 as ready
Prepair 1000+ v1.251 COL17A1 Lilian Downie Gene: col17a1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.251 COL17A1 Lilian Downie Phenotypes for gene: COL17A1 were changed from Epidermolysis bullosa, junctional, non-Herlitz type, 226650 (3) to Epidermolysis bullosa, junctional 4, intermediate, MIM# 619787
Prepair 1000+ v1.250 COL17A1 Lilian Downie Publications for gene: COL17A1 were set to
Prepair 1000+ v1.249 GPC6 Lilian Downie Marked gene: GPC6 as ready
Prepair 1000+ v1.249 GPC6 Lilian Downie Gene: gpc6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.249 GPC6 Lilian Downie Publications for gene: GPC6 were set to
Mendeliome v1.1974 ATP6V1C1 Ain Roesley edited their review of gene: ATP6V1C1: Changed phenotypes: neurodevelopmental disorder MONDO:0700092, ATP6V1C1-related
Mendeliome v1.1974 ATP6V1C1 Ain Roesley gene: ATP6V1C1 was added
gene: ATP6V1C1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP6V1C1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP6V1C1 were set to 39210597
Review for gene: ATP6V1C1 was set to AMBER
gene: ATP6V1C1 was marked as current diagnostic
Added comment: 1x de novo missense p.Glu289Lys (absent in v4 gnomad). Manual inspection of IGV found the dad was mosaic 7% VAF and he shared some of the clinical features (minor digit anomalies).

Some functional studies using patient fibroblasts were performed, demonstrating similar effects as known pathogenic variants in ATP6V1B2.
- lysosomal morphology
- autophagic flux dysregulation
- increased acidification of lysosome

borderline red/amber
Sources: Literature
Prepair 1000+ v1.248 GPC6 Andrew Coventry reviewed gene: GPC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 19481194 32655339 37353964; Phenotypes: Omodysplasia 1 MIM#258315; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.248 COL17A1 Kate Scarff reviewed gene: COL17A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301304, 21357940; Phenotypes: Epidermolysis bullosa, junctional 4, intermediate, MIM# 619787; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1973 REPS2 Mark Cleghorn gene: REPS2 was added
gene: REPS2 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: REPS2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: REPS2 were set to complex neurodevelopmental disorder MONDO:0100038; Cerebral palsy HP:0100021
Penetrance for gene: REPS2 were set to unknown
Review for gene: REPS2 was set to AMBER
Added comment: REPS2
Hao Hu, Guangzhou Women and Children’s MC
ESHG talk 1/6/24, unpublished

Proposed X-linked cerebral palsy + NDD gene

4 unrelated males with predicted deleterious hemizygous REPS2 variants, 2 PTC, 2 missense. 2 de novo, 2 maternally inherited
Phenotypes: 2 w CP + moderate ID/ASD, 2 w NDD NOS
Variants described:
c.1050_1052delGAA;p.K351del
c.1040T>C; p.I347T
c.962C>G; p.S321C
c.1736delA; p.N579Tfs*17

In vitro assay of above 4 variants suggest reduced REPS2 protein stability
Zebrafish model: REPS2 expressed in neuronal cells, REPS2 knock down have reduced motor activity and abN neuronal morphology
Mouse model hemizygous w one of above variants (not specified): reduced performance in cognitive tasks, abnormal neuronal migration pattern on post mortem examination
Mechanism may relate to dopamine signalling?
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6123 REPS2 Mark Cleghorn gene: REPS2 was added
gene: REPS2 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: REPS2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: REPS2 were set to complex neurodevelopmental disorder MONDO:0100038; Cerebral palsy HP:0100021
Penetrance for gene: REPS2 were set to unknown
Review for gene: REPS2 was set to AMBER
Added comment: REPS2
Hao Hu, Guangzhou Women and Children’s MC
ESHG talk 1/6/24, unpublished

Proposed X-linked cerebral palsy + NDD gene

4 unrelated males with predicted deleterious hemizygous REPS2 variants, 2 PTC, 2 missense. 2 de novo, 2 maternally inherited
Phenotypes: 2 w CP + moderate ID/ASD, 2 w NDD NOS
Variants described:
c.1050_1052delGAA;p.K351del
c.1040T>C; p.I347T
c.962C>G; p.S321C
c.1736delA; p.N579Tfs*17

In vitro assay of above 4 variants suggest reduced REPS2 protein stability
Zebrafish model: REPS2 expressed in neuronal cells, REPS2 knock down have reduced motor activity and abN neuronal morphology
Mouse model hemizygous w one of above variants (not specified): reduced performance in cognitive tasks, abnormal neuronal migration pattern on post mortem examination
Mechanism may relate to dopamine signalling?
Sources: Other
Cerebral Palsy v1.367 REPS2 Mark Cleghorn gene: REPS2 was added
gene: REPS2 was added to Cerebral Palsy. Sources: Other
Mode of inheritance for gene: REPS2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: REPS2 were set to complex neurodevelopmental disorder MONDO:0100038; Cerebral palsy HP:0100021
Penetrance for gene: REPS2 were set to unknown
Review for gene: REPS2 was set to AMBER
Added comment: REPS2
Hao Hu, Guangzhou Women and Children’s MC
ESHG talk 1/6/24, unpublished

Proposed X-linked cerebral palsy + NDD gene

4 unrelated males with predicted deleterious hemizygous REPS2 variants, 2 PTC, 2 missense. 2 de novo, 2 maternally inherited
Phenotypes: 2 w CP + moderate ID/ASD, 2 w NDD NOS
Variants described:
c.1050_1052delGAA;p.K351del
c.1040T>C; p.I347T
c.962C>G; p.S321C
c.1736delA; p.N579Tfs*17

In vitro assay of above 4 variants suggest reduced REPS2 protein stability
Zebrafish model: REPS2 expressed in neuronal cells, REPS2 knock down have reduced motor activity and abN neuronal morphology
Mouse model hemizygous w one of above variants (not specified): reduced performance in cognitive tasks, abnormal neuronal migration pattern on post mortem examination
Mechanism may relate to dopamine signalling?
Sources: Other
Mendeliome v1.1973 TTL Mark Cleghorn gene: TTL was added
gene: TTL was added to Mendeliome. Sources: Other
Mode of inheritance for gene: TTL was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTL were set to complex neurodevelopmental disorderMONDO:0100038
Added comment: TTL
Valentina Serpieri, University of Pavia
ESHG talk 1/6/24

FAM1 (Italy)
2 affected sisters born to consanguineous Pakistani parents
GDD, spastic tetraparesis, optic atrophy, brain anomalies resembling tubulinopathies (dysplasia of corpus callosum, basal ganglia, brainstem)
WES: homozygous TTL:c.1013G>A; p.Cys338Tyr in both affected sisters

Via genematcher
5 more families (9 individuals) w similar phenotypes and biallelic variants in TTL

FAM2 (Egypt): homozygous p.Arg46Pro
FAM3 (Egypt): homozygous p.Arg46Pro
FAM4 (Australia): homozygous p.Gln183Arg
FAM5 (France): homozygous p.Trp147*
FAM6 (Saudi Arabia): homozygous p.His243Tyr

TTL KO mice: death soon after birth, no overt malformations, but defects in organisation of cerebral layers

Functional work on patient fibroblasts
FAM1 – reduced quantity of TTL protein compared to control on Western blot, decreased function of TTL protein (increase in detyrosinated tubulin) compared to controls – infer LoF as mechanism
FAM3 – mentioned but no details
FAM4– mentioned but no details
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6123 TTL Mark Cleghorn gene: TTL was added
gene: TTL was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: TTL was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTL were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: TTL was set to AMBER
Added comment: TTL
Valentina Serpieri, University of Pavia
ESHG talk 1/6/24

FAM1 (Italy)
2 affected sisters born to consanguineous Pakistani parents
GDD, spastic tetraparesis, optic atrophy, brain anomalies resembling tubulinopathies (dysplasia of corpus callosum, basal ganglia, brainstem)
WES: homozygous TTL:c.1013G>A; p.Cys338Tyr in both affected sisters

Via genematcher
5 more families (9 individuals) w similar phenotypes and biallelic variants in TTL

FAM2 (Egypt): homozygous p.Arg46Pro
FAM3 (Egypt): homozygous p.Arg46Pro
FAM4 (Australia): homozygous p.Gln183Arg
FAM5 (France): homozygous p.Trp147*
FAM6 (Saudi Arabia): homozygous p.His243Tyr

TTL KO mice: death soon after birth, no overt malformations, but defects in organisation of cerebral layers

Functional work on patient fibroblasts
FAM1 – reduced quantity of TTL protein compared to control on Western blot, decreased function of TTL protein (increase in detyrosinated tubulin) compared to controls – infer LoF as mechanism
FAM3 – mentioned but no details
FAM4– mentioned but no details
Sources: Other
Tubulinopathies v1.1 TTL Mark Cleghorn gene: TTL was added
gene: TTL was added to Tubulinopathies. Sources: Other
Mode of inheritance for gene: TTL was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTL were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: TTL were set to unknown
Review for gene: TTL was set to AMBER
Added comment: TTL
Valentina Serpieri, University of Pavia
ESHG talk 1/6/24

FAM1 (Italy)
2 affected sisters born to consanguineous Pakistani parents
GDD, spastic tetraparesis, optic atrophy, brain anomalies resembling tubulinopathies (dysplasia of corpus callosum, basal ganglia, brainstem)
WES: homozygous TTL:c.1013G>A; p.Cys338Tyr in both affected sisters

Via genematcher
5 more families (9 individuals) w similar phenotypes and biallelic variants in TTL

FAM2 (Egypt): homozygous p.Arg46Pro
FAM3 (Egypt): homozygous p.Arg46Pro
FAM4 (Australia): homozygous p.Gln183Arg
FAM5 (France): homozygous p.Trp147*
FAM6 (Saudi Arabia): homozygous p.His243Tyr

TTL KO mice: death soon after birth, no overt malformations, but defects in organisation of cerebral layers

Functional work on patient fibroblasts
FAM1 – reduced quantity of TTL protein compared to control on Western blot, decreased function of TTL protein (increase in detyrosinated tubulin) compared to controls – infer LoF as mechanism
FAM3 – mentioned but no details
FAM4– mentioned but no details
Sources: Other
Prepair 1000+ v1.248 FTO Marta Cifuentes Ochoa reviewed gene: FTO: Rating: GREEN; Mode of pathogenicity: None; Publications: 19234441, 19559399, 26378117, 26697951, 26378117, 26740239; Phenotypes: Growth retardation, developmental delay, facial dysmorphism MIM#612938, lethal polymalformative syndrome, Boissel type MONDO:0013050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.248 FREM1 Marta Cifuentes Ochoa reviewed gene: FREM1: Rating: ; Mode of pathogenicity: None; Publications: 32016392, 21931569, 21507892, 19732862, 20301721, 28111185, 19732862; Phenotypes: Manitoba oculotrichoanal syndrome MIM# 248450, Bifid nose with or without anorectal and renal anomalies, MIM# 608980, oculotrichoanal syndrome MONDO:0009560, BNAR syndrome MONDO:0012165; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.248 F2 Marta Cifuentes Ochoa changed review comment from: Prothrombin deficiency type I, known as true prothrombin deficiency or 'hypoprothrombinemia,' is defined as plasma levels of prothrombin being less than 10% of normal with a concomitant decrease in activity. These patients have severe bleeding from birth, including umbilical cord hemorrhage, hematomas, ecchymoses, hematuria, mucosal bleeding, hemarthroses, intracranial bleeding, gastrointestinal bleeding, and menorrhagia.

HGNC approved symbol/name: F2
Is the phenotype(s) severe and onset <18yo ? Y
Known technical challenges? N
Gene reported in >3 independent families

Type II deficiency, known as 'dysprothrombinemia,' is characterized by normal or low-normal synthesis of a dysfunctional protein; to: Prothrombin deficiency type I, known as true prothrombin deficiency or 'hypoprothrombinemia,' is defined as plasma levels of prothrombin being less than 10% of normal with a concomitant decrease in activity. These patients have severe bleeding from birth, including umbilical cord hemorrhage, hematomas, ecchymoses, hematuria, mucosal bleeding, hemarthroses, intracranial bleeding, gastrointestinal bleeding, and menorrhagia.

HGNC approved symbol/name: F2
Is the phenotype(s) severe and onset <18yo ? Y
Known technical challenges? N
Gene reported in >3 independent families

Type II deficiency, known as 'dysprothrombinemia,' is characterized by normal or low-normal synthesis of a dysfunctional protein

AD forms and multifactorial conditions described for this gene not reportable in screening context
Prepair 1000+ v1.248 EPM2A Marta Cifuentes Ochoa reviewed gene: EPM2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 9771710 9931343 11175283 12019207 12560877 14722920, 30947044, 22036712, 16311711, 28818698; Phenotypes: Myoclonic epilepsy of Lafora 1 MIM#254780, MONDO:0958199; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.248 F2 Marta Cifuentes Ochoa reviewed gene: F2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23852823; Phenotypes: Hypoprothrombinemia MIM# 613679, congenital prothrombin deficiency MONDO:0013361; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.248 CBS Marta Cifuentes Ochoa reviewed gene: CBS: Rating: AMBER; Mode of pathogenicity: None; Publications: 7506602, 10338090, 7967489, 27778219; Phenotypes: Homocystinuria, B6-responsive and nonresponsive types, Thrombosis, hyperhomocysteinemic MIM#236200, classic homocystinuria, MONDO:0009352; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.248 GNE Andrew Coventry changed review comment from: Nonaka myopathy - Well established gene disease relationship. However, age of onset of myopathy reported to usually occur between age 20 and 40. Marginal for childhood onset condition.

Thrombocytopenia - well reported association of affected individuals experiencing bleeding episodes that commence from neonatal to early childhood. Myopathy variably reported in those affected - possibly due to young age of individuals presenting with bleeding symptoms. Myopathy, when reported, occurs at similar age of onset to Nonaka. Publication (25257349) indicates myopathy onset in affected sibs at mid-late teens. Also reported renal complications at age 7. Mouse model for GNE knockout shows renal involvement (PMID: 17549255). Condition reported to have caused cerebral haemorrhages in neonatal period (PMID:29941673). Unsure if phenotypic variability of condition, and isolated bleeding phenotype (as in ClinGen) suitable or adequate for screening context.; to: Nonaka myopathy - Well established gene disease relationship. However, age of onset of myopathy reported to usually occur between age 20 and 40. Myopathy then progresses, usually over ~10 year period to then require wheelchair assistance for mobility. Severe condition but onset is marginal for childhood onset screening context.

Thrombocytopenia - well reported association of affected individuals experiencing bleeding episodes that commence from neonatal to early childhood. Myopathy variably reported in those affected - possibly due to young age of individuals presenting with bleeding symptoms. Myopathy, when reported, occurs at similar age of onset to Nonaka. Publication (25257349) indicates myopathy onset in affected sibs at mid-late teens. Also reported renal complications at age 7. Mouse model for GNE knockout shows renal involvement (PMID: 17549255). Condition reported to have caused cerebral haemorrhages in neonatal period (PMID:29941673). Unsure if phenotypic variability of condition, and isolated bleeding phenotype (as in ClinGen) suitable or adequate for screening context.
Prepair 1000+ v1.248 GNE Andrew Coventry reviewed gene: GNE: Rating: AMBER; Mode of pathogenicity: None; Publications: 25257349 17549255 25061177 30171045 29941673; Phenotypes: Nonaka myopathy MIM#605820, Thrombocytopenia 12 with or without myopathy MIM#620757; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.248 GNAT2 Andrew Coventry reviewed gene: GNAT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32203983 17251445 15557429 23580486 31058429 12077706 12205108 27718025 21107338 28041643; Phenotypes: Achromatopsia 4 MIM#613856; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.367 TBCK Clare van Eyk gene: TBCK was added
gene: TBCK was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TBCK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBCK were set to PMID: 39213953
Phenotypes for gene: TBCK were set to Hypotonia, infantiale with psychomotor retardation and characteristic facies 3, MIM#616900
Review for gene: TBCK was set to RED
Added comment: Single individual with biallelic variants in TBCK reported in a monocentric cohort study (PMID: 39213953). Clinically, hypotonic CP, DD, muscle weakness, hyperlaxicity, epilepsy.
Sources: Literature
Cerebral Palsy v1.367 TBCD Clare van Eyk gene: TBCD was added
gene: TBCD was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TBCD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBCD were set to PMID: 39213953
Phenotypes for gene: TBCD were set to Encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum MIM#617193
Review for gene: TBCD was set to RED
Added comment: Single individual with homozygous missense variant reported in a monocentric cohort study (PMID: 39213953). Clinically, spastic quadriplegia, DD, ID, regression, focal epilepsy, cerebral atrophy, atrophy corpus callosum and brainstem. Initially diagnosed with CP.
Sources: Literature
Cerebral Palsy v1.367 RTN4IP1 Clare van Eyk gene: RTN4IP1 was added
gene: RTN4IP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RTN4IP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RTN4IP1 were set to PMID: 39213953
Phenotypes for gene: RTN4IP1 were set to Optic atrophy 10 with or without ataxia, impaired intellectual development, and seizures, MIM#616732
Review for gene: RTN4IP1 was set to RED
Added comment: Single individual with biallelic variants in RTN4IP1 reported in a monocentric cohort study (PMID: 39213953). Clinically, ataxia, axial hypotonia, DD, epilepsy, nystagmus, opticus neuropathy, dysmorphic features.
Sources: Literature
Cerebral Palsy v1.367 COQ4 Clare van Eyk gene: COQ4 was added
gene: COQ4 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: COQ4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ4 were set to PMID: 39213953
Phenotypes for gene: COQ4 were set to Coenzyme Q10 deficiency, primary, MIM#616276; Spastic ataxia 10, autosomal recessive, MIM#620666
Review for gene: COQ4 was set to RED
Added comment: Two individuals with homozygous p.Thr77Ile variant reported in a monocentric cohort study (PMID: 39213953), both with spastic diplegia, DD but one also with hearing loss.
Sources: Literature
Cerebral Palsy v1.367 RNU7-1 Clare van Eyk gene: RNU7-1 was added
gene: RNU7-1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RNU7-1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU7-1 were set to PMID: 39213953
Phenotypes for gene: RNU7-1 were set to Aicardi-Goutières syndrome 9, MIM#619487
Review for gene: RNU7-1 was set to AMBER
Added comment: Two individuals with biallelic LP/P variants in RNU7-1 reported in a monocentric cohort study (PMID: 39213953). Both have recurrent RNU7-1 40_47DEL.

One with spastic quadriplegia, epilepsy, DD, hypomyelination, cerebral atrophy, old ishemic lesions, calcifications on CT.

Other with peripheral hypertonia, axial hypotonia, dystonia, calcifications, PVL, delayed myelination.
Sources: Literature
Cerebral Palsy v1.367 KMT2D Clare van Eyk edited their review of gene: KMT2D: Added comment: Additional individual with de novo splice variant reported in a monocentric cohort study (PMID: 39213953). Clinically, hypotonia, DD, ASD, dysmorphic features. No functional assessment of variant impact.; Changed publications: PMID: 38693247, PMID: 39213953
Cerebral Palsy v1.367 CLN6 Clare van Eyk gene: CLN6 was added
gene: CLN6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CLN6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLN6 were set to PMID: 39213953
Phenotypes for gene: CLN6 were set to Neuronal Ceroid Lipofuscinosis 6, MIM#601780
Review for gene: CLN6 was set to RED
Added comment: Single individual with compound heterozygous LP/P variants in CLN6 reported in a monocentric cohort study (PMID: 39213953). Patient reported to have progressive dystonia, developmental regression, DD, ID, with initial diagnosis of CP.
Sources: Literature
Cerebral Palsy v1.367 SMG8 Clare van Eyk gene: SMG8 was added
gene: SMG8 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SMG8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMG8 were set to PMID: 39213953
Phenotypes for gene: SMG8 were set to Alzahrani-Kuwahara syndrome, MIM#619268
Review for gene: SMG8 was set to RED
Added comment: Single individual with biallelic variants in SMG8 reported in a monocentric CP cohort study (PMID: 39213953). Clinically, spastic CP with DD, ID, peripheral hypertonia, dysmorphic features.
Sources: Literature
Prepair 1000+ v1.248 GLA Shakira Heerah reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: None; Publications: 17224688, 29649853, 26937390, 20301469; Phenotypes: Fabry disease, 301500, (3); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.248 FANCC Shakira Heerah reviewed gene: FANCC: Rating: GREEN; Mode of pathogenicity: None; Publications: 29376519, 31044565, 30792206, 28717661; Phenotypes: Fanconi anemia, complementation group C, 227645 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.367 CHD3 Clare van Eyk edited their review of gene: CHD3: Added comment: Additional individual with de novo missense variant reported in a monocentric cohort study (PMID: 39213953). Clinically, ataxic CP, DD, ID, bilateral widened frontal subarachnoid space.; Changed publications: PMID: 38168508, PMID: 39213953
Cerebral Palsy v1.367 TSEN54 Clare van Eyk gene: TSEN54 was added
gene: TSEN54 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TSEN54 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSEN54 were set to PMID: 39213953
Phenotypes for gene: TSEN54 were set to Pontocerebellar hypoplasia type 2, MIM#277470
Review for gene: TSEN54 was set to RED
Added comment: Two individuals with recurrent homozygous variant reported in a monocentric cohort study (PMID: 39213953). Not clear if they are related.

One with spastic CP, DD, epilepsy, feeding difficulties, behavioral problems, vision problems, pontocerebellar atrophy. Other with spastic CP and axial hypotonia, peripheral hypertonia, DD, ID, cortical visual impairment, pontocerebellar atrophy.
Sources: Literature
Cerebral Palsy v1.367 KCNK9 Clare van Eyk gene: KCNK9 was added
gene: KCNK9 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KCNK9 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: KCNK9 were set to PMID: 39213953
Phenotypes for gene: KCNK9 were set to Birk-Barel syndrome (KCNK9 imprinting syndrome), MIM#612292
Review for gene: KCNK9 was set to RED
Added comment: Single individual with de novo missense variant reported in a monocentric cohort study (PMID: 39213953). Clinically, hypotonic CP, hyperlaxicity, DD, ID.
Sources: Literature
Prepair 1000+ v1.248 GDF5 Andrew Coventry reviewed gene: GDF5: Rating: GREEN; Mode of pathogenicity: None; Publications: 33333243 20683927 33872773; Phenotypes: Acromesomelic dysplasia 2A MIM#200700, Acromesomelic dysplasia 2B MIM#228900, Brachydactyly, type A1, C MIM#615072; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral Palsy v1.367 PIK3CA Clare van Eyk gene: PIK3CA was added
gene: PIK3CA was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PIK3CA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIK3CA were set to PMID: 39213953
Phenotypes for gene: PIK3CA were set to Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic, MIM#602501
Review for gene: PIK3CA was set to RED
Added comment: Single individual with novel de novo in-frame deletion reported in a monocentric cohort study (PMID: 39213953). Clinically hypotonia, hyperlaxity, bilateral polymicrogyria, incomplete inversion hippocampi, prominent cerebellum.
Sources: Literature
Cerebral Palsy v1.367 ERCC8 Clare van Eyk changed review comment from: An additional individual reported with CP and a homozygous frameshift variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.; to: An additional individual reported with CP and a homozygous frameshift variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

Single individual with homozygous splice variant reported in a monocentric cohort study (PMID: 39213953). Clinically, spastic CP with hypertonia, DD, ID, corpus callosum hypoplasia, hyperintensities in the deep white matter.
Cerebral Palsy v1.367 ALDH7A1 Clare van Eyk gene: ALDH7A1 was added
gene: ALDH7A1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ALDH7A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALDH7A1 were set to PMID: 39213953
Phenotypes for gene: ALDH7A1 were set to Epilepsy, pyridoxine-dependent, MIM#266100
Review for gene: ALDH7A1 was set to RED
Added comment: Single individual with compound heterozygous varianta reported in a monocentric cohort study (PMID: 39213953). Clinically, spastic CP with mild hypertonia, ASD, ADHD, epilepsy not reported. Movement disorders, including CP in one case, are reported in one study of young adults with PDE-ALDH7A1 (PMID: 35782612).
Sources: Literature
Cerebral Palsy v1.367 BRAF Clare van Eyk gene: BRAF was added
gene: BRAF was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRAF were set to PMID: 39213953
Phenotypes for gene: BRAF were set to Cardiofaciocutaneous syndrome, MIM#115150
Review for gene: BRAF was set to AMBER
Added comment: Two individuals each with a de novo missense variant reported in a monocentric cohort study (PMID: 39213953).

One with spastic CP with spasticity, hypertonia, ASD, PFO, mild pulmonary artery stenosis, failure to thrive, nystagmus, dysmorphic features.

The other with hypotonic CP with axial and peripheral hypotonia, DD, ID, mild pulmonary artery stenosis, dysmorphic features, hypothyroidism, small subacute subdural bleeding, small intraventricular haemorrhage, small cerebellum.
Sources: Literature
Cerebral Palsy v1.367 TRIT1 Clare van Eyk gene: TRIT1 was added
gene: TRIT1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TRIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIT1 were set to PMID: 39213953
Phenotypes for gene: TRIT1 were set to Combined oxidative phosphorylation deficiency 35, MIM#617873
Review for gene: TRIT1 was set to RED
Added comment: Single individual with compound heterozygous variants (nonsense and missense) reported in a monocentric cohort study (PMID: 39213953). Clinically axial hypotonia, peripheral hypertonia, microcephaly, spastic CP, widened ventricular system, widened subarachnoid space.
Sources: Literature
Prepair 1000+ v1.248 FKTN Andrew Coventry reviewed gene: FKTN: Rating: ; Mode of pathogenicity: None; Publications: 9690476 19017726 20301385 28680109 17036286; Phenotypes: Muscular dystrophy-dystroglycanopathy MONDO:0018276, Cardiomyopathy, dilated, 1X MIM#611615; Mode of inheritance: None
Cerebral Palsy v1.367 KIF5C Clare van Eyk gene: KIF5C was added
gene: KIF5C was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KIF5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF5C were set to PMID: 39213953
Phenotypes for gene: KIF5C were set to Cortical dysplasia, complex, with other brain malformations 2 MIM#615282
Review for gene: KIF5C was set to RED
Added comment: Single individual with de novo missense variant reported in a monocentric cohort study (PMID: 39213953). Clinically spastic diplegia, DD, severe ID, epilepsy, polymicrogyria.
Sources: Literature
Cerebral Palsy v1.367 KIAA1109 Clare van Eyk gene: KIAA1109 was added
gene: KIAA1109 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KIAA1109 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA1109 were set to PMID: 39213953
Phenotypes for gene: KIAA1109 were set to Alkuraya-Kucinskas syndrome, MIM#617822
Review for gene: KIAA1109 was set to RED
Added comment: Single individual with compound heterozygous variants (1 nonsense, 1 missense) reported in a monocentric cohort study (PMID: 39213953). Clinically West syndrome with evolution to Lennox-Gastaut, severe DD, ID, vision problems, microcephaly, feeding difficulties, spasticity, corpus callosum hypoplasia, cerebral atrophy, heterotopia.
Sources: Literature
Cerebral Palsy v1.367 CYFIP2 Clare van Eyk edited their review of gene: CYFIP2: Added comment: Additional individual with de novo missense variant in CYFIP2 reported in a monocentric cohort study (PMID: 39213953). Clinically ID, spastic quadriplegia, ASD.; Changed rating: AMBER; Changed publications: PMID: 38843839, PMID: 39213953
Prepair 1000+ v1.248 FAT4 Andrew Coventry reviewed gene: FAT4: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681106 24913602 24056717 22473091; Phenotypes: Hennekam lymphangiectasia-lymphedema syndrome 2 MIM#616006, Van Maldergem syndrome 2 MIM#615546; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.367 CLCN4 Clare van Eyk edited their review of gene: CLCN4: Added comment: Additional hemizygous male (de novo missense mutation) in monocentric cohort study (PMID: 39213953). Clinically spastic quadriplegia, epilepsy, osteoporosis, cerebral atrophy, corpus callosum hypoplasia.; Changed publications: PMID: 38693247, PMID: 37789889, PMID: 39213953
Cerebral Palsy v1.367 TRIO Clare van Eyk gene: TRIO was added
gene: TRIO was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TRIO was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIO were set to PMID: 39213953
Phenotypes for gene: TRIO were set to Intellectual developmental disorder, autosomal dominant 44, with microcephaly MIM#617061
Review for gene: TRIO was set to RED
Added comment: Single individual with de novo missense variant in TRIO reported in a monocentric cohort study (PMID: 39213953). Clinically spastic quadriplegia, microcephaly, cortical visual impairment, Lennox Gastaut epilepsy, cerebral atrophy, megacisterna magna, aberrant skull morphology.
Sources: Literature
Cerebral Palsy v1.367 EBF3 Clare van Eyk gene: EBF3 was added
gene: EBF3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: EBF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EBF3 were set to PMID: 39213953
Phenotypes for gene: EBF3 were set to Hypotonia, ataxia and delayed development syndrome MIM#617330
Review for gene: EBF3 was set to RED
Added comment: Single individual with de novo missense variant in EBF3 reported in a monocentric cohort study (PMID: 39213953). Clinically DD, ataxia, dysarthria, strabism, cortical visual impairment.
Sources: Literature
Cerebral Palsy v1.367 ZMYND11 Clare van Eyk gene: ZMYND11 was added
gene: ZMYND11 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ZMYND11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMYND11 were set to PMID: 39213953
Phenotypes for gene: ZMYND11 were set to Intellectual developmental disorder 30, MIM#616083
Review for gene: ZMYND11 was set to RED
Added comment: Single individual with novel de novo missense variant and dyskinetic CP with ID, dystonia, peripheral hypertonia and delayed myelination.
Sources: Literature
Prepair 1000+ v1.248 F5 Andrew Coventry reviewed gene: F5: Rating: AMBER; Mode of pathogenicity: None; Publications: 35593819 31121608; Phenotypes: Factor V deficiency MIM#227400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.367 PGAP2 Clare van Eyk gene: PGAP2 was added
gene: PGAP2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PGAP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PGAP2 were set to PMID: 39213953
Phenotypes for gene: PGAP2 were set to Hyperphosphatasia with impaired intellectual development syndrome 3, MIM#614207
Review for gene: PGAP2 was set to RED
Added comment: Single individual with homozygous missense variant and severe DD, epilepsy, axial hypotonia, dyskinetic quadriplegia, feeding difficulties.
Sources: Literature
Cerebral Palsy v1.367 PUM1 Clare van Eyk gene: PUM1 was added
gene: PUM1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PUM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PUM1 were set to PMID: 39213953
Phenotypes for gene: PUM1 were set to Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM#620719; Spinocerebellar ataxia 47, MIM#617931
Review for gene: PUM1 was set to RED
Added comment: Single individual with de novo missense variant in PUM1 reported in a monocentric cohort study (PMID: 39213953). Reported with spastic CP, severe DD, epilepsy, microcephaly, cerebral atrophy, thin corpus callosum.
Sources: Literature
Cerebral Palsy v1.367 IREB2 Clare van Eyk gene: IREB2 was added
gene: IREB2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: IREB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IREB2 were set to PMID: 39213953
Phenotypes for gene: IREB2 were set to Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia, MIM#618451
Review for gene: IREB2 was set to RED
Added comment: Single individual with compound heterozygous LP/P variants in IREB2 and hypotonic quadriplegia, severe DD, microcytic anemia, elevated ferritin, retinal dystrophy.
Sources: Literature
Cerebral Palsy v1.367 FRRS1L Clare van Eyk reviewed gene: FRRS1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528536, 27236917, 39213953; Phenotypes: Developmental and epileptic encephalopathy MIM#616981; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.248 EVC2 Andrew Coventry reviewed gene: EVC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23220543 10700184 33050204; Phenotypes: Ellis-van Creveld syndrome MIM#225500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.248 B3GALNT2 Shakira Heerah reviewed gene: B3GALNT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35338537, 38585583, 23453667, 33290285, 29791932, 29273094, 28688748, 28303321; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 11, 615181 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.248 B3GALNT2 Shakira Heerah Deleted their review
Prepair 1000+ v1.248 B3GALNT2 Shakira Heerah reviewed gene: B3GALNT2: Rating: ; Mode of pathogenicity: None; Publications: 35338537, 38585583, 23453667, 33290285, 29791932, 29273094, 28688748, 28303321; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 11, 615181 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.248 ERBB3 Andrew Coventry reviewed gene: ERBB3: Rating: AMBER; Mode of pathogenicity: None; Publications: 17701904 31752936 33497358 12548738 38009810; Phenotypes: Visceral neuropathy, familial, 1, autosomal recessive MIM#243180, Lethal congenital contractural syndrome 2 MIM#607598; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.248 EIF2B4 Andrew Coventry reviewed gene: EIF2B4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11835386 12707859 18263758 25843247 25761052 30014503 39139316; Phenotypes: Leukoencephalopathy with vanishing white matter 4, with or without ovarian failure MIM#620314; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hyperinsulinism v1.23 GPC3 Ain Roesley gene: GPC3 was added
gene: GPC3 was added to Hyperinsulinism. Sources: Literature
Mode of inheritance for gene: GPC3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GPC3 were set to 20301398
Phenotypes for gene: GPC3 were set to Simpson-Golabi-Behmel syndrome, type 1 MIM#312870
Review for gene: GPC3 was set to RED
gene: GPC3 was marked as current diagnostic
Added comment: from genereviews:

hypoglycemia may be present in the neonatal period; however, hypoglycemia is rare in SGBS1 and is not considered to be a cardinal feature.
Sources: Literature
Hyperinsulinism v1.22 AKT2 Ain Roesley Classified gene: AKT2 as Red List (low evidence)
Hyperinsulinism v1.22 AKT2 Ain Roesley Gene: akt2 has been classified as Red List (Low Evidence).
Hyperinsulinism v1.21 AKT2 Ain Roesley edited their review of gene: AKT2: Changed rating: RED
Hyperinsulinism v1.21 AKT2 Ain Roesley Classified gene: AKT2 as Amber List (moderate evidence)
Hyperinsulinism v1.21 AKT2 Ain Roesley Gene: akt2 has been classified as Amber List (Moderate Evidence).
Hyperinsulinism v1.21 AKT2 Ain Roesley Classified gene: AKT2 as Amber List (moderate evidence)
Hyperinsulinism v1.21 AKT2 Ain Roesley Gene: akt2 has been classified as Amber List (Moderate Evidence).
Hyperinsulinism v1.20 AKT2 Ain Roesley edited their review of gene: AKT2: Changed rating: AMBER; Changed phenotypes: Diabetes mellitus, type II MIM#125853, Hypoinsulinemic hypoglycemia with hemihypertrophy MIM#240900
Hyperinsulinism v1.20 AKT2 Ain Roesley changed review comment from: at least 5x individuals with hypoglycemia and de novo missense

Glu17Lys is a hotspot and GoF as a mechanism of disease
Sources: Literature; to: at least 5x individuals with hypoglycemia and de novo missense

Glu17Lys is a hotspot and GoF as a mechanism of disease

However, undetectable levels of serum insulin and C-peptide

Sources: Literature
Hyperinsulinism v1.20 AKT2 Ain Roesley Classified gene: AKT2 as Green List (high evidence)
Hyperinsulinism v1.20 AKT2 Ain Roesley Gene: akt2 has been classified as Green List (High Evidence).
Hyperinsulinism v1.19 AKT2 Ain Roesley gene: AKT2 was added
gene: AKT2 was added to Hyperinsulinism. Sources: Literature
Mode of inheritance for gene: AKT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AKT2 were set to 21979934; 35602880; 24285683
Phenotypes for gene: AKT2 were set to Diabetes mellitus, type II MIM#125853; Hypoinsulinemic hypoglycemia with hemihypertrophy MIM#240900
Review for gene: AKT2 was set to GREEN
gene: AKT2 was marked as current diagnostic
Added comment: at least 5x individuals with hypoglycemia and de novo missense

Glu17Lys is a hotspot and GoF as a mechanism of disease
Sources: Literature
Mendeliome v1.1973 PLEKHM2 Bryony Thompson Marked gene: PLEKHM2 as ready
Mendeliome v1.1973 PLEKHM2 Bryony Thompson Gene: plekhm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1973 PLEKHM2 Bryony Thompson Classified gene: PLEKHM2 as Amber List (moderate evidence)
Mendeliome v1.1973 PLEKHM2 Bryony Thompson Gene: plekhm2 has been classified as Amber List (Moderate Evidence).
Dilated Cardiomyopathy v1.37 PLEKHM2 Bryony Thompson Marked gene: PLEKHM2 as ready
Dilated Cardiomyopathy v1.37 PLEKHM2 Bryony Thompson Gene: plekhm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1972 PLEKHM2 Bryony Thompson gene: PLEKHM2 was added
gene: PLEKHM2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLEKHM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLEKHM2 were set to 35862026; 26464484; 38942823; 38490981; 37349842
Phenotypes for gene: PLEKHM2 were set to Dilated cardiomyopathy MONDO:0005021
Review for gene: PLEKHM2 was set to AMBER
Added comment: 2 unrelated families reported with DCM and supporting functional evidence
PMID: 35862026 - 21 yo with DCM with bialleic PLEKHM2 variants. Loss PLEKHM2 expression was found in the proband’s myocardial tissue

PMID: 26464484 - a homozygous frameshift variant (p.Lys645AlafsTer12) segregates with early-onset (adolescent) DCM and LVNC in a large consanguineous Bedouin family

PMID: 38942823 - murine model suggests Plekhm2 acts as an autophagy modulator in cardiofibroblasts

PMID: 38490981, 37349842 - supportive PLEKHM2 knockout iPSC-cardiomyocyte models
Sources: Literature
Dilated Cardiomyopathy v1.37 PLEKHM2 Bryony Thompson Classified gene: PLEKHM2 as Amber List (moderate evidence)
Dilated Cardiomyopathy v1.37 PLEKHM2 Bryony Thompson Gene: plekhm2 has been classified as Amber List (Moderate Evidence).
Dilated Cardiomyopathy v1.36 PLEKHM2 Bryony Thompson gene: PLEKHM2 was added
gene: PLEKHM2 was added to Dilated Cardiomyopathy. Sources: Literature
Mode of inheritance for gene: PLEKHM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLEKHM2 were set to 35862026; 26464484; 38942823; 38490981; 37349842
Phenotypes for gene: PLEKHM2 were set to Dilated cardiomyopathy MONDO:0005021
Review for gene: PLEKHM2 was set to AMBER
Added comment: 2 unrelated families reported with DCM and supporting functional evidence
PMID: 35862026 - 21 yo with DCM with bialleic PLEKHM2 variants. Loss PLEKHM2 expression was found in the proband’s myocardial tissue

PMID: 26464484 - a homozygous frameshift variant (p.Lys645AlafsTer12) segregates with early-onset (adolescent) DCM and LVNC in a large consanguineous Bedouin family

PMID: 38942823 - murine model suggests Plekhm2 acts as an autophagy modulator in cardiofibroblasts

PMID: 38490981, 37349842 - supportive PLEKHM2 knockout iPSC-cardiomyocyte models
Sources: Literature
Dilated Cardiomyopathy v1.35 BMP10 Bryony Thompson Marked gene: BMP10 as ready
Dilated Cardiomyopathy v1.35 BMP10 Bryony Thompson Gene: bmp10 has been classified as Red List (Low Evidence).
Dilated Cardiomyopathy v1.35 BMP10 Bryony Thompson gene: BMP10 was added
gene: BMP10 was added to Dilated Cardiomyopathy. Sources: Literature
Mode of inheritance for gene: BMP10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP10 were set to 36673052
Phenotypes for gene: BMP10 were set to Dilated cardiomyopathy MONDO:0005021
Review for gene: BMP10 was set to RED
Added comment: A single family cosegregating NM_014482.3:c.166C > T;p.(Gln56*) with DCM.
Sources: Literature
Dilated Cardiomyopathy v1.34 NKX2-5 Bryony Thompson Publications for gene: NKX2-5 were set to 30354339; 28690296; 25503402; 27855642
Dilated Cardiomyopathy v1.34 NKX2-5 Bryony Thompson Classified gene: NKX2-5 as Green List (high evidence)
Dilated Cardiomyopathy v1.34 NKX2-5 Bryony Thompson Gene: nkx2-5 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.33 NKX2-5 Bryony Thompson reviewed gene: NKX2-5: Rating: GREEN; Mode of pathogenicity: None; Publications: 39018455, 37326999, 25503402, 23661673, 27855642, 30354339; Phenotypes: Dilated cardiomyopathy MONDO:0005021; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6123 DHTKD1 Sumudu Perera reviewed gene: DHTKD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23141293, 37499576, 1112064, 6434826, 4442872, 4430147; Phenotypes: 2-aminoadipic 2-oxoadipic aciduria MIM#204750, Disorders of histidine, tryptophan or lysine metabolism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1971 FLT3LG Zornitza Stark Phenotypes for gene: FLT3LG were changed from Increased susceptibility to infections to Immunodeficiency 125, MIM# 620926
Mendeliome v1.1970 FLT3LG Zornitza Stark reviewed gene: FLT3LG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 125, MIM# 620926; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bone Marrow Failure v1.94 FLT3LG Zornitza Stark Phenotypes for gene: FLT3LG were changed from Increased susceptibility to infections to Immunodeficiency 125, MIM# 620926
Bone Marrow Failure v1.93 FLT3LG Zornitza Stark reviewed gene: FLT3LG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 125, MIM# 620926; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6123 DCX Sumudu Perera edited their review of gene: DCX: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.6123 DARS2 Sumudu Perera reviewed gene: DARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 17384640, 21815884, 20506600; Phenotypes: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, MIM# 611105; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6123 DCX Sumudu Perera changed review comment from: Pathology:
PMID: 26743950 - DCX mutations usually cause anterior dominant lissencephaly in males and subcortical band heterotopia (SBH) in females

Phenotype:
Demelas et al. (2001) (PMID:11468322) demonstrated three brothers with phenotype of microcephaly, mild to moderate developmental delay, seizures and other neurologic abnormalities, as well as classic lissencephaly on MRI.

Lawrence et al. (2010) (PMID: 20726879) discuss 3 male members had severe epilepsy and intellectual disability; finding of missense mutation in DCX. Of note all 3 had been diagnosed with Lennox-Gastaut syndrome.

GeneReviews (PMID: 20301364): "Males with classic DCX-related lissencephaly typically have early and profound cognitive and language impairment, cerebral palsy, and epileptic seizures. The clinical phenotype in females with SBH varies widely with cognitive abilities that range from average or mild cognitive impairment to severe intellectual disability and language impairment."

Other papers:
1) Somatic mosaicism and variable penetrance - PMID: 12552055
2) Functional testing: PMID: 9489699; to: Pathology:
PMID: 26743950 - DCX mutations usually cause anterior dominant lissencephaly in males and subcortical band heterotopia (SBH) in females

Phenotype:
Demelas et al. (2001) (PMID:11468322) demonstrated three brothers with phenotype of microcephaly, mild to moderate developmental delay, seizures and other neurologic abnormalities, as well as classic lissencephaly on MRI.

Lawrence et al. (2010) (PMID: 20726879) discuss 3 male members had severe epilepsy and intellectual disability; finding of missense mutation in DCX. Of note all 3 had been diagnosed with Lennox-Gastaut syndrome.

GeneReviews (PMID: 20301364): "Males with classic DCX-related lissencephaly typically have early and profound cognitive and language impairment, cerebral palsy, and epileptic seizures. The clinical phenotype in females with SBH varies widely with cognitive abilities that range from average or mild cognitive impairment to severe intellectual disability and language impairment."

Other papers:
1) Somatic mosaicism and variable penetrance - PMID: 12552055
2) Functional testing: PMID: 9489699
Intellectual disability syndromic and non-syndromic v0.6123 DCX Sumudu Perera reviewed gene: DCX: Rating: ; Mode of pathogenicity: None; Publications: 26743950, 11468322, 20726879, 20301364, 12552055, 9489699; Phenotypes: Lissencephaly, X-linked, MIM# 300067, Subcortical laminal heterotopia, X-linked 300067; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.248 CIB2 Lilian Downie Marked gene: CIB2 as ready
Prepair 1000+ v1.248 CIB2 Lilian Downie Gene: cib2 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.248 CIB2 Lilian Downie Phenotypes for gene: CIB2 were changed from Usher syndrome, type IJ, 614869 (3) to Deafness, autosomal recessive 48 MIM#609439
Prepair 1000+ v1.247 CIB2 Lilian Downie Publications for gene: CIB2 were set to
Prepair 1000+ v1.246 CLCF1 Lilian Downie Marked gene: CLCF1 as ready
Prepair 1000+ v1.246 CLCF1 Lilian Downie Gene: clcf1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.246 CLCF1 Lilian Downie Publications for gene: CLCF1 were set to
Prepair 1000+ v1.245 CLCN7 Lilian Downie Marked gene: CLCN7 as ready
Prepair 1000+ v1.245 CLCN7 Lilian Downie Gene: clcn7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.245 CLCN7 Lilian Downie Publications for gene: CLCN7 were set to
Prepair 1000+ v1.244 CCDC114 Lilian Downie Marked gene: CCDC114 as ready
Prepair 1000+ v1.244 CCDC114 Lilian Downie Gene: ccdc114 has been classified as Green List (High Evidence).
Prepair 1000+ v1.244 CCDC114 Lilian Downie Publications for gene: CCDC114 were set to
Prepair 1000+ v1.243 CCDC8 Lilian Downie Marked gene: CCDC8 as ready
Prepair 1000+ v1.243 CCDC8 Lilian Downie Added comment: Comment when marking as ready: Primordial dwarfism with normal intelligence, final adult height approx -5SD from the mean, subtle facial dysmorphism
Prepair 1000+ v1.243 CCDC8 Lilian Downie Gene: ccdc8 has been classified as Green List (High Evidence).
Prepair 1000+ v1.243 CCDC8 Lilian Downie Tag for review tag was added to gene: CCDC8.
Prepair 1000+ v1.243 CCDC8 Lilian Downie Publications for gene: CCDC8 were set to
Prepair 1000+ v1.242 CHRNG Lilian Downie Marked gene: CHRNG as ready
Prepair 1000+ v1.242 CHRNG Lilian Downie Gene: chrng has been classified as Green List (High Evidence).
Prepair 1000+ v1.242 CHRNG Lilian Downie Phenotypes for gene: CHRNG were changed from Escobar syndrome, 265000 (3) to Escobar syndrome (MIM# 265000); Multiple pterygium syndrome, lethal type, (MIM# 253290)
Prepair 1000+ v1.241 CHRNG Lilian Downie Publications for gene: CHRNG were set to
Prepair 1000+ v1.240 COQ6 Lilian Downie Marked gene: COQ6 as ready
Prepair 1000+ v1.240 COQ6 Lilian Downie Gene: coq6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.240 COQ6 Lilian Downie Publications for gene: COQ6 were set to
Prepair 1000+ v1.239 COQ8A Lilian Downie Marked gene: COQ8A as ready
Prepair 1000+ v1.239 COQ8A Lilian Downie Gene: coq8a has been classified as Green List (High Evidence).
Prepair 1000+ v1.239 COQ8A Lilian Downie Publications for gene: COQ8A were set to
Prepair 1000+ v1.238 COQ2 Lilian Downie Marked gene: COQ2 as ready
Prepair 1000+ v1.238 COQ2 Lilian Downie Gene: coq2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.238 COQ2 Lilian Downie Publications for gene: COQ2 were set to
Prepair 1000+ v1.237 CRTAP Lilian Downie Marked gene: CRTAP as ready
Prepair 1000+ v1.237 CRTAP Lilian Downie Gene: crtap has been classified as Green List (High Evidence).
Prepair 1000+ v1.237 CRTAP Lilian Downie Publications for gene: CRTAP were set to
Intellectual disability syndromic and non-syndromic v0.6123 D2HGDH Sumudu Perera reviewed gene: D2HGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 15609246, 16081310, 31349060, 20020533, 38825343; Phenotypes: D-2-hydroxyglutaric aciduria MIM#600721; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.236 CRTAP Ee Ming Wong reviewed gene: CRTAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 21955071, 19846465, 17192541; Phenotypes: Osteogenesis imperfecta, type VII MIM#610682; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.236 COQ2 Cassandra Muller reviewed gene: COQ2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16400613, 17855635, 17332895; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.236 COQ8A Ee Ming Wong reviewed gene: COQ8A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32337771; Phenotypes: Coenzyme Q10 deficiency, primary, 4 MIM#612016; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.236 COQ2 Cassandra Muller Deleted their review
Prepair 1000+ v1.236 COQ2 Cassandra Muller reviewed gene: COQ2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16400613, 17332895, 17855635; Phenotypes: Coenzyme Q10 deficiency, primary, 1, 607426 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.236 COQ6 Ee Ming Wong reviewed gene: COQ6: Rating: GREEN; Mode of pathogenicity: None; Publications: 28125198; Phenotypes: Coenzyme Q10 deficiency, primary, 6 MIM#614650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.236 CHRNG Ee Ming Wong reviewed gene: CHRNG: Rating: GREEN; Mode of pathogenicity: None; Publications: 16826520, 16826531, 22167768; Phenotypes: Escobar syndrome (MIM# 265000), Multiple pterygium syndrome, lethal type, (MIM# 253290); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.236 CCDC8 Ee Ming Wong reviewed gene: CCDC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 21737058; Phenotypes: 3-M syndrome 3, MIM#614205; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.236 CCDC114 Ee Ming Wong reviewed gene: CCDC114: Rating: GREEN; Mode of pathogenicity: None; Publications: 23261303, 23261302, 32855706, 23506398; Phenotypes: Ciliary dyskinesia, primary, 20, MIM# 615067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.236 CLCN7 Cassandra Muller reviewed gene: CLCN7: Rating: GREEN; Mode of pathogenicity: None; Publications: 19507210, 11207362, 11741829, 14584882, 19953639; Phenotypes: Osteopetrosis, autosomal recessive 4, 611490 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.236 CLCF1 Cassandra Muller changed review comment from: Severe early in life, can result in death. Features typically improve after 2 years.; to: Severe early in life and can result in early death.
Cerebral Palsy v1.367 CACNA1B Clare van Eyk Deleted their comment
Cerebral Palsy v1.367 CACNA1B Clare van Eyk edited their review of gene: CACNA1B: Added comment: 1 individual reported with biallelic variants (1 missense, 1 splice variant but functional assessment not performed) in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

Additional case study reporting compound heterozygous frameshift variants in a child with epilepsy and cerebral palsy (PMID: 39005920).
Sources: Literature; Changed publications: PMID: 38693247, PMID: 39005920
Cerebral Palsy v1.367 CACNA1B Clare van Eyk changed review comment from: 1 individual reported with biallelic variants (1 missense, 1 splice) in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature; to: 1 individual reported with biallelic variants (1 missense, 1 splice variant but functional assessment not performed) in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

Additional case study reporting compound heterozygous frameshift variants in a child with epilepsy and cerebral palsy (PMID: 39005920).
Sources: Literature
Prepair 1000+ v1.236 CLCF1 Cassandra Muller reviewed gene: CLCF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16782820, 21370513, 20400119; Phenotypes: Cold-induced sweating syndrome 2, 610313 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.236 CIB2 Cassandra Muller reviewed gene: CIB2: Rating: RED; Mode of pathogenicity: None; Publications: 29112224; Phenotypes: Usher syndrome, type IJ 614869; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.115 WNT1 Bryony Thompson Mode of inheritance for gene: WNT1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Fetal anomalies v1.265 LAMA5 Tashunka Taylor-Miller reviewed gene: LAMA5: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 36322204; Phenotypes: cleft lip, cleft palate; Mode of inheritance: Unknown
Intellectual disability syndromic and non-syndromic v0.6123 GTPBP1 Zornitza Stark Phenotypes for gene: GTPBP1 were changed from Neurodevelopmental disorder (MONDO#0700092), GTPBP1-related to Neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1, MIM# 620888
Intellectual disability syndromic and non-syndromic v0.6122 GTPBP1 Zornitza Stark reviewed gene: GTPBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1, MIM# 620888; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.272 GTPBP1 Zornitza Stark Phenotypes for gene: GTPBP1 were changed from Neurodevelopmental disorder (MONDO#0700092), GTPBP1-related to Neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1, MIM# 620888
Microcephaly v1.271 GTPBP1 Zornitza Stark reviewed gene: GTPBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1, MIM# 620888; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1970 GTPBP1 Zornitza Stark Phenotypes for gene: GTPBP1 were changed from Neurodevelopmental disorder (MONDO#0700092), GTPBP1-related to Neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1, MIM# 620888
Mendeliome v1.1969 GTPBP1 Zornitza Stark reviewed gene: GTPBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1, MIM# 620888; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.265 NME8 Achchuthan Shanmugasundram reviewed gene: NME8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.1969 LRP1 Zornitza Stark Phenotypes for gene: LRP1 were changed from to Developmental dysplasia of the hip 3, MIM# 620690; Keratosis pilaris atrophicans MIM#604093
Mendeliome v1.1968 LRP1 Zornitza Stark Publications for gene: LRP1 were set to
Mendeliome v1.1967 LRP1 Zornitza Stark Mode of inheritance for gene: LRP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1966 LRP1 Zornitza Stark Classified gene: LRP1 as Amber List (moderate evidence)
Mendeliome v1.1966 LRP1 Zornitza Stark Gene: lrp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1965 LRP1 Zornitza Stark reviewed gene: LRP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 36067312; Phenotypes: Developmental dysplasia of the hip 3, MIM# 620690; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1965 RAB32 Zornitza Stark Phenotypes for gene: RAB32 were changed from Parkinson disease MONDO:0005180 to {Parkinson disease 26, autosomal dominant, susceptibility to}, MIM# 620923
Mendeliome v1.1964 RAB32 Zornitza Stark Publications for gene: RAB32 were set to 38614108
Mendeliome v1.1963 RAB32 Zornitza Stark Classified gene: RAB32 as Amber List (moderate evidence)
Mendeliome v1.1963 RAB32 Zornitza Stark Gene: rab32 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1962 RAB32 Zornitza Stark reviewed gene: RAB32: Rating: AMBER; Mode of pathogenicity: None; Publications: 38858457; Phenotypes: {Parkinson disease 26, autosomal dominant, susceptibility to}, MIM# 620923; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v2.7 RAB32 Zornitza Stark Phenotypes for gene: RAB32 were changed from Parkinson disease MONDO:0005180 to {Parkinson disease 26, autosomal dominant, susceptibility to}, MIM# 620923
Early-onset Parkinson disease v2.6 RAB32 Zornitza Stark Publications for gene: RAB32 were set to 38614108; 38858457
Early-onset Parkinson disease v2.5 RAB32 Zornitza Stark Publications for gene: RAB32 were set to 38614108
Early-onset Parkinson disease v2.4 RAB32 Zornitza Stark Classified gene: RAB32 as Amber List (moderate evidence)
Early-onset Parkinson disease v2.4 RAB32 Zornitza Stark Gene: rab32 has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v2.3 RAB32 Zornitza Stark reviewed gene: RAB32: Rating: AMBER; Mode of pathogenicity: None; Publications: 38858457; Phenotypes: {Parkinson disease 26, autosomal dominant, susceptibility to}, MIM# 620923; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1962 VPS52 Bryony Thompson Marked gene: VPS52 as ready
Mendeliome v1.1962 VPS52 Bryony Thompson Gene: vps52 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1962 VPS52 Bryony Thompson Classified gene: VPS52 as Amber List (moderate evidence)
Mendeliome v1.1962 VPS52 Bryony Thompson Gene: vps52 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1961 VPS52 Bryony Thompson gene: VPS52 was added
gene: VPS52 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: VPS52 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS52 were set to complex neurodevelopmental disorder with or without congenital anomalies MONDO:0100465
Review for gene: VPS52 was set to AMBER
Added comment: HGSA poster (P110) from Louise Bicknell's group at the University of Otago. 11 cases from 8 families (USA, NZ, Saudi Arabia) with a broad syndromic developmental delay phenotype with biallelic variants (both missense & truncating).
Sources: Other
Hyperinsulinism v1.18 CACNA1D Chirag Patel edited their review of gene: CACNA1D: Added comment: 2nd case reported of child with persistent diazoxide-responsive HH, mild aortic insufficiency, severe hypotonia, and developmental delay. WES identified a de novo CACNA1D mutation (p.G403D). CACNA1D encodes the main L-type voltage-gated calcium channel in the pancreatic β-cell, a key component of the insulin secretion pathway. The p.G403D mutation had been reported previously as an activating mutation in an individual with primary hyper-aldosteronism, neuromuscular abnormalities, and transient hypoglycaemia.; Changed mode of pathogenicity: Other; Changed phenotypes: hyperinsulinaemic hypoglycaemia, heart defects, and severe hypotonia; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hyperinsulinism v1.18 MAFA Chirag Patel Classified gene: MAFA as Green List (high evidence)
Hyperinsulinism v1.18 MAFA Chirag Patel Gene: mafa has been classified as Green List (High Evidence).
Hyperinsulinism v1.17 MAFA Chirag Patel gene: MAFA was added
gene: MAFA was added to Hyperinsulinism. Sources: Literature
Mode of inheritance for gene: MAFA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAFA were set to PMID: 29339498
Phenotypes for gene: MAFA were set to Insulinomatosis and diabetes mellitus, OMIM #:147630
Review for gene: MAFA was set to GREEN
gene: MAFA was marked as current diagnostic
Added comment: 2 families with 36 individuals with AD inheritance of diabetes mellitus or insulinomatosis (adult-onset recurrent hyperinsulinemic hypoglycemia caused by multiple insulin-secreting neuroendocrine tumours of pancreas). WES identified the same missense MAFA mutation (p.Ser64Phe, c.191C>T) segregating with both phenotypes of insulinomatosis and diabetes in both families. The p.Ser64Phe mutation was found to impair phosphorylation within the transactivation domain of MAFA and profoundly increased MAFA protein stability under both high and low glucose concentrations in β-cell lines. In addition, the transactivation potential of p.Ser64Phe MAFA in β-cell lines was enhanced compared with wild-type MAFA. The human phenotypes associated with the p.Ser64Phe MAFA missense mutation reflect both the oncogenic capacity of MAFA and its key role in islet β-cell activity.
Sources: Literature
Hypertrophic cardiomyopathy_HCM v1.0 Bryony Thompson promoted panel to version 1.0
Hypertrophic cardiomyopathy_HCM v0.196 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Hypertrophic cardiomyopathy_HCM v0.195 RIT1 Bryony Thompson Marked gene: RIT1 as ready
Hypertrophic cardiomyopathy_HCM v0.195 RIT1 Bryony Thompson Gene: rit1 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.195 RIT1 Bryony Thompson Classified gene: RIT1 as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.195 RIT1 Bryony Thompson Gene: rit1 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.194 RIT1 Bryony Thompson gene: RIT1 was added
gene: RIT1 was added to Hypertrophic cardiomyopathy_HCM. Sources: ClinGen
Mode of inheritance for gene: RIT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RIT1 were set to 39132495
Phenotypes for gene: RIT1 were set to Noonan syndrome MONDO:0018997
Mode of pathogenicity for gene: RIT1 was set to Other
Review for gene: RIT1 was set to GREEN
gene: RIT1 was marked as current diagnostic
Added comment: Included as one of the recommended 29 HCM genes to test by the ClinGen HCVD GCEP due to syndromic LVH being a feature of the condition that can be mistaken for HCM
Sources: ClinGen
Hypertrophic cardiomyopathy_HCM v0.193 RAF1 Bryony Thompson Publications for gene: RAF1 were set to 24777450
Hypertrophic cardiomyopathy_HCM v0.192 RAF1 Bryony Thompson Classified gene: RAF1 as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.192 RAF1 Bryony Thompson Added comment: Comment on list classification: Included as one of the recommended 29 HCM genes to test by the ClinGen HCVD GCEP due to syndromic LVH being a feature of the condition that can be mistaken for HCM
Hypertrophic cardiomyopathy_HCM v0.192 RAF1 Bryony Thompson Gene: raf1 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.191 PTPN11 Bryony Thompson Publications for gene: PTPN11 were set to
Hypertrophic cardiomyopathy_HCM v0.190 PTPN11 Bryony Thompson Classified gene: PTPN11 as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.190 PTPN11 Bryony Thompson Added comment: Comment on list classification: Included as one of the recommended 29 HCM genes to test by the ClinGen HCVD GCEP due to syndromic LVH being a feature of the condition that can be mistaken for HCM
Hypertrophic cardiomyopathy_HCM v0.190 PTPN11 Bryony Thompson Gene: ptpn11 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.189 DES Bryony Thompson Publications for gene: DES were set to
Hypertrophic cardiomyopathy_HCM v0.188 DES Bryony Thompson Phenotypes for gene: DES were changed from Hypertrophic cardiomyopathy; Dilated cardiomyopathy; Myofibrillar myopathy; ARVC to Desminopathy
Hypertrophic cardiomyopathy_HCM v0.187 DES Bryony Thompson Classified gene: DES as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.187 DES Bryony Thompson Added comment: Comment on list classification: Included as one of the 29 recommended HCM genes to test by the ClinGen HCVD GCEP for a syndromic LVH association - LV cardiomyopathy (including hypertrophy, dilation, restrictive, hypertrabeculation/ LVNC) is part of the phenotype of desminopathy
Hypertrophic cardiomyopathy_HCM v0.187 DES Bryony Thompson Gene: des has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.186 DES Bryony Thompson Mode of inheritance for gene: DES was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.185 CACNA1C Bryony Thompson Publications for gene: CACNA1C were set to 26253506; 28490369; 28866666
Hypertrophic cardiomyopathy_HCM v0.184 CACNA1C Bryony Thompson Classified gene: CACNA1C as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.184 CACNA1C Bryony Thompson Added comment: Comment on list classification: Classified as Definitive by the ClinGen HCVD GCEP for Timothy Syndrome, including left ventricular hypertrophy as a feature of the condition associated with some specific missense variants - https://search.clinicalgenome.org/CCID:008324. One of the 29 recommended HCM genes.
Hypertrophic cardiomyopathy_HCM v0.184 CACNA1C Bryony Thompson Gene: cacna1c has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.183 UQCRFS1 Bryony Thompson Classified gene: UQCRFS1 as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.183 UQCRFS1 Bryony Thompson Added comment: Comment on list classification: Paediatric onset condition. This gene is on the paediatric cardiomyopathy panel. Not one of the 29 genes recommended for HCM testing by the ClinGen HCVD GCEP.
Hypertrophic cardiomyopathy_HCM v0.183 UQCRFS1 Bryony Thompson Gene: uqcrfs1 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.182 TULP3 Bryony Thompson Classified gene: TULP3 as Amber List (moderate evidence)
Hypertrophic cardiomyopathy_HCM v0.182 TULP3 Bryony Thompson Added comment: Comment on list classification: Currently, only 3 adult individuals from 2 unrelated families presented with hypertrophic non-obstructive cardiomyopathy (HNCM). More evidence required for the HCM association
Hypertrophic cardiomyopathy_HCM v0.182 TULP3 Bryony Thompson Gene: tulp3 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.181 C1QBP Bryony Thompson Classified gene: C1QBP as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.181 C1QBP Bryony Thompson Added comment: Comment on list classification: Paediatric onset condition. Has been moved to the paediatric cardiomyopathy panel. Not one of the 29 genes the ClinGen HCVD GCEP recommends for HCM testing
Hypertrophic cardiomyopathy_HCM v0.181 C1QBP Bryony Thompson Gene: c1qbp has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v0.196 C1QBP Bryony Thompson Classified gene: C1QBP as Green List (high evidence)
Cardiomyopathy_Paediatric v0.196 C1QBP Bryony Thompson Gene: c1qbp has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.194 C1QBP Bryony Thompson gene: C1QBP was added
gene: C1QBP was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: C1QBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C1QBP were set to 28942965
Phenotypes for gene: C1QBP were set to Combined oxidative phosphorylation deficiency 33, MIM#617713
Cardiomyopathy_Paediatric v0.193 MYH6 Bryony Thompson Marked gene: MYH6 as ready
Cardiomyopathy_Paediatric v0.193 MYH6 Bryony Thompson Gene: myh6 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v0.193 MYH6 Bryony Thompson Classified gene: MYH6 as Red List (low evidence)
Cardiomyopathy_Paediatric v0.193 MYH6 Bryony Thompson Added comment: Comment on list classification: ClinGen HCVD GCEP has classified the HCM association as Disputed (https://search.clinicalgenome.org/CCID:008325) and the DCM association as Limited (https://search.clinicalgenome.org/CCID:005520)
Cardiomyopathy_Paediatric v0.193 MYH6 Bryony Thompson Gene: myh6 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.180 RPS6KB1 Bryony Thompson Classified gene: RPS6KB1 as Amber List (moderate evidence)
Hypertrophic cardiomyopathy_HCM v0.180 RPS6KB1 Bryony Thompson Added comment: Comment on list classification: ClinGen HCVD GCEP has classified this gene as Limited for HCM on 13/09/2023 - https://search.clinicalgenome.org/CCID:006034
Hypertrophic cardiomyopathy_HCM v0.180 RPS6KB1 Bryony Thompson Gene: rps6kb1 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.236 ALG2 Lana Giameos reviewed gene: ALG2: Rating: AMBER; Mode of pathogenicity: None; Publications: 33644825, 23404334, 24461433, 12684507, 30397276, 34980536, 34106226; Phenotypes: Congenital disorder of glycosylation, type Ii, MIM# 607906, Myasthenic syndrome, congenital, 14, MIM# 616228; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.236 DYSF Zornitza Stark Marked gene: DYSF as ready
Prepair 1000+ v1.236 DYSF Zornitza Stark Gene: dysf has been classified as Green List (High Evidence).
Prepair 1000+ v1.236 DYSF Zornitza Stark Phenotypes for gene: DYSF were changed from Muscular dystrophy, limb-girdle, type 2B, 253601 (3) to Miyoshi muscular dystrophy 1 MIM#254130; MONDO:0024545; Muscular dystrophy, limb-girdle, autosomal recessive 2 MIM#253601; MONDO:0009676; Myopathy, distal, with anterior tibial onset MIM#606768; MONDO:0011721
Prepair 1000+ v1.235 DYSF Zornitza Stark Publications for gene: DYSF were set to
Prepair 1000+ v1.234 DYSF Zornitza Stark reviewed gene: DYSF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Miyoshi muscular dystrophy 1 MIM#254130, MONDO:0024545, Muscular dystrophy, limb-girdle, autosomal recessive 2 MIM#253601, MONDO:0009676, Myopathy, distal, with anterior tibial onset MIM#606768, MONDO:0011721; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.234 DYSF Marta Cifuentes Ochoa reviewed gene: DYSF: Rating: GREEN; Mode of pathogenicity: None; Publications: 37762951, 38540676, 36542547, 32400077; Phenotypes: Miyoshi muscular dystrophy 1 MIM#254130, MONDO:0024545, Muscular dystrophy, limb-girdle, autosomal recessive 2 MIM#253601, MONDO:0009676, Myopathy, distal, with anterior tibial onset MIM#606768, MONDO:0011721; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.234 DYSF Marta Cifuentes Ochoa Deleted their review
Prepair 1000+ v1.234 SURF1 Zornitza Stark Marked gene: SURF1 as ready
Prepair 1000+ v1.234 SURF1 Zornitza Stark Added comment: Comment when marking as ready: Agree Mitochondrial complex IV deficiency, nuclear type 1, MIM# 220110 is the appropriate term to use.
Prepair 1000+ v1.234 SURF1 Zornitza Stark Gene: surf1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.234 SURF1 Zornitza Stark Phenotypes for gene: SURF1 were changed from Leigh syndrome, due to COX deficiency, 256000 (3) to Mitochondrial complex IV deficiency, nuclear type 1, MIM# 220110
Prepair 1000+ v1.233 YIF1B Zornitza Stark Marked gene: YIF1B as ready
Prepair 1000+ v1.233 YIF1B Zornitza Stark Gene: yif1b has been classified as Red List (Low Evidence).
Prepair 1000+ v1.233 YIF1B Zornitza Stark Phenotypes for gene: YIF1B were changed from Abnormality of movement; Seizures; Failure to thrive; Spasticity; Central hypotonia; Intellectual disability; Global developmental delay; Microcephaly to Kaya-Barakat-Masson syndrome, MIM# 619125
Prepair 1000+ v1.232 GTPBP2 Zornitza Stark Marked gene: GTPBP2 as ready
Prepair 1000+ v1.232 GTPBP2 Zornitza Stark Gene: gtpbp2 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.232 CSMD1 Zornitza Stark Marked gene: CSMD1 as ready
Prepair 1000+ v1.232 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.232 AFF2 Zornitza Stark Marked gene: AFF2 as ready
Prepair 1000+ v1.232 AFF2 Zornitza Stark Gene: aff2 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.232 AFF2 Zornitza Stark Phenotypes for gene: AFF2 were changed from Mental retardation, X-linked, FRAXE type, #309548 to Intellectual disability, X-linked, FRAXE type 309548
Prepair 1000+ v1.231 AFF2 Zornitza Stark Publications for gene: AFF2 were set to
Prepair 1000+ v1.230 AFF2 Zornitza Stark Classified gene: AFF2 as Amber List (moderate evidence)
Prepair 1000+ v1.230 AFF2 Zornitza Stark Gene: aff2 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.229 AFF2 Zornitza Stark reviewed gene: AFF2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual disability, X-linked, FRAXE type 309548; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.229 ACY1 Zornitza Stark Marked gene: ACY1 as ready
Prepair 1000+ v1.229 ACY1 Zornitza Stark Gene: acy1 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.229 DYSF Marta Cifuentes Ochoa Deleted their comment
Prepair 1000+ v1.229 DYSF Marta Cifuentes Ochoa commented on gene: DYSF: Miyoshi myopathy (MM) is the most common form of recessive distal myopathy in populations with founder mutations such as Libyan and Israeli Jewish population, Italian and Spanish populations.The typical age of onset of MM lies between 15 and 30 years

Autosomal recessive limb-girdle muscular dystrophy type 2B (LGMD2B) is a subtype of autosomal recessive limb-girdle muscular dystrophy characterized by an onset in late adolescence or early adulthood of slowly progressive, proximal weakness and atrophy of shoulder and pelvic girdle muscles. Cardiac and respiratory muscles are not involved. Hypertrophy of the calf muscles and highly elevated serum creatine kinase levels are frequently observed.

Myopathy, distal, with anterior tibial onset is a rare genetic neuromuscular disease with characteristics of a progressive muscle weakness starting in the anterior tibial muscles, later involving lower and upper limb muscles, associated with an increased serum creatine kinase levels and absence of dysferlin on muscle biopsy. Patients become wheelchair dependent.

HGNC approved symbol/name: DYSF
Is the phenotype(s) severe and onset <18yo ? ? chidhood, early adulthood to late onset
Known technical challenges? N but large‐scale copy number variants have been identified.
Gene reported in >3 independent families

Unsure due genotype/phenotype correlation and onset
Prepair 1000+ v1.229 DYSF Marta Cifuentes Ochoa reviewed gene: DYSF: Rating: AMBER; Mode of pathogenicity: None; Publications: 37762951, 38540676, 36542547, 32400077; Phenotypes: Miyoshi muscular dystrophy 1 MIM#254130, MONDO:0024545, Muscular dystrophy, limb-girdle, autosomal recessive 2 MIM#253601, MONDO:0009676, Myopathy, distal, with anterior tibial onset MIM#606768, MONDO:0011721; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.229 LIG4 Zornitza Stark Marked gene: LIG4 as ready
Prepair 1000+ v1.229 LIG4 Zornitza Stark Gene: lig4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.229 LIG4 Zornitza Stark Phenotypes for gene: LIG4 were changed from LIG4 syndrome, MIM# 606593 DNA ligase IV deficiency, MONDO:0011686 to LIG4 syndrome, MIM# 606593; DNA ligase IV deficiency, MONDO:0011686
Prepair 1000+ v1.228 LIG4 Zornitza Stark Phenotypes for gene: LIG4 were changed from LIG4 syndrome, 606593 (3) to LIG4 syndrome, MIM# 606593 DNA ligase IV deficiency, MONDO:0011686
Prepair 1000+ v1.227 LIG4 Zornitza Stark Publications for gene: LIG4 were set to
Prepair 1000+ v1.226 LIG4 Zornitza Stark commented on gene: LIG4: Congenital onset, presents with combined immunodeficiency and features of radiosensitivity, chromosomal instability, pancytopenia, and developmental and growth delay.
Prepair 1000+ v1.226 LIG4 Zornitza Stark reviewed gene: LIG4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: LIG4 syndrome, MIM# 606593 DNA ligase IV deficiency, MONDO:0011686; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.226 ECHS1 Zornitza Stark Marked gene: ECHS1 as ready
Prepair 1000+ v1.226 ECHS1 Zornitza Stark Gene: echs1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.226 ECHS1 Zornitza Stark Publications for gene: ECHS1 were set to
Prepair 1000+ v1.225 CHM Zornitza Stark Tag for review tag was added to gene: CHM.
Prepair 1000+ v1.225 CISD2 Zornitza Stark Marked gene: CISD2 as ready
Prepair 1000+ v1.225 CISD2 Zornitza Stark Gene: cisd2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.225 CISD2 Zornitza Stark Phenotypes for gene: CISD2 were changed from Wolfram syndrome 2, 604928 (3) to Wolfram syndrome 2 MIM#604928; MONDO:0011502
Prepair 1000+ v1.224 CISD2 Zornitza Stark Publications for gene: CISD2 were set to
Prepair 1000+ v1.223 CLCN2 Zornitza Stark Marked gene: CLCN2 as ready
Prepair 1000+ v1.223 CLCN2 Zornitza Stark Gene: clcn2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.223 CLCN2 Zornitza Stark Phenotypes for gene: CLCN2 were changed from Leukoencephalopathy with ataxia, 615651 (3) to Leukoencephalopathy with ataxia MIM#615651; leukoencephalopathy with mild cerebellar ataxia and white matter oedema MONDO:0014292
Prepair 1000+ v1.222 CLCN2 Zornitza Stark Publications for gene: CLCN2 were set to
Prepair 1000+ v1.221 CLN3 Zornitza Stark Marked gene: CLN3 as ready
Prepair 1000+ v1.221 CLN3 Zornitza Stark Gene: cln3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.221 CLN3 Zornitza Stark Phenotypes for gene: CLN3 were changed from Ceroid lipofuscinosis, neuronal, 3, 204200 (3) to Ceroid lipofuscinosis, neuronal, 3, MIM# 204200; MONDO:0008767
Prepair 1000+ v1.220 CLN3 Zornitza Stark Publications for gene: CLN3 were set to
Prepair 1000+ v1.219 COL4A3 Zornitza Stark Marked gene: COL4A3 as ready
Prepair 1000+ v1.219 COL4A3 Zornitza Stark Gene: col4a3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.219 COL4A3 Zornitza Stark Phenotypes for gene: COL4A3 were changed from Alport syndrome, autosomal recessive, 203780 (3) to Alport syndrome 3b, autosomal recessive MIM#620536; MONDO:0957811
Prepair 1000+ v1.218 COL4A3 Zornitza Stark Publications for gene: COL4A3 were set to
Prepair 1000+ v1.217 COLEC11 Zornitza Stark Marked gene: COLEC11 as ready
Prepair 1000+ v1.217 COLEC11 Zornitza Stark Gene: colec11 has been classified as Green List (High Evidence).
Prepair 1000+ v1.217 COLEC11 Zornitza Stark Phenotypes for gene: COLEC11 were changed from 3MC syndrome 2, 265050 (3) to 3MC syndrome 2, MIM# 265050; MONDO:0009927
Prepair 1000+ v1.216 COLEC11 Zornitza Stark Publications for gene: COLEC11 were set to
Prepair 1000+ v1.215 COLQ Zornitza Stark Marked gene: COLQ as ready
Prepair 1000+ v1.215 COLQ Zornitza Stark Gene: colq has been classified as Green List (High Evidence).
Prepair 1000+ v1.215 COLQ Zornitza Stark Phenotypes for gene: COLQ were changed from Myasthenic syndrome, congenital, 5, 603034 (3) to Myasthenic syndrome, congenital, 5 MIM#603034; MONDO:0011281
Prepair 1000+ v1.214 COLQ Zornitza Stark Publications for gene: COLQ were set to
Prepair 1000+ v1.213 CRB2 Zornitza Stark Marked gene: CRB2 as ready
Prepair 1000+ v1.213 CRB2 Zornitza Stark Gene: crb2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.213 CRB2 Zornitza Stark Phenotypes for gene: CRB2 were changed from Ventriculomegaly with cystic kidney disease, 219730 (3) to Ventriculomegaly with cystic kidney disease, MIM# 219730; MONDO:0009063; Focal segmental glomerulosclerosis 9, MIM# 616220; MONDO:0014539
Prepair 1000+ v1.212 CRB2 Zornitza Stark Publications for gene: CRB2 were set to
Prepair 1000+ v1.211 DGAT1 Zornitza Stark Marked gene: DGAT1 as ready
Prepair 1000+ v1.211 DGAT1 Zornitza Stark Gene: dgat1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.211 DGAT1 Zornitza Stark Phenotypes for gene: DGAT1 were changed from ?Diarrhea 7, protein-losing enteropathy type to Diarrhoea 7, protein-losing enteropathy type, MIM# 615863; congenital diarrhoea 7 with exudative enteropathy MONDO:0014375
Prepair 1000+ v1.210 DGAT1 Zornitza Stark Publications for gene: DGAT1 were set to
Prepair 1000+ v1.209 B3GALT6 Zornitza Stark Marked gene: B3GALT6 as ready
Prepair 1000+ v1.209 B3GALT6 Zornitza Stark Gene: b3galt6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.209 B3GALT6 Zornitza Stark Phenotypes for gene: B3GALT6 were changed from Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures, 271640 (3) to Al-Gazali syndrome, MIM# 609465; Ehlers-Danlos syndrome, spondylodysplastic type, 2, MIM# 615349; Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures, MIM#271640
Prepair 1000+ v1.208 B3GLCT Zornitza Stark Marked gene: B3GLCT as ready
Prepair 1000+ v1.208 B3GLCT Zornitza Stark Gene: b3glct has been classified as Green List (High Evidence).
Prepair 1000+ v1.208 B3GLCT Zornitza Stark Phenotypes for gene: B3GLCT were changed from Peters-plus syndrome, 261540 (3) to Peters-plus syndrome, MIM# 261540
Prepair 1000+ v1.207 B3GLCT Zornitza Stark Publications for gene: B3GLCT were set to
Prepair 1000+ v1.206 APOPT1 Zornitza Stark Marked gene: APOPT1 as ready
Prepair 1000+ v1.206 APOPT1 Zornitza Stark Gene: apopt1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.206 APOPT1 Zornitza Stark Phenotypes for gene: APOPT1 were changed from Mitochondrial complex IV deficiency, 220110 (3) to Mitochondrial complex IV deficiency, MIM#220110
Prepair 1000+ v1.205 APOPT1 Zornitza Stark Publications for gene: APOPT1 were set to
Prepair 1000+ v1.204 APOPT1 Zornitza Stark Tag new gene name tag was added to gene: APOPT1.
Prepair 1000+ v1.204 ARFGEF2 Zornitza Stark Marked gene: ARFGEF2 as ready
Prepair 1000+ v1.204 ARFGEF2 Zornitza Stark Gene: arfgef2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.204 ARFGEF2 Zornitza Stark Phenotypes for gene: ARFGEF2 were changed from Periventricular heterotopia with microcephaly, 608097 (3) to Periventricular heterotopia with microcephaly, MIM#608097
Prepair 1000+ v1.203 ARFGEF2 Zornitza Stark Publications for gene: ARFGEF2 were set to
Prepair 1000+ v1.202 ARL13B Zornitza Stark Marked gene: ARL13B as ready
Prepair 1000+ v1.202 ARL13B Zornitza Stark Gene: arl13b has been classified as Green List (High Evidence).
Prepair 1000+ v1.202 ARL13B Zornitza Stark Publications for gene: ARL13B were set to
Prepair 1000+ v1.201 ARL13B Zornitza Stark reviewed gene: ARL13B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Joubert syndrome 8, MIM# 612291; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.201 ASNS Zornitza Stark Marked gene: ASNS as ready
Prepair 1000+ v1.201 ASNS Zornitza Stark Gene: asns has been classified as Green List (High Evidence).
Prepair 1000+ v1.201 ASNS Zornitza Stark Phenotypes for gene: ASNS were changed from Asparagine synthetase deficiency, 615574 (3) to Asparagine synthetase deficiency, MIM#615574
Prepair 1000+ v1.200 ASNS Zornitza Stark Publications for gene: ASNS were set to
Prepair 1000+ v1.199 ATP8B1 Zornitza Stark Marked gene: ATP8B1 as ready
Prepair 1000+ v1.199 ATP8B1 Zornitza Stark Gene: atp8b1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.199 CSMD1 Zornitza Stark Tag for review tag was added to gene: CSMD1.
Prepair 1000+ v1.199 ASCC1 Zornitza Stark Marked gene: ASCC1 as ready
Prepair 1000+ v1.199 ASCC1 Zornitza Stark Gene: ascc1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.199 ASCC1 Zornitza Stark Phenotypes for gene: ASCC1 were changed from Spinal muscular atrophy with congenital bone fractures 2, MIM#616867 to Spinal muscular atrophy with congenital bone fractures 2, MIM#616867; spinal muscular atrophy with congenital bone fractures 2 MONDO:0014807
Prepair 1000+ v1.198 ASCC1 Zornitza Stark Publications for gene: ASCC1 were set to
Prepair 1000+ v1.197 AUH Zornitza Stark Marked gene: AUH as ready
Prepair 1000+ v1.197 AUH Zornitza Stark Gene: auh has been classified as Green List (High Evidence).
Prepair 1000+ v1.197 AUH Zornitza Stark Phenotypes for gene: AUH were changed from 3-methylglutaconic aciduria, type I, 250950 (3) to 3-methylglutaconic aciduria, type I, MIM# 250950; MONDO:0009610
Prepair 1000+ v1.196 AUH Zornitza Stark Publications for gene: AUH were set to
Prepair 1000+ v1.195 B4GALT7 Zornitza Stark Marked gene: B4GALT7 as ready
Prepair 1000+ v1.195 B4GALT7 Zornitza Stark Gene: b4galt7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.195 B4GALT7 Zornitza Stark Phenotypes for gene: B4GALT7 were changed from Ehlers-Danlos syndrome, progeroid type, 1, 130070 (3) to Ehlers-Danlos syndrome, spondylodysplastic type, 1, MIM# 130070; MONDO:0020682
Prepair 1000+ v1.194 B4GALT7 Zornitza Stark Publications for gene: B4GALT7 were set to
Prepair 1000+ v1.193 BRF1 Zornitza Stark Marked gene: BRF1 as ready
Prepair 1000+ v1.193 BRF1 Zornitza Stark Gene: brf1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.193 BRF1 Zornitza Stark Phenotypes for gene: BRF1 were changed from Cerebellofaciodental syndrome, 616202 (3) to Cerebellofaciodental syndrome, MIM# 616202; Cerebellar-facial-dental syndrome MONDO:0014529
Prepair 1000+ v1.192 BRF1 Zornitza Stark Publications for gene: BRF1 were set to
Prepair 1000+ v1.191 DLL3 Marta Cifuentes Ochoa reviewed gene: DLL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10742114, 12746394, 36506336; Phenotypes: Spondylocostal dysostosis 1, autosomal recessive, MIM# 277300, MONDO:0020692; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.191 HBA1 Zornitza Stark Publications for gene: HBA1 were set to
Prepair 1000+ v1.190 HBA1 Zornitza Stark Tag for review tag was added to gene: HBA1.
Prepair 1000+ v1.190 HBA2 Zornitza Stark Publications for gene: HBA2 were set to
Prepair 1000+ v1.189 HBA2 Zornitza Stark Tag for review tag was added to gene: HBA2.
Prepair 1000+ v1.189 BTK Zornitza Stark Marked gene: BTK as ready
Prepair 1000+ v1.189 BTK Zornitza Stark Gene: btk has been classified as Green List (High Evidence).
Prepair 1000+ v1.189 BTK Zornitza Stark Phenotypes for gene: BTK were changed from Agammaglobulinemia and isolated hormone deficiency, 307200 (3) to Agammaglobulinemia, X-linked 1 MIM#300755; Bruton-type agammaglobulinemia MONDO:0010421; Isolated growth hormone deficiency, type III, with agammaglobulinemia MIM#307200 MONDO:0010615
Prepair 1000+ v1.188 BTK Zornitza Stark Publications for gene: BTK were set to
Prepair 1000+ v1.187 DGAT1 Marta Cifuentes Ochoa reviewed gene: DGAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33261563, 32786057, 31778854, 28373485, 29604290, 31778854; Phenotypes: Diarrhoea 7, protein-losing enteropathy type, MIM# 615863, congenital diarrhea 7 with exudative enteropathy MONDO:0014375; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.187 CRB2 Marta Cifuentes Ochoa reviewed gene: CRB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25557780, 33687977, 32051522, 30212996, 33575434, 31438467, 30593785, 25557779, 27004616; Phenotypes: Ventriculomegaly with cystic kidney disease, MIM# 219730, MONDO:0009063 Focal segmental glomerulosclerosis 9, MIM# 616220, MONDO:0014539; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.187 CEP152 Marta Cifuentes Ochoa changed review comment from: Primary microcephaly (head circumference more than 3 standard deviations below the age- and sex-matched population mean). Causes Intellectual disability.

Seckel syndrome is a rare autosomal recessive inherited disorder, which is mainly characterized by intrauterine and postnatal growth restrictions, microcephaly, intellectual disability, and a typical “bird-head” facial appearance.

Established gene-disease association.

Congenital onset, severe disorder

HGNC approved symbol/name: CEP152

Is the phenotype(s) severe and onset <18yo ? Y

Known technical challenges? N

Gene reported in >3 independent families; to: Primary microcephaly (head circumference more than 3 standard deviations below the age- and sex-matched population mean). Causes Intellectual disability.

Seckel syndrome is a rare autosomal recessive inherited disorder, which is mainly characterized by intrauterine and postnatal growth restrictions, microcephaly, intellectual disability, facial dysmorphic features.

Established gene-disease association.

Congenital onset, severe disorder

HGNC approved symbol/name: CEP152

Is the phenotype(s) severe and onset <18yo ? Y

Known technical challenges? N

Gene reported in >3 independent families
Prepair 1000+ v1.187 COLQ Marta Cifuentes Ochoa changed review comment from: Patients with congenital myasthenic syndromes present clinically with onset of variable muscle weakness between infancy and adulthood.

Well established gene-disease association, more than 10 families reported.
HGNC approved symbol/name: COLQ
Is the phenotype(s) severe and onset <18yo ? Y
Known technical challenges?N; to: Patients with congenital myasthenic syndromes present clinically with onset of variable muscle weakness between infancy and adulthood.
Presentations:
-neonatal: respiratory insufficiency, multiple joint contractures (often described as arthrogryposis multiplex congenita) resulting from a lack of fetal movement in utero. Feeding difficulties, poor suck and cry, choking spells, eyelid ptosis, and facial, bulbar, and generalized weakness.In some individuals, long face, narrow jaw, and a high-arched palate have been reported
-childhood: delayed motr milestones, fluctuating eyelid ptosis and fixed or fluctuating extraocular muscle weakness. Ptosis may involve one or both eyelids. Facial and bulbar weakness with nasal speech and difficulties in coughing and swallowing may be present.Spinal deformity or muscle atrophy may occur
-limb-girdle

Well established gene-disease association, more than 10 families reported.
HGNC approved symbol/name: COLQ
Is the phenotype(s) severe and onset <18yo ? Y
Known technical challenges?N
Prepair 1000+ v1.187 COLQ Marta Cifuentes Ochoa reviewed gene: COLQ: Rating: GREEN; Mode of pathogenicity: None; Publications: 9689136, 9758617, 11865139, 32978031, 31831253, 29478601, 23995276, 36835142; Phenotypes: Myasthenic syndrome, congenital, 5 MIM#603034, MONDO:0011281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v1.46 Zornitza Stark List of related panels changed from Seizure; HP:0001250; Epileptic encephalopathy; HP:0200134 to Seizure; HP:0001250; Epileptic encephalopathy; HP:0200134; EEG abnormality; HP:0002353
Prepair 1000+ v1.187 COLEC11 Marta Cifuentes Ochoa reviewed gene: COLEC11: Rating: GREEN; Mode of pathogenicity: None; Publications: 21258343, 26789649, 28301481; Phenotypes: 3MC syndrome 2, MIM# 265050, MONDO:0009927; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.187 COL4A3 Marta Cifuentes Ochoa reviewed gene: COL4A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24052634, 35419377, 39071776; Phenotypes: Alport syndrome 3b, autosomal recessive MIM#620536, MONDO:0957811; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.187 CLN3 Marta Cifuentes Ochoa Deleted their comment
Prepair 1000+ v1.187 CLN3 Marta Cifuentes Ochoa commented on gene: CLN3: Well established gene disease association.

Severe neurodegenerative disorder.

HGNC approved symbol/name: CLN3
Is the phenotype(s) severe and onset <18yo ? Y
Known technical challenges? N
Gene reported in >3 independent families
Prepair 1000+ v1.187 CLN3 Marta Cifuentes Ochoa reviewed gene: CLN3: Rating: GREEN; Mode of pathogenicity: None; Publications: 7553855, 31926949; Phenotypes: Ceroid lipofuscinosis, neuronal, 3, MIM# 204200, MONDO:0008767; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.187 CLCN2 Marta Cifuentes Ochoa reviewed gene: CLCN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23707145, 38173802, 29403011, 29403012; Phenotypes: Leukoencephalopathy with ataxia MIM#615651, leukoencephalopathy with mild cerebellar ataxia and white matter edema MONDO:0014292; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.187 CISD2 Marta Cifuentes Ochoa reviewed gene: CISD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35055657, 29237418, 28335035, 27459537, 26230298, 17846994; Phenotypes: Wolfram syndrome 2 MIM#604928, MONDO:0011502; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.187 CHM Marta Cifuentes Ochoa reviewed gene: CHM: Rating: AMBER; Mode of pathogenicity: None; Publications: 31021898, 27506488, 27820636, 33110609; Phenotypes: Choroideremia MIM#303100, MONDO:0010557; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Ciliary Dyskinesia v1.39 SCNN1G Jonathon Bradshaw reviewed gene: SCNN1G: Rating: RED; Mode of pathogenicity: None; Publications: 29997923, 30801930, 18507830; Phenotypes: Bronchiectasis with or without elevated sweat chloride 3, MIM# 613071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliary Dyskinesia v1.39 SCNN1G Jonathon Bradshaw Deleted their review
Ciliary Dyskinesia v1.39 SCNN1G Jonathon Bradshaw changed review comment from: Context: The Epithelial sodium channel (ENaC) is a heterotrimer composed of 3 subunits coded by the SCNN1A, SCNN1B, SCNN1G, and SCNN1D genes.

Bush, A and Floto, R. (2019): The classical single gene disorder is α-1 antitrypsin deficiency (MIM#613490), which also causes liver disease. ENaC mutations, especially in-trans with a CFTR mutation, are thought to be risk factors for bronchiectasis, rather than actually causative. However, bronchiectasis is likely to be a very complex disease, of heterogeneous etiology, and genetic studies are likely to approach the complexity of those of asthma, rather than the classic single gene disorders such as CF.

Fajac, I. et al. (2008): Identified 3 idiopathic bronchiectasis affected individuals without CFTR variants. They found 2 variants - one of which is reported ten times as B/LB in ClinVar, and the other is reported nine times as B/LB in ClinVar.

Guan, W. et al. (2018): NGS screening study. 192 bronchiectasis patients and 100 healthy subjects. 32 genes thought to be clinically relevant were screened. No SCNN1G variants were detected in healthy or affected groups. 6 affected individuals had variants in SCNN1A and SCNN1B.; to: Context: The Epithelial sodium channel (ENaC) is a heterotrimer composed of 3 subunits coded by the SCNN1A, SCNN1B, SCNN1G, and SCNN1D genes.

Bush, A and Floto, R. (2019): The classical single gene disorder is α-1 antitrypsin deficiency (MIM#613490), which also causes liver disease. ENaC mutations, especially in-trans with a CFTR mutation, are thought to be risk factors for bronchiectasis, rather than actually causative. However, bronchiectasis is likely to be a very complex disease, of heterogeneous etiology, and genetic studies are likely to approach the complexity of those of asthma, rather than the classic single gene disorders such as CF.

Fajac, I. et al. (2008): Identified 3 idiopathic bronchiectasis affected individuals without CFTR variants. They found 2 variants - one of which is reported ten times as B/LB in ClinVar, and the other is reported nine times as B/LB in ClinVar.

Guan, W. et al. (2018): NGS screening study. 192 bronchiectasis patients and 100 healthy subjects. 32 genes thought to be clinically relevant were screened. No SCNN1G variants were detected in healthy or affected groups. 6 affected individuals had variants in SCNN1A and SCNN1B.
Ciliary Dyskinesia v1.39 SCNN1G Jonathon Bradshaw reviewed gene: SCNN1G: Rating: RED; Mode of pathogenicity: None; Publications: 30801930, 18507830, 29997923; Phenotypes: Bronchiectasis with or without elevated sweat chloride 3, MIM# 613071; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.179 TNNC1 Bryony Thompson Classified gene: TNNC1 as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.179 TNNC1 Bryony Thompson Added comment: Comment on list classification: Classified as Definitive by ClinGen Hereditary Cardiovascular Disease GCEP - 13/09/2023
Hypertrophic cardiomyopathy_HCM v0.179 TNNC1 Bryony Thompson Gene: tnnc1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.213 MPDZ Bryony Thompson Marked gene: MPDZ as ready
Syndromic Retinopathy v0.213 MPDZ Bryony Thompson Gene: mpdz has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.213 MPDZ Bryony Thompson Classified gene: MPDZ as Amber List (moderate evidence)
Syndromic Retinopathy v0.213 MPDZ Bryony Thompson Gene: mpdz has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.212 MPDZ Bryony Thompson gene: MPDZ was added
gene: MPDZ was added to Syndromic Retinopathy. Sources: Literature
Mode of inheritance for gene: MPDZ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPDZ were set to 36594712; 22159006; 21862650
Phenotypes for gene: MPDZ were set to hydrocephalus, congenital, 2, with or without brain or eye anomalies MIM:615219
Review for gene: MPDZ was set to AMBER
gene: MPDZ was marked as current diagnostic
Added comment: 2 reported siblings with syndromic maculopathy and 1 unpublished case with syndromic macular dystrophy (RMH). Multiple animal models with retinal degeneration consistent with RP/LCA.
Sources: Literature
Monogenic Diabetes v0.135 PPARG Bryony Thompson Classified gene: PPARG as Green List (high evidence)
Monogenic Diabetes v0.135 PPARG Bryony Thompson Added comment: Comment on list classification: Diabetes can be a feature of lipodystrophy which is an established gene-disease association for PPARG
Monogenic Diabetes v0.135 PPARG Bryony Thompson Gene: pparg has been classified as Green List (High Evidence).
Prepair 1000+ v1.187 CEP152 Zornitza Stark Marked gene: CEP152 as ready
Prepair 1000+ v1.187 CEP152 Zornitza Stark Gene: cep152 has been classified as Green List (High Evidence).
Prepair 1000+ v1.187 CEP152 Zornitza Stark Phenotypes for gene: CEP152 were changed from Seckel syndrome 5, 613823 (3) to Microcephaly 9, primary, autosomal recessive, MIM# 614852; MONDO:0013923; Seckel syndrome 5, MIM# 613823; MONDO:0013443
Prepair 1000+ v1.186 CEP152 Zornitza Stark Publications for gene: CEP152 were set to
Prepair 1000+ v1.185 C1QC Zornitza Stark Marked gene: C1QC as ready
Prepair 1000+ v1.185 C1QC Zornitza Stark Gene: c1qc has been classified as Green List (High Evidence).
Prepair 1000+ v1.185 C1QC Zornitza Stark Phenotypes for gene: C1QC were changed from C1q deficiency, 613652 (3) to C1q deficiency, MIM# 613652
Prepair 1000+ v1.184 C1QC Zornitza Stark Publications for gene: C1QC were set to
Prepair 1000+ v1.183 C1QC Zornitza Stark reviewed gene: C1QC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: C1q deficiency, MIM# 613652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.183 CEP41 Zornitza Stark Marked gene: CEP41 as ready
Prepair 1000+ v1.183 CEP41 Zornitza Stark Gene: cep41 has been classified as Green List (High Evidence).
Prepair 1000+ v1.183 CEP41 Zornitza Stark Phenotypes for gene: CEP41 were changed from Joubert syndrome 15, 614464 (3) to Joubert syndrome 15, MIM# 614464
Prepair 1000+ v1.182 CEP41 Zornitza Stark Publications for gene: CEP41 were set to
Prepair 1000+ v1.181 CEP41 Zornitza Stark reviewed gene: CEP41: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Joubert syndrome 15, MIM# 614464; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.181 CHRNA1 Zornitza Stark Marked gene: CHRNA1 as ready
Prepair 1000+ v1.181 CHRNA1 Zornitza Stark Gene: chrna1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.181 CHRNA1 Zornitza Stark Phenotypes for gene: CHRNA1 were changed from Multiple pterygium syndrome, lethal type, 253290 (3) to Multiple pterygium syndrome, lethal type, MIM#253290; Myasthenic syndrome, congenital, 1B, fast-channel , MIM#608930; Myasthenic syndrome, congenital, 1B, fast-channel , MIM#608930
Prepair 1000+ v1.180 CHRNA1 Zornitza Stark Publications for gene: CHRNA1 were set to
Prepair 1000+ v1.179 ETFA Zornitza Stark Marked gene: ETFA as ready
Prepair 1000+ v1.179 ETFA Zornitza Stark Gene: etfa has been classified as Green List (High Evidence).
Prepair 1000+ v1.179 ETFA Zornitza Stark Publications for gene: ETFA were set to
Prepair 1000+ v1.178 FANCB Zornitza Stark Marked gene: FANCB as ready
Prepair 1000+ v1.178 FANCB Zornitza Stark Gene: fancb has been classified as Green List (High Evidence).
Prepair 1000+ v1.178 CERS3 Zornitza Stark Marked gene: CERS3 as ready
Prepair 1000+ v1.178 CERS3 Zornitza Stark Gene: cers3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.178 CERS3 Zornitza Stark Phenotypes for gene: CERS3 were changed from Ichthyosis, congenital, autosomal recessive 9, 615023 (3) to Ichthyosis, congenital, autosomal recessive 9, MIM# 615023; MONDO:0014010
Prepair 1000+ v1.177 CERS3 Zornitza Stark Publications for gene: CERS3 were set to
Prepair 1000+ v1.176 FUCA1 Zornitza Stark Marked gene: FUCA1 as ready
Prepair 1000+ v1.176 FUCA1 Zornitza Stark Gene: fuca1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.176 FUCA1 Zornitza Stark Phenotypes for gene: FUCA1 were changed from Fucosidosis, 230000 (3) to Fucosidosis, MIM# 230000
Prepair 1000+ v1.175 G6PC3 Zornitza Stark Marked gene: G6PC3 as ready
Prepair 1000+ v1.175 G6PC3 Zornitza Stark Gene: g6pc3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.175 G6PC3 Zornitza Stark Phenotypes for gene: G6PC3 were changed from Dursun syndrome, 612541 (3) to Dursun syndrome, MIM# 612541; Neutropenia, severe congenital 4, autosomal recessive, MIM# 612541
Prepair 1000+ v1.174 G6PC3 Zornitza Stark reviewed gene: G6PC3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dursun syndrome, MIM# 612541, Neutropenia, severe congenital 4, autosomal recessive, MIM# 612541; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.174 GALT Zornitza Stark Marked gene: GALT as ready
Prepair 1000+ v1.174 GALT Zornitza Stark Gene: galt has been classified as Green List (High Evidence).
Prepair 1000+ v1.174 GALT Zornitza Stark Phenotypes for gene: GALT were changed from Galactosemia, 230400 (3) to Galactosemia MIM# 230400
Prepair 1000+ v1.173 CFTR Zornitza Stark Marked gene: CFTR as ready
Prepair 1000+ v1.173 CFTR Zornitza Stark Gene: cftr has been classified as Green List (High Evidence).
Prepair 1000+ v1.173 CFTR Zornitza Stark Phenotypes for gene: CFTR were changed from Cystic fibrosis, 219700 (3) to Cystic fibrosis, MIM#219700; MONDO:0009061
Prepair 1000+ v1.172 CFTR Zornitza Stark Publications for gene: CFTR were set to
Prepair 1000+ v1.171 ABCC8 Zornitza Stark Marked gene: ABCC8 as ready
Prepair 1000+ v1.171 ABCC8 Zornitza Stark Gene: abcc8 has been classified as Green List (High Evidence).
Prepair 1000+ v1.171 ABCC8 Zornitza Stark Phenotypes for gene: ABCC8 were changed from Hyperinsulinemic hypoglycemia, familial, 1, 256450 (3) to Diabetes mellitus, permanent neonatal 3, with or without neurologic features MIM#618857; Hyperinsulinemic hypoglycemia, familial, 1 MIM#256450
Prepair 1000+ v1.170 ABCC8 Zornitza Stark Publications for gene: ABCC8 were set to
Prepair 1000+ v1.169 ISPD Zornitza Stark Marked gene: ISPD as ready
Prepair 1000+ v1.169 ISPD Zornitza Stark Gene: ispd has been classified as Green List (High Evidence).
Prepair 1000+ v1.169 ISPD Zornitza Stark Publications for gene: ISPD were set to
Prepair 1000+ v1.168 ISPD Zornitza Stark Tag new gene name tag was added to gene: ISPD.
Pulmonary Fibrosis_Interstitial Lung Disease v0.77 CCBE1 Zornitza Stark Mode of inheritance for gene: CCBE1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Pulmonary Fibrosis_Interstitial Lung Disease v0.76 CCBE1 Zornitza Stark edited their review of gene: CCBE1: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.168 BCAP31 Zornitza Stark Marked gene: BCAP31 as ready
Prepair 1000+ v1.168 BCAP31 Zornitza Stark Added comment: Comment when marking as ready: Promote to Green at V2.
Prepair 1000+ v1.168 BCAP31 Zornitza Stark Gene: bcap31 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.168 BCAP31 Zornitza Stark Tag for review tag was added to gene: BCAP31.
Mendeliome v1.1960 ELMOD3 Zornitza Stark Classified gene: ELMOD3 as Red List (low evidence)
Mendeliome v1.1960 ELMOD3 Zornitza Stark Gene: elmod3 has been classified as Red List (Low Evidence).
Mendeliome v1.1959 ELMOD3 Zornitza Stark edited their review of gene: ELMOD3: Added comment: Discussed at GenCC: limited.; Changed rating: RED
Deafness_IsolatedAndComplex v1.196 ELMOD3 Zornitza Stark Classified gene: ELMOD3 as Red List (low evidence)
Deafness_IsolatedAndComplex v1.196 ELMOD3 Zornitza Stark Gene: elmod3 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.195 ELMOD3 Zornitza Stark edited their review of gene: ELMOD3: Added comment: Discussed at GenCC: LIMITED.; Changed rating: RED
Deafness_Isolated v1.64 ELMOD3 Zornitza Stark Classified gene: ELMOD3 as Red List (low evidence)
Deafness_Isolated v1.64 ELMOD3 Zornitza Stark Gene: elmod3 has been classified as Red List (Low Evidence).
Deafness_Isolated v1.63 ELMOD3 Zornitza Stark edited their review of gene: ELMOD3: Added comment: Discussed at GenCC: LIMITED.; Changed rating: RED
Prepair 1000+ v1.168 GTPBP2 Zornitza Stark Tag for review tag was added to gene: GTPBP2.
Prepair 1000+ v1.168 GTPBP2 Zornitza Stark reviewed gene: GTPBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26675814, 28454995, 29449720, 30790272, 38852771, 38118446; Phenotypes: Jaberi-Elahi syndrome, MIM#617988; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v1.45 YIF1B Zornitza Stark Classified gene: YIF1B as Green List (high evidence)
Genetic Epilepsy v1.45 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Genetic Epilepsy v1.44 YIF1B Zornitza Stark edited their review of gene: YIF1B: Changed rating: GREEN
Genetic Epilepsy v1.44 YIF1B Zornitza Stark edited their review of gene: YIF1B: Added comment: Multiple additional individuals now reported, including others with seizures. DEFINITIVE by ClinGen.; Changed publications: 36948290, 33103737
Prepair 1000+ v1.168 YIF1B Zornitza Stark Tag for review tag was added to gene: YIF1B.
Prepair 1000+ v1.168 YIF1B Zornitza Stark edited their review of gene: YIF1B: Added comment: DEFINITIVE gene-disease association by ClinGen. Over 20 individuals now reported in the literature.; Changed publications: 33103737, 32006098, 36948290, 34373908
Prepair 1000+ v1.168 YIF1B Zornitza Stark reviewed gene: YIF1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Kaya-Barakat-Masson syndrome, MIM# 619125; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1959 CFAP57 Zornitza Stark Phenotypes for gene: CFAP57 were changed from to Spermatogenic failure 95, MIM# 620917; Van der Woude Syndrome; Primary ciliary dyskinesia
Mendeliome v1.1958 CFAP57 Zornitza Stark Publications for gene: CFAP57 were set to
Mendeliome v1.1957 CFAP57 Zornitza Stark Classified gene: CFAP57 as Green List (high evidence)
Mendeliome v1.1957 CFAP57 Zornitza Stark Gene: cfap57 has been classified as Green List (High Evidence).
Mendeliome v1.1956 CFAP57 Zornitza Stark edited their review of gene: CFAP57: Added comment: PMID 36752199: 5 individuals from three families reported with biallelic LoF variants (two homozygous variants) and spermatogenic failure. Mouse model recapitulated the phenotype.; Changed rating: GREEN; Changed publications: 21574244, 32764743, 36752199; Changed phenotypes: Spermatogenic failure 95, MIM# 620917, Van der Woude Syndrome, Primary ciliary dyskinesia
Hereditary Neuropathy_CMT - isolated v1.49 FICD Zornitza Stark Phenotypes for gene: FICD were changed from Hereditary motor neurone disease, FICD-related, MONDO:0024257 to Spastic paraplegia 92, autosomal recessive, MIM# 620911
Hereditary Spastic Paraplegia - paediatric v1.80 FICD Zornitza Stark Phenotypes for gene: FICD were changed from Hereditary motor neurone disease, FICD-related, MONDO:0024257 to Spastic paraplegia 92, autosomal recessive, MIM# 620911
Mendeliome v1.1956 FICD Zornitza Stark Phenotypes for gene: FICD were changed from Hereditary motor neurone disease, FICD-related, MONDO:0024257 to Spastic paraplegia 92, autosomal recessive, MIM# 620911
Prepair 1000+ v1.168 CFTR Marta Cifuentes Ochoa reviewed gene: CFTR: Rating: GREEN; Mode of pathogenicity: None; Publications: 31199594, 19092437, 38153325, 26708955, 32172939; Phenotypes: Cystic fibrosis, MIM#219700, MONDO:0009061; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.168 GALT Lucy Spencer reviewed gene: GALT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Galactosemia MIM# 230400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.168 G6PC3 Lucy Spencer reviewed gene: G6PC3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.168 FUCA1 Lucy Spencer reviewed gene: FUCA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fucosidosis, MIM# 230000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.168 CERS3 Marta Cifuentes Ochoa reviewed gene: CERS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23754960, 23549421, 31168818, 30578701, 37128664; Phenotypes: Ichthyosis, congenital, autosomal recessive 9, MIM# 615023, MONDO:0014010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.168 FANCB Lucy Spencer reviewed gene: FANCB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anaemia, complementation group B, MIM#300514; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.168 ETFA Lucy Spencer reviewed gene: ETFA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31904027; Phenotypes: Glutaric acidemia IIA, MIM# 231680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v1.58 PSKH1 Chirag Patel Classified gene: PSKH1 as Green List (high evidence)
Ciliopathies v1.58 PSKH1 Chirag Patel Gene: pskh1 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v1.25 PSKH1 Chirag Patel Classified gene: PSKH1 as Green List (high evidence)
Renal Ciliopathies and Nephronophthisis v1.25 PSKH1 Chirag Patel Gene: pskh1 has been classified as Green List (High Evidence).
Cholestasis v0.242 PSKH1 Chirag Patel Classified gene: PSKH1 as Green List (high evidence)
Cholestasis v0.242 PSKH1 Chirag Patel Gene: pskh1 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v1.24 PSKH1 Chirag Patel gene: PSKH1 was added
gene: PSKH1 was added to Renal Ciliopathies and Nephronophthisis. Sources: Literature
Mode of inheritance for gene: PSKH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSKH1 were set to PMID: 39132680
Phenotypes for gene: PSKH1 were set to Hepatorenal syndrome, MONDO:0001382
Review for gene: PSKH1 was set to GREEN
gene: PSKH1 was marked as current diagnostic
Added comment: 4 consanguineous families (out of 279 families) with intrahepatic cholestasis:
-1 patient died at 10mths with cholestasis/liver impairment and kidney impairment
-3 cousins with cholestasis (2 with liver failure needing transplant) and kidney features (2 with kidney failure, 1 with renal echogenicity)
-2 siblings with hepatic fibrosis (1 with unilateral renal agenesis)
-2 siblings with unexplained liver cirrhosis (1 needing transplant) but normal kidney function

WES identified 3 different homozygous variants in PSKH1 (Arg121Trp, Ile126Val, Arg183Cys). Patient fibroblasts displayed abnormal cilia that are long and show abnormal transport. A homozygous Pskh1 mutant mouse faithfully recapitulated the human phenotype and displayed abnormally long cilia. The phenotype could be rationalized by the loss of catalytic activity observed for each recombinant PSKH1 variant using in vitro kinase assays. Human PSKH1 is a poorly understood gene that may play important role in intracellular trafficking, is sensitive to intracellular Ca2+ concentration, and is localized to centrosomes, suggesting a link to cystogenesis.
Sources: Literature
Ciliopathies v1.57 PSKH1 Chirag Patel gene: PSKH1 was added
gene: PSKH1 was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: PSKH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSKH1 were set to PMID: 39132680
Phenotypes for gene: PSKH1 were set to Hepatorenal syndrome, MONDO:0001382
Review for gene: PSKH1 was set to GREEN
gene: PSKH1 was marked as current diagnostic
Added comment: 4 consanguineous families (out of 279 families) with intrahepatic cholestasis:
-1 patient died at 10mths with cholestasis/liver impairment and kidney impairment
-3 cousins with cholestasis (2 with liver failure needing transplant) and kidney features (2 with kidney failure, 1 with renal echogenicity)
-2 siblings with hepatic fibrosis (1 with unilateral renal agenesis)
-2 siblings with unexplained liver cirrhosis (1 needing transplant) but normal kidney function

WES identified 3 different homozygous variants in PSKH1 (Arg121Trp, Ile126Val, Arg183Cys). Patient fibroblasts displayed abnormal cilia that are long and show abnormal transport. A homozygous Pskh1 mutant mouse faithfully recapitulated the human phenotype and displayed abnormally long cilia. The phenotype could be rationalized by the loss of catalytic activity observed for each recombinant PSKH1 variant using in vitro kinase assays. Human PSKH1 is a poorly understood gene that may play important role in intracellular trafficking, is sensitive to intracellular Ca2+ concentration, and is localized to centrosomes, suggesting a link to cystogenesis.
Sources: Literature
Cholestasis v0.241 PSKH1 Chirag Patel gene: PSKH1 was added
gene: PSKH1 was added to Cholestasis. Sources: Literature
Mode of inheritance for gene: PSKH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSKH1 were set to PMID: 39132680
Phenotypes for gene: PSKH1 were set to Hepatorenal syndrome, MONDO:0001382
Review for gene: PSKH1 was set to GREEN
gene: PSKH1 was marked as current diagnostic
Added comment: 4 consanguineous families (out of 279 families) with intrahepatic cholestasis:
-1 patient died at 10mths with cholestasis/liver impairment and kidney impairment
-3 cousins with cholestasis (2 with liver failure needing transplant) and kidney features (2 with kidney failure, 1 with renal echogenicity)
-2 siblings with hepatic fibrosis (1 with unilateral renal agenesis)
-2 siblings with unexplained liver cirrhosis (1 needing transplant) but normal kidney function

WES identified 3 different homozygous variants in PSKH1 (Arg121Trp, Ile126Val, Arg183Cys). Patient fibroblasts displayed abnormal cilia that are long and show abnormal transport. A homozygous Pskh1 mutant mouse faithfully recapitulated the human phenotype and displayed abnormally long cilia. The phenotype could be rationalized by the loss of catalytic activity observed for each recombinant PSKH1 variant using in vitro kinase assays. Human PSKH1 is a poorly understood gene that may play important role in intracellular trafficking, is sensitive to intracellular Ca2+ concentration, and is localized to centrosomes, suggesting a link to cystogenesis.
Sources: Literature
Renal Ciliopathies and Nephronophthisis v1.23 IFT140 Chirag Patel reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 39136524; Phenotypes: Cystic Kidney Disease, MONDO# 0002473; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Renal Macrocystic Disease v0.70 IFT140 Chirag Patel edited their review of gene: IFT140: Added comment: 368 patients with IFT140 LoF variants and a spectrum of phenotypic findings that support the association of IFT140 with PKD. A cystic phenotype was reported in 223 of the 368 (60.6%) individuals harboring an IFT140 LoF variant, 98% of which had no other identified cause for their cystic disease. Of 122 unique LoF IFT140 variants identified, 56 (46%) were frameshift, 38 (31%) nonsense, 22 (18%) splice site and 6 (5%) exon-level deletions. Only six IFT140 individuals were reported with end-stage kidney disease, consistent with observed milder clinical presentations in IFT140-related PKD.; Changed publications: PMID: 39136524; Changed phenotypes: Cystic Kidney Disease, MONDO# 0002473; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Set current diagnostic: yes
Mendeliome v1.1955 FIG4 Zornitza Stark Marked gene: FIG4 as ready
Mendeliome v1.1955 FIG4 Zornitza Stark Gene: fig4 has been classified as Green List (High Evidence).
Incidentalome v0.308 FIG4 Zornitza Stark Marked gene: FIG4 as ready
Incidentalome v0.308 FIG4 Zornitza Stark Added comment: Comment when marking as ready: Moved to Mendeliome. Associations with CMT and Yunis-Varon are well established whereas association with ALS/FTD is not.
Incidentalome v0.308 FIG4 Zornitza Stark Gene: fig4 has been removed from the panel.
Incidentalome v0.308 FIG4 Zornitza Stark Classified gene: FIG4 as No list
Incidentalome v0.308 FIG4 Zornitza Stark Gene: fig4 has been removed from the panel.
Mendeliome v1.1955 FIG4 Zornitza Stark Classified gene: FIG4 as Green List (high evidence)
Mendeliome v1.1955 FIG4 Zornitza Stark Gene: fig4 has been classified as Green List (High Evidence).
Mendeliome v1.1954 FIG4 Zornitza Stark gene: FIG4 was added
gene: FIG4 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: FIG4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FIG4 were set to 23623387; 17572665; 21705420; 24878229; 18758830; 24598713
Phenotypes for gene: FIG4 were set to Yunis-Varon syndrome - MIM#216340; Polymicrogyria with epilepsy MIM# 612691; Charcot-Marie-Tooth disease, type 4J 611228; Amyotrophic lateral sclerosis 11, MIM# 612577
Review for gene: FIG4 was set to GREEN
Added comment: Associations between biallelic variants and CMT and Yunis Varon syndrome are well established.

Limited evidence for association with brain malformations and with ALS/FTD.
Sources: Expert Review
Incidentalome v0.307 DICER1 Zornitza Stark Mode of inheritance for gene: DICER1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.306 CDH1 Zornitza Stark Mode of inheritance for gene: CDH1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.305 CACNA1S Zornitza Stark Marked gene: CACNA1S as ready
Incidentalome v0.305 CACNA1S Zornitza Stark Gene: cacna1s has been classified as Green List (High Evidence).
Incidentalome v0.305 CACNA1S Zornitza Stark Phenotypes for gene: CACNA1S were changed from to Malignant hyperthermia susceptibility 5, MIM# 601887
Incidentalome v0.304 CACNA1S Zornitza Stark Mode of inheritance for gene: CACNA1S was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.303 APOE Zornitza Stark Marked gene: APOE as ready
Incidentalome v0.303 APOE Zornitza Stark Gene: apoe has been classified as Green List (High Evidence).
Incidentalome v0.303 APOE Zornitza Stark Publications for gene: APOE were set to
Incidentalome v0.302 APOE Zornitza Stark Mode of inheritance for gene: APOE was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Proteinuria v0.227 WT1 Zornitza Stark Marked gene: WT1 as ready
Proteinuria v0.227 WT1 Zornitza Stark Gene: wt1 has been classified as Green List (High Evidence).
Proteinuria v0.227 WT1 Zornitza Stark Phenotypes for gene: WT1 were changed from to Denys-Drash syndrome, MIM# 194080; Frasier syndrome, MIM#136680; Wilms tumor, type 1, MIM#194070; Nephrotic syndrome, type 4, MIM#256370
Proteinuria v0.226 WT1 Zornitza Stark Mode of inheritance for gene: WT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.168 CHRNA1 Cassandra Muller reviewed gene: CHRNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18806275, 10195214, 12588888, 18252226, 36092864; Phenotypes: Myasthenic syndrome, congenital, 1B, fast-channel , MIM#608930, Myasthenic syndrome, congenital, 1B, fast-channel , MIM#608930; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.235 NACC1 Shekeeb Mohammad gene: NACC1 was added
gene: NACC1 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: NACC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NACC1 were set to 38698576
Phenotypes for gene: NACC1 were set to chorea; dystonia; epilepsy; microcephaly; cataracts; dysautonomia; iron deficiency anemia; stereotypies
Penetrance for gene: NACC1 were set to unknown
Review for gene: NACC1 was set to GREEN
gene: NACC1 was marked as current diagnostic
Added comment: Sources: Literature
Genomic newborn screening: BabyScreen+ v1.114 GCH1 Lilian Downie Mode of inheritance for gene: GCH1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v1.113 GCH1 Lilian Downie reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301681; Phenotypes: Dystonia, DOPA-responsive MIM#128230; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.168 MAN2B1 Lilian Downie Marked gene: MAN2B1 as ready
Prepair 1000+ v1.168 MAN2B1 Lilian Downie Gene: man2b1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.168 MAN2B1 Lilian Downie Publications for gene: MAN2B1 were set to
Prepair 1000+ v1.167 MEGF8 Lilian Downie Marked gene: MEGF8 as ready
Prepair 1000+ v1.167 MEGF8 Lilian Downie Gene: megf8 has been classified as Green List (High Evidence).
Prepair 1000+ v1.167 MEGF8 Lilian Downie Publications for gene: MEGF8 were set to 23063620
Prepair 1000+ v1.166 MEGF8 Lilian Downie Publications for gene: MEGF8 were set to
Prepair 1000+ v1.165 MMADHC Lilian Downie Marked gene: MMADHC as ready
Prepair 1000+ v1.165 MMADHC Lilian Downie Gene: mmadhc has been classified as Green List (High Evidence).
Prepair 1000+ v1.165 MMADHC Lilian Downie Publications for gene: MMADHC were set to
Prepair 1000+ v1.164 MOCS2 Lilian Downie Marked gene: MOCS2 as ready
Prepair 1000+ v1.164 MOCS2 Lilian Downie Gene: mocs2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.164 MOCS2 Lilian Downie Publications for gene: MOCS2 were set to
Prepair 1000+ v1.163 MOGS Lilian Downie Marked gene: MOGS as ready
Prepair 1000+ v1.163 MOGS Lilian Downie Added comment: Comment when marking as ready: To upgrade to green
Prepair 1000+ v1.163 MOGS Lilian Downie Gene: mogs has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.163 MOGS Lilian Downie Tag for review tag was added to gene: MOGS.
Prepair 1000+ v1.163 MOGS Lilian Downie Publications for gene: MOGS were set to 30587846; 33058492; 31925597
Prepair 1000+ v1.162 NGLY1 Lilian Downie Marked gene: NGLY1 as ready
Prepair 1000+ v1.162 NGLY1 Lilian Downie Gene: ngly1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.162 NGLY1 Lilian Downie Publications for gene: NGLY1 were set to
Prepair 1000+ v1.161 NKX3-2 Lilian Downie Marked gene: NKX3-2 as ready
Prepair 1000+ v1.161 NKX3-2 Lilian Downie Gene: nkx3-2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.161 NKX3-2 Lilian Downie Publications for gene: NKX3-2 were set to
Prepair 1000+ v1.160 NTNG2 Lilian Downie Marked gene: NTNG2 as ready
Prepair 1000+ v1.160 NTNG2 Lilian Downie Added comment: Comment when marking as ready: To be upgraded to green
Prepair 1000+ v1.160 NTNG2 Lilian Downie Gene: ntng2 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.160 NTNG2 Lilian Downie Tag for review tag was added to gene: NTNG2.
Prepair 1000+ v1.160 OBSL1 Lilian Downie Marked gene: OBSL1 as ready
Prepair 1000+ v1.160 OBSL1 Lilian Downie Gene: obsl1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.160 OBSL1 Lilian Downie Publications for gene: OBSL1 were set to
Prepair 1000+ v1.159 CEP41 Cassandra Muller reviewed gene: CEP41: Rating: ; Mode of pathogenicity: None; Publications: 22246503, 36580738; Phenotypes: Joubert syndrome 15, 614464 (3); Mode of inheritance: None
Prepair 1000+ v1.159 C1QC Cassandra Muller reviewed gene: C1QC: Rating: GREEN; Mode of pathogenicity: None; Publications: 21654842, 8630118, 31357913; Phenotypes: C1q deficiency, 613652 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.159 CEP152 Marta Cifuentes Ochoa reviewed gene: CEP152: Rating: GREEN; Mode of pathogenicity: None; Publications: 20598275, 22775483, 21131973, 23199753, 36685824; Phenotypes: Microcephaly 9, primary, autosomal recessive, MIM# 614852, MONDO:0013923, Seckel syndrome 5, MIM# 613823, MONDO:0013443; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.159 BTK Marta Cifuentes Ochoa reviewed gene: BTK: Rating: GREEN; Mode of pathogenicity: None; Publications: 8013627, 7849697, 31481959, 15024743, 34182127, 16951917; Phenotypes: Agammaglobulinemia, X-linked 1 MIM#300755, Bruton-type agammaglobulinemia MONDO:0010421, Isolated growth hormone deficiency, type III, with agammaglobulinemia MIM#307200 MONDO:0010615; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.159 HBA2 Andrew Coventry reviewed gene: HBA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 21345100 12393486 23715323 6725554 6725554 36907606; Phenotypes: Thalassemias, alpha- MIM#604131, Hemoglobin H disease, nondeletional MIM#613978; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.159 HBA2 Andrew Coventry Deleted their review
Prepair 1000+ v1.159 HBA2 Andrew Coventry changed review comment from: Well established and strong gene-disease association. Alpha-thalassemia result in anaemias from early childhood when fetal haemoglobin expression is diminished. Haemoglobinopathies of alpha-globin can result from variants at either of the 2 alpha-globin loci, HBA1 or HBA2.

Subtypes:
Haemoglobin H disease is a subtype of alpha-thalassemia:
Deletional' Hb H disease is caused by the combination of alpha(0)-thalassemia with deletional alpha(+)-thalassemia.
Deletional Haemoglobin H - phenotypic variability ranging from asymptomatic, to needing periodic transfusions, to severe anaemia with haemolysis and hepatosplenomegaly, to fatal hydrops fetalis in utero. Variable age of onset and features - see PMID: 21345100

'Nondeletional' Hb H disease is caused by an alpha(0)-thalassemia plus an alpha(+)-thalassemia point mutation or small insertion/deletion. Disease phenotype is usually are greater levels of anaemia, more symptomatic, more likely to have significant hepatosplenomegaly, and greater likelihood to require transfusions.

Note: Deletions are well known and frequent cause of these alpha thalassemia phenotypes and subtypes. Diverse range of non-deletional HBA2 variants also described. Possible technological challenge due to deletions which are prevalent.; to: Well established gene-disease association. The alpha-thalassemia phenotype ranges from asymptomatic to lethal. The severity of the disorder is usually well correlated with the number of non-functional copies of the alpha-globin genes (HBA1/HBA2). Gene function can be lost by deletion, or by SNVs (total loss or partial).The clinically relevant forms of alpha-thalassemia usually involve alpha(0)-thalassemia, either coinherited with alpha(+)-thalassemia and resulting in HbH disease, or inherited from both parents and resulting in haemoglobin Bart hydrops fetalis.

Note: Deletions are well known and frequent cause of these alpha thalassemia phenotypes and subtypes. Diverse range of non-deletional HBA2 variants also described. Possible technological challenge due to deletions which are prevalent.
Prepair 1000+ v1.159 HBA1 Andrew Coventry reviewed gene: HBA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21381239 11722414 36907606; Phenotypes: Thalassemias, alpha- MIM#604131, Hemoglobin H disease, nondeletional MIM#613978; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.159 BRF1 Marta Cifuentes Ochoa reviewed gene: BRF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25561519, 25561519, 27748960, 33645901, 32896090, 34628026; Phenotypes: Cerebellofaciodental syndrome, MIM# 616202, Cerebellar-facial-dental syndrome MONDO:0014529; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.159 BRF1 Marta Cifuentes Ochoa Deleted their review
Prepair 1000+ v1.159 BRF1 Marta Cifuentes Ochoa reviewed gene: BRF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25561519, 25561519, 27748960, 33645901, 32896090, 34628026; Phenotypes: Cerebellofaciodental syndrome, MIM# 616202, Cerebellar-facial-dental syndrome MONDO:0014529; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.159 HBA2 Andrew Coventry reviewed gene: HBA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 21345100 12393486 23715323 6725554 6725554; Phenotypes: Thalassemias, alpha- MIM#604131, Hemoglobin H disease, deletional and nondeletional MIM#613978; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.159 B4GALT7 Marta Cifuentes Ochoa reviewed gene: B4GALT7: Rating: GREEN; Mode of pathogenicity: None; Publications: 23956117, 24755949, 31614862, 34193099, 26940150; Phenotypes: Ehlers-Danlos syndrome, spondylodysplastic type, 1, MIM# 130070, MONDO:0020682; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.159 AUH Marta Cifuentes Ochoa reviewed gene: AUH: Rating: GREEN; Mode of pathogenicity: None; Publications: 12434311, 16354225, 20855850, 21840233; Phenotypes: 3-methylglutaconic aciduria, type I, MIM# 250950, MONDO:0009610; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.159 AUH Marta Cifuentes Ochoa Deleted their review
Prepair 1000+ v1.159 AUH Marta Cifuentes Ochoa reviewed gene: AUH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 12434311, 16354225, 20855850, 21840233; Phenotypes: 3-methylglutaconic aciduria, type I MIM#250950, MONDO:0009610; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.159 ASCC1 Marta Cifuentes Ochoa reviewed gene: ASCC1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30327447, 12077347, 26924529, 31880396, 26503956; Phenotypes: Arthrogryposis, congenital bone fractures, spinal muscular atrophy, spinal muscular atrophy with congenital bone fractures 2 MONDO:0014807, SMABF2 MIM#616867; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.159 PGM1 Lilian Downie Marked gene: PGM1 as ready
Prepair 1000+ v1.159 PGM1 Lilian Downie Gene: pgm1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.159 PGM1 Lilian Downie Publications for gene: PGM1 were set to
Prepair 1000+ v1.158 ORC1 Lilian Downie Marked gene: ORC1 as ready
Prepair 1000+ v1.158 ORC1 Lilian Downie Gene: orc1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.158 ORC1 Lilian Downie Publications for gene: ORC1 were set to
Prepair 1000+ v1.157 PGM3 Lilian Downie Marked gene: PGM3 as ready
Prepair 1000+ v1.157 PGM3 Lilian Downie Gene: pgm3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.157 PGM3 Lilian Downie Publications for gene: PGM3 were set to
Prepair 1000+ v1.156 PIGA Lilian Downie Publications for gene: PIGA were set to
Prepair 1000+ v1.155 PIGA Lilian Downie Marked gene: PIGA as ready
Prepair 1000+ v1.155 PIGA Lilian Downie Gene: piga has been classified as Green List (High Evidence).
Prepair 1000+ v1.155 PIGA Lilian Downie Phenotypes for gene: PIGA were changed from Multiple congenital anomalies-hypotonia-seizures syndrome 2, 300868 (3) to Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM#300868; Neurodevelopmental disorder with epilepsy and hemochromatosis, MIM#301072
Prepair 1000+ v1.154 PLPBP Lilian Downie Marked gene: PLPBP as ready
Prepair 1000+ v1.154 PLPBP Lilian Downie Gene: plpbp has been classified as Green List (High Evidence).
Prepair 1000+ v1.154 PLPBP Lilian Downie Publications for gene: PLPBP were set to
Prepair 1000+ v1.153 PMM2 Lilian Downie Marked gene: PMM2 as ready
Prepair 1000+ v1.153 PMM2 Lilian Downie Gene: pmm2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.153 PMM2 Lilian Downie Publications for gene: PMM2 were set to
Prepair 1000+ v1.152 RAB3GAP1 Lilian Downie Marked gene: RAB3GAP1 as ready
Prepair 1000+ v1.152 RAB3GAP1 Lilian Downie Gene: rab3gap1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.152 RIN2 Lilian Downie Marked gene: RIN2 as ready
Prepair 1000+ v1.152 RIN2 Lilian Downie Gene: rin2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.152 RIN2 Lilian Downie Publications for gene: RIN2 were set to
Prepair 1000+ v1.151 RNASEH2C Lilian Downie Marked gene: RNASEH2C as ready
Prepair 1000+ v1.151 RNASEH2C Lilian Downie Gene: rnaseh2c has been classified as Green List (High Evidence).
Prepair 1000+ v1.151 RNASEH2C Lilian Downie Publications for gene: RNASEH2C were set to
Prepair 1000+ v1.150 SGCG Lilian Downie Marked gene: SGCG as ready
Prepair 1000+ v1.150 SGCG Lilian Downie Gene: sgcg has been classified as Green List (High Evidence).
Prepair 1000+ v1.150 SGCG Lilian Downie Publications for gene: SGCG were set to
Prepair 1000+ v1.149 SLC46A1 Lilian Downie Marked gene: SLC46A1 as ready
Prepair 1000+ v1.149 SLC46A1 Lilian Downie Gene: slc46a1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.149 SLC46A1 Lilian Downie Publications for gene: SLC46A1 were set to
Prepair 1000+ v1.148 SUCLG1 Lilian Downie Marked gene: SUCLG1 as ready
Prepair 1000+ v1.148 SUCLG1 Lilian Downie Gene: suclg1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.148 SUCLG1 Lilian Downie Publications for gene: SUCLG1 were set to
Prepair 1000+ v1.147 SURF1 Lilian Downie Marked gene: SURF1 as ready
Prepair 1000+ v1.147 SURF1 Lilian Downie Added comment: Comment when marking as ready: Consider most appropriate name- literature commonly refers to as Leigh syndrome but MIM 256000 doesn't have SURF1 attached to it. No overarching MONDO. Maybe MItochondrial complex IV deficiency MIM220110 is the most appropriate
Prepair 1000+ v1.147 SURF1 Lilian Downie Gene: surf1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.147 SURF1 Lilian Downie Tag for review tag was added to gene: SURF1.
Prepair 1000+ v1.147 SURF1 Lilian Downie Publications for gene: SURF1 were set to
Prepair 1000+ v1.146 TPK1 Lilian Downie Marked gene: TPK1 as ready
Prepair 1000+ v1.146 TPK1 Lilian Downie Gene: tpk1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.146 TPK1 Lilian Downie Publications for gene: TPK1 were set to
Prepair 1000+ v1.145 TUBGCP4 Lilian Downie Marked gene: TUBGCP4 as ready
Prepair 1000+ v1.145 TUBGCP4 Lilian Downie Gene: tubgcp4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.145 TUBGCP4 Lilian Downie Publications for gene: TUBGCP4 were set to
Prepair 1000+ v1.144 TUFM Lilian Downie Marked gene: TUFM as ready
Prepair 1000+ v1.144 TUFM Lilian Downie Added comment: Comment when marking as ready: PMID: 37433570 can have a milder, later onset
Prepair 1000+ v1.144 TUFM Lilian Downie Gene: tufm has been classified as Green List (High Evidence).
Prepair 1000+ v1.144 TUFM Lilian Downie Publications for gene: TUFM were set to
Prepair 1000+ v1.143 CSMD1 Krithika Murali gene: CSMD1 was added
gene: CSMD1 was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to PMID:38816421
Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CSMD1 was set to GREEN
Added comment: PMID 38816421 Werren et al 2024 report 8 individuals from 6 families with biallelic missense CSMD1 variants identified through exome sequencing and subsequent gene-sharing efforts. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected.

Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells. ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autism and ID GCEP.
Sources: Literature
Prepair 1000+ v1.142 ATP8B1 Cassandra Muller reviewed gene: ATP8B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cholestasis, progressive familial intrahepatic 1, 211600 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Spontaneous coronary artery dissection v0.52 Zornitza Stark Panel status changed from internal to public
Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Spontaneous coronary artery dissection v0.51 YY1AP1 Zornitza Stark reviewed gene: YY1AP1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Grange syndrome, MIM# 602531; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6122 CSNK1G1 Rylee Peters reviewed gene: CSNK1G1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 33009664; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CSNK1G-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1953 CSNK1G1 Rylee Peters reviewed gene: CSNK1G1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 33009664; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CSNK1G-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Spontaneous coronary artery dissection v0.51 TGFBR1 Zornitza Stark reviewed gene: TGFBR1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Loeys-Dietz syndrome 1, MIM# 609192; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Spontaneous coronary artery dissection v0.51 MYLK Zornitza Stark Marked gene: MYLK as ready
Spontaneous coronary artery dissection v0.51 MYLK Zornitza Stark Gene: mylk has been classified as Amber List (Moderate Evidence).
Spontaneous coronary artery dissection v0.51 MYLK Zornitza Stark reviewed gene: MYLK: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Aortic aneurysm, familial thoracic 7 MIM#613780; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Spontaneous coronary artery dissection v0.51 LOX Zornitza Stark reviewed gene: LOX: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Aortic aneurysm, familial thoracic 10 MIM#617168; Mode of inheritance: None
Spontaneous coronary artery dissection v0.51 LMX1B Zornitza Stark Classified gene: LMX1B as Red List (low evidence)
Spontaneous coronary artery dissection v0.51 LMX1B Zornitza Stark Gene: lmx1b has been classified as Red List (Low Evidence).
Spontaneous coronary artery dissection v0.50 LMX1B Zornitza Stark reviewed gene: LMX1B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Nail-patella syndrome MIM#161200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Spontaneous coronary artery dissection v0.50 FLNA Zornitza Stark reviewed gene: FLNA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: periventricular heterotopia 1 MIM#300049; Mode of inheritance: None
Mendeliome v1.1953 REXO2 Zornitza Stark Marked gene: REXO2 as ready
Mendeliome v1.1953 REXO2 Zornitza Stark Gene: rexo2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1953 REXO2 Zornitza Stark Classified gene: REXO2 as Amber List (moderate evidence)
Mendeliome v1.1953 REXO2 Zornitza Stark Gene: rexo2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1952 REXO2 Zornitza Stark gene: REXO2 was added
gene: REXO2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: REXO2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: REXO2 were set to 39107301
Phenotypes for gene: REXO2 were set to Type 1 interferonopathy of childhood, MONDO:0957408, REXO2-related
Review for gene: REXO2 was set to AMBER
Added comment: Female infant of Chinese ancestry, presented at 2 years of age with whole-body rash with histological features of hyperkeratosis, parakeratosis and acanthosis with elongated rete ridges, focal liquefaction and degeneration of the basal layers of epidermis, vascular proliferation in the superficial dermis, infiltration of lymphocytes and eosinophils around small blood vessels in the dermis. She has recurrent infections (frequent and severe pneumonia). Extensive functional validation demonstrating heterozygous de novo mutation (p.T132A) impairs REXO2’s ability to cleave RNA leading to activation of the dsRNA sensor MDA5 leading to a Type 1 interferonopathy.
Sources: Literature
Autoinflammatory Disorders v1.50 REXO2 Zornitza Stark Marked gene: REXO2 as ready
Autoinflammatory Disorders v1.50 REXO2 Zornitza Stark Gene: rexo2 has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v1.50 REXO2 Zornitza Stark Phenotypes for gene: REXO2 were changed from type 1 interferonopathy to Type 1 interferonopathy of childhood, MONDO:0957408, REXO2-related
Autoinflammatory Disorders v1.49 REXO2 Zornitza Stark Classified gene: REXO2 as Amber List (moderate evidence)
Autoinflammatory Disorders v1.49 REXO2 Zornitza Stark Gene: rexo2 has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v1.48 REXO2 Zornitza Stark reviewed gene: REXO2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Type 1 interferonopathy of childhood, MONDO:0957408, REXO2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1951 TMEFF1 Zornitza Stark Marked gene: TMEFF1 as ready
Mendeliome v1.1951 TMEFF1 Zornitza Stark Gene: tmeff1 has been classified as Green List (High Evidence).
Mendeliome v1.1951 TMEFF1 Zornitza Stark Classified gene: TMEFF1 as Green List (high evidence)
Mendeliome v1.1951 TMEFF1 Zornitza Stark Gene: tmeff1 has been classified as Green List (High Evidence).
Mendeliome v1.1950 TMEFF1 Zornitza Stark gene: TMEFF1 was added
gene: TMEFF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEFF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEFF1 were set to 39048830
Phenotypes for gene: TMEFF1 were set to Hereditary susceptibility to infections, MONDO:0015979, TMEFF1-related; HSV encephalitis
Review for gene: TMEFF1 was set to GREEN
Added comment: 2 unrelated patients with severe HSV encephalitis. Functional validation showing that human TMEFF1 encodes a type I IFN-independent, cortical neuron- and CNS-intrinsic restriction factor that is effective against HSV-1 that operates by impairing the entry of HSV-1 into cortical neurons.
Sources: Literature
Susceptibility to Viral Infections v0.128 TMEFF1 Zornitza Stark Marked gene: TMEFF1 as ready
Susceptibility to Viral Infections v0.128 TMEFF1 Zornitza Stark Gene: tmeff1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.142 ASNS Cassandra Muller reviewed gene: ASNS: Rating: GREEN; Mode of pathogenicity: None; Publications: 24139043, 27469131, 29375865, 28776279; Phenotypes: Asparagine synthetase deficiency, 615574; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Susceptibility to Viral Infections v0.128 TMEFF1 Zornitza Stark Phenotypes for gene: TMEFF1 were changed from hsv encephalitis to Hereditary susceptibility to infections, MONDO:0015979, TMEFF1-related; HSV encephalitis
Susceptibility to Viral Infections v0.127 TMEFF1 Zornitza Stark Classified gene: TMEFF1 as Green List (high evidence)
Susceptibility to Viral Infections v0.127 TMEFF1 Zornitza Stark Gene: tmeff1 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.126 TMEFF1 Zornitza Stark reviewed gene: TMEFF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hereditary susceptibility to infections, MONDO:0015979, TMEFF1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.52 PROS1 Zornitza Stark Marked gene: PROS1 as ready
Bleeding and Platelet Disorders v1.52 PROS1 Zornitza Stark Gene: pros1 has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.52 PROS1 Zornitza Stark Classified gene: PROS1 as Green List (high evidence)
Bleeding and Platelet Disorders v1.52 PROS1 Zornitza Stark Gene: pros1 has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.51 SERPINC1 Zornitza Stark Marked gene: SERPINC1 as ready
Bleeding and Platelet Disorders v1.51 SERPINC1 Zornitza Stark Gene: serpinc1 has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.51 SERPINC1 Zornitza Stark edited their review of gene: SERPINC1: Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.51 SERPINC1 Zornitza Stark Classified gene: SERPINC1 as Green List (high evidence)
Bleeding and Platelet Disorders v1.51 SERPINC1 Zornitza Stark Gene: serpinc1 has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.50 SERPINC1 Zornitza Stark reviewed gene: SERPINC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombophilia 7 due to antithrombin III deficiency #613118; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bleeding and Platelet Disorders v1.50 SERPIND1 Zornitza Stark Marked gene: SERPIND1 as ready
Bleeding and Platelet Disorders v1.50 SERPIND1 Zornitza Stark Gene: serpind1 has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.50 SERPIND1 Zornitza Stark Phenotypes for gene: SERPIND1 were changed from HEPARIN COFACTOR II DEFICIENCY #612356 to heparin cofactor 2 deficiency, MONDO:0012876; Thrombophilia 10 due to heparin cofactor II deficiency, MIM#612356
Bleeding and Platelet Disorders v1.49 SERPIND1 Zornitza Stark Publications for gene: SERPIND1 were set to PMID: 12421148; PMID: 35592395; PMID: 2647747; PMID: 11204559; PMID: 10494755
Bleeding and Platelet Disorders v1.48 SERPIND1 Zornitza Stark Classified gene: SERPIND1 as Green List (high evidence)
Bleeding and Platelet Disorders v1.48 SERPIND1 Zornitza Stark Gene: serpind1 has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.47 SERPIND1 Zornitza Stark reviewed gene: SERPIND1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8902986, 15337701, 31064749, 11204559, 8562924, 29296762, 2863444, 2647747, 17549254, 11805133; Phenotypes: heparin cofactor 2 deficiency, MONDO:0012876, Thrombophilia 10 due to heparin cofactor II deficiency, MIM#612356; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.142 ARL13B Cassandra Muller reviewed gene: ARL13B: Rating: GREEN; Mode of pathogenicity: None; Publications: 38219074, 18674751, 25138100, 26092869, 27894351, 29255182; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.265 CSMD1 Zornitza Stark Marked gene: CSMD1 as ready
Fetal anomalies v1.265 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Fetal anomalies v1.265 CSMD1 Zornitza Stark Classified gene: CSMD1 as Green List (high evidence)
Fetal anomalies v1.265 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.310 CSMD1 Zornitza Stark Marked gene: CSMD1 as ready
Leukodystrophy - paediatric v0.310 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.310 CSMD1 Zornitza Stark Classified gene: CSMD1 as Green List (high evidence)
Leukodystrophy - paediatric v0.310 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6122 CSMD1 Zornitza Stark Marked gene: CSMD1 as ready
Intellectual disability syndromic and non-syndromic v0.6122 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6122 CSMD1 Zornitza Stark Classified gene: CSMD1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6122 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Callosome v0.527 CSMD1 Zornitza Stark Marked gene: CSMD1 as ready
Callosome v0.527 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Callosome v0.527 CSMD1 Zornitza Stark Classified gene: CSMD1 as Green List (high evidence)
Callosome v0.527 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.44 CSMD1 Zornitza Stark Marked gene: CSMD1 as ready
Genetic Epilepsy v1.44 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.44 CSMD1 Zornitza Stark Classified gene: CSMD1 as Green List (high evidence)
Genetic Epilepsy v1.44 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.67 CSMD1 Zornitza Stark Marked gene: CSMD1 as ready
Muscular dystrophy and myopathy_Paediatric v1.67 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.67 CSMD1 Zornitza Stark Classified gene: CSMD1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.67 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Microcephaly v1.271 CSMD1 Zornitza Stark Marked gene: CSMD1 as ready
Microcephaly v1.271 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Microcephaly v1.271 CSMD1 Zornitza Stark Classified gene: CSMD1 as Green List (high evidence)
Microcephaly v1.271 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Mendeliome v1.1949 CSMD1 Zornitza Stark Marked gene: CSMD1 as ready
Mendeliome v1.1949 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Mendeliome v1.1949 CSMD1 Zornitza Stark Classified gene: CSMD1 as Green List (high evidence)
Mendeliome v1.1949 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Arthrogryposis v0.413 CSMD1 Zornitza Stark Marked gene: CSMD1 as ready
Arthrogryposis v0.413 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Arthrogryposis v0.413 CSMD1 Zornitza Stark Classified gene: CSMD1 as Green List (high evidence)
Arthrogryposis v0.413 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.191 CSMD1 Zornitza Stark Marked gene: CSMD1 as ready
Polymicrogyria and Schizencephaly v0.191 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.191 CSMD1 Zornitza Stark Classified gene: CSMD1 as Green List (high evidence)
Polymicrogyria and Schizencephaly v0.191 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.367 CSMD1 Zornitza Stark Marked gene: CSMD1 as ready
Cerebral Palsy v1.367 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.367 CSMD1 Zornitza Stark Classified gene: CSMD1 as Green List (high evidence)
Cerebral Palsy v1.367 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.47 SERPIND1 Jane Lin gene: SERPIND1 was added
gene: SERPIND1 was added to Bleeding and Platelet Disorders. Sources: Expert list
Mode of inheritance for gene: SERPIND1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SERPIND1 were set to PMID: 12421148; PMID: 35592395; PMID: 2647747; PMID: 11204559; PMID: 10494755
Phenotypes for gene: SERPIND1 were set to HEPARIN COFACTOR II DEFICIENCY #612356
Review for gene: SERPIND1 was set to AMBER
gene: SERPIND1 was marked as current diagnostic
Added comment: Also known as HCF2. There is evidence of protein to phenotype links but not many recent papers linking specific genetic variants to phenotype. Expect more given the first link to inherited thrombosis was published in 1985 (PMID: 2863444). There are two papers that used PCR to determine mutation in an affected individual (PMID: 2647747) published in 1989 and a paper in 2001 (PMID: 11204559). There is a paper reporting homozygous HCII but could not access paper (abstract only) (PMID: 10494755). This 2002 review (PMID: 12421148) lists 5 publications with 5 different molecular mutations linked to Heparin Cofactor II Deficiency. This review also notes that most of the case reports concluded that "inherited HCII deficiency is not a strong risk factor for thrombosis or that it contributes to thrombotic risk only when combined with other deficiencies." A more recent review (PMID: 35592395) has similar view and literature searches don't reveal recent papers with reports of variants linked to thrombosis.
Sources: Expert list
Cerebral Palsy v1.366 CSMD1 Krithika Murali gene: CSMD1 was added
gene: CSMD1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to PMID: 38816421
Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CSMD1 was set to GREEN
Added comment: PMID 38816421 Werren et al 2024 report 8 individuals from 6 families with biallelic missense CSMD1 variants identified through exome sequencing and subsequent gene-sharing efforts. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected.

Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells. ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autism and ID GCEP.
Sources: Literature
Genetic Epilepsy v1.43 CSMD1 Krithika Murali gene: CSMD1 was added
gene: CSMD1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to PMID: 38816421
Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CSMD1 was set to GREEN
Added comment: PMID 38816421 Werren et al 2024 report 8 individuals from 6 families with biallelic missense CSMD1 variants identified through exome sequencing and subsequent gene-sharing efforts. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected.

Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells. ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autism and ID GCEP.
Sources: Literature
Leukodystrophy - paediatric v0.309 CSMD1 Krithika Murali gene: CSMD1 was added
gene: CSMD1 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to PMID 38816421
Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CSMD1 was set to GREEN
Added comment: PMID 38816421 Werren et al 2024 report 8 individuals from 6 families with biallelic missense CSMD1 variants identified through exome sequencing and subsequent gene-sharing efforts. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected.

Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells. ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autism and ID GCEP.
Sources: Literature
Microcephaly v1.270 CSMD1 Krithika Murali gene: CSMD1 was added
gene: CSMD1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to PMID:38816421
Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CSMD1 was set to GREEN
Added comment: PMID 38816421 Werren et al 2024 report 8 individuals from 6 families with biallelic missense CSMD1 variants identified through exome sequencing and subsequent gene-sharing efforts. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected.

Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells. ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autism and ID GCEP.
Sources: Literature
Callosome v0.526 CSMD1 Krithika Murali gene: CSMD1 was added
gene: CSMD1 was added to Callosome. Sources: Literature
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to PMID: 38816421
Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CSMD1 was set to GREEN
Added comment: PMID 38816421 Werren et al 2024 report 8 individuals from 6 families with biallelic missense CSMD1 variants identified through exome sequencing and subsequent gene-sharing efforts. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected.

Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells. ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autism and ID GCEP.
Sources: Literature
Arthrogryposis v0.412 CSMD1 Krithika Murali gene: CSMD1 was added
gene: CSMD1 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to PMID 38816421
Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CSMD1 was set to GREEN
Added comment: PMID 38816421 Werren et al 2024 report 8 individuals from 6 families with biallelic missense CSMD1 variants identified through exome sequencing and subsequent gene-sharing efforts. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected.

Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells. ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autism and ID GCEP.
Sources: Literature
Fetal anomalies v1.264 CSMD1 Krithika Murali gene: CSMD1 was added
gene: CSMD1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to PMID: 38816421
Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CSMD1 was set to GREEN
Added comment: Prenatal features reported include polyhydramnios, IUGR, preterm labour. Other reported features such as brain anomalies, arthrogryposis have the potential to be ascertained prenatally also.
--
PMID 38816421 Werren et al 2024 report 8 individuals from 6 families with biallelic missense CSMD1 variants identified through exome sequencing and subsequent gene-sharing efforts. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected.

Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells. ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autism and ID GCEP.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.66 CSMD1 Krithika Murali gene: CSMD1 was added
gene: CSMD1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to PMID 38816421
Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038
Added comment: PMID 38816421 Werren et al 2024 report 8 individuals from 6 families with biallelic missense CSMD1 variants identified through exome sequencing and subsequent gene-sharing efforts. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected.

Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells. ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autisim and ID GCEP.
Sources: Literature
Polymicrogyria and Schizencephaly v0.190 CSMD1 Krithika Murali gene: CSMD1 was added
gene: CSMD1 was added to Polymicrogyria and Schizencephaly. Sources: Literature
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to PMID 38816421
Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CSMD1 was set to GREEN
Added comment: PMID 38816421 Werren et al 2024 report 8 individuals from 6 families with biallelic missense CSMD1 variants identified through exome sequencing and subsequent gene-sharing efforts. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected.

Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells. ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autisim and ID GCEP.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6121 CSMD1 Krithika Murali gene: CSMD1 was added
gene: CSMD1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to PMID 38816421
Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CSMD1 was set to GREEN
Added comment: PMID 38816421 Werren et al 2024 report 8 individuals from 6 families with biallelic missense CSMD1 variants identified through exome sequencing and subsequent gene-sharing efforts. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected.

Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells. ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autisim and ID GCEP.
Sources: Literature
Mendeliome v1.1948 CSMD1 Krithika Murali gene: CSMD1 was added
gene: CSMD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to PMID:38816421
Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CSMD1 was set to GREEN
Added comment: PMID 38816421 Werren et al 2024 report 8 individuals from 6 families identified through exome sequencing and subsequent gene-sharing efforts with biallelic missense CSMD1 variants. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected.

Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells (hESCs).

ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autisim and ID GCEP.
Sources: Literature
Bleeding and Platelet Disorders v1.47 SERPINC1 Jane Lin gene: SERPINC1 was added
gene: SERPINC1 was added to Bleeding and Platelet Disorders. Sources: Expert list
Mode of inheritance for gene: SERPINC1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SERPINC1 were set to PMID: 14347873; PMID: 36624481; PMID: 28300866
Phenotypes for gene: SERPINC1 were set to Thrombophilia 7 due to antithrombin III deficiency #613118
Review for gene: SERPINC1 was set to GREEN
gene: SERPINC1 was marked as current diagnostic
Added comment: Well established gene-phenotype relationship. Mostly autosomal dominant inheritance (autosomal recessive inheritance is rare but has been published). Have listed an early publication (1965) establishing this link and two more recent papers.
Sources: Expert list
Prepair 1000+ v1.142 ARFGEF2 Cassandra Muller reviewed gene: ARFGEF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25160555, 26126837, 23812912, 23755938; Phenotypes: Periventricular heterotopia with microcephaly, 608097 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.47 PROS1 Jane Lin gene: PROS1 was added
gene: PROS1 was added to Bleeding and Platelet Disorders. Sources: Expert list
Mode of inheritance for gene: PROS1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: PROS1 were set to PMID: 2521801; PMID: 7545463; PMID: 2231208; PMID: 10063989
Phenotypes for gene: PROS1 were set to Thrombophilia 5 due to protein S deficiency, autosomal dominant #612336; Thrombophilia 5 due to protein S deficiency, autosomal recessive #614514
Review for gene: PROS1 was set to GREEN
gene: PROS1 was marked as current diagnostic
Added comment: Strong gene-phenotype link. Many publications for both both autosomal dominant and autosomal recessive inheritance of PROS1 variants and thrombosis phenotype.
Sources: Expert list
Bleeding and Platelet Disorders v1.47 PIGA Jane Lin changed review comment from: PIGA variants linked to Paroxysmal nocturnal hemoglobinuria (PNH), clinical features which include thrombosis, but as somatic changes.
Sources: Expert list; to: PIGA variants linked to Paroxysmal nocturnal hemoglobinuria (PNH), clinical features which include thrombosis, but as somatic changes.
Sources: Expert list

Note: a few publications on constitutive PIGA mutations don't describe thrombosis as part of the phenotype. Note that homozygous/hemizygous mutations are rare and quite lethal.

PMID: 22305531
PMID: 34875027
Susceptibility to Viral Infections v0.126 TMEFF1 Peter McNaughton gene: TMEFF1 was added
gene: TMEFF1 was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: TMEFF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEFF1 were set to PMID: 39048830
Phenotypes for gene: TMEFF1 were set to hsv encephalitis
Review for gene: TMEFF1 was set to GREEN
Added comment: 2 unrelated patients with severe HSV encephalitis. Functional validation showing that human TMEFF1 encodes a type I IFN-independent, cortical neuron- and CNS-intrinsic restriction factor that is effective against HSV-1 that operates by impairing the entry of HSV-1 into cortical neurons.
Sources: Literature
Autoinflammatory Disorders v1.48 REXO2 Peter McNaughton gene: REXO2 was added
gene: REXO2 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: REXO2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: REXO2 were set to PMID: 39107301
Phenotypes for gene: REXO2 were set to type 1 interferonopathy
Mode of pathogenicity for gene: REXO2 was set to Other
Review for gene: REXO2 was set to AMBER
Added comment: Female infant of Chinese ancestry, presented at 2 years of age with whole-body rash with histological features of hyperkeratosis, parakeratosis and acanthosis with elongated rete ridges, focal liquefaction and degeneration of the basal layers of epidermis, vascular proliferation in the superficial dermis, infiltration of lymphocytes and eosinophils around small blood vessels in the dermis. She has recurrent infections (frequent and severe pneumonia).
Extensive functional validation demonstrating heterozygous de novo mutation (p.T132A) impairs REXO2’s ability to cleave RNA leading to activation of the dsRNA sensor MDA5 leading to a Type 1 interferonopathy.
Sources: Literature
Pulmonary Fibrosis_Interstitial Lung Disease v0.76 NKX2-1 Zornitza Stark Marked gene: NKX2-1 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.76 NKX2-1 Zornitza Stark Gene: nkx2-1 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.76 NKX2-1 Zornitza Stark Publications for gene: NKX2-1 were set to
Pulmonary Fibrosis_Interstitial Lung Disease v0.75 NKX2-1 Zornitza Stark Phenotypes for gene: NKX2-1 were changed from to Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978
Pulmonary Fibrosis_Interstitial Lung Disease v0.74 NKX2-1 Zornitza Stark Mode of inheritance for gene: NKX2-1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.142 APOPT1 Cassandra Muller reviewed gene: APOPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25175347, 32637636; Phenotypes: Mitochondrial complex IV deficiency, 220110 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.142 B3GLCT Karina Sandoval reviewed gene: B3GLCT: Rating: GREEN; Mode of pathogenicity: None; Publications: 23161355, 18798333, 19796186, 32533185, 32204707, 31795264, 20301637, 16909395; Phenotypes: Peters-plus syndrome(MIM#261540); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting disorders v0.254 CREBBP Zornitza Stark Marked gene: CREBBP as ready
Clefting disorders v0.254 CREBBP Zornitza Stark Gene: crebbp has been classified as Green List (High Evidence).
Clefting disorders v0.254 CREBBP Zornitza Stark Classified gene: CREBBP as Green List (high evidence)
Clefting disorders v0.254 CREBBP Zornitza Stark Gene: crebbp has been classified as Green List (High Evidence).
Clefting disorders v0.253 CREBBP Zornitza Stark gene: CREBBP was added
gene: CREBBP was added to Clefting disorders. Sources: Expert Review
Mode of inheritance for gene: CREBBP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CREBBP were set to 35626936
Phenotypes for gene: CREBBP were set to Menke-Hennekam syndrome 1, MIM# 618332
Review for gene: CREBBP was set to GREEN
Added comment: Cleft palate is a reported feature in several patients.
Sources: Expert Review
Prepair 1000+ v1.142 B3GALT6 Karina Sandoval reviewed gene: B3GALT6: Rating: GREEN; Mode of pathogenicity: None; Publications: 23664117, 29931299, 29443383, 23664118, 28306229, 25149931; Phenotypes: Al-Gazali syndrome(MIM#609465), Ehlers-Danlos syndrome, spondylodysplastic type, 2(MIM#615349), Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures(MIM#271640); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.142 MFRP Zornitza Stark Marked gene: MFRP as ready
Prepair 1000+ v1.142 MFRP Zornitza Stark Added comment: Comment when marking as ready: Promote to Green for V2.
Prepair 1000+ v1.142 MFRP Zornitza Stark Gene: mfrp has been classified as Red List (Low Evidence).
Prepair 1000+ v1.142 MFRP Zornitza Stark gene: MFRP was added
gene: MFRP was added to Prepair 1000+. Sources: Expert Review
Mode of inheritance for gene: MFRP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MFRP were set to 17167404; 18554571; 20361016
Phenotypes for gene: MFRP were set to Microphthalmia, isolated 5, MIM# 611040
Review for gene: MFRP was set to GREEN
Added comment: More than 10 unrelated families reported with bi-allelic variants in this gene associated with posterior microphthalmia with retinitis pigmentosa, foveoschisis, and optic disc drusen. Causes congenital visual impairment.
Sources: Expert Review
Spontaneous coronary artery dissection v0.50 TLN1 Ain Roesley changed review comment from: PMID: 30888838
10x families with a single affected, all missense
5x unknown inheritance
5x inherited from n unaffected parent

1x 2 generational fam with an unaffected obligate carrier, missense variant

variants reported and their counts in gnomad v4:
Ala2013Thr 1091 hets 1 hom
Arg297His 97 hets
Thr585Met 36 hets
Pro942Leu 62 hets
Ala1219Val 44 hets
Arg1241Trp 13 hets
Ser1333Thr absent
Val1964Ile 185 hets
Thr2098Met 358 hets
Val2440Glu absent

PMID: 36103205
2x individual however only 1 has a personal history of R-SCAD
Ala1574Val

Sources: Literature; to: PMID: 30888838
10x families with a single affected, all missense
5x unknown inheritance
5x inherited from an unaffected parent

1x 2 generational fam with an unaffected obligate carrier, missense variant

variants reported and their counts in gnomad v4:
Ala2013Thr 1091 hets 1 hom
Arg297His 97 hets
Thr585Met 36 hets
Pro942Leu 62 hets
Ala1219Val 44 hets
Arg1241Trp 13 hets
Ser1333Thr absent
Val1964Ile 185 hets
Thr2098Met 358 hets
Val2440Glu absent

PMID: 36103205
2x individual however only 1 has a personal history of R-SCAD
Ala1574Val

Sources: Literature
Spontaneous coronary artery dissection v0.50 LMX1B Ain Roesley Publications for gene: LMX1B were set to 37979122; 29650765
Spontaneous coronary artery dissection v0.49 LMX1B Ain Roesley Classified gene: LMX1B as Amber List (moderate evidence)
Spontaneous coronary artery dissection v0.49 LMX1B Ain Roesley Gene: lmx1b has been classified as Amber List (Moderate Evidence).
Spontaneous coronary artery dissection v0.48 LMX1B Ain Roesley edited their review of gene: LMX1B: Changed rating: AMBER; Changed publications: 29650765; Changed phenotypes: Nail-patella syndrome MIM#161200
Spontaneous coronary artery dissection v0.48 LMX1B Ain Roesley changed review comment from: PMID: 37979122; listed as "likely monogenic disease effect"

However, only a single patient found in literature
PMID: 29650765; 1x individual with SCAD and an NMD fs

this gene is constraint for LoF in gnomad v4 with only 2 hets for an NMD variant.

amber so as to not miss a diagnosis
Sources: Literature; to:
PMID: 29650765; 1x individual with SCAD and an NMD fs

this gene is constraint for LoF in gnomad v4 with only 2 hets for an NMD variant.

amber so as to not miss a diagnosis
Sources: Literature
Spontaneous coronary artery dissection v0.48 LMX1B Ain Roesley changed review comment from: PMID: 37979122; listed as "likely monogenic disease effect"

However, only a single patient found in literature
PMID: 29650765; 1x individual with SCAD and an NMD fs
Sources: Literature; to: PMID: 37979122; listed as "likely monogenic disease effect"

However, only a single patient found in literature
PMID: 29650765; 1x individual with SCAD and an NMD fs

this gene is constraint for LoF in gnomad v4 with only 2 hets for an NMD variant.

amber so as to not miss a diagnosis
Sources: Literature
Spontaneous coronary artery dissection v0.48 YY1AP1 Ain Roesley Publications for gene: YY1AP1 were set to
Spontaneous coronary artery dissection v0.47 YY1AP1 Ain Roesley Classified gene: YY1AP1 as Amber List (moderate evidence)
Spontaneous coronary artery dissection v0.47 YY1AP1 Ain Roesley Gene: yy1ap1 has been classified as Amber List (Moderate Evidence).
Spontaneous coronary artery dissection v0.46 YY1AP1 Ain Roesley edited their review of gene: YY1AP1: Changed rating: AMBER; Changed publications: 33125268
Spontaneous coronary artery dissection v0.46 YY1AP1 Ain Roesley changed review comment from:
PMID: 33125268
1x individual with a canonical splice + 1x protein truncating variant. However, phasing could not be performed

no other literature found
Sources: Literature; to:
PMID: 33125268
1x individual with a canonical splice + 1x protein truncating variant. However, phasing could not be performed

no other literature found

amber so as to not miss a diagnosis
Sources: Literature
Spontaneous coronary artery dissection v0.46 YY1AP1 Ain Roesley changed review comment from: PMID: 37979122; listed as "likely monogenic disease effect"

PMID: 33125268 was cited in paper above.
1x individual with a canonical splice + 1x protein truncating variant. However, phasing could not be performed

no other literature found
Sources: Literature; to:
PMID: 33125268
1x individual with a canonical splice + 1x protein truncating variant. However, phasing could not be performed

no other literature found
Sources: Literature
Spontaneous coronary artery dissection v0.46 PTGIR Ain Roesley Publications for gene: PTGIR were set to 32531060; 37979122
Spontaneous coronary artery dissection v0.45 PTGIR Ain Roesley changed review comment from: PMID: 37979122; listed as "likely monogenic disease effect"

PMID: 32531060; searched for 'rare' LoF variants in individuals with fibromuscular dysplasia.
However, this gene is NOT LoF constraint in gnomad v4.
200 hets for an NMD variant
Sources: Literature; to: PMID: 32531060; searched for 'rare' LoF variants in individuals with fibromuscular dysplasia.
However, this gene is NOT LoF constraint in gnomad v4.
200 hets for an NMD variant

All other papers cited PMID: 32531060
Sources: Literature
Spontaneous coronary artery dissection v0.45 TLN1 Ain Roesley Publications for gene: TLN1 were set to 30888838; 37979122
Spontaneous coronary artery dissection v0.44 TLN1 Ain Roesley edited their review of gene: TLN1: Changed publications: 30888838, 36103205
Spontaneous coronary artery dissection v0.44 TLN1 Ain Roesley changed review comment from: PMID: 37979122; listed as "likely monogenic disease effect"

but AMBER rating
10 unique rare heterozygous missense variants in 11 individuals were identified in a 2 generation SCAD family and 56 unrelated individuals with sporadic SCAD. All variants had a MAF of less than 0.06% and occurred within highly conserved β-integrin, F-actin, or vinculin binding domains. Incomplete penetrance was evident in the familial case and five individuals with unaffected heterozygous parents. No functional assays were conducted.
Sources: Literature; to: PMID: 30888838
10x families with a single affected, all missense
5x unknown inheritance
5x inherited from n unaffected parent

1x 2 generational fam with an unaffected obligate carrier, missense variant

variants reported and their counts in gnomad v4:
Ala2013Thr 1091 hets 1 hom
Arg297His 97 hets
Thr585Met 36 hets
Pro942Leu 62 hets
Ala1219Val 44 hets
Arg1241Trp 13 hets
Ser1333Thr absent
Val1964Ile 185 hets
Thr2098Met 358 hets
Val2440Glu absent

PMID: 36103205
2x individual however only 1 has a personal history of R-SCAD
Ala1574Val

Sources: Literature
Prepair 1000+ v1.141 USP9X Lilian Downie Marked gene: USP9X as ready
Prepair 1000+ v1.141 USP9X Lilian Downie Gene: usp9x has been classified as Green List (High Evidence).
Prepair 1000+ v1.141 USP9X Lilian Downie Phenotypes for gene: USP9X were changed from Mental retardation, X-linked 99, 300919 (3) to Intellectual developmental disorder, X-linked 99, MIM#300919
Prepair 1000+ v1.140 USP9X Lilian Downie Publications for gene: USP9X were set to
Prepair 1000+ v1.139 USP9X Lilian Downie Added comment: Comment on mode of inheritance: X-linked dominant, females can be severely affected
Prepair 1000+ v1.139 USP9X Lilian Downie Mode of inheritance for gene: USP9X was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.138 USP9X Lilian Downie Mode of inheritance for gene: USP9X was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.137 VLDLR Lilian Downie Marked gene: VLDLR as ready
Prepair 1000+ v1.137 VLDLR Lilian Downie Gene: vldlr has been classified as Green List (High Evidence).
Prepair 1000+ v1.137 VLDLR Lilian Downie Phenotypes for gene: VLDLR were changed from Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1, 224050 (3) to Cerebellar hypoplasia, impaired intellectual development, and dysequilibrium syndrome MIM#224050
Prepair 1000+ v1.136 VLDLR Lilian Downie Publications for gene: VLDLR were set to
Prepair 1000+ v1.135 WDR45B Lilian Downie Marked gene: WDR45B as ready
Prepair 1000+ v1.135 WDR45B Lilian Downie Gene: wdr45b has been classified as Green List (High Evidence).
Prepair 1000+ v1.135 WDR45B Lilian Downie Publications for gene: WDR45B were set to
Prepair 1000+ v1.134 WNT1 Lilian Downie Marked gene: WNT1 as ready
Prepair 1000+ v1.134 WNT1 Lilian Downie Gene: wnt1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.134 WNT1 Lilian Downie Publications for gene: WNT1 were set to
Prepair 1000+ v1.133 COX20 Lilian Downie Phenotypes for gene: COX20 were changed from Mitochondrial complex IV deficiency, 220110 (3) to Mitochondrial complex IV deficiency, nuclear type 11, MIM#619054
Prepair 1000+ v1.132 COX20 Lilian Downie Marked gene: COX20 as ready
Prepair 1000+ v1.132 COX20 Lilian Downie Gene: cox20 has been classified as Green List (High Evidence).
Prepair 1000+ v1.132 COX20 Lilian Downie Publications for gene: COX20 were set to
Prepair 1000+ v1.131 CPT2 Lilian Downie Marked gene: CPT2 as ready
Prepair 1000+ v1.131 CPT2 Lilian Downie Gene: cpt2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.131 CPT2 Lilian Downie Phenotypes for gene: CPT2 were changed from CPT II deficiency, lethal neonatal, 608836 (3) to CPT II deficiency, infantile MIM#600649; CPT II deficiency, lethal neonatal MIM#608836; CPT II deficiency, myopathic, stress-induced MIM#255110
Prepair 1000+ v1.130 CPT2 Lilian Downie Publications for gene: CPT2 were set to
Prepair 1000+ v1.129 DHODH Lilian Downie Marked gene: DHODH as ready
Prepair 1000+ v1.129 DHODH Lilian Downie Gene: dhodh has been classified as Green List (High Evidence).
Prepair 1000+ v1.129 DHODH Lilian Downie Publications for gene: DHODH were set to
Prepair 1000+ v1.128 ACADM Lilian Downie Marked gene: ACADM as ready
Prepair 1000+ v1.128 ACADM Lilian Downie Gene: acadm has been classified as Green List (High Evidence).
Prepair 1000+ v1.128 ACADM Lilian Downie Publications for gene: ACADM were set to
Prepair 1000+ v1.127 ERCC6L2 Lilian Downie Marked gene: ERCC6L2 as ready
Prepair 1000+ v1.127 ERCC6L2 Lilian Downie Gene: ercc6l2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.127 ERCC6L2 Lilian Downie Publications for gene: ERCC6L2 were set to
Genetic Epilepsy v1.42 Zornitza Stark List of related panels changed from Seizure; HP:0001250 to Seizure; HP:0001250; Epileptic encephalopathy; HP:0200134
Prepair 1000+ v1.126 ADAT3 Lilian Downie Marked gene: ADAT3 as ready
Prepair 1000+ v1.126 ADAT3 Lilian Downie Gene: adat3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.126 ADAT3 Lilian Downie Phenotypes for gene: ADAT3 were changed from Mental retardation, autosomal recessive 36, 615286 (3) to Neurodevelopmental disorder with brain abnormalities, poor growth, and dysmorphic facies, MIM#615286
Prepair 1000+ v1.125 ADAT3 Lilian Downie Publications for gene: ADAT3 were set to
Prepair 1000+ v1.124 CYP11A1 Lilian Downie Marked gene: CYP11A1 as ready
Prepair 1000+ v1.124 CYP11A1 Lilian Downie Gene: cyp11a1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.124 CYP11A1 Lilian Downie Publications for gene: CYP11A1 were set to
Prepair 1000+ v1.123 ARMC4 Lilian Downie Marked gene: ARMC4 as ready
Prepair 1000+ v1.123 ARMC4 Lilian Downie Added comment: Comment when marking as ready: Primary ciliary dyskinesia-23 is an autosomal recessive disorder resulting from defective ciliary motility. Affected individuals have respiratory distress and recurrent upper and lower airway infections, and they often develop bronchiectasis. About 50% of patients have situs inversus or laterality defects. Ultrastructural analysis of respiratory cilia shows defects in the outer dynein arm
Prepair 1000+ v1.123 ARMC4 Lilian Downie Gene: armc4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.123 ARMC4 Lilian Downie Publications for gene: ARMC4 were set to
Prepair 1000+ v1.122 ARV1 Lilian Downie Marked gene: ARV1 as ready
Prepair 1000+ v1.122 ARV1 Lilian Downie Added comment: Comment when marking as ready: Developmental and epileptic encephalopathy-38 (DEE38) is an autosomal recessive neurologic and neurodegenerative disorder characterized by the onset of various type of seizures usually between about 4 and 7 months of age. Prior to the onset of seizures, most infants show severely impaired global development, hypotonia with poor head control, and visual inattention with roving eye movements and nystagmus. Seizures are usually refractory to treatment and associated with status epilepticus. Patients have little or no development with inability to walk or speak, spasticity or abnormal movements, and often cortical blindness. There is failure to thrive, and many require tube-feeding. Death in early childhood due to aspiration or intractable epilepsy may occur.
Prepair 1000+ v1.122 ARV1 Lilian Downie Gene: arv1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.122 BUB1B Zornitza Stark Marked gene: BUB1B as ready
Prepair 1000+ v1.122 BUB1B Zornitza Stark Gene: bub1b has been classified as Green List (High Evidence).
Prepair 1000+ v1.122 BUB1B Zornitza Stark Phenotypes for gene: BUB1B were changed from Mosaic variegated aneuploidy syndrome 1, 257300 (3) to Mosaic variegated aneuploidy syndrome 1, MIM# 257300
Prepair 1000+ v1.121 BUB1B Zornitza Stark Publications for gene: BUB1B were set to
Prepair 1000+ v1.120 C12orf57 Zornitza Stark Marked gene: C12orf57 as ready
Prepair 1000+ v1.120 C12orf57 Zornitza Stark Gene: c12orf57 has been classified as Green List (High Evidence).
Prepair 1000+ v1.120 C12orf57 Zornitza Stark Phenotypes for gene: C12orf57 were changed from Temtamy syndrome, 218340 (3) to Temtamy syndrome, MIM # 218340
Prepair 1000+ v1.119 C12orf57 Zornitza Stark Publications for gene: C12orf57 were set to
Prepair 1000+ v1.118 C12orf57 Zornitza Stark Tag founder tag was added to gene: C12orf57.
Prepair 1000+ v1.118 CHST3 Zornitza Stark Marked gene: CHST3 as ready
Prepair 1000+ v1.118 CHST3 Zornitza Stark Gene: chst3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.118 CHST3 Zornitza Stark Publications for gene: CHST3 were set to
Prepair 1000+ v1.117 CNTNAP1 Zornitza Stark Marked gene: CNTNAP1 as ready
Prepair 1000+ v1.117 CNTNAP1 Zornitza Stark Gene: cntnap1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.117 CNTNAP1 Zornitza Stark Phenotypes for gene: CNTNAP1 were changed from Lethal congenital contracture syndrome 7, 616286 (3) to Lethal congenital contracture syndrome 7, MIM # 616286; Hypomyelinating neuropathy, congenital, 3, MIM # 618186
Prepair 1000+ v1.116 CNTNAP1 Zornitza Stark Publications for gene: CNTNAP1 were set to
Prepair 1000+ v1.115 COG7 Zornitza Stark Marked gene: COG7 as ready
Prepair 1000+ v1.115 COG7 Zornitza Stark Gene: cog7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.115 COG7 Zornitza Stark Phenotypes for gene: COG7 were changed from Congenital disorder of glycosylation, type IIe, 608779 (3) to Congenital disorder of glycosylation, type IIe, MIM # 608779
Prepair 1000+ v1.114 COG7 Zornitza Stark Publications for gene: COG7 were set to
Prepair 1000+ v1.113 CYP17A1 Zornitza Stark Marked gene: CYP17A1 as ready
Prepair 1000+ v1.113 CYP17A1 Zornitza Stark Gene: cyp17a1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.113 CYP17A1 Zornitza Stark Phenotypes for gene: CYP17A1 were changed from 17,20-lyase deficiency, isolated, 202110 (3) to 17-alpha-hydroxylase/17,20-lyase deficiency MIM#202110
Prepair 1000+ v1.112 CYP17A1 Zornitza Stark Publications for gene: CYP17A1 were set to
Prepair 1000+ v1.111 CYP2U1 Zornitza Stark Marked gene: CYP2U1 as ready
Prepair 1000+ v1.111 CYP2U1 Zornitza Stark Gene: cyp2u1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.111 CYP2U1 Zornitza Stark Phenotypes for gene: CYP2U1 were changed from Spastic paraplegia 56, autosomal recessive, 615030 (3) to Spastic paraplegia 56, autosomal recessive MIM#615030
Prepair 1000+ v1.110 CYP2U1 Zornitza Stark Publications for gene: CYP2U1 were set to
Prepair 1000+ v1.109 DCX Zornitza Stark Marked gene: DCX as ready
Prepair 1000+ v1.109 DCX Zornitza Stark Gene: dcx has been classified as Green List (High Evidence).
Prepair 1000+ v1.109 DCX Zornitza Stark Phenotypes for gene: DCX were changed from Lissencephaly, X-linked, 300067 (3) to Lissencephaly, X-linked MIM#300067; Subcortical laminal heterotopia, X-linked MIM#300067
Prepair 1000+ v1.108 DCX Zornitza Stark Publications for gene: DCX were set to
Prepair 1000+ v1.107 DDX59 Zornitza Stark Marked gene: DDX59 as ready
Prepair 1000+ v1.107 DDX59 Zornitza Stark Gene: ddx59 has been classified as Green List (High Evidence).
Prepair 1000+ v1.107 DDX59 Zornitza Stark Publications for gene: DDX59 were set to
Prepair 1000+ v1.106 EIF2AK3 Zornitza Stark Marked gene: EIF2AK3 as ready
Prepair 1000+ v1.106 EIF2AK3 Zornitza Stark Gene: eif2ak3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.106 EIF2AK3 Zornitza Stark Phenotypes for gene: EIF2AK3 were changed from Wolcott-Rallison syndrome, 226980 (3) to Wolcott-Rallison syndrome MIM#226980
Prepair 1000+ v1.105 EIF2AK3 Zornitza Stark Publications for gene: EIF2AK3 were set to
Prepair 1000+ v1.104 ASPM Zornitza Stark Marked gene: ASPM as ready
Prepair 1000+ v1.104 ASPM Zornitza Stark Gene: aspm has been classified as Green List (High Evidence).
Prepair 1000+ v1.104 ASPM Zornitza Stark Phenotypes for gene: ASPM were changed from Microcephaly 5, primary, autosomal recessive, 608716 (3) to Microcephaly 5, primary, autosomal recessive (MIM#608716)
Prepair 1000+ v1.103 ASPM Zornitza Stark Publications for gene: ASPM were set to
Prepair 1000+ v1.102 ATP7A Zornitza Stark Marked gene: ATP7A as ready
Prepair 1000+ v1.102 ATP7A Zornitza Stark Gene: atp7a has been classified as Green List (High Evidence).
Prepair 1000+ v1.102 ATP7A Zornitza Stark Phenotypes for gene: ATP7A were changed from Menkes disease, 309400 (3) to Menkes disease(MIM#309400); Occipital horn syndrome(MIM#304150)
Prepair 1000+ v1.101 ATP7A Zornitza Stark Publications for gene: ATP7A were set to
Prepair 1000+ v1.100 ADAMTS2 Zornitza Stark Marked gene: ADAMTS2 as ready
Prepair 1000+ v1.100 ADAMTS2 Zornitza Stark Gene: adamts2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.100 ADAMTS2 Zornitza Stark Phenotypes for gene: ADAMTS2 were changed from Ehlers-Danlos syndrome, type VIIC, 225410 (3) to Ehlers-Danlos syndrome, dermatosparaxis type (MIM# 225410)
Prepair 1000+ v1.99 ADAMTS2 Zornitza Stark Publications for gene: ADAMTS2 were set to
Prepair 1000+ v1.98 ADAMTS2 Zornitza Stark changed review comment from: Congenital onset, severe CTD.; to: Congenital onset, marked joint hyper mobility, skin abnormalities, risk of organ rupture.
Prepair 1000+ v1.98 ADAMTS2 Zornitza Stark reviewed gene: ADAMTS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ehlers-Danlos syndrome, dermatosparaxis type (MIM# 225410); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.98 AGRN Zornitza Stark Marked gene: AGRN as ready
Prepair 1000+ v1.98 AGRN Zornitza Stark Gene: agrn has been classified as Green List (High Evidence).
Prepair 1000+ v1.98 AGRN Zornitza Stark Publications for gene: AGRN were set to
Prepair 1000+ v1.97 ARSA Zornitza Stark Marked gene: ARSA as ready
Prepair 1000+ v1.97 ARSA Zornitza Stark Gene: arsa has been classified as Green List (High Evidence).
Prepair 1000+ v1.97 ARSA Zornitza Stark Publications for gene: ARSA were set to
Prepair 1000+ v1.96 ATAD1 Zornitza Stark Marked gene: ATAD1 as ready
Prepair 1000+ v1.96 ATAD1 Zornitza Stark Gene: atad1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.96 ATAD1 Zornitza Stark Phenotypes for gene: ATAD1 were changed from Hyperekplexia 4, 618011 (3), Autosomal recessive to Hyperekplexia 4, MIM#618011
Prepair 1000+ v1.95 ATAD1 Zornitza Stark Publications for gene: ATAD1 were set to
Prepair 1000+ v1.94 ATR Zornitza Stark Marked gene: ATR as ready
Prepair 1000+ v1.94 ATR Zornitza Stark Gene: atr has been classified as Green List (High Evidence).
Prepair 1000+ v1.94 ATR Zornitza Stark Phenotypes for gene: ATR were changed from Seckel syndrome 1, 210600 (3) to Seckel syndrome 1(MIM#210600)
Prepair 1000+ v1.93 ATR Zornitza Stark Publications for gene: ATR were set to
Prepair 1000+ v1.92 ATP8A2 Zornitza Stark Marked gene: ATP8A2 as ready
Prepair 1000+ v1.92 ATP8A2 Zornitza Stark Gene: atp8a2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.92 ATP8A2 Zornitza Stark Phenotypes for gene: ATP8A2 were changed from ?Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 to Cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome 4 (MIM#615268)
Prepair 1000+ v1.91 ATP8A2 Zornitza Stark Publications for gene: ATP8A2 were set to
Prepair 1000+ v1.90 ABCA3 Zornitza Stark Marked gene: ABCA3 as ready
Prepair 1000+ v1.90 ABCA3 Zornitza Stark Gene: abca3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.90 ABCA3 Zornitza Stark Publications for gene: ABCA3 were set to
Prepair 1000+ v1.89 ADAR Zornitza Stark Marked gene: ADAR as ready
Prepair 1000+ v1.89 ADAR Zornitza Stark Gene: adar has been classified as Green List (High Evidence).
Prepair 1000+ v1.89 DYNC1I2 Zornitza Stark Marked gene: DYNC1I2 as ready
Prepair 1000+ v1.89 DYNC1I2 Zornitza Stark Added comment: Comment when marking as ready: Ready to be promoted to Green at next version.
Prepair 1000+ v1.89 DYNC1I2 Zornitza Stark Gene: dync1i2 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.89 CTSC Zornitza Stark Marked gene: CTSC as ready
Prepair 1000+ v1.89 CTSC Zornitza Stark Gene: ctsc has been classified as Green List (High Evidence).
Prepair 1000+ v1.89 CTSC Zornitza Stark Phenotypes for gene: CTSC were changed from Papillon-Lefevre syndrome, 245000 (3) to Haim-Munk syndrome MIM#245010; Papillon-Lefevre syndrome MIM#245000
Prepair 1000+ v1.88 CTSC Zornitza Stark reviewed gene: CTSC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Haim-Munk syndrome MIM#245010, Papillon-Lefevre syndrome MIM#245000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.88 CERKL Zornitza Stark Marked gene: CERKL as ready
Prepair 1000+ v1.88 CERKL Zornitza Stark Gene: cerkl has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.88 CERKL Zornitza Stark Tag for review tag was added to gene: CERKL.
Prepair 1000+ v1.88 RMRP Lilian Downie Marked gene: RMRP as ready
Prepair 1000+ v1.88 RMRP Lilian Downie Added comment: Comment when marking as ready: A range of phenotypes from mild skeletal dysplasia to a severe (anauxetic dysplasia), there is not a clear genotype phenotype correlation, however loss of function variants are more often reported in the severe phenotypes
Prepair 1000+ v1.88 RMRP Lilian Downie Gene: rmrp has been classified as Green List (High Evidence).
Prepair 1000+ v1.88 RMRP Lilian Downie Publications for gene: RMRP were set to
Prepair 1000+ v1.87 CCDC103 Lilian Downie Marked gene: CCDC103 as ready
Prepair 1000+ v1.87 CCDC103 Lilian Downie Gene: ccdc103 has been classified as Green List (High Evidence).
Prepair 1000+ v1.87 CCDC103 Lilian Downie Publications for gene: CCDC103 were set to
Prepair 1000+ v1.86 AKR1D1 Lilian Downie Marked gene: AKR1D1 as ready
Prepair 1000+ v1.86 AKR1D1 Lilian Downie Gene: akr1d1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.86 AKR1D1 Lilian Downie Publications for gene: AKR1D1 were set to
Prepair 1000+ v1.85 AMT Lilian Downie Marked gene: AMT as ready
Prepair 1000+ v1.85 AMT Lilian Downie Gene: amt has been classified as Green List (High Evidence).
Prepair 1000+ v1.85 AMT Lilian Downie Publications for gene: AMT were set to
Prepair 1000+ v1.84 AMT Lilian Downie reviewed gene: AMT: Rating: ; Mode of pathogenicity: None; Publications: PMID: 16450403,; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6120 ZSCAN10 Zornitza Stark reviewed gene: ZSCAN10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Otofacial neurodevelopmental syndrome, MIM# 620910; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.195 ZSCAN10 Zornitza Stark Phenotypes for gene: ZSCAN10 were changed from Syndromic disease MONDO:0002254 to Otofacial neurodevelopmental syndrome, MIM# 620910
Deafness_IsolatedAndComplex v1.194 ZSCAN10 Zornitza Stark reviewed gene: ZSCAN10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Otofacial neurodevelopmental syndrome, MIM# 620910; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1947 ZSCAN10 Zornitza Stark Phenotypes for gene: ZSCAN10 were changed from syndromic disease MONDO:0002254 to Otofacial neurodevelopmental syndrome, MIM# 620910
Mendeliome v1.1946 ZSCAN10 Zornitza Stark reviewed gene: ZSCAN10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Otofacial neurodevelopmental syndrome, MIM# 620910; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.84 ALG9 Lilian Downie Marked gene: ALG9 as ready
Prepair 1000+ v1.84 ALG9 Lilian Downie Gene: alg9 has been classified as Green List (High Evidence).
Prepair 1000+ v1.84 ALG9 Lilian Downie Publications for gene: ALG9 were set to
Prepair 1000+ v1.83 ATOH7 Lilian Downie Marked gene: ATOH7 as ready
Prepair 1000+ v1.83 ATOH7 Lilian Downie Gene: atoh7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.83 ATOH7 Lilian Downie Publications for gene: ATOH7 were set to
Spontaneous coronary artery dissection v0.44 TGFBR2 Ain Roesley Publications for gene: TGFBR2 were set to 30071989; 27879313
Spontaneous coronary artery dissection v0.43 TGFBR2 Ain Roesley edited their review of gene: TGFBR2: Changed publications: 32897753, 35092149, 36103205; Changed phenotypes: Loeys-Dietz syndrome 2 MIM#610168
Spontaneous coronary artery dissection v0.43 TGFBR2 Ain Roesley changed review comment from: "Definitive" by ClinGen Aortopathy working group.

Reviewed in PMID 27879313 (265 cases with variants in TGFBR2).
Sources: Literature; to: PMID: 32897753
3x individuals with 2x missense and 1x +5G splice
both missense variants are absent in gnomad v4
reported SCADs: circumflex coronary artery, right descending posterior coronary artery and cervico-cephalic aneurysm and arterial dissection

PMID: 35092149
2x individuals from a SCAD cohort, however both without variant information

PMID: 36103205
3x SCAD individuals with 2x missense variants
p.Val387Leu has 569 hets + 1 hom in gnomad v4
p.Ala531Thr has 3 hets


Sources: Literature
Spontaneous coronary artery dissection v0.43 TGFBR1 Ain Roesley Publications for gene: TGFBR1 were set to 36584339; 30071989; 27879313
Spontaneous coronary artery dissection v0.42 TGFBR1 Ain Roesley Classified gene: TGFBR1 as Amber List (moderate evidence)
Spontaneous coronary artery dissection v0.42 TGFBR1 Ain Roesley Gene: tgfbr1 has been classified as Amber List (Moderate Evidence).
Spontaneous coronary artery dissection v0.41 TGFBR1 Ain Roesley edited their review of gene: TGFBR1: Changed rating: AMBER; Changed publications: 35092149, 36103205; Changed phenotypes: Loeys-Dietz syndrome 1 MIM#609192
Spontaneous coronary artery dissection v0.41 TGFBR1 Ain Roesley changed review comment from: "Definitive" by ClinGen Aortopathy working group.

Reviewed in PMID 27879313 (176 cases with variants in TGFBR1).

AMBER for AR disease: PMID 36584339
Biallelic variants reported in a single family with two sibs. Presented with severe dilatation of aorta, diaphragmatic hernia, skin translucency, and profound joint laxity at birth
Sources: Radboud University Medical Center, Nijmegen; to: PMID: 35092149
1x individual with SCAD, the missense has 3 hets in gnomad v4

PMID: 36103205
1x individual with R-SCAD and fhx, however the missense has 60 hets in gnomad v4

Amber so as to not miss a diagnosis
Spontaneous coronary artery dissection v0.41 TGFB3 Ain Roesley Publications for gene: TGFB3 were set to 30071989; 25835445
Spontaneous coronary artery dissection v0.40 TGFB3 Ain Roesley edited their review of gene: TGFB3: Changed publications: 32897753
Spontaneous coronary artery dissection v0.40 TGFB3 Ain Roesley changed review comment from: Uncertain for isolated aneurysm, but causes broader connective tissue disorder phenotype. 43 patients from 11 reported with significant cardiovascular involvement, including thoracic/abdominal aortic aneurysm and dissection, and mitral valve disease. Other systemic features overlapped clinically with Loeys-Dietz, Shprintzen-Goldberg, and Marfan syndromes, including cleft palate, bifid uvula, skeletal overgrowth, cervical spine instability and clubfoot deformity
Sources: Literature; to: PMID: 32897753
4x individuals with missense, however only 3x with personal history of SCAD


Sources: Literature
Spontaneous coronary artery dissection v0.40 TGFB2 Ain Roesley Publications for gene: TGFB2 were set to 30071989; 22772371
Spontaneous coronary artery dissection v0.39 TGFB2 Ain Roesley edited their review of gene: TGFB2: Changed publications: 33125268, 36103205; Changed phenotypes: Loeys-Dietz syndrome 4 MIM#614816
Spontaneous coronary artery dissection v0.39 TGFB2 Ain Roesley changed review comment from:
PMID: 33125268:
2x missense in SCAD individuals

PMID: 36103205
3x individuals with missense, however no personal history of SCAD, only fam history

borderline amber/green

Sources: Literature; to:
PMID: 33125268:
2x missense in SCAD individuals

PMID: 36103205
1x individual with missense and peripartum SCAD


Sources: Literature
Spontaneous coronary artery dissection v0.39 TGFB2 Ain Roesley changed review comment from: "Definitive" by ClinGen Aortopathy Working Group.

PMID: 22772371: 4 families
Sources: Literature; to:
PMID: 33125268:
2x missense in SCAD individuals

PMID: 36103205
3x individuals with missense, however no personal history of SCAD, only fam history

borderline amber/green

Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6120 COQ8A Zornitza Stark Marked gene: COQ8A as ready
Intellectual disability syndromic and non-syndromic v0.6120 COQ8A Zornitza Stark Gene: coq8a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6120 COQ8A Zornitza Stark Phenotypes for gene: COQ8A were changed from to coenzyme Q10 deficiency MONDO:0018151
Intellectual disability syndromic and non-syndromic v0.6119 COQ8A Zornitza Stark Publications for gene: COQ8A were set to
Intellectual disability syndromic and non-syndromic v0.6118 COQ8A Zornitza Stark Mode of inheritance for gene: COQ8A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6117 CTDP1 Zornitza Stark Marked gene: CTDP1 as ready
Intellectual disability syndromic and non-syndromic v0.6117 CTDP1 Zornitza Stark Gene: ctdp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6117 CTDP1 Zornitza Stark Phenotypes for gene: CTDP1 were changed from to congenital cataracts-facial dysmorphism-neuropathy syndrome MONDO:0011402
Intellectual disability syndromic and non-syndromic v0.6116 CTDP1 Zornitza Stark Publications for gene: CTDP1 were set to
Intellectual disability syndromic and non-syndromic v0.6115 CTDP1 Zornitza Stark Mode of inheritance for gene: CTDP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6114 CTSA Zornitza Stark Marked gene: CTSA as ready
Intellectual disability syndromic and non-syndromic v0.6114 CTSA Zornitza Stark Gene: ctsa has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6114 CTSA Zornitza Stark Phenotypes for gene: CTSA were changed from to Galactosialidosis MONDO:0009737
Intellectual disability syndromic and non-syndromic v0.6113 CTSA Zornitza Stark Publications for gene: CTSA were set to
Intellectual disability syndromic and non-syndromic v0.6112 CTSA Zornitza Stark Mode of inheritance for gene: CTSA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6111 CTSD Zornitza Stark Marked gene: CTSD as ready
Intellectual disability syndromic and non-syndromic v0.6111 CTSD Zornitza Stark Gene: ctsd has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6111 CTSD Zornitza Stark Phenotypes for gene: CTSD were changed from to neuronal ceroid lipofuscinosis MONDO:0016295
Intellectual disability syndromic and non-syndromic v0.6110 CTSD Zornitza Stark Mode of inheritance for gene: CTSD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6109 CYB5R3 Zornitza Stark Marked gene: CYB5R3 as ready
Intellectual disability syndromic and non-syndromic v0.6109 CYB5R3 Zornitza Stark Gene: cyb5r3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6109 CYB5R3 Zornitza Stark Phenotypes for gene: CYB5R3 were changed from to Methemoglobinemia MONDO:0001117
Intellectual disability syndromic and non-syndromic v0.6108 CYB5R3 Zornitza Stark Publications for gene: CYB5R3 were set to
Intellectual disability syndromic and non-syndromic v0.6107 CYB5R3 Zornitza Stark Mode of inheritance for gene: CYB5R3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6106 SOX9 Zornitza Stark Marked gene: SOX9 as ready
Intellectual disability syndromic and non-syndromic v0.6106 SOX9 Zornitza Stark Gene: sox9 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6106 SOX9 Zornitza Stark Phenotypes for gene: SOX9 were changed from to campomelic dysplasia MONDO:0007251
Intellectual disability syndromic and non-syndromic v0.6105 SOX9 Zornitza Stark Publications for gene: SOX9 were set to
Intellectual disability syndromic and non-syndromic v0.6104 SOX9 Zornitza Stark Mode of inheritance for gene: SOX9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6103 SOX9 Zornitza Stark Classified gene: SOX9 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6103 SOX9 Zornitza Stark Gene: sox9 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6102 SOX9 Zornitza Stark changed review comment from: Agree ID typically not part of the phenotype. Note reports of milder cases and DD/ID reported in some survivors, therefore downgraded to Amber.; to: Agree ID typically not part of the phenotype. Note reports of milder cases and DD/ID reported in some survivors (this publication suggests >80%), therefore downgraded to Amber.
Intellectual disability syndromic and non-syndromic v0.6102 SOX9 Zornitza Stark reviewed gene: SOX9: Rating: AMBER; Mode of pathogenicity: None; Publications: 21373255; Phenotypes: campomelic dysplasia MONDO:0007251; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6102 SOX9 Zornitza Stark Classified gene: SOX9 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.6102 SOX9 Zornitza Stark Gene: sox9 has been classified as Red List (Low Evidence).
Miscellaneous Metabolic Disorders v1.47 GLS Zornitza Stark Mode of inheritance for gene: GLS was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6101 GLS Zornitza Stark Phenotypes for gene: GLS were changed from Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412 to Epileptic encephalopathy, early infantile, 71, MIM# 618328; Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412
Intellectual disability syndromic and non-syndromic v0.6100 GLS Zornitza Stark Mode of inheritance for gene: GLS was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v1.41 GLS Zornitza Stark Phenotypes for gene: GLS were changed from Epileptic encephalopathy, early infantile, 71, MIM# 618328; Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development MONDO:0032685 to Epileptic encephalopathy, early infantile, 71, MIM# 618328; Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development MONDO:0032685
Genetic Epilepsy v1.40 GLS Zornitza Stark Phenotypes for gene: GLS were changed from Epileptic encephalopathy, early infantile, 71, MIM# 618328 to Epileptic encephalopathy, early infantile, 71, MIM# 618328; Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development MONDO:0032685
Genetic Epilepsy v1.39 GLS Zornitza Stark Publications for gene: GLS were set to 30575854
Genetic Epilepsy v1.38 GLS Zornitza Stark Mode of inheritance for gene: GLS was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v1.37 GLS Zornitza Stark Classified gene: GLS as Green List (high evidence)
Genetic Epilepsy v1.37 GLS Zornitza Stark Gene: gls has been classified as Green List (High Evidence).
Genetic Epilepsy v1.36 GLS Zornitza Stark edited their review of gene: GLS: Added comment: PMID 38622440: additional individual reported with bi-allelic variants.

Note GoF variants also postulated to cause a neurodevelopmental phenotype, including seizures, though evidence is more limited, PMID 37151363. Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development MONDO:0032685; Changed rating: GREEN; Changed publications: 30575854, 38622440, 37151363; Changed phenotypes: Epileptic encephalopathy, early infantile, 71, MIM# 618328, Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development MONDO:0032685; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cataract v0.368 GLS Zornitza Stark Phenotypes for gene: GLS were changed from Infantile cataracts to Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development MONDO:0032685
Cataract v0.367 GLS Zornitza Stark Mode of pathogenicity for gene: GLS was changed from None to Other
Cataract v0.367 GLS Zornitza Stark Mode of inheritance for gene: GLS was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.366 GLS Zornitza Stark edited their review of gene: GLS: Changed phenotypes: Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development MONDO:0032685; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aminoacidopathy v1.132 GLS Zornitza Stark Publications for gene: GLS were set to 29468182; 30575854; 30970188; 16641247; 30239721, 37151363
Aminoacidopathy v1.131 GLS Zornitza Stark Phenotypes for gene: GLS were changed from glutaminase deficiency MONDO:0600001 to Glutaminase deficiency MONDO:0600001; Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development MONDO:0032685
Aminoacidopathy v1.130 GLS Zornitza Stark Publications for gene: GLS were set to 29468182, 30575854, 30970188; 16641247
Aminoacidopathy v1.129 GLS Zornitza Stark Mode of inheritance for gene: GLS was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Aminoacidopathy v1.128 GLS Zornitza Stark reviewed gene: GLS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glutaminase deficiency MONDO:0600001, Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development MONDO:0032685; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1946 ACOX2 Zornitza Stark Publications for gene: ACOX2 were set to 27647924; 27884763
Peroxisomal Disorders v0.54 ACOX2 Zornitza Stark Publications for gene: ACOX2 were set to 27647924; 27884763; 29287774
Pancreatitis v1.6 CLDN2 Zornitza Stark Classified gene: CLDN2 as Red List (low evidence)
Pancreatitis v1.6 CLDN2 Zornitza Stark Gene: cldn2 has been classified as Red List (Low Evidence).
Pancreatitis v1.5 CLDN2 Zornitza Stark edited their review of gene: CLDN2: Changed rating: RED
Mendeliome v1.1945 CLDN2 Zornitza Stark Classified gene: CLDN2 as Red List (low evidence)
Mendeliome v1.1945 CLDN2 Zornitza Stark Gene: cldn2 has been classified as Red List (Low Evidence).
Mendeliome v1.1944 CLDN2 Zornitza Stark changed review comment from: Azoospermia and nephrolithiasis: single multigenerational family reported.; to: Azoospermia and nephrolithiasis: single multigenerational family reported.

LIMITED by ClinGen.
Mendeliome v1.1944 CLDN2 Zornitza Stark changed review comment from: Pancreatitis: Numerous publications linking common variants at this locus with susceptibility to pancreatitis. KO mice do not have a pancreatic phenotype. Likely polygenic susceptibility rather than Mendelian disorder.; to: Pancreatitis: Numerous publications linking common variants at this locus with susceptibility to pancreatitis. KO mice do not have a pancreatic phenotype; have calciuria. Likely polygenic susceptibility rather than Mendelian disorder.
Mendeliome v1.1944 CLDN2 Zornitza Stark changed review comment from: Azoospermia: single multigenerational family reported.; to: Azoospermia and nephrolithiasis: single multigenerational family reported.
Mendeliome v1.1944 CLDN2 Zornitza Stark edited their review of gene: CLDN2: Changed rating: RED
Prepair 1000+ v1.82 ADAR Lisa Norbart reviewed gene: ADAR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 6, MIM#615010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.82 ABCA3 Lisa Norbart reviewed gene: ABCA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 15044640; Phenotypes: Surfactant metabolism dysfunction, pulmonary, 3, MIM#610921; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.82 ATP8A2 Ee Ming Wong reviewed gene: ATP8A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22892528, 31612321; Phenotypes: Cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome 4 (MIM#615268); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.82 ATR Karina Sandoval reviewed gene: ATR: Rating: GREEN; Mode of pathogenicity: None; Publications: 12640452, 19620979, 30199583, 23111928, 23111928; Phenotypes: Seckel syndrome 1(MIM#210600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.82 ATOH7 Ee Ming Wong reviewed gene: ATOH7: Rating: GREEN; Mode of pathogenicity: None; Publications: 22068589, 22645276, 31696227, 11493566, 11493566; Phenotypes: Persistent hyperplastic primary vitreous, autosomal recessive, MIM# 221900, microphthalmia, cataract, glaucoma, congenital retinal nonattachment; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.82 ALG9 Cassandra Muller reviewed gene: ALG9: Rating: GREEN; Mode of pathogenicity: None; Publications: 28932688, 25966638, 26453364, 30676690, 36326140; Phenotypes: Congenital disorder of glycosylation, type Il, MIM#608776, Gillessen-Kaesbach-Nishimura syndrome, MIM# 263210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.82 ATAD1 Ee Ming Wong reviewed gene: ATAD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28180185, 29390050, 29659736; Phenotypes: Hyperekplexia 4, MIM#618011; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.82 ARSA Ee Ming Wong reviewed gene: ARSA: Rating: GREEN; Mode of pathogenicity: None; Publications: 25987178, 23348427, 33195324; Phenotypes: Metachromatic leukodystrophy, MIM# 250100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.82 AKR1D1 Ee Ming Wong changed review comment from: Well established gene-disease association.
Inborn error of bile acid metabolism. At least 6 cases (with 5 variants) in 5 families reported.
Severe condition with congenital onset, leads to liver failure.; to: Well established gene-disease association.
Inborn error of bile acid metabolism. At least 6 cases (with 5 variants) in 5 families reported.
Severe condition with congenital onset, leads to liver failure.
Prepair 1000+ v1.82 AKR1D1 Ee Ming Wong reviewed gene: AKR1D1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 12970144, 20522910, 30373615; Phenotypes: Bile acid synthesis defect, congenital, 2, MIM# 235555; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.82 AGRN Cassandra Muller reviewed gene: AGRN: Rating: GREEN; Mode of pathogenicity: None; Publications: 19631309, 22205389, 32221959; Phenotypes: Myasthenic syndrome, congenital, 8, with pre- and postsynaptic defects, MIM# 615120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.82 ADAMTS2 Ee Ming Wong reviewed gene: ADAMTS2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30071989, 26765342, 28306229; Phenotypes: Ehlers-Danlos syndrome, dermatosparaxis type (MIM# 225410); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Spontaneous coronary artery dissection v0.39 SMAD3 Ain Roesley changed review comment from: Missense variants within the MH2 domain have been suggested to exert dominant negative mechanism by disprupting the formation of homo-oligomers (PMID: 30661052) Loss-of-function proven for PTCs (PMID: 30661052)

"Definitive" by ClinGen Aortopathy working group.
Sources: Literature; to: PMID: 32897753
1x individual with SCAD, canonical splice variant

PMID: 29650765
1x individual with SCAD, missense D258H absent in gnomad v4

PMID: 33125268
2x individuals with SCAD, 1x start loss and 1x fs

PMID: 33190788
1x individual with another variant in MYH11

Sources: Literature
Spontaneous coronary artery dissection v0.39 SMAD2 Ain Roesley Publications for gene: SMAD2 were set to 29967133
Spontaneous coronary artery dissection v0.38 SMAD2 Ain Roesley edited their review of gene: SMAD2: Changed publications: 32897753, 30448172
Spontaneous coronary artery dissection v0.38 SMAD2 Ain Roesley edited their review of gene: SMAD2: Changed publications: PMID: 32897753, 30448172
Spontaneous coronary artery dissection v0.38 SMAD2 Ain Roesley changed review comment from: 9 individuals from 5 families with wide spectrum of autosomal dominant aortic and arterial aneurysmal disease combined with connective tissue disease similar to Marfan syndrome and Loeys-Dietz syndrome.
Sources: Literature; to: PMID: 32897753
3x individuals with SCAD, all missense and absent/1 het in gnomad v4

PMID: 30448172
1x individual with a missense, absent in gnomad v4

Sources: Literature
Spontaneous coronary artery dissection v0.38 MYLK Ain Roesley Publications for gene: MYLK were set to 30071989; 27586135; 21055718; 25907466
Spontaneous coronary artery dissection v0.37 MYLK Ain Roesley Classified gene: MYLK as Amber List (moderate evidence)
Spontaneous coronary artery dissection v0.37 MYLK Ain Roesley Gene: mylk has been classified as Amber List (Moderate Evidence).
Spontaneous coronary artery dissection v0.36 MYLK Ain Roesley edited their review of gene: MYLK: Changed rating: AMBER; Changed publications: 33125268; Changed phenotypes: Aortic aneurysm, familial thoracic 7 MIM#613780
Spontaneous coronary artery dissection v0.36 MYLK Ain Roesley changed review comment from: Association between variants in this gene and aortic dissection established in multiple individuals and a 5-generation family (PMID 27586135;21055718;25907466).

"Definitive" by Clingen Aortopathy Working Group.
Sources: Literature; to: PMID: 33125268
1x SCAD individual with a stop gain

1x indiv from google search (https://medwinpublishers.com/CRIJ/unraveling-the-genetic-complexity-a-case-report-of-mylk-gene-mutation-in-a-patient-with-scad.pdf)
however, the specific variant was not provided - Authors said 'a VUS was identified'

Other papers from Google cite PMID: 33125268

Red/Amber rating, amber so as to not miss a diagnosis

Sources: Literature
Spontaneous coronary artery dissection v0.36 LOX Ain Roesley Publications for gene: LOX were set to 30071989; 26838787; 30675029.
Spontaneous coronary artery dissection v0.35 LOX Ain Roesley Classified gene: LOX as Amber List (moderate evidence)
Spontaneous coronary artery dissection v0.35 LOX Ain Roesley Gene: lox has been classified as Amber List (Moderate Evidence).
Spontaneous coronary artery dissection v0.34 LOX Ain Roesley edited their review of gene: LOX: Changed rating: AMBER; Changed publications: 32897753, 36103205; Changed phenotypes: Aortic aneurysm, familial thoracic 10 MIM#617168
Spontaneous coronary artery dissection v0.34 LOX Ain Roesley changed review comment from: Reviewed as having 'strong' gene-disease association by the HTAAD working group, based on ClinGen framework (PMID: 30071989).

Missense and nonsense variants described in six unrelated families with HTAAD and functional studies of three missense variants demonstrated a reduction in LOX activity (Guo et.al. (2016); PMID: 26838787).

Two further individuals with negative family history: one individual has pathogenic nonsense variant and second individual has VUS missense variant (Renner et al. (2019); PMID: 30675029).
Sources: Literature; to: PMID: 32897753
1x with circumflex coronary artery, possibly the same individual reported in PMID: 33125268
Met298Arg is absent in gnomad

PMID: 36103205
1x however, the missense was curated as benign (97 hets in gnomad v4)

Red/Amber rating - amber so as to not miss a diagnosis

Sources: Literature
Prepair 1000+ v1.82 ATP7A Karina Sandoval reviewed gene: ATP7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 20170900, 33137485, 31969342, 31558336, 7842019, 8981948; Phenotypes: Menkes disease(MIM#309400), Occipital horn syndrome(MIM#304150); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.82 ATP13A2 Karina Sandoval reviewed gene: ATP13A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30868101, 21362476, 31588715, 22388936; Phenotypes: Kufor-Rakeb syndrome (MIM#606693); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.82 ASPM Karina Sandoval reviewed gene: ASPM: Rating: GREEN; Mode of pathogenicity: None; Publications: 18452193, 19332161, 19770472, 27250695, 29243349; Phenotypes: Microcephaly 5, primary, autosomal recessive (MIM#608716); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Spontaneous coronary artery dissection v0.34 FLNA Ain Roesley changed review comment from:

PMID: 32897753
1x individual with left anterior descending coronary artery

Sources: Literature

; to: borderline red/amber but amber so as to not miss a diagnosis

PMID: 32897753
1x individual with left anterior descending coronary artery

Sources: Literature
Spontaneous coronary artery dissection v0.34 FLNA Ain Roesley Phenotypes for gene: FLNA were changed from periventricular heterotopia 1 MIM#300049 to Spontaneous coronary artery dissection
Spontaneous coronary artery dissection v0.33 FLNA Ain Roesley Classified gene: FLNA as Amber List (moderate evidence)
Spontaneous coronary artery dissection v0.33 FLNA Ain Roesley Gene: flna has been classified as Amber List (Moderate Evidence).
Spontaneous coronary artery dissection v0.32 FLNA Ain Roesley edited their review of gene: FLNA: Changed publications: 32897753
Spontaneous coronary artery dissection v0.32 FLNA Ain Roesley changed review comment from: Large review of 114 patients with loss-of-function FLNA mutations with periventricular nodular heterotopia (PVNH), found that most subjects had a cardiac anomaly or vascular abnormality (64.9%). Thoracic aortic aneurysms or dilatation (TAA) were found in 18.4%, and were associated with other structural cardiac malformations in 57.1% of patients (Chen et al. 2018; PMID: 29334594).

PMID: 32897753
1x individual with left anterior descending coronary artery

Sources: Literature

; to:

PMID: 32897753
1x individual with left anterior descending coronary artery

Sources: Literature
Spontaneous coronary artery dissection v0.32 FLNA Ain Roesley edited their review of gene: FLNA: Changed rating: AMBER; Changed publications: 29334594, 32897753; Changed phenotypes: periventricular heterotopia 1 MIM#300049
Spontaneous coronary artery dissection v0.32 FLNA Ain Roesley changed review comment from: Large review of 114 patients with loss-of-function FLNA mutations with periventricular nodular heterotopia (PVNH), found that most subjects had a cardiac anomaly or vascular abnormality (64.9%). Thoracic aortic aneurysms or dilatation (TAA) were found in 18.4%, and were associated with other structural cardiac malformations in 57.1% of patients (Chen et al. 2018; PMID: 29334594).
Sources: Literature; to: Large review of 114 patients with loss-of-function FLNA mutations with periventricular nodular heterotopia (PVNH), found that most subjects had a cardiac anomaly or vascular abnormality (64.9%). Thoracic aortic aneurysms or dilatation (TAA) were found in 18.4%, and were associated with other structural cardiac malformations in 57.1% of patients (Chen et al. 2018; PMID: 29334594).

PMID: 32897753
1x individual with left anterior descending coronary artery

Sources: Literature
Spontaneous coronary artery dissection v0.32 FBN1 Ain Roesley edited their review of gene: FBN1: Changed publications: 29357934, 34842564, 35092149; Changed phenotypes: Marfan syndrome MIM#154700, familial thoracic aortic aneurysm and aortic dissection MONDO:0019625, FBN1-related
Spontaneous coronary artery dissection v0.32 FBN1 Ain Roesley changed review comment from: Dominant-negative and LoF (haploinsufficiency) have been reported as disease mechanisms (OMIM). PTV are associated with more severe MFS and with aortic events. Missense are associated with a milder MFS and less often result in aortic events (PMID: 29357934 ).

definitive by clingen curation
Sources: Literature; to: Dominant-negative and LoF (haploinsufficiency) have been reported as disease mechanisms (OMIM). PTV are associated with more severe MFS and with aortic events. Missense are associated with a milder MFS and less often result in aortic events (PMID: 29357934 ).

definitive by clingen curation

at least 3x individuals with Marfan + FBN1 variant have been reported with SCAD
PMID: 34842564, 35092149

Sources: Literature
Spontaneous coronary artery dissection v0.32 COL5A1 Ain Roesley edited their review of gene: COL5A1: Changed publications: 32938213, 35234813; Changed phenotypes: Ehlers-Danlos syndrome, classic type, 1 MIM#130000, Fibromuscular dysplasia, multifocal MIM#619329
Spontaneous coronary artery dissection v0.32 COL5A1 Ain Roesley changed review comment from: GeneReviews: 75-78% of classical EDS is caused by pathogenic variants in COL5A1. Haploinsufficiency is the more common disease mechanism whoeever, missense variants in the triple helical domain of the α1(V) or α2(V) chains are likely to have dominant-negative activity.
(https://www.ncbi.nlm.nih.gov/books/NBK1244/)

Multifocal fibromuscular dysplasia (FMDMF) is characterized histologically by medial fibroplasia and angiographically by multiple arterial stenoses with intervening mural dilations. Arterial tortuosity, macroaneurysms, dissections, and rupture may occur.

4 unrelated individuals reported, but all had the same variant, p.Gly514Ser, and haplotype analysis was consistent with founder effect. Further rare missense variants were identified in a cohort, although limited information available.
Sources: Literature; to: GeneReviews: 75-78% of classical EDS is caused by pathogenic variants in COL5A1. Haploinsufficiency is the more common disease mechanism whoeever, missense variants in the triple helical domain of the α1(V) or α2(V) chains are likely to have dominant-negative activity.
(https://www.ncbi.nlm.nih.gov/books/NBK1244/)

SCAD individuals with variants in COL5A1 have been reported
PMID: 35234813

Sources: Literature
Prepair 1000+ v1.82 EIF2AK3 Andrew Coventry reviewed gene: EIF2AK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10932183 12960215 16813601 11997520 20202148 11430819; Phenotypes: Wolcott-Rallison syndrome MIM#226980; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.82 DDX59 Andrew Coventry reviewed gene: DDX59: Rating: GREEN; Mode of pathogenicity: None; Publications: 28711741 29127725 23972372 28289185; Phenotypes: Orofaciodigital syndrome V MIM#174300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Spontaneous coronary artery dissection v0.32 COL3A1 Ain Roesley edited their review of gene: COL3A1: Changed publications: 30071989, 32897753, 35234813
Spontaneous coronary artery dissection v0.32 COL3A1 Ain Roesley changed review comment from: Classified as Definitive by Clingen for heritable thoracic aortic aneurysm and dissection; Ehlers-Danlos syndrome, vascular type.
Sources: Literature; to: Classified as Definitive by Clingen for heritable thoracic aortic aneurysm and dissection; Ehlers-Danlos syndrome, vascular type.

Several individuals with SCAD have also been reported with variants in COL3A1
PMID: 32897753
PMID: 36103205
PMID: 35234813


Sources: Literature
Prepair 1000+ v1.82 DCX Andrew Coventry reviewed gene: DCX: Rating: GREEN; Mode of pathogenicity: None; Publications: 10915612 9489699 12552055 20301364 14625554; Phenotypes: Lissencephaly, X-linked MIM#300067, Subcortical laminal heterotopia, X-linked MIM#300067; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Spontaneous coronary artery dissection v0.32 COL3A1 Ain Roesley edited their review of gene: COL3A1: Changed publications: 30071989, 32897753; Changed phenotypes: Ehlers-Danlos syndrome, vascular type MIM#130050
Prepair 1000+ v1.82 CYP2U1 Andrew Coventry reviewed gene: CYP2U1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23176821 32006740 29034544 26914923 24337409 28725025; Phenotypes: Spastic paraplegia 56, autosomal recessive MIM#615030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.82 CYP17A1 Andrew Coventry changed review comment from: Established gene-disease association. Congenital onset. More than 100 families reported. Mechanism impacts hormone production in gonads and adrenal glands. Phenotype typically includes hypertension, low blood potassium, and abnormal development of sexual characteristics including genitalia (disorder of sexual development) in both males and females. Phenotypic spectrum for those affected is variable.; to: Established gene-disease association. Congenital onset. More than 100 families reported. Mechanism impacts hormone production in gonads and adrenal glands. Phenotype typically includes hypertension, low blood potassium, and abnormal development of sexual characteristics including genitalia (disorder of sexual development) in both males and females. Phenotypic spectrum of severity for those affected is variable.
Prepair 1000+ v1.82 CYP17A1 Andrew Coventry reviewed gene: CYP17A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 2843762 14671162 2026124 35178494 35043964; Phenotypes: 17-alpha-hydroxylase/17,20-lyase deficiency MIM#202110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.82 COG7 Kate Scarff reviewed gene: COG7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 15107842, 17356545, 28883096, 17395513, 16151902; Phenotypes: Congenital disorder of glycosylation, type IIe, MIM # 608779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.82 CNTNAP1 Kate Scarff reviewed gene: CNTNAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28374019, 29511323, 29882456, 27668699; Phenotypes: Lethal congenital contracture syndrome 7, MIM # 616286, Hypomyelinating neuropathy, congenital, 3, MIM # 618186; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.82 CHST3 Kate Scarff reviewed gene: CHST3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 18513679; Phenotypes: Spondyloepiphyseal dysplasia with congenital joint dislocations, MIM # 143095; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.82 CCDC103 Kate Scarff reviewed gene: CCDC103: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22581229, 32447765, 31858719, 28790179; Phenotypes: Primary ciliary dyskinesia-17, MIM # 614679; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.82 C12orf57 Kate Scarff reviewed gene: C12orf57: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23453666, 29383837, 31853307; Phenotypes: Temtamy syndrome, MIM # 218340; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.82 CNNM4 Lilian Downie Marked gene: CNNM4 as ready
Prepair 1000+ v1.82 CNNM4 Lilian Downie Gene: cnnm4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.82 CNNM4 Lilian Downie Publications for gene: CNNM4 were set to
Prepair 1000+ v1.81 CNGB3 Lilian Downie Marked gene: CNGB3 as ready
Prepair 1000+ v1.81 CNGB3 Lilian Downie Gene: cngb3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.81 CNGB3 Lilian Downie Publications for gene: CNGB3 were set to
Prepair 1000+ v1.80 CNGB3 Lilian Downie Tag SV/CNV tag was added to gene: CNGB3.
Prepair 1000+ v1.80 CLP1 Lilian Downie Marked gene: CLP1 as ready
Prepair 1000+ v1.80 CLP1 Lilian Downie Gene: clp1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.80 CLP1 Lilian Downie Publications for gene: CLP1 were set to
Prepair 1000+ v1.79 B3GAT3 Lilian Downie Marked gene: B3GAT3 as ready
Prepair 1000+ v1.79 B3GAT3 Lilian Downie Gene: b3gat3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.79 B3GAT3 Lilian Downie Publications for gene: B3GAT3 were set to
Prepair 1000+ v1.78 CLN6 Lilian Downie Marked gene: CLN6 as ready
Prepair 1000+ v1.78 CLN6 Lilian Downie Gene: cln6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.78 CLN6 Lilian Downie Publications for gene: CLN6 were set to
Prepair 1000+ v1.77 CLDN1 Lilian Downie Marked gene: CLDN1 as ready
Prepair 1000+ v1.77 CLDN1 Lilian Downie Gene: cldn1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.77 CLDN1 Lilian Downie Publications for gene: CLDN1 were set to
Prepair 1000+ v1.76 CLCNKB Lilian Downie Tag for review tag was added to gene: CLCNKB.
Prepair 1000+ v1.76 BUB1B Kate Scarff reviewed gene: BUB1B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 18548531; Phenotypes: Mosaic variegated aneuploidy syndrome 1, MIM# 257300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.76 CLCNKB Lilian Downie Marked gene: CLCNKB as ready
Prepair 1000+ v1.76 CLCNKB Lilian Downie Added comment: Comment when marking as ready: The digenic inheritance is not clearly proven, patients with variants in both genes also had biallelic variants in this gene which is just as likely to have been the cause. Not enough evidence to report in carrier screening as a digenic condition. PMID: 18310267
Prepair 1000+ v1.76 CLCNKB Lilian Downie Gene: clcnkb has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.32 TLN1 Ain Roesley changed review comment from: PMID: 37979122; listed as "likely monogenic disease effect"

but AMBER rating
10 unique rare heterozygous missense variants in 11 individuals were identified in a 2 generation SCAD family and 56 unrelated individuals with sporadic SCAD. All variants had a MAF of less than 0.06% and occurred within highly conserved β-integrin, F-actin, or vinculin binding domains. Incomplete penetrance was evident in the familial case and five individuals with sporadic SCAD from whom parental DNA was available. No functional assays were conducted.
Sources: Literature; to: PMID: 37979122; listed as "likely monogenic disease effect"

but AMBER rating
10 unique rare heterozygous missense variants in 11 individuals were identified in a 2 generation SCAD family and 56 unrelated individuals with sporadic SCAD. All variants had a MAF of less than 0.06% and occurred within highly conserved β-integrin, F-actin, or vinculin binding domains. Incomplete penetrance was evident in the familial case and five individuals with unaffected heterozygous parents. No functional assays were conducted.
Sources: Literature
Prepair 1000+ v1.76 ARV1 Marta Cifuentes Ochoa reviewed gene: ARV1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35227294, 27270415, 25558065, 34017911, 34296759; Phenotypes: Developmental and epileptic encephalopathy 38 MIM#617020 MONDO:0014868; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.76 ARMC4 Marta Cifuentes Ochoa reviewed gene: ARMC4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31765523, 23849778; Phenotypes: Ciliary dyskinesia, primary, 23, MIM# 615451 primary ciliary dyskinesia 23 MONDO:0014193; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.76 AMT Marta Cifuentes Ochoa reviewed gene: AMT: Rating: GREEN; Mode of pathogenicity: None; Publications: 27362913, 16450403, 30350008, 26179960, 20301531, 25231368, 35646099; Phenotypes: Nonketotic Hyperglycinemia, Glycine encephalopathy MIM#620398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1944 EMILIN1 Zornitza Stark Phenotypes for gene: EMILIN1 were changed from Neuronopathy, distal hereditary motor, type X, MIM# 620080; Aortic aneurysm, MONDO:0005160, EMILIN2-related to Neuronopathy, distal hereditary motor, type X, MIM# 620080; Arterial tortuosity-bone fragility syndrome, MIM# 620908
Aortopathy_Connective Tissue Disorders v1.86 EMILIN1 Zornitza Stark Phenotypes for gene: EMILIN1 were changed from Neuronopathy, distal hereditary motor, type X, MIM# 620080 Aortic aneurysm, MONDO:0005160, EMILIN2-related to Neuronopathy, distal hereditary motor, type X, MIM# 620080; Arterial tortuosity-bone fragility syndrome, MIM# 620908
Aortopathy_Connective Tissue Disorders v1.85 EMILIN1 Zornitza Stark edited their review of gene: EMILIN1: Changed phenotypes: Neuronopathy, distal hereditary motor, type X, MIM# 620080, Peripheral neuropathy
Aortopathy_Connective Tissue Disorders v1.85 EMILIN1 Zornitza Stark edited their review of gene: EMILIN1: Changed phenotypes: Neuronopathy, distal hereditary motor, type X, MIM# 620080, Peripheral neuropathy, Arterial tortuosity-bone fragility syndrome, MIM# 620908
Peroxisomal Disorders v0.53 ACOX2 Sangavi Sivagnanasundram reviewed gene: ACOX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27647924, 27884763, 35395098; Phenotypes: congenital bile acid synthesis defect 6 MONDO:0015015; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1943 ACOX2 Sangavi Sivagnanasundram reviewed gene: ACOX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27647924, 27884763, 35395098; Phenotypes: congenital bile acid synthesis defect 6 MONDO:0015015; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.128 GLS Sangavi Sivagnanasundram edited their review of gene: GLS: Added comment: Classified as Moderate by ClinGen Aminoacidopathy GCEP on 26/07/2024 - https://search.clinicalgenome.org/CCID:004966

Two unrelated probands have been reported with an increased glutamate production level. Two missense variants have been reported (Ser482Cys and His461Leu - both absent from gnomAD v4.1). A zebrafish model partially recapitulated the disease.; Changed rating: AMBER; 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: 30239721, 37151363; Changed phenotypes: infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development MONDO:0032685; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1943 PRPF4 Sangavi Sivagnanasundram reviewed gene: PRPF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24419317; Phenotypes: inherited retinal dystrophy MONDO:0019118; Mode of inheritance: None
Retinitis pigmentosa_Autosomal Dominant v0.57 PRPF4 Sangavi Sivagnanasundram reviewed gene: PRPF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24419317; Phenotypes: inherited retinal dystrophy MONDO:0019118; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.76 CYP11A1 Andrew Coventry reviewed gene: CYP11A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12161514 16705068 18182448 28425981; Phenotypes: Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete MIM#613743; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.76 CNNM4 Andrew Coventry reviewed gene: CNNM4: Rating: ; Mode of pathogenicity: None; Publications: 30705057 29421294 19200527 19200525; Phenotypes: Jalili syndrome MIM#217080; Mode of inheritance: None
Prepair 1000+ v1.76 CNGB3 Andrew Coventry reviewed gene: CNGB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 17265047 28795510 12140185 28795510; Phenotypes: Achromatopsia 3 MIM#262300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.76 CLP1 Andrew Coventry reviewed gene: CLP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24766809 24766810 23474986 29307788; Phenotypes: Pontocerebellar hypoplasia, type 10 MIM#615803; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6099 HDAC3 Zornitza Stark Marked gene: HDAC3 as ready
Intellectual disability syndromic and non-syndromic v0.6099 HDAC3 Zornitza Stark Gene: hdac3 has been classified as Green List (High Evidence).
Hydrops fetalis v0.317 ANGPT2 Zornitza Stark Marked gene: ANGPT2 as ready
Hydrops fetalis v0.317 ANGPT2 Zornitza Stark Gene: angpt2 has been classified as Green List (High Evidence).
Hydrops fetalis v0.317 ANGPT2 Zornitza Stark Classified gene: ANGPT2 as Green List (high evidence)
Hydrops fetalis v0.317 ANGPT2 Zornitza Stark Gene: angpt2 has been classified as Green List (High Evidence).
Hydrops fetalis v0.316 ANGPT2 Zornitza Stark gene: ANGPT2 was added
gene: ANGPT2 was added to Hydrops fetalis. Sources: Expert list
Mode of inheritance for gene: ANGPT2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ANGPT2 were set to 32908006; 34876502
Phenotypes for gene: ANGPT2 were set to Lymphatic malformation-10, MIM#619369; Primary lymphoedema Hydrops
Review for gene: ANGPT2 was set to GREEN
Added comment: Mono-allelic disease: association with lymphoedema in 5 unrelated individuals PMID 32908006

Bi-allelic disease PMID 34876502: single family reported with four fetuses with hydrops fetalis homozygous for ANGPT2 NM_001147.2:c.557A>G. The consanguineous parents and surviving sibblings (a girl and a boy), were heterozygous for this variant. This variant is predicted to create a cryptic exonic splice site, resulting in a r.557_566del and nonsense-mediated mRNA decay. This prediction was supported by the lack of a transcript from this allele in the parents.
Sources: Expert list
Mendeliome v1.1943 FZD6 Zornitza Stark Phenotypes for gene: FZD6 were changed from Nail disorder, nonsyndromic congenital, 1, MIM# 161050 to Nail disorder, nonsyndromic congenital, 1, MIM# 161050; Hydrops fetalis, MONDO:0015193, FZD6-related
Mendeliome v1.1942 FZD6 Zornitza Stark Publications for gene: FZD6 were set to 21665003; 23374899
Mendeliome v1.1941 FZD6 Zornitza Stark changed review comment from: PMIDs 33082562; 26036949; 28425981. Three FZD6 variants have been associated with two unrelated cases of fetal hyrdrops.; to: PMIDs 33082562; 26036949; 28425981. Three FZD6 variants have been associated with two unrelated cases of fetal hyrdrops. AMBER for this indication.
Mendeliome v1.1941 FZD6 Zornitza Stark edited their review of gene: FZD6: Changed phenotypes: Nail disorder, nonsyndromic congenital, 1, MIM# 161050, Hydrops fetalis, MONDO:0015193, FZD6-related
Mendeliome v1.1941 FZD6 Zornitza Stark edited their review of gene: FZD6: Added comment: PMIDs 33082562; 26036949; 28425981. Three FZD6 variants have been associated with two unrelated cases of fetal hyrdrops.; Changed publications: 21665003, 23374899, 33082562, 26036949, 28425981
Hydrops fetalis v0.315 FZD6 Zornitza Stark Marked gene: FZD6 as ready
Hydrops fetalis v0.315 FZD6 Zornitza Stark Gene: fzd6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.263 FZD6 Zornitza Stark Marked gene: FZD6 as ready
Fetal anomalies v1.263 FZD6 Zornitza Stark Gene: fzd6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.263 FZD6 Zornitza Stark Classified gene: FZD6 as Amber List (moderate evidence)
Fetal anomalies v1.263 FZD6 Zornitza Stark Gene: fzd6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.262 FZD6 Zornitza Stark gene: FZD6 was added
gene: FZD6 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: FZD6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FZD6 were set to 33082562; 26036949; 28425981
Phenotypes for gene: FZD6 were set to Hydrops fetalis, MONDO:0015193, FZD6-related
Review for gene: FZD6 was set to AMBER
Added comment: Three FZD6 variants have been associated with two unrelated cases of fetal hyrdrops.
Sources: Expert list
Hydrops fetalis v0.315 FZD6 Zornitza Stark Classified gene: FZD6 as Amber List (moderate evidence)
Hydrops fetalis v0.315 FZD6 Zornitza Stark Gene: fzd6 has been classified as Amber List (Moderate Evidence).
Hydrops fetalis v0.314 FZD6 Zornitza Stark gene: FZD6 was added
gene: FZD6 was added to Hydrops fetalis. Sources: Literature
Mode of inheritance for gene: FZD6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FZD6 were set to 33082562; 26036949; 28425981
Phenotypes for gene: FZD6 were set to Hydrops fetalis, MONDO:0015193, FZD6-related
Review for gene: FZD6 was set to AMBER
Added comment: Three FZD6 variants have been associated with two unrelated cases of fetal hyrdrops
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6099 SOX9 Ken Lee Wan reviewed gene: SOX9: Rating: RED; Mode of pathogenicity: None; Publications: 20301724, 26663529; Phenotypes: campomelic dysplasia MONDO:0007251; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v1.261 TBC1D7 Zornitza Stark Classified gene: TBC1D7 as Amber List (moderate evidence)
Fetal anomalies v1.261 TBC1D7 Zornitza Stark Gene: tbc1d7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.260 TBC1D7 Zornitza Stark Publications for gene: TBC1D7 were set to 23687350; 24515783
Fetal anomalies v1.259 TBC1D7 Zornitza Stark Classified gene: TBC1D7 as Green List (high evidence)
Fetal anomalies v1.259 TBC1D7 Zornitza Stark Gene: tbc1d7 has been classified as Green List (High Evidence).
Fetal anomalies v1.258 TBC1D7 Zornitza Stark reviewed gene: TBC1D7: Rating: GREEN; Mode of pathogenicity: None; Publications: 36669495; Phenotypes: Macrocephaly/megalencephaly syndrome, autosomal recessive - MIM#248000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Macrocephaly_Megalencephaly v0.142 TBC1D7 Zornitza Stark Publications for gene: TBC1D7 were set to 24515783; 23687350; 36669495
Macrocephaly_Megalencephaly v0.142 TBC1D7 Zornitza Stark Publications for gene: TBC1D7 were set to 24515783; 23687350
Intellectual disability syndromic and non-syndromic v0.6099 TBC1D7 Zornitza Stark Publications for gene: TBC1D7 were set to 24515783; 23687350
Intellectual disability syndromic and non-syndromic v0.6098 TBC1D7 Zornitza Stark Classified gene: TBC1D7 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6098 TBC1D7 Zornitza Stark Gene: tbc1d7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6097 TBC1D7 Zornitza Stark edited their review of gene: TBC1D7: Added comment: PMID: 36669495 reports additional individuals with compound het variants identified via trio RNASeq.; Changed rating: GREEN; Changed publications: 24515783, 23687350, 36669495
Macrocephaly_Megalencephaly v0.141 TBC1D7 Zornitza Stark Classified gene: TBC1D7 as Green List (high evidence)
Macrocephaly_Megalencephaly v0.141 TBC1D7 Zornitza Stark Gene: tbc1d7 has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.140 TBC1D7 Zornitza Stark edited their review of gene: TBC1D7: Added comment: PMID: 36669495 reports additional individuals with compound het variants identified via trio RNASeq.; Changed rating: GREEN; Changed publications: 24515783, 23687350, 36669495
Mendeliome v1.1941 TBC1D7 Zornitza Stark Publications for gene: TBC1D7 were set to 24515783; 23687350
Mendeliome v1.1940 TBC1D7 Zornitza Stark Classified gene: TBC1D7 as Green List (high evidence)
Mendeliome v1.1940 TBC1D7 Zornitza Stark Gene: tbc1d7 has been classified as Green List (High Evidence).
Mendeliome v1.1939 TBC1D7 Zornitza Stark edited their review of gene: TBC1D7: Changed rating: GREEN
Mendeliome v1.1939 TBC1D7 Zornitza Stark edited their review of gene: TBC1D7: Added comment: PMID: 36669495 reports additional individuals with compound het variants identified via trio RNASeq.; Changed publications: 24515783, 23687350, 36669495
Fetal anomalies v1.258 GLIS2 Zornitza Stark Classified gene: GLIS2 as Green List (high evidence)
Fetal anomalies v1.258 GLIS2 Zornitza Stark Gene: glis2 has been classified as Green List (High Evidence).
Fetal anomalies v1.257 GLIS2 Zornitza Stark edited their review of gene: GLIS2: Added comment: Five individuals from three unrelated families reported, albeit with homozygous variants. Functional data.; Changed rating: GREEN; Changed publications: 31676329, 17618285, 23559409
Ciliopathies v1.56 GLIS2 Zornitza Stark Classified gene: GLIS2 as Green List (high evidence)
Ciliopathies v1.56 GLIS2 Zornitza Stark Gene: glis2 has been classified as Green List (High Evidence).
Ciliopathies v1.55 GLIS2 Zornitza Stark changed review comment from: Two families reported.; to: Three families (5 individuals) reported, albeit with homozygous variants. Functional data.
Ciliopathies v1.55 GLIS2 Zornitza Stark edited their review of gene: GLIS2: Changed rating: GREEN
Mendeliome v1.1939 GLIS2 Zornitza Stark Classified gene: GLIS2 as Green List (high evidence)
Mendeliome v1.1939 GLIS2 Zornitza Stark Gene: glis2 has been classified as Green List (High Evidence).
Mendeliome v1.1938 GLIS2 Zornitza Stark changed review comment from: Two families reported.; to: Three families (5 individuals) reported. Functional data.
Mendeliome v1.1938 GLIS2 Zornitza Stark edited their review of gene: GLIS2: Changed rating: GREEN
Renal Ciliopathies and Nephronophthisis v1.23 GLIS2 Zornitza Stark Classified gene: GLIS2 as Green List (high evidence)
Renal Ciliopathies and Nephronophthisis v1.23 GLIS2 Zornitza Stark Gene: glis2 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v1.22 GLIS2 Zornitza Stark changed review comment from: Good functional data, but limited reports in humans.; to: Good functional data. Three unrelated families reported (5 individuals) but note all had homozygous variants.
Renal Ciliopathies and Nephronophthisis v1.22 GLIS2 Zornitza Stark edited their review of gene: GLIS2: Changed rating: GREEN
Regression v0.557 LNPK Zornitza Stark Marked gene: LNPK as ready
Regression v0.557 LNPK Zornitza Stark Gene: lnpk has been classified as Green List (High Evidence).
Regression v0.557 LNPK Zornitza Stark Classified gene: LNPK as Green List (high evidence)
Regression v0.557 LNPK Zornitza Stark Gene: lnpk has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6097 MSL2 Zornitza Stark Classified gene: MSL2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6097 MSL2 Zornitza Stark Gene: msl2 has been classified as Green List (High Evidence).
Mendeliome v1.1938 C17orf53 Zornitza Stark Phenotypes for gene: C17orf53 were changed from Primary ovarian insufficiency to Ovarian dysgenesis 11, MIM# 620897
Mendeliome v1.1937 C17orf53 Zornitza Stark Classified gene: C17orf53 as Green List (high evidence)
Mendeliome v1.1937 C17orf53 Zornitza Stark Gene: c17orf53 has been classified as Green List (High Evidence).
Mendeliome v1.1936 C17orf53 Zornitza Stark edited their review of gene: C17orf53: Added comment: PMID 38105698: Additional family reported with two sibs and compound het LoF variants.

HGNC approved name is HROB.; Changed rating: GREEN; Changed publications: 34707299, 31467087, 38105698; Changed phenotypes: Ovarian dysgenesis 11, MIM# 620897
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.333 C17orf53 Zornitza Stark Marked gene: C17orf53 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.333 C17orf53 Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name is HROB.
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.333 C17orf53 Zornitza Stark Gene: c17orf53 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.333 C17orf53 Zornitza Stark Tag new gene name tag was added to gene: C17orf53.
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.333 C17orf53 Zornitza Stark Phenotypes for gene: C17orf53 were changed from Primary ovarian insufficiency to Ovarian dysgenesis 11, MIM# 620897
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.332 C17orf53 Zornitza Stark Publications for gene: C17orf53 were set to PMID: 34707299; PMID: 31467087
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.331 C17orf53 Zornitza Stark Classified gene: C17orf53 as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.331 C17orf53 Zornitza Stark Gene: c17orf53 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.330 C17orf53 Zornitza Stark reviewed gene: C17orf53: Rating: GREEN; Mode of pathogenicity: None; Publications: 38105698; Phenotypes: Ovarian dysgenesis 11, MIM# 620897; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1936 CD274 Zornitza Stark Marked gene: CD274 as ready
Mendeliome v1.1936 CD274 Zornitza Stark Gene: cd274 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1936 CD274 Zornitza Stark Classified gene: CD274 as Amber List (moderate evidence)
Mendeliome v1.1936 CD274 Zornitza Stark Gene: cd274 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1935 RINT1 Zornitza Stark Phenotypes for gene: RINT1 were changed from Infantile liver failure syndrome 3, MIM# 618641 to Infantile liver failure syndrome 3, MIM# 618641; Hereditary spastic paraplegia, MONDO:0019064, RINT1-related
Mendeliome v1.1934 RINT1 Zornitza Stark Publications for gene: RINT1 were set to PMID: 31204009
Mendeliome v1.1933 RINT1 Zornitza Stark reviewed gene: RINT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37463447, 38990652; Phenotypes: Hereditary spastic paraplegia, MONDO:0019064, RINT1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6096 CYB5R3 Ken Lee Wan reviewed gene: CYB5R3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38303731; Phenotypes: Methemoglobinemia MONDO:0001117; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary Spastic Paraplegia - paediatric v1.79 RINT1 Zornitza Stark Phenotypes for gene: RINT1 were changed from Infantile liver failure syndrome 3, MIM# 618641; Hereditary spastic paraplegia, MONDO:0019064, RINT1-related to Hereditary spastic paraplegia, MONDO:0019064, RINT1-related
Hereditary Spastic Paraplegia - paediatric v1.78 RINT1 Zornitza Stark Publications for gene: RINT1 were set to 37463447
Hereditary Spastic Paraplegia - paediatric v1.77 RINT1 Zornitza Stark Classified gene: RINT1 as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v1.77 RINT1 Zornitza Stark Gene: rint1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.76 RINT1 Zornitza Stark reviewed gene: RINT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38990652; Phenotypes: Hereditary spastic paraplegia, MONDO:0019064, RINT1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v1.36 HDAC3 Zornitza Stark Marked gene: HDAC3 as ready
Genetic Epilepsy v1.36 HDAC3 Zornitza Stark Gene: hdac3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6096 CTSD Ken Lee Wan reviewed gene: CTSD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neuronal ceroid lipofuscinosis MONDO:0016295; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6096 CTSA Ken Lee Wan reviewed gene: CTSA: Rating: GREEN; Mode of pathogenicity: None; Publications: 23915561, 36713078; Phenotypes: Galactosialidosis MONDO:0009737; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v1.36 HDAC3 Zornitza Stark Classified gene: HDAC3 as Green List (high evidence)
Genetic Epilepsy v1.36 HDAC3 Zornitza Stark Gene: hdac3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6096 CTDP1 Ken Lee Wan reviewed gene: CTDP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301787; Phenotypes: congenital cataracts-facial dysmorphism-neuropathy syndrome MONDO:0011402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v1.35 HDAC3 Zornitza Stark Classified gene: HDAC3 as Green List (high evidence)
Genetic Epilepsy v1.35 HDAC3 Zornitza Stark Gene: hdac3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6096 HDAC3 Zornitza Stark edited their review of gene: HDAC3: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, HDAC3-related
Mendeliome v1.1933 HDAC3 Zornitza Stark Marked gene: HDAC3 as ready
Mendeliome v1.1933 HDAC3 Zornitza Stark Gene: hdac3 has been classified as Green List (High Evidence).
Mendeliome v1.1933 HDAC3 Zornitza Stark Classified gene: HDAC3 as Green List (high evidence)
Mendeliome v1.1933 HDAC3 Zornitza Stark Gene: hdac3 has been classified as Green List (High Evidence).
Mendeliome v1.1932 HDAC3 Zornitza Stark gene: HDAC3 was added
gene: HDAC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HDAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HDAC3 were set to 39047730
Phenotypes for gene: HDAC3 were set to Neurodevelopmental disorder, MONDO:0700092, HDAC3-related
Review for gene: HDAC3 was set to GREEN
Added comment: Six individuals with de novo missense variants in this gene and variable NDD phenotypes, including ID, seizures. Supportive functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6096 HDAC3 Zornitza Stark Phenotypes for gene: HDAC3 were changed from to Neurodevelopmental disorder, MONDO:0700092, HDAC3-related
Genetic Epilepsy v1.34 HDAC3 Zornitza Stark gene: HDAC3 was added
gene: HDAC3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: HDAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HDAC3 were set to 39047730
Phenotypes for gene: HDAC3 were set to Neurodevelopmental disorder, MONDO:0700092, HDAC3-related
Review for gene: HDAC3 was set to GREEN
Added comment: Six individuals with de novo missense variants in this gene and variable NDD phenotypes, including ID, seizures. Supportive functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6095 HDAC3 Zornitza Stark Classified gene: HDAC3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6095 HDAC3 Zornitza Stark Gene: hdac3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6094 HDAC3 Zornitza Stark Classified gene: HDAC3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6094 HDAC3 Zornitza Stark Gene: hdac3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6093 HDAC3 Zornitza Stark gene: HDAC3 was added
gene: HDAC3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HDAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HDAC3 were set to 39047730
Review for gene: HDAC3 was set to GREEN
Added comment: Six individuals with de novo missense variants in this gene and variable NDD phenotypes, including ID, seizures. Supportive functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6092 SLC39A14 Zornitza Stark Marked gene: SLC39A14 as ready
Intellectual disability syndromic and non-syndromic v0.6092 SLC39A14 Zornitza Stark Gene: slc39a14 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6092 SLC39A14 Zornitza Stark Mode of inheritance for gene: SLC39A14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6091 SLC39A14 Zornitza Stark Publications for gene: SLC39A14 were set to
Intellectual disability syndromic and non-syndromic v0.6090 SLC39A14 Zornitza Stark Phenotypes for gene: SLC39A14 were changed from to Hypermanganesemia with dystonia 2 (MIM# 617013)
Cerebral Palsy v1.365 TRPM3 Zornitza Stark Marked gene: TRPM3 as ready
Cerebral Palsy v1.365 TRPM3 Zornitza Stark Gene: trpm3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.365 TRPM3 Zornitza Stark Classified gene: TRPM3 as Red List (low evidence)
Cerebral Palsy v1.365 TRPM3 Zornitza Stark Gene: trpm3 has been classified as Red List (Low Evidence).
Mendeliome v1.1931 ITPR3 Zornitza Stark Phenotypes for gene: ITPR3 were changed from Charcot-Marie-Tooth disease, demyelinating, type 1J, MIM# 620111 to Charcot-Marie-Tooth disease, demyelinating, type 1J, MIM# 620111; Combined immunodeficiency, MONDO:0015131, ITPR3-related
Mendeliome v1.1930 ITPR3 Zornitza Stark Publications for gene: ITPR3 were set to 32949214; 24627108
Mendeliome v1.1929 ITPR3 Zornitza Stark Mode of inheritance for gene: ITPR3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1928 ITPR3 Zornitza Stark edited their review of gene: ITPR3: Changed publications: 32949214, 24627108, 36302985; Changed phenotypes: Charcot-Marie-Tooth disease, demyelinating, type 1J, MIM# 620111, Combined immunodeficiency, MONDO:0015131, ITPR3-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6089 COQ8A Ken Lee Wan reviewed gene: COQ8A: Rating: GREEN; Mode of pathogenicity: None; Publications: 31621627, 31741144; Phenotypes: coenzyme Q10 deficiency MONDO:0018151; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Combined Immunodeficiency v1.69 ITPR3 Zornitza Stark Phenotypes for gene: ITPR3 were changed from Combined immunodeficiency, MONDO:0015131, ITPR3-related to Combined immunodeficiency, MONDO:0015131, ITPR3-related
Combined Immunodeficiency v1.68 ITPR3 Zornitza Stark Marked gene: ITPR3 as ready
Combined Immunodeficiency v1.68 ITPR3 Zornitza Stark Gene: itpr3 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.68 ITPR3 Zornitza Stark Phenotypes for gene: ITPR3 were changed from ombined immunodeficiency, MONDO:0015131, ITPR3-related to Combined immunodeficiency, MONDO:0015131, ITPR3-related
Combined Immunodeficiency v1.68 ITPR3 Zornitza Stark Phenotypes for gene: ITPR3 were changed from Combined Immune deficiency, immune dysregulation to ombined immunodeficiency, MONDO:0015131, ITPR3-related
Combined Immunodeficiency v1.67 ITPR3 Zornitza Stark Classified gene: ITPR3 as Green List (high evidence)
Combined Immunodeficiency v1.67 ITPR3 Zornitza Stark Gene: itpr3 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.66 ITPR3 Zornitza Stark reviewed gene: ITPR3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined immunodeficiency, MONDO:0015131, ITPR3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6089 COL4A2 Zornitza Stark Marked gene: COL4A2 as ready
Intellectual disability syndromic and non-syndromic v0.6089 COL4A2 Zornitza Stark Gene: col4a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6089 COL4A2 Zornitza Stark Phenotypes for gene: COL4A2 were changed from Brain small vessel disease 2, MIM# 614483; familial porencephaly MONDO:0020496 to Brain small vessel disease 2, MIM# 614483; familial porencephaly MONDO:0020496
Intellectual disability syndromic and non-syndromic v0.6088 COL4A2 Zornitza Stark Phenotypes for gene: COL4A2 were changed from to Brain small vessel disease 2, MIM# 614483; familial porencephaly MONDO:0020496
Intellectual disability syndromic and non-syndromic v0.6087 COL4A2 Zornitza Stark Publications for gene: COL4A2 were set to
Intellectual disability syndromic and non-syndromic v0.6086 COL4A2 Zornitza Stark Mode of inheritance for gene: COL4A2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6085 COQ4 Zornitza Stark Marked gene: COQ4 as ready
Intellectual disability syndromic and non-syndromic v0.6085 COQ4 Zornitza Stark Gene: coq4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6085 COQ4 Zornitza Stark Phenotypes for gene: COQ4 were changed from Coenzyme Q10 deficiency, primary, 7, MIM# 616276; neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome MONDO:0014562 to Coenzyme Q10 deficiency, primary, 7, MIM# 616276; neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome MONDO:0014562
Intellectual disability syndromic and non-syndromic v0.6084 COQ4 Zornitza Stark Phenotypes for gene: COQ4 were changed from Coenzyme Q10 deficiency, primary, 7, MIM# 616276 to Coenzyme Q10 deficiency, primary, 7, MIM# 616276; neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome MONDO:0014562
Intellectual disability syndromic and non-syndromic v0.6084 COQ4 Zornitza Stark Phenotypes for gene: COQ4 were changed from to Coenzyme Q10 deficiency, primary, 7, MIM# 616276
Intellectual disability syndromic and non-syndromic v0.6083 COQ4 Zornitza Stark Publications for gene: COQ4 were set to 34656997
Intellectual disability syndromic and non-syndromic v0.6083 COQ4 Zornitza Stark Publications for gene: COQ4 were set to
Intellectual disability syndromic and non-syndromic v0.6082 COQ4 Zornitza Stark Mode of inheritance for gene: COQ4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1928 UNC93B1 Zornitza Stark Phenotypes for gene: UNC93B1 were changed from Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1 to Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1, MIM#610551; Autoinflammatory syndrome, MONDO:0019751, UNC93B1-related
Mendeliome v1.1927 UNC93B1 Zornitza Stark Publications for gene: UNC93B1 were set to 16973841; 29768176
Mendeliome v1.1926 UNC93B1 Zornitza Stark Mode of inheritance for gene: UNC93B1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1925 UNC93B1 Zornitza Stark Classified gene: UNC93B1 as Green List (high evidence)
Mendeliome v1.1925 UNC93B1 Zornitza Stark Gene: unc93b1 has been classified as Green List (High Evidence).
Mendeliome v1.1924 UNC93B1 Zornitza Stark edited their review of gene: UNC93B1: Changed phenotypes: Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1, MIM#610551, Autoinflammatory syndrome, MONDO:0019751, UNC93B1-related
Mendeliome v1.1924 UNC93B1 Zornitza Stark edited their review of gene: UNC93B1: Added comment: PMID 38869500: Rare missense substitutions in UNC93B1 in probands from five unrelated kindreds presenting with early onset SLE (two probands) or CBL (three probands). Clinical, genetic, and functional in vitro and ex vivo data demonstrating changes in TLR7/8 signalling and trafficking.; Changed rating: GREEN; Changed publications: 29768176, 38869500; Changed phenotypes: Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1, Autoinflammatory syndrome, MONDO:0019751, UNC93B1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.194 UNC93B1 Zornitza Stark Marked gene: UNC93B1 as ready
Disorders of immune dysregulation v0.194 UNC93B1 Zornitza Stark Gene: unc93b1 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.194 UNC93B1 Zornitza Stark Phenotypes for gene: UNC93B1 were changed from SLE, chilblain lupus to Autoinflammatory syndrome, MONDO:0019751, UNC93B1-related
Disorders of immune dysregulation v0.193 UNC93B1 Zornitza Stark Classified gene: UNC93B1 as Green List (high evidence)
Disorders of immune dysregulation v0.193 UNC93B1 Zornitza Stark Gene: unc93b1 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.192 UNC93B1 Zornitza Stark reviewed gene: UNC93B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoinflammatory syndrome, MONDO:0019751, UNC93B1-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6081 COQ4 Ken Lee Wan reviewed gene: COQ4: Rating: GREEN; Mode of pathogenicity: None; Publications: 34656997; Phenotypes: mitochondrial disease MONDO:0044970, neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome MONDO:0014562; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1924 CD274 Zornitza Stark gene: CD274 was added
gene: CD274 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CD274 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD274 were set to 38634869
Phenotypes for gene: CD274 were set to Immune dysregulation, autoimmunity and auto inflammation, MONDO:0957790
Review for gene: CD274 was set to AMBER
Added comment: Two siblings, born to second-degree consanguineous parents of Moroccan descent, both developed neonatal-onset T1D (diagnosed at the ages of 1 day and 7 wk, respectively). One sibling was subsequently diagnosed with asthma at the age of 5 mo, auto-immune hypothyroidism at the age of 3 years, and growth hormone (GH) deficiency at the age of 10 years. He also had mild intellectual disability with delayed language development. By contrast, his sister had no clinical manifestations other than T1D.

Homozygous for splicing variant. This is the ligand of PD1, deficiency of which is also linked to immune dysregulation. Functional data.
Sources: Literature
Susceptibility to Viral Infections v0.126 RNASEL Zornitza Stark Marked gene: RNASEL as ready
Susceptibility to Viral Infections v0.126 RNASEL Zornitza Stark Gene: rnasel has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.192 CD274 Zornitza Stark Marked gene: CD274 as ready
Disorders of immune dysregulation v0.192 CD274 Zornitza Stark Gene: cd274 has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.192 CD274 Zornitza Stark Phenotypes for gene: CD274 were changed from Immune dysregulation to Immune dysregulation, autoimmunity and auto inflammation, MONDO:0957790
Disorders of immune dysregulation v0.191 CD274 Zornitza Stark Classified gene: CD274 as Amber List (moderate evidence)
Disorders of immune dysregulation v0.191 CD274 Zornitza Stark Gene: cd274 has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.190 CD274 Zornitza Stark reviewed gene: CD274: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Immune dysregulation, autoimmunity and auto inflammation, MONDO:0957790; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.190 SH2B3 Zornitza Stark Marked gene: SH2B3 as ready
Disorders of immune dysregulation v0.190 SH2B3 Zornitza Stark Gene: sh2b3 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.190 SH2B3 Zornitza Stark Phenotypes for gene: SH2B3 were changed from Immune to Predisposition to haematological malignancies; Myeloproliferation and multi-organ autoimmunity; juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related
Disorders of immune dysregulation v0.189 SH2B3 Zornitza Stark Classified gene: SH2B3 as Green List (high evidence)
Disorders of immune dysregulation v0.189 SH2B3 Zornitza Stark Gene: sh2b3 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.188 SH2B3 Zornitza Stark reviewed gene: SH2B3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Predisposition to haematological malignancies, Myeloproliferation and multi-organ autoimmunity, juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.188 NBEAL2 Zornitza Stark Marked gene: NBEAL2 as ready
Disorders of immune dysregulation v0.188 NBEAL2 Zornitza Stark Gene: nbeal2 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.188 NBEAL2 Zornitza Stark Phenotypes for gene: NBEAL2 were changed from Immune dysregulation to Gray platelet syndrome, MIM# 139090; Immune dysregulation
Intellectual disability syndromic and non-syndromic v0.6081 COL4A2 Ken Lee Wan reviewed gene: COL4A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 36324412, 39016117; Phenotypes: familial porencephaly MONDO:0020496; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Disorders of immune dysregulation v0.187 NBEAL2 Zornitza Stark Classified gene: NBEAL2 as Green List (high evidence)
Disorders of immune dysregulation v0.187 NBEAL2 Zornitza Stark Gene: nbeal2 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.186 NBEAL2 Zornitza Stark reviewed gene: NBEAL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Gray platelet syndrome, MIM# 139090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Susceptibility to Viral Infections v0.126 RNASEL Zornitza Stark Phenotypes for gene: RNASEL were changed from MIS-C to Multisystem inflammatory syndrome, MONDO:0035375, RNASEL-related
Susceptibility to Viral Infections v0.125 RNASEL Zornitza Stark Classified gene: RNASEL as Amber List (moderate evidence)
Susceptibility to Viral Infections v0.125 RNASEL Zornitza Stark Gene: rnasel has been classified as Amber List (Moderate Evidence).
Susceptibility to Viral Infections v0.124 RNASEL Zornitza Stark reviewed gene: RNASEL: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Multisystem inflammatory syndrome, MONDO:0035375, RNASEL-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1923 OAS2 Zornitza Stark Marked gene: OAS2 as ready
Mendeliome v1.1923 OAS2 Zornitza Stark Gene: oas2 has been classified as Green List (High Evidence).
Mendeliome v1.1923 OAS2 Zornitza Stark Classified gene: OAS2 as Green List (high evidence)
Mendeliome v1.1923 OAS2 Zornitza Stark Gene: oas2 has been classified as Green List (High Evidence).
Mendeliome v1.1922 OAS2 Zornitza Stark gene: OAS2 was added
gene: OAS2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: OAS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OAS2 were set to 36538032
Phenotypes for gene: OAS2 were set to Multisystem inflammatory syndrome, MONDO:0035375, OAS2-related
Review for gene: OAS2 was set to GREEN
Added comment: 3x unrelated patients with MIS-C after COVID infection. Patients displayed excessive inflammatory responses to intracellular dsRNA, SARS-CoV-2, SARS-CoV-2–infected cells, and their RNA, providing a plausible mechanism for MIS-C. Similar presentation to OAS1 and RNASEL. Functional data.
Sources: Literature
Susceptibility to Viral Infections v0.124 OAS2 Zornitza Stark Marked gene: OAS2 as ready
Susceptibility to Viral Infections v0.124 OAS2 Zornitza Stark Gene: oas2 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.124 OAS2 Zornitza Stark Phenotypes for gene: OAS2 were changed from MIS-C to Multisystem inflammatory syndrome, MONDO:0035375, OAS2-related
Susceptibility to Viral Infections v0.123 OAS2 Zornitza Stark Classified gene: OAS2 as Green List (high evidence)
Susceptibility to Viral Infections v0.123 OAS2 Zornitza Stark Gene: oas2 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.122 OAS2 Zornitza Stark reviewed gene: OAS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 36538032; Phenotypes: Multisystem inflammatory syndrome, MONDO:0035375, OAS2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1921 NFATC2 Zornitza Stark Phenotypes for gene: NFATC2 were changed from Skeletal system disorder MONDO:0005172 to Skeletal system disorder MONDO:0005172; Lymphoproliferative syndrome, MONDO:0016537, NFATC2-related
Mendeliome v1.1920 NFATC2 Zornitza Stark Publications for gene: NFATC2 were set to 35789258
Mendeliome v1.1919 NFATC2 Zornitza Stark reviewed gene: NFATC2: Rating: RED; Mode of pathogenicity: None; Publications: 38427060; Phenotypes: Lymphoproliferative syndrome, MONDO:0016537, NFATC2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Susceptibility to Viral Infections v0.122 NFATC2 Zornitza Stark Marked gene: NFATC2 as ready
Susceptibility to Viral Infections v0.122 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Susceptibility to Viral Infections v0.122 NFATC2 Zornitza Stark Phenotypes for gene: NFATC2 were changed from EBV associated lymphoproliferative disease to Lymphoproliferative syndrome, MONDO:0016537, NFATC2-related
Susceptibility to Viral Infections v0.121 NFATC2 Zornitza Stark Classified gene: NFATC2 as Red List (low evidence)
Susceptibility to Viral Infections v0.121 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Susceptibility to Viral Infections v0.120 NFATC2 Zornitza Stark reviewed gene: NFATC2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Lymphoproliferative syndrome, MONDO:0016537, NFATC2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6081 CLN8 Zornitza Stark Marked gene: CLN8 as ready
Intellectual disability syndromic and non-syndromic v0.6081 CLN8 Zornitza Stark Gene: cln8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6081 CLN8 Zornitza Stark Phenotypes for gene: CLN8 were changed from to neuronal ceroid lipofuscinosis MONDO:0016295
Intellectual disability syndromic and non-syndromic v0.6080 CLN8 Zornitza Stark Mode of inheritance for gene: CLN8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6079 CLN8 Ken Lee Wan reviewed gene: CLN8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neuronal ceroid lipofuscinosis MONDO:0016295; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Susceptibility to Viral Infections v0.120 IKBKE Zornitza Stark Marked gene: IKBKE as ready
Susceptibility to Viral Infections v0.120 IKBKE Zornitza Stark Gene: ikbke has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1919 IKBKE Zornitza Stark Marked gene: IKBKE as ready
Mendeliome v1.1919 IKBKE Zornitza Stark Gene: ikbke has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1919 IKBKE Zornitza Stark Classified gene: IKBKE as Amber List (moderate evidence)
Mendeliome v1.1919 IKBKE Zornitza Stark Gene: ikbke has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1918 IKBKE Zornitza Stark gene: IKBKE was added
gene: IKBKE was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IKBKE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IKBKE were set to 37937644
Phenotypes for gene: IKBKE were set to Encephalitis, acute, infection-induced, susceptibility to, MONDO:0800174, IKBKE-related
Review for gene: IKBKE was set to AMBER
Added comment: Single patient with recurrent HSV meningitis with supportive functional data.
Sources: Literature
Susceptibility to Viral Infections v0.120 IKBKE Zornitza Stark Phenotypes for gene: IKBKE were changed from Recurrent HSV encephalitis to Encephalitis, acute, infection-induced, susceptibility to, MONDO:0800174, IKBKE-related
Susceptibility to Viral Infections v0.119 IKBKE Zornitza Stark Classified gene: IKBKE as Amber List (moderate evidence)
Susceptibility to Viral Infections v0.119 IKBKE Zornitza Stark Gene: ikbke has been classified as Amber List (Moderate Evidence).
Susceptibility to Viral Infections v0.118 IKBKE Zornitza Stark reviewed gene: IKBKE: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Encephalitis, acute, infection-induced, susceptibility to, MONDO:0800174, IKBKE-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1917 SYCP2L Zornitza Stark Publications for gene: SYCP2L were set to 32303603
Mendeliome v1.1916 SYCP2L Zornitza Stark Classified gene: SYCP2L as Green List (high evidence)
Mendeliome v1.1916 SYCP2L Zornitza Stark Gene: sycp2l has been classified as Green List (High Evidence).
Mendeliome v1.1915 SYCP2L Zornitza Stark changed review comment from: PMID: 38521400 - A homozygous nonsense variant segregated with POI in a pedigree with two affected sisters (c.1528C>T, p.(Gln510Ter)) PMID: 32303603 - Two unrelated individuals with premature ovarian insufficiency and homozygous variants (c.150_151del (p.Ser52Profs*7), c.999A>G (p.Ile333Met)) in SYCP2L. Concordant mouse model.; to: PMID: 38521400 - A homozygous nonsense variant segregated with POI in a pedigree with two affected sisters c.1528C>T, p.(Gln510Ter)
Mendeliome v1.1915 SYCP2L Zornitza Stark reviewed gene: SYCP2L: Rating: GREEN; Mode of pathogenicity: None; Publications: 38521400; Phenotypes: Premature ovarian failure 24, MIM# 620840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.330 SYCP2L Zornitza Stark Publications for gene: SYCP2L were set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.329 SYCP2L Zornitza Stark Classified gene: SYCP2L as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.329 SYCP2L Zornitza Stark Gene: sycp2l has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.211 HBS1L Zornitza Stark Marked gene: HBS1L as ready
Syndromic Retinopathy v0.211 HBS1L Zornitza Stark Gene: hbs1l has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6079 LEO1 Zornitza Stark Marked gene: LEO1 as ready
Intellectual disability syndromic and non-syndromic v0.6079 LEO1 Zornitza Stark Gene: leo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6079 LEO1 Zornitza Stark Classified gene: LEO1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6079 LEO1 Zornitza Stark Gene: leo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6078 LEO1 Zornitza Stark gene: LEO1 was added
gene: LEO1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: LEO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LEO1 were set to 38965372
Phenotypes for gene: LEO1 were set to neurodevelopmental disorder MONDO:0700092, LEO-1 related
Review for gene: LEO1 was set to AMBER
Added comment: cohort of individuals with delayed motor and speech development, ASD

8x de novo – 6x missense + 2x PTC
1x pat splice (father unaffected)
2x unknown_inh PTCs

Of the missense variants, G370E has 8 hets in gnomad v4

This gene is not constraint for LoF with 4 hets with an NMD variant in gnomad v4
3 of the missense are said to lie within a region of missense constraint, however this isn't the case in v4
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6077 CHD2 Zornitza Stark Phenotypes for gene: CHD2 were changed from Epileptic encephalopathy, childhood-onset (MIM # 615369) to Developmental and epileptic encephalopathy 94, MIM# 615369
Intellectual disability syndromic and non-syndromic v0.6076 CHD2 Zornitza Stark Publications for gene: CHD2 were set to
Intellectual disability syndromic and non-syndromic v0.6075 CHD2 Zornitza Stark reviewed gene: CHD2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 94, MIM# 615369; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6075 CHD2 Ken Lee Wan reviewed gene: CHD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26677509; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Susceptibility to Viral Infections v0.118 CD28 Zornitza Stark Phenotypes for gene: CD28 were changed from Immunodeficiency-123 with HPV-related verrucosis (IMD123), MIM#620901; isolated susceptibility to cutaneous α- and γ-HPVs to Immunodeficiency-123 with HPV-related verrucosis (IMD123), MIM#620901; isolated susceptibility to cutaneous α- and γ-HPVs
Susceptibility to Viral Infections v0.118 CD28 Zornitza Stark Phenotypes for gene: CD28 were changed from Hereditary predisposition to infections, MONDO:0015979, CD28-related; isolated susceptibility to cutaneous α- and γ-HPVs to Immunodeficiency-123 with HPV-related verrucosis (IMD123), MIM#620901; isolated susceptibility to cutaneous α- and γ-HPVs
Susceptibility to Viral Infections v0.117 CD28 Zornitza Stark edited their review of gene: CD28: Changed phenotypes: Immunodeficiency-123 with HPV-related verrucosis (IMD123), MIM#620901
Mendeliome v1.1915 CD28 Zornitza Stark Phenotypes for gene: CD28 were changed from Hereditary predisposition to infections, MONDO:0015979, CD28-related; isolated susceptibility to cutaneous α- and γ-HPVs to Immunodeficiency-123 with HPV-related verrucosis (IMD123), MIM#620901; isolated susceptibility to cutaneous α- and γ-HPVs
Mendeliome v1.1914 CD28 Zornitza Stark edited their review of gene: CD28: Changed phenotypes: Immunodeficiency-123 with HPV-related verrucosis (IMD123), MIM#620901, isolated susceptibility to cutaneous α- and γ-HPVs
Mendeliome v1.1914 CD28 Zornitza Stark edited their review of gene: CD28: Changed phenotypes: Immunodeficiency-123 with HPV-related verrucosis (IMD123), MIM#62090, isolated susceptibility to cutaneous α- and γ-HPVs
Renal Macrocystic Disease v0.70 NEK8 Zornitza Stark Phenotypes for gene: NEK8 were changed from Familial renal cystic disease MONDO:0019741, NEK8-related, dominant to Polycystic kidney disease 8, MIM# 620903
Renal Macrocystic Disease v0.69 NEK8 Zornitza Stark reviewed gene: NEK8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polycystic kidney disease 8, MIM# 620903; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1914 NEK8 Zornitza Stark Phenotypes for gene: NEK8 were changed from Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174; Familial renal cystic disease MONDO:0019741, NEK8-related, dominant to Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174; Polycystic kidney disease 8, MIM# 620903
Mendeliome v1.1913 NEK8 Zornitza Stark edited their review of gene: NEK8: Changed phenotypes: Renal-hepatic-pancreatic dysplasia 2, MIM# 615415, MONDO:0014174, Polycystic kidney disease 8, MIM# 620903
Ciliopathies v1.55 NEK8 Zornitza Stark Phenotypes for gene: NEK8 were changed from Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174; Familial renal cystic disease MONDO:0019741, NEK8-related, dominant to Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174; Polycystic kidney disease 8, MIM# 620903
Ciliopathies v1.54 NEK8 Zornitza Stark edited their review of gene: NEK8: Changed phenotypes: Renal-hepatic-pancreatic dysplasia 2, MIM# 615415, MONDO:0014174, Polycystic kidney disease 8, MIM# 620903
Intellectual disability syndromic and non-syndromic v0.6075 RBBP5 Ain Roesley Phenotypes for gene: RBBP5 were changed from to neurodevelopmental disorder MONDO:0700092, RBBP5-related
Intellectual disability syndromic and non-syndromic v0.6074 RBBP5 Ain Roesley edited their review of gene: RBBP5: Changed phenotypes: neurodevelopmental disorder MONDO:0700092, RBBP5-related
Intellectual disability syndromic and non-syndromic v0.6074 PCBP2 Ain Roesley Marked gene: PCBP2 as ready
Intellectual disability syndromic and non-syndromic v0.6074 PCBP2 Ain Roesley Gene: pcbp2 has been classified as Green List (High Evidence).
Mendeliome v1.1913 LEO1 Ain Roesley changed review comment from: cohort of individuals with delayed motor and speech development, ASD

8x de novo – 6x missense + 2x PTC
1x pat splice (father unaffected)
2x unknown_inh PTCs

Of the missense variants, G370E has 8 hets in gnomad v4

This gene is not constraint for LoF with 4 hets with an NMD variant in gnomad v4
Sources: Literature; to: cohort of individuals with delayed motor and speech development, ASD

8x de novo – 6x missense + 2x PTC
1x pat splice (father unaffected)
2x unknown_inh PTCs

Of the missense variants, G370E has 8 hets in gnomad v4

This gene is not constraint for LoF with 4 hets with an NMD variant in gnomad v4
3 of the missense are said to lie within a region of missense constraint, however this isn't the case in v4

Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6074 PCBP2 Ain Roesley Classified gene: PCBP2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6074 PCBP2 Ain Roesley Gene: pcbp2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6073 PCBP2 Ain Roesley gene: PCBP2 was added
gene: PCBP2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PCBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PCBP2 were set to 38965372
Phenotypes for gene: PCBP2 were set to neurodevelopmental disorder MONDO:0700092, PCBP2-related
Review for gene: PCBP2 was set to GREEN
gene: PCBP2 was marked as current diagnostic
Added comment: 3x individuals with de novo variants
Motor and speech delay and ASD
2x missense + 1x fs

There are 2 NMD variants with 9 and 8 hets respectively in gnomad v4, however the IGV looks to be low quality
Sources: Literature
Mendeliome v1.1913 PCBP2 Ain Roesley Marked gene: PCBP2 as ready
Mendeliome v1.1913 PCBP2 Ain Roesley Gene: pcbp2 has been classified as Green List (High Evidence).
Mendeliome v1.1913 PCBP2 Ain Roesley Classified gene: PCBP2 as Green List (high evidence)
Mendeliome v1.1913 PCBP2 Ain Roesley Gene: pcbp2 has been classified as Green List (High Evidence).
Mendeliome v1.1912 PCBP2 Ain Roesley gene: PCBP2 was added
gene: PCBP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PCBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PCBP2 were set to 38965372
Phenotypes for gene: PCBP2 were set to neurodevelopmental disorder MONDO:0700092, PCBP2-related
Review for gene: PCBP2 was set to GREEN
gene: PCBP2 was marked as current diagnostic
Added comment: 3x individuals with de novo variants
Motor and speech delay and ASD
2x missense + 1x fs

There are 2 NMD variants with 9 and 8 hets respectively in gnomad v4, however the IGV looks to be low quality
Sources: Literature
Prepair 1000+ v1.76 ADAT3 Cassandra Muller changed review comment from: 20+ unrelated Arab families reported in the literature with the same homozygous missense variant in this gene causing intellectual disability (p.(Val128Met))
Other features can include microcephaly, growth failure, epilepsy.; to: 20+ unrelated Arab families reported in the literature with the same homozygous missense variant in this gene causing intellectual disability (p.(Val128Met)). One known family with a different variant in the same gene.
Other features can include microcephaly, growth failure, epilepsy.
Prepair 1000+ v1.76 ADAT3 Cassandra Muller reviewed gene: ADAT3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23620220, 26842963, 29796286, 30296593, 35118659; Phenotypes: Neurodevelopmental disorder with brain abnormalities, poor growth, and dysmorphic facies, MIM#615286; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1911 LEO1 Ain Roesley changed review comment from: enrichment of a neurodev cohort
LEO1:
8x de novo – 6x missense + 2x PTC
1x pat splice (father unaffected)
2x unknown_inh PTCs

Of the missense variants, G370E has 8 hets in gnomad v4

This gene is not constraint for LoF with 4 hets with an NMD variant in gnomad v4
Sources: Literature; to: cohort of individuals with delayed motor and speech development, ASD

8x de novo – 6x missense + 2x PTC
1x pat splice (father unaffected)
2x unknown_inh PTCs

Of the missense variants, G370E has 8 hets in gnomad v4

This gene is not constraint for LoF with 4 hets with an NMD variant in gnomad v4
Sources: Literature
Mendeliome v1.1911 LEO1 Ain Roesley changed review comment from: enrichment of a neurodev cohort
LEO1:
8x de novo – 6x missense + 2x PTC
1x pat splice
2x unknown_inh PTCs

Of the missense variants, G370E has 8 hets in gnomad v4

This gene is not constraint for LoF with 4 hets with an NMD variant in gnomad v4
Sources: Literature; to: enrichment of a neurodev cohort
LEO1:
8x de novo – 6x missense + 2x PTC
1x pat splice (father unaffected)
2x unknown_inh PTCs

Of the missense variants, G370E has 8 hets in gnomad v4

This gene is not constraint for LoF with 4 hets with an NMD variant in gnomad v4
Sources: Literature
Prepair 1000+ v1.76 ERCC6L2 Lucy Spencer reviewed gene: ERCC6L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37696499, 29987015; Phenotypes: Bone marrow failure syndrome 2 MIM#615715; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1911 LEO1 Ain Roesley Marked gene: LEO1 as ready
Mendeliome v1.1911 LEO1 Ain Roesley Gene: leo1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1911 LEO1 Ain Roesley Classified gene: LEO1 as Amber List (moderate evidence)
Mendeliome v1.1911 LEO1 Ain Roesley Gene: leo1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1910 LEO1 Ain Roesley gene: LEO1 was added
gene: LEO1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LEO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LEO1 were set to 38965372
Phenotypes for gene: LEO1 were set to neurodevelopmental disorder MONDO:0700092, LEO-1 related
Review for gene: LEO1 was set to AMBER
gene: LEO1 was marked as current diagnostic
Added comment: enrichment of a neurodev cohort
LEO1:
8x de novo – 6x missense + 2x PTC
1x pat splice
2x unknown_inh PTCs

Of the missense variants, G370E has 8 hets in gnomad v4

This gene is not constraint for LoF with 4 hets with an NMD variant in gnomad v4
Sources: Literature
Prepair 1000+ v1.76 DYNC1I2 Lucy Spencer reviewed gene: DYNC1I2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31079899; Phenotypes: Neurodevelopmental disorder with microcephaly and structural brain anomalies , MIM#618492; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.76 ACADM Cassandra Muller reviewed gene: ACADM: Rating: GREEN; Mode of pathogenicity: None; Publications: 9158144; Phenotypes: Acyl-CoA dehydrogenase, medium chain, deficiency of, MIM #201450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.76 DHODH Lucy Spencer reviewed gene: DHODH: Rating: GREEN; Mode of pathogenicity: None; Publications: 19915526; Phenotypes: Miller syndrome, MIM# 263750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.76 CTSC Lucy Spencer reviewed gene: CTSC: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Haim-Munk syndrome MIM#245010, Papillon-Lefevre syndrome MIM#245000, Periodontitis 1, juvenile MIM#170650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.76 CPT2 Lucy Spencer reviewed gene: CPT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32295037; Phenotypes: CPT II deficiency, infantile MIM#600649, CPT II deficiency, lethal neonatal MIM#608836, CPT II deficiency, myopathic, stress-induced MIM#255110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.76 COX20 Lucy Spencer reviewed gene: COX20: Rating: GREEN; Mode of pathogenicity: None; Publications: 33751098; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 11, MIM#619054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.76 CLN6 Lucy Spencer reviewed gene: CLN6: Rating: GREEN; Mode of pathogenicity: None; Publications: 30561534; Phenotypes: Ceroid lipofuscinosis, neuronal, 6, MIM# 601780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v1.65 EXOSC3 Zornitza Stark Marked gene: EXOSC3 as ready
Muscular dystrophy and myopathy_Paediatric v1.65 EXOSC3 Zornitza Stark Gene: exosc3 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.76 CERKL Lucy Spencer reviewed gene: CERKL: Rating: AMBER; Mode of pathogenicity: None; Publications: 37331655; Phenotypes: Retinitis pigmentosa 26 (MIM#608380); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v1.16 EMILIN1 Zornitza Stark edited their review of gene: EMILIN1: Added comment: PMID 38963291: additional variant reported in an individual with neuropathy; however limited supporting evidence.; Changed publications: 31978608, 26462740, 38963291
Paroxysmal Dyskinesia v0.133 KCNJ10 Zornitza Stark Marked gene: KCNJ10 as ready
Paroxysmal Dyskinesia v0.133 KCNJ10 Zornitza Stark Gene: kcnj10 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.133 KCNJ10 Zornitza Stark Classified gene: KCNJ10 as Green List (high evidence)
Paroxysmal Dyskinesia v0.133 KCNJ10 Zornitza Stark Gene: kcnj10 has been classified as Green List (High Evidence).
Mendeliome v1.1909 KCNJ10 Zornitza Stark Phenotypes for gene: KCNJ10 were changed from SESAME syndrome, MIM# 612780 to SESAME syndrome, MIM# 612780; Paroxysmal dyskinesia, MONDO:0015427, KCNJ10-related
Mendeliome v1.1908 KCNJ10 Zornitza Stark Publications for gene: KCNJ10 were set to 19289823; 19420365; 21849804; 11466414
Mendeliome v1.1907 KCNJ10 Zornitza Stark Mode of inheritance for gene: KCNJ10 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1906 KCNJ10 Zornitza Stark edited their review of gene: KCNJ10: Added comment: PMID 38979912: 11 individuals from 8 unrelated families reported with variants in this gene and paroxysmal dyskinesia. Notably one was the parent of a child with recessive SeSAME syndrome (established gene-disease association). Patch-clamp recordings in HEK293T cells revealed apparent reductions in K+ currents of the patient-derived variants, indicating a loss-of-function. In Drosophila, milder hyperexcitability phenotypes were observed in heterozygous Irk2 knock-in flies compared to homozygotes, supporting haploinsufficiency as the mechanism for the detected heterozygous variants. Electrophysiological recordings showed that excitatory neurons in Irk2 haploinsufficiency flies exhibited increased excitability, and glia-specific complementation with human Kir4.1 rescued the Irk2 mutant phenotypes.; Changed publications: 19289823, 19420365, 21849804, 11466414, 38979912; Changed phenotypes: SESAME syndrome, MIM# 612780, Paroxysmal dyskinesia, MONDO:0015427, KCNJ10-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paroxysmal Dyskinesia v0.132 KCNJ10 Zornitza Stark gene: KCNJ10 was added
gene: KCNJ10 was added to Paroxysmal Dyskinesia. Sources: Literature
Mode of inheritance for gene: KCNJ10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNJ10 were set to 38979912
Phenotypes for gene: KCNJ10 were set to Paroxysmal dyskinesia, MONDO:0015427, KCNJ10-related
Review for gene: KCNJ10 was set to GREEN
Added comment: 11 individuals from 8 unrelated families reported with variants in this gene and paroxysmal dyskinesia. Notably one was the parent of a child with recessive SeSAME syndrome (established gene-disease association). Patch-clamp recordings in HEK293T cells revealed apparent reductions in K+ currents of the patient-derived variants, indicating a loss-of-function. In Drosophila, milder hyperexcitability phenotypes were observed in heterozygous Irk2 knock-in flies compared to homozygotes, supporting haploinsufficiency as the mechanism for the detected heterozygous variants. Electrophysiological recordings showed that excitatory neurons in Irk2 haploinsufficiency flies exhibited increased excitability, and glia-specific complementation with human Kir4.1 rescued the Irk2 mutant phenotypes.
Sources: Literature
Mendeliome v1.1906 SLC45A1 Zornitza Stark Publications for gene: SLC45A1 were set to 28434495
Mendeliome v1.1905 SLC45A1 Zornitza Stark Classified gene: SLC45A1 as Green List (high evidence)
Mendeliome v1.1905 SLC45A1 Zornitza Stark Gene: slc45a1 has been classified as Green List (High Evidence).
Mendeliome v1.1904 SLC45A1 Zornitza Stark edited their review of gene: SLC45A1: Added comment: PMID 39003656: additional individual with compound het missense variants and supportive functional data.; Changed rating: GREEN; Changed publications: 28434495, 39003656
Intellectual disability syndromic and non-syndromic v0.6072 SLC45A1 Zornitza Stark Publications for gene: SLC45A1 were set to 28434495
Intellectual disability syndromic and non-syndromic v0.6071 SLC45A1 Zornitza Stark Classified gene: SLC45A1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6071 SLC45A1 Zornitza Stark Gene: slc45a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6070 SLC45A1 Zornitza Stark edited their review of gene: SLC45A1: Added comment: PMID 39003656: additional individual with compound het missense variants and supportive functional data.; Changed rating: GREEN; Changed publications: 28434495, 39003656
Callosome v0.525 SRPK3 Zornitza Stark Publications for gene: SRPK3 were set to 38429495; 39073169
Callosome v0.524 SRPK3 Zornitza Stark edited their review of gene: SRPK3: Changed publications: 39073169
Syndromic Retinopathy v0.211 HBS1L Bryony Thompson Classified gene: HBS1L as Amber List (moderate evidence)
Syndromic Retinopathy v0.211 HBS1L Bryony Thompson Gene: hbs1l has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6070 SRPK3 Zornitza Stark Publications for gene: SRPK3 were set to 38429495; 39073169
Intellectual disability syndromic and non-syndromic v0.6069 SRPK3 Zornitza Stark edited their review of gene: SRPK3: Changed publications: 39073169
Fetal anomalies v1.257 SRPK3 Zornitza Stark Marked gene: SRPK3 as ready
Fetal anomalies v1.257 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.257 SRPK3 Zornitza Stark Classified gene: SRPK3 as Amber List (moderate evidence)
Fetal anomalies v1.257 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.210 HBS1L Bryony Thompson gene: HBS1L was added
gene: HBS1L was added to Syndromic Retinopathy. Sources: Literature
Mode of inheritance for gene: HBS1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HBS1L were set to 38966981; 24288412; 30707697
Phenotypes for gene: HBS1L were set to Retinal disorder MONDO:0005283
Review for gene: HBS1L was set to AMBER
Added comment: A single case with biallelic variants reported with retinal dystrophy, poor growth and neurodevelopmental delay (originally reported in 2013). A hypomorph mouse model demonstrated defective development of photoreceptor cells.
Sources: Literature
Fetal anomalies v1.256 SRPK3 Zornitza Stark gene: SRPK3 was added
gene: SRPK3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SRPK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SRPK3 were set to 39073169
Phenotypes for gene: SRPK3 were set to Neurodevelopmental disorder, MONDO:0700092, SRPK3-related
Review for gene: SRPK3 was set to AMBER
Added comment: PMID 39073169: 9 individuals from 5 unrelated families reported with 4 missense and 1 putative truncating variant and a neurodevelopmental phenotype. The 8 patients ascertained postnatally shared common clinical features including intellectual disability, agenesis of the corpus callosum, abnormal eye movement, and ataxia. A ninth case, ascertained prenatally, had a complex structural brain phenotype. Supportive animal model data (mouse and zebrafish).
Sources: Literature
Callosome v0.524 SRPK3 Zornitza Stark Marked gene: SRPK3 as ready
Callosome v0.524 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Green List (High Evidence).
Callosome v0.524 SRPK3 Zornitza Stark Classified gene: SRPK3 as Green List (high evidence)
Callosome v0.524 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Green List (High Evidence).
Callosome v0.523 SRPK3 Zornitza Stark gene: SRPK3 was added
gene: SRPK3 was added to Callosome. Sources: Literature
Mode of inheritance for gene: SRPK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SRPK3 were set to 38429495; 39073169
Phenotypes for gene: SRPK3 were set to Neurodevelopmental disorder, MONDO:0700092, SRPK3-related
Review for gene: SRPK3 was set to GREEN
Added comment: PMID 39073169: 9 individuals from 5 unrelated families reported with 4 missense and 1 putative truncating variant and a neurodevelopmental phenotype. The 8 patients ascertained postnatally shared common clinical features including intellectual disability, agenesis of the corpus callosum, abnormal eye movement, and ataxia. A ninth case, ascertained prenatally, had a complex structural brain phenotype. Supportive animal model data (mouse and zebrafish).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6069 SRPK3 Zornitza Stark Marked gene: SRPK3 as ready
Intellectual disability syndromic and non-syndromic v0.6069 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Green List (High Evidence).
Mendeliome v1.1904 HBS1L Bryony Thompson Marked gene: HBS1L as ready
Mendeliome v1.1904 HBS1L Bryony Thompson Gene: hbs1l has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6069 SRPK3 Zornitza Stark Classified gene: SRPK3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6069 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6068 SRPK3 Zornitza Stark gene: SRPK3 was added
gene: SRPK3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SRPK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SRPK3 were set to 38429495; 39073169
Phenotypes for gene: SRPK3 were set to Neurodevelopmental disorder, MONDO:0700092, SRPK3-related
Review for gene: SRPK3 was set to GREEN
Added comment: PMID 39073169: 9 individuals from 5 unrelated families reported with 4 missense and 1 putative truncating variant and a neurodevelopmental phenotype. The 8 patients ascertained postnatally shared common clinical features including intellectual disability, agenesis of the corpus callosum, abnormal eye movement, and ataxia. A ninth case, ascertained prenatally, had a complex structural brain phenotype. Supportive animal model data (mouse and zebrafish).
Sources: Literature
Mendeliome v1.1904 HBS1L Bryony Thompson Classified gene: HBS1L as Amber List (moderate evidence)
Mendeliome v1.1904 HBS1L Bryony Thompson Gene: hbs1l has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1903 HBS1L Bryony Thompson gene: HBS1L was added
gene: HBS1L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HBS1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HBS1L were set to 38966981; 24288412; 30707697
Phenotypes for gene: HBS1L were set to Retinal disorder MONDO:0005283
Review for gene: HBS1L was set to AMBER
Added comment: A single case with biallelic variants reported with retinal dystrophy, poor growth and neurodevelopmental delay (originally reported in 2013). A hypomorph mouse model demonstrated defective development of photoreceptor cells.
Sources: Literature
Mendeliome v1.1902 SRPK3 Zornitza Stark Phenotypes for gene: SRPK3 were changed from Myopathy, MONDO:0005336, digenic SRPK3- and TTN-related to Myopathy, MONDO:0005336, digenic SRPK3- and TTN-related; Neurodevelopmental disorder, MONDO:0700092, SRPK3-related
Mendeliome v1.1901 SRPK3 Zornitza Stark Publications for gene: SRPK3 were set to 38429495
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.37 OPDM4_RILPL1_CGG Bryony Thompson Marked STR: OPDM4_RILPL1_CGG as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.37 OPDM4_RILPL1_CGG Bryony Thompson Str: opdm4_rilpl1_cgg has been classified as Green List (High Evidence).
Mendeliome v1.1900 SRPK3 Zornitza Stark edited their review of gene: SRPK3: Changed phenotypes: Myopathy, MONDO:0005336, digenic SRPK3- and TTN-related, Neurodevelopmental disorder, MONDO:0700092, SRPK3-related
Mendeliome v1.1900 SRPK3 Zornitza Stark edited their review of gene: SRPK3: Added comment: PMID 39073169: 9 individuals from 5 unrelated families reported with 4 missense and 1 putative truncating variant and a neurodevelopmental phenotype. The 8 patients ascertained postnatally shared common clinical features including intellectual disability, agenesis of the corpus callosum, abnormal eye movement, and ataxia. A ninth case, ascertained prenatally, had a complex structural brain phenotype. Supportive animal model data (mouse and zebrafish).; Changed publications: 38429495, 39073169
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.37 OPDM4_RILPL1_CGG Bryony Thompson Classified STR: OPDM4_RILPL1_CGG as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.37 OPDM4_RILPL1_CGG Bryony Thompson Str: opdm4_rilpl1_cgg has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.36 OPDM4_RILPL1_CGG Bryony Thompson STR: OPDM4_RILPL1_CGG was added
STR: OPDM4_RILPL1_CGG was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for STR: OPDM4_RILPL1_CGG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: OPDM4_RILPL1_CGG were set to 35148830
Phenotypes for STR: OPDM4_RILPL1_CGG were set to Oculopharyngodistal myopathy MONDO:0025193
Review for STR: OPDM4_RILPL1_CGG was set to GREEN
STR: OPDM4_RILPL1_CGG was marked as clinically relevant
Added comment: 5'UTR repeat upstream of RILPL1. Analyses suggest that toxic RNA gain-of-function is the mechanism of disease for the repeat expansion.
Distribution of CGG repeat units in RILPL1 ranged from 9 to 16 among 200 normal controls. The size of the CGG repeat ranged from 139 to 197 (169.91 ± 21.82) repeats in 11 unrelated individuals with OPDM. Segregation evidence from 1 family, with 2 affected individuals with the repeat expansion and 1 individual with essential tremor but not OPDM and 86 repeats (intermediate).
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.35 Bryony Thompson removed STR:OPDM1_LRP12_CGG from the panel
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.34 OPDM1_LRP12_CGG Bryony Thompson Classified STR: OPDM1_LRP12_CGG as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.34 OPDM1_LRP12_CGG Bryony Thompson Str: opdm1_lrp12_cgg has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.33 OPDM1_LRP12_CGG Bryony Thompson STR: OPDM1_LRP12_CGG was added
STR: OPDM1_LRP12_CGG was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for STR: OPDM1_LRP12_CGG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: OPDM1_LRP12_CGG were set to 31332380; 34047774
Phenotypes for STR: OPDM1_LRP12_CGG were set to oculopharyngodistal myopathy 1 MONDO:0020793
Review for STR: OPDM1_LRP12_CGG was set to GREEN
STR: OPDM1_LRP12_CGG was marked as clinically relevant
Added comment: NM_013437.5:c.-102CGG[X]
RNA-mediated toxicity is thought to be the mechanism of disease. Sixty-five Japanese patients with oculopharyngodistal myopathy (OPDM) from 59 families with CGG repeat expansions in LRP12. This represents the most common OPDM subtype among all patients in Japan with genetically diagnosed OPDM.
Normal: 13 to 45 repeats.
Pathogenic: 85 to 289 repeats.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6067 RBBP5 Ain Roesley Marked gene: RBBP5 as ready
Intellectual disability syndromic and non-syndromic v0.6067 RBBP5 Ain Roesley Gene: rbbp5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6067 RBBP5 Ain Roesley Classified gene: RBBP5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6067 RBBP5 Ain Roesley Gene: rbbp5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6067 RBBP5 Ain Roesley Classified gene: RBBP5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6067 RBBP5 Ain Roesley Gene: rbbp5 has been classified as Green List (High Evidence).
Mendeliome v1.1900 RBBP5 Ain Roesley Marked gene: RBBP5 as ready
Mendeliome v1.1900 RBBP5 Ain Roesley Gene: rbbp5 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.32 OPDM_ABCD3_GCC Bryony Thompson Marked STR: OPDM_ABCD3_GCC as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.32 OPDM_ABCD3_GCC Bryony Thompson Str: opdm_abcd3_gcc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6066 RBBP5 Ain Roesley gene: RBBP5 was added
gene: RBBP5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RBBP5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBBP5 were set to 39036895
Review for gene: RBBP5 was set to GREEN
gene: RBBP5 was marked as current diagnostic
Added comment: 5x Indivs (4x de novo) = 3x PTCs + 2x missense

4/5 dev delay/ID
2/5 short stature (<=-3 SD) + 2/5 <= -2 SD
1/5 microcephaly (<= -3 SD) + 3/5 <= -2 SD
2/5 SNHL
2/5 seizures
3/5 hypotonia
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.32 OPDM_ABCD3_GCC Bryony Thompson Classified STR: OPDM_ABCD3_GCC as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.32 OPDM_ABCD3_GCC Bryony Thompson Str: opdm_abcd3_gcc has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.31 OPDM_ABCD3_GCC Bryony Thompson STR: OPDM_ABCD3_GCC was added
STR: OPDM_ABCD3_GCC was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for STR: OPDM_ABCD3_GCC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: OPDM_ABCD3_GCC were set to 39068203
Phenotypes for STR: OPDM_ABCD3_GCC were set to Oculopharyngodistal myopathy MONDO:0025193
Review for STR: OPDM_ABCD3_GCC was set to GREEN
STR: OPDM_ABCD3_GCC was marked as clinically relevant
Added comment: 35 OPDM individuals from 8 unrelated families from Australia, the UK, and France with an ABCD3 5’UTR CGG repeat. Affected individuals had repeat expansions ranging from 118-694 (n=19). 7 repeats is the median repeat size in non-neurological controls from the GE 100,000 Genome Project. 10 controls had estimated repeats >50, up to ~93. 50 repeats would be a safe cut-off for normal
Sources: Literature
Mendeliome v1.1900 NDC1 Bryony Thompson Marked gene: NDC1 as ready
Mendeliome v1.1900 NDC1 Bryony Thompson Gene: ndc1 has been classified as Green List (High Evidence).
Mendeliome v1.1900 RBBP5 Ain Roesley changed review comment from: 5x Indivis (4x de novo) = 3x PTCs + 2x missense

4/5 dev delay/ID
2/5 short stature (<=-3 SD) + 2/5 <= -2 SD
1/5 microcephaly (< -3 SD) + 3/5 <= -2 SD
2/5 SNHL
2/5 seizures
3/5 hypotonia; to: 5x Indivs (4x de novo) = 3x PTCs + 2x missense

4/5 dev delay/ID
2/5 short stature (<=-3 SD) + 2/5 <= -2 SD
1/5 microcephaly (< -3 SD) + 3/5 <= -2 SD
2/5 SNHL
2/5 seizures
3/5 hypotonia
Mendeliome v1.1900 NDC1 Bryony Thompson Classified gene: NDC1 as Green List (high evidence)
Mendeliome v1.1900 NDC1 Bryony Thompson Gene: ndc1 has been classified as Green List (High Evidence).
Mendeliome v1.1899 NDC1 Bryony Thompson gene: NDC1 was added
gene: NDC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NDC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDC1 were set to 39003500; 19782045
Phenotypes for gene: NDC1 were set to triple-A syndrome MONDO:0009279
Review for gene: NDC1 was set to GREEN
Added comment: 7 cases from 4 consanguineous families (3 different variants: 1 intronic variants that causes in-frame RNA splice impact, 2 missense) with a Triple-A-like syndrome (including ID and neuropathy). Supporting cellular localisation studies were conducted in patient cell lines with the splice variant. NDC1 is required to anchor ALADIN (encoded by AAAS, the gene that causes Triple-A syndrome) in the nuclear pore complex.
Sources: Literature
Hereditary Neuropathy - complex v1.16 NDC1 Bryony Thompson Marked gene: NDC1 as ready
Hereditary Neuropathy - complex v1.16 NDC1 Bryony Thompson Gene: ndc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6065 NDC1 Bryony Thompson Marked gene: NDC1 as ready
Intellectual disability syndromic and non-syndromic v0.6065 NDC1 Bryony Thompson Gene: ndc1 has been classified as Green List (High Evidence).
Mendeliome v1.1898 OPDM_ABCD3_GCC Bryony Thompson Marked STR: OPDM_ABCD3_GCC as ready
Mendeliome v1.1898 OPDM_ABCD3_GCC Bryony Thompson Str: opdm_abcd3_gcc has been classified as Green List (High Evidence).
Mendeliome v1.1898 OPDM_ABCD3_GCC Bryony Thompson Classified STR: OPDM_ABCD3_GCC as Green List (high evidence)
Mendeliome v1.1898 OPDM_ABCD3_GCC Bryony Thompson Str: opdm_abcd3_gcc has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.16 NDC1 Bryony Thompson Classified gene: NDC1 as Green List (high evidence)
Hereditary Neuropathy - complex v1.16 NDC1 Bryony Thompson Gene: ndc1 has been classified as Green List (High Evidence).
Mendeliome v1.1897 OPDM_ABCD3_GCC Bryony Thompson STR: OPDM_ABCD3_GCC was added
STR: OPDM_ABCD3_GCC was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: OPDM_ABCD3_GCC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: OPDM_ABCD3_GCC were set to 39068203
Phenotypes for STR: OPDM_ABCD3_GCC were set to Oculopharyngodistal myopathy MONDO:0025193
Review for STR: OPDM_ABCD3_GCC was set to GREEN
STR: OPDM_ABCD3_GCC was marked as clinically relevant
Added comment: 35 OPDM individuals from 8 unrelated families from Australia, the UK, and France with an ABCD3 5’UTR CGG repeat. Affected individuals had repeat expansions ranging from 118-694 (n=19). 7 repeats is the median repeat size in non-neurological controls from the GE 100,000 Genome Project. 10 controls had estimated repeats >50, up to ~93. 50 repeats would be a safe cut-off for normal
Sources: Literature
Hereditary Neuropathy - complex v1.15 NDC1 Bryony Thompson gene: NDC1 was added
gene: NDC1 was added to Hereditary Neuropathy - complex. Sources: Literature
Mode of inheritance for gene: NDC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDC1 were set to 39003500; 19782045
Phenotypes for gene: NDC1 were set to triple-A syndrome MONDO:0009279
Review for gene: NDC1 was set to GREEN
Added comment: 7 cases from 4 consanguineous families (3 different variants: 1 intronic variants that causes in-frame RNA splice impact, 2 missense) with a Triple-A-like syndrome (including ID and neuropathy). Supporting cellular localisation studies were conducted in patient cell lines with the splice variant. NDC1 is required to anchor ALADIN (encoded by AAAS, the gene that causes Triple-A syndrome) in the nuclear pore complex.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6065 NDC1 Bryony Thompson Classified gene: NDC1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6065 NDC1 Bryony Thompson Gene: ndc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6064 NDC1 Bryony Thompson gene: NDC1 was added
gene: NDC1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NDC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDC1 were set to 39003500; 19782045
Phenotypes for gene: NDC1 were set to triple-A syndrome MONDO:0009279
Review for gene: NDC1 was set to GREEN
Added comment: 7 cases from 4 consanguineous families (3 different variants: 1 intronic variants that causes in-frame RNA splice impact, 2 missense) with a Triple-A-like syndrome (including ID and neuropathy). Supporting cellular localisation studies were conducted in patient cell lines with the splice variant. NDC1 is required to anchor ALADIN (encoded by AAAS, the gene that causes Triple-A syndrome) in the nuclear pore complex.
Sources: Literature
Mendeliome v1.1896 RBBP5 Ain Roesley Classified gene: RBBP5 as Green List (high evidence)
Mendeliome v1.1896 RBBP5 Ain Roesley Gene: rbbp5 has been classified as Green List (High Evidence).
Mendeliome v1.1895 RBBP5 Ain Roesley commented on gene: RBBP5: 5x Indivis (4x de novo) = 3x PTCs + 2x missense

4/5 dev delay/ID
2/5 short stature (<=-3 SD) + 2/5 <= -2 SD
1/5 microcephaly (< -3 SD) + 3/5 <= -2 SD
2/5 SNHL
2/5 seizures
3/5 hypotonia
Mendeliome v1.1895 RBBP5 Ain Roesley Deleted their comment
Mendeliome v1.1895 RBBP5 Ain Roesley gene: RBBP5 was added
gene: RBBP5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RBBP5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBBP5 were set to 39036895
Phenotypes for gene: RBBP5 were set to neurodevelopmental disorder MONDO:0700092, RBBP5-related
Review for gene: RBBP5 was set to GREEN
gene: RBBP5 was marked as current diagnostic
Added comment: 5 individuals with de novo variants - 3x PTCs + 2x missense

2/5 short stature (> 3SD; 2x >=-2SD)
1/5 microcephaly (> 3SD; 3x >=-2SD)
4/5 dev delay/ID
2/5 SNHL
2/5 Seizures
3/5 hypotonia
Sources: Literature
Repeat Disorders v0.167 OPDM_ABCD3_GCC Bryony Thompson edited their review of STR: OPDM_ABCD3_GCC: Changed publications: 39068203
Muscular dystrophy and myopathy_Paediatric v1.65 DPAGT1 Bryony Thompson Marked gene: DPAGT1 as ready
Muscular dystrophy and myopathy_Paediatric v1.65 DPAGT1 Bryony Thompson Gene: dpagt1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.65 DPAGT1 Bryony Thompson Classified gene: DPAGT1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.65 DPAGT1 Bryony Thompson Gene: dpagt1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.64 DPAGT1 Bryony Thompson gene: DPAGT1 was added
gene: DPAGT1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: DPAGT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPAGT1 were set to 38982518; 38443029; 38124360; 29356258; 24759841
Phenotypes for gene: DPAGT1 were set to tubular aggregate myopathy MONDO:0008051
Review for gene: DPAGT1 was set to GREEN
gene: DPAGT1 was marked as current diagnostic
Added comment: 3 cases reported with congenital myopathy, and at least 2 case with CMS mimicking a congenital myopathy
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.63 ALG14 Bryony Thompson Marked gene: ALG14 as ready
Muscular dystrophy and myopathy_Paediatric v1.63 ALG14 Bryony Thompson Gene: alg14 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.63 ALG14 Bryony Thompson Classified gene: ALG14 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.63 ALG14 Bryony Thompson Gene: alg14 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.76 CLCNKB Lilian Downie Publications for gene: CLCNKB were set to
Muscular dystrophy and myopathy_Paediatric v1.62 ALG14 Bryony Thompson gene: ALG14 was added
gene: ALG14 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: ALG14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALG14 were set to 38982518; 28733338
Phenotypes for gene: ALG14 were set to congenital myopathy MONDO:0019952
Review for gene: ALG14 was set to AMBER
gene: ALG14 was marked as current diagnostic
Added comment: 2 cases have been reported with congenital myopathy with biallelic variants.
Sources: Literature
Prepair 1000+ v1.75 CLCN4 Lilian Downie Marked gene: CLCN4 as ready
Prepair 1000+ v1.75 CLCN4 Lilian Downie Gene: clcn4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.75 CLCN4 Lilian Downie Publications for gene: CLCN4 were set to 27550844
Prepair 1000+ v1.74 CIITA Lilian Downie Marked gene: CIITA as ready
Prepair 1000+ v1.74 CIITA Lilian Downie Gene: ciita has been classified as Green List (High Evidence).
Prepair 1000+ v1.74 CIITA Lilian Downie Publications for gene: CIITA were set to
Prepair 1000+ v1.73 CEP290 Lilian Downie Marked gene: CEP290 as ready
Prepair 1000+ v1.73 CEP290 Lilian Downie Gene: cep290 has been classified as Green List (High Evidence).
Prepair 1000+ v1.73 CEP290 Lilian Downie Publications for gene: CEP290 were set to
Prepair 1000+ v1.72 CDT1 Lilian Downie Marked gene: CDT1 as ready
Prepair 1000+ v1.72 CDT1 Lilian Downie Gene: cdt1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.72 CDT1 Lilian Downie Publications for gene: CDT1 were set to
Muscular dystrophy and myopathy_Paediatric v1.61 UNC45B Bryony Thompson Marked gene: UNC45B as ready
Muscular dystrophy and myopathy_Paediatric v1.61 UNC45B Bryony Thompson Gene: unc45b has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.61 UNC45B Bryony Thompson Classified gene: UNC45B as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.61 UNC45B Bryony Thompson Gene: unc45b has been classified as Green List (High Evidence).
Prepair 1000+ v1.71 CDK10 Lilian Downie Marked gene: CDK10 as ready
Prepair 1000+ v1.71 CDK10 Lilian Downie Gene: cdk10 has been classified as Green List (High Evidence).
Prepair 1000+ v1.71 CDK10 Lilian Downie Publications for gene: CDK10 were set to
Muscular dystrophy and myopathy_Paediatric v1.59 UNC45B Bryony Thompson gene: UNC45B was added
gene: UNC45B was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: UNC45B was set to BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.70 CD55 Lilian Downie Marked gene: CD55 as ready
Prepair 1000+ v1.70 CD55 Lilian Downie Gene: cd55 has been classified as Green List (High Evidence).
Prepair 1000+ v1.70 CD55 Lilian Downie Publications for gene: CD55 were set to
Muscular dystrophy and myopathy_Paediatric v1.58 CASQ1 Bryony Thompson Marked gene: CASQ1 as ready
Muscular dystrophy and myopathy_Paediatric v1.58 CASQ1 Bryony Thompson Gene: casq1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.58 CASQ1 Bryony Thompson Classified gene: CASQ1 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.58 CASQ1 Bryony Thompson Gene: casq1 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.69 CARD11 Lilian Downie Marked gene: CARD11 as ready
Prepair 1000+ v1.69 CARD11 Lilian Downie Added comment: Comment when marking as ready: Dominant negative suggested as possible mechanism for AD disease PMID:28826773
Prepair 1000+ v1.69 CARD11 Lilian Downie Gene: card11 has been classified as Green List (High Evidence).
Prepair 1000+ v1.69 CARD11 Lilian Downie Publications for gene: CARD11 were set to
Muscular dystrophy and myopathy_Paediatric v1.57 CASQ1 Bryony Thompson gene: CASQ1 was added
gene: CASQ1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CASQ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CASQ1 were set to 38982518
Phenotypes for gene: CASQ1 were set to tubular aggregate myopathy MONDO:0008051
Mode of pathogenicity for gene: CASQ1 was set to Other
Review for gene: CASQ1 was set to AMBER
gene: CASQ1 was marked as current diagnostic
Added comment: 2 cases have been reported with congenital myopathy. Gain of function is expected to be the mechanism of disease.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.56 ORAI1 Bryony Thompson Marked gene: ORAI1 as ready
Muscular dystrophy and myopathy_Paediatric v1.56 ORAI1 Bryony Thompson Gene: orai1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.56 ORAI1 Bryony Thompson Classified gene: ORAI1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.56 ORAI1 Bryony Thompson Gene: orai1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.55 ORAI1 Bryony Thompson gene: ORAI1 was added
gene: ORAI1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: ORAI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ORAI1 were set to 31448844; 38982518
Phenotypes for gene: ORAI1 were set to tubular aggregate myopathy MONDO:0008051
Mode of pathogenicity for gene: ORAI1 was set to Other
Review for gene: ORAI1 was set to GREEN
gene: ORAI1 was marked as current diagnostic
Added comment: >4 cases with congenital myopathy. Gain of function is the mechanism of disease.
Sources: Literature
Prepair 1000+ v1.68 C19orf12 Lilian Downie Marked gene: C19orf12 as ready
Prepair 1000+ v1.68 C19orf12 Lilian Downie Gene: c19orf12 has been classified as Green List (High Evidence).
Prepair 1000+ v1.68 C19orf12 Lilian Downie Publications for gene: C19orf12 were set to
Prepair 1000+ v1.67 ATM Lilian Downie Marked gene: ATM as ready
Prepair 1000+ v1.67 ATM Lilian Downie Added comment: Comment when marking as ready: NB for reporting carrier mother may need additional breast cancer surveillance
Prepair 1000+ v1.67 ATM Lilian Downie Gene: atm has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.54 STIM1 Bryony Thompson Marked gene: STIM1 as ready
Muscular dystrophy and myopathy_Paediatric v1.54 STIM1 Bryony Thompson Gene: stim1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.67 ATM Lilian Downie Publications for gene: ATM were set to 30137827
Muscular dystrophy and myopathy_Paediatric v1.54 STIM1 Bryony Thompson Classified gene: STIM1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.54 STIM1 Bryony Thompson Gene: stim1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.53 STIM1 Bryony Thompson gene: STIM1 was added
gene: STIM1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: STIM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STIM1 were set to 38982518; 31448844
Phenotypes for gene: STIM1 were set to tubular aggregate myopathy MONDO:0008051
Mode of pathogenicity for gene: STIM1 was set to Other
Review for gene: STIM1 was set to GREEN
gene: STIM1 was marked as current diagnostic
Added comment: >4 cases with congenital myopathy. Gain of function is the mechanism of disease.
Sources: Literature
Prepair 1000+ v1.66 ATM Lilian Downie Publications for gene: ATM were set to
Muscular dystrophy and myopathy_Paediatric v1.52 OPA1 Bryony Thompson Marked gene: OPA1 as ready
Muscular dystrophy and myopathy_Paediatric v1.52 OPA1 Bryony Thompson Gene: opa1 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.52 OPA1 Bryony Thompson gene: OPA1 was added
gene: OPA1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: OPA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OPA1 were set to 38982518
Phenotypes for gene: OPA1 were set to congenital myopathy MONDO:0019952
Review for gene: OPA1 was set to RED
Added comment: A single case with centronuclear myopathy
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.51 IDUA Bryony Thompson Marked gene: IDUA as ready
Muscular dystrophy and myopathy_Paediatric v1.51 IDUA Bryony Thompson Gene: idua has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.51 IDUA Bryony Thompson gene: IDUA was added
gene: IDUA was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: IDUA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IDUA were set to 38982518
Phenotypes for gene: IDUA were set to congenital myopathy MONDO:0019952
Review for gene: IDUA was set to RED
gene: IDUA was marked as current diagnostic
Added comment: A single case reported with core myopathy.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.50 FOXP3 Bryony Thompson Marked gene: FOXP3 as ready
Muscular dystrophy and myopathy_Paediatric v1.50 FOXP3 Bryony Thompson Gene: foxp3 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.50 FOXP3 Bryony Thompson gene: FOXP3 was added
gene: FOXP3 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: FOXP3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FOXP3 were set to 38982518
Phenotypes for gene: FOXP3 were set to congenital myopathy MONDO:0019952
Review for gene: FOXP3 was set to RED
gene: FOXP3 was marked as current diagnostic
Added comment: Single case reported with centronuclear myopathy.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.49 EXOSC3 Bryony Thompson gene: EXOSC3 was added
gene: EXOSC3 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: EXOSC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOSC3 were set to 30025162; 38982518
Phenotypes for gene: EXOSC3 were set to congenital myopathy MONDO:0019952
Review for gene: EXOSC3 was set to RED
Added comment: A single case reported with congenital myopathy as a feature of the condition (also including PCH).
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.30 CHRNA1 Bryony Thompson Marked gene: CHRNA1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.30 CHRNA1 Bryony Thompson Gene: chrna1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.30 CHRNA1 Bryony Thompson Classified gene: CHRNA1 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.30 CHRNA1 Bryony Thompson Gene: chrna1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.48 CHRND Bryony Thompson Marked gene: CHRND as ready
Muscular dystrophy and myopathy_Paediatric v1.48 CHRND Bryony Thompson Gene: chrnd has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.48 CHRND Bryony Thompson gene: CHRND was added
gene: CHRND was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CHRND was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHRND were set to 38982518
Phenotypes for gene: CHRND were set to congenital myopathy MONDO:0019952
Review for gene: CHRND was set to RED
gene: CHRND was marked as current diagnostic
Added comment: Single case with congenital centronuclear myopathy reported
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.29 CHRNA1 Bryony Thompson gene: CHRNA1 was added
gene: CHRNA1 was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for gene: CHRNA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHRNA1 were set to 36634413
Phenotypes for gene: CHRNA1 were set to myasthenic syndrome, congenital, 1B, fast-channel MONDO:0012156
Review for gene: CHRNA1 was set to GREEN
gene: CHRNA1 was marked as current diagnostic
Added comment: 13 patients from nine unrelated families with acetylcholine receptor deficiency harbouring the CHRNA1 variant NM_001039523.3:c.257G>A (p.Arg86His) in homozygosity or compound heterozygosity with a predominant pattern of distal upper limb weakness in adulthood, similar to distal myopathy.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.47 CHRNA1 Bryony Thompson Classified gene: CHRNA1 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.47 CHRNA1 Bryony Thompson Gene: chrna1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.47 CHRNA1 Bryony Thompson Classified gene: CHRNA1 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.47 CHRNA1 Bryony Thompson Gene: chrna1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.46 CHRNA1 Bryony Thompson Marked gene: CHRNA1 as ready
Muscular dystrophy and myopathy_Paediatric v1.46 CHRNA1 Bryony Thompson Gene: chrna1 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.46 CHRNA1 Bryony Thompson gene: CHRNA1 was added
gene: CHRNA1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CHRNA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CHRNA1 were set to 36634413; 38982518
Phenotypes for gene: CHRNA1 were set to Congenital myopathy MONDO:0019952
Review for gene: CHRNA1 was set to AMBER
Added comment: Congenital myopathy reported in at least 2 cases. One biallelic (loss of function) and one monoallelic (gain of function).
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.45 TTN Bryony Thompson Marked gene: TTN as ready
Muscular dystrophy and myopathy_Paediatric v1.45 TTN Bryony Thompson Gene: ttn has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.45 TTN Bryony Thompson Classified gene: TTN as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.45 TTN Bryony Thompson Gene: ttn has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.44 TTN Bryony Thompson gene: TTN was added
gene: TTN was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
digenic tags were added to gene: TTN.
Mode of inheritance for gene: TTN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTN were set to 38429495; 38982518
Phenotypes for gene: TTN were set to TTN-related myopathy MONDO:0100175
Review for gene: TTN was set to GREEN
gene: TTN was marked as current diagnostic
Added comment: >4 cases reported with biallelic variants and congenital myopathy (e.g. centronuclear myopathy, cytoplasmic bodies). Digenic heterozygous TTN/SRPK3 variants are also reported with core myopathy.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.43 MYH7 Bryony Thompson Marked gene: MYH7 as ready
Muscular dystrophy and myopathy_Paediatric v1.43 MYH7 Bryony Thompson Gene: myh7 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.43 MYH7 Bryony Thompson Mode of pathogenicity for gene: MYH7 was changed from None to None
Muscular dystrophy and myopathy_Paediatric v1.42 MYH7 Bryony Thompson Classified gene: MYH7 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.42 MYH7 Bryony Thompson Gene: myh7 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.41 MYH7 Bryony Thompson edited their review of gene: MYH7: Changed mode of pathogenicity: Other
Muscular dystrophy and myopathy_Paediatric v1.41 MYH7 Bryony Thompson gene: MYH7 was added
gene: MYH7 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: MYH7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYH7 were set to 38982518; 15322983
Phenotypes for gene: MYH7 were set to MYH7-related skeletal myopathy MONDO:0008050
Review for gene: MYH7 was set to GREEN
gene: MYH7 was marked as current diagnostic
Added comment: Congenital myopathy reported in >4 cases/families (e.g. core myopathy). The mechanism for disease is dominant negative.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.40 MTM1 Bryony Thompson Marked gene: MTM1 as ready
Muscular dystrophy and myopathy_Paediatric v1.40 MTM1 Bryony Thompson Gene: mtm1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.40 MTM1 Bryony Thompson Classified gene: MTM1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.40 MTM1 Bryony Thompson Gene: mtm1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.39 MTM1 Bryony Thompson gene: MTM1 was added
gene: MTM1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: MTM1 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: MTM1 were set to 30232666; 38982518; 10790201
Phenotypes for gene: MTM1 were set to X-linked myotubular myopathy MONDO:0010683
Review for gene: MTM1 was set to GREEN
gene: MTM1 was marked as current diagnostic
Added comment: >4 cases reported with congenital myopathy (congenital fiber type disorder, centronuclear myopathy, myotubular myopathy). Hemizygous males and heterozygous females are reported.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.38 FHL1 Bryony Thompson Classified gene: FHL1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.38 FHL1 Bryony Thompson Gene: fhl1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.38 FHL1 Bryony Thompson Publications for gene: FHL1 were set to PMID: 19181672; 19171836
Muscular dystrophy and myopathy_Paediatric v1.37 CAV3 Bryony Thompson Marked gene: CAV3 as ready
Muscular dystrophy and myopathy_Paediatric v1.37 CAV3 Bryony Thompson Gene: cav3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.37 CAV3 Bryony Thompson Classified gene: CAV3 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.37 CAV3 Bryony Thompson Gene: cav3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.36 CAV3 Bryony Thompson gene: CAV3 was added
gene: CAV3 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CAV3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAV3 were set to 38982518; 30174172
Phenotypes for gene: CAV3 were set to Caveolinopathy MONDO:0016146
Mode of pathogenicity for gene: CAV3 was set to Other
Review for gene: CAV3 was set to GREEN
gene: CAV3 was marked as current diagnostic
Added comment: At least 4 probands/families reported with congenital/paediatric onset myopathy (1 tubular aggregate myopathy and 3 rippling muscle disease). The mechanism for disease is expected to be dominant negative.
Sources: Literature
Prepair 1000+ v1.65 WNT1 Lauren Rogers reviewed gene: WNT1: Rating: ; Mode of pathogenicity: None; Publications: 23499310; Phenotypes: Osteogenesis imperfecta, type XV (MIM#615220); Mode of inheritance: None
Prepair 1000+ v1.65 WDR45B Lauren Rogers reviewed gene: WDR45B: Rating: GREEN; Mode of pathogenicity: None; Publications: 28503735; Phenotypes: Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, MIM# 617977; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 VLDLR Lauren Rogers reviewed gene: VLDLR: Rating: GREEN; Mode of pathogenicity: None; Publications: 16080122, 18326629, 10380922; Phenotypes: Cerebellar hypoplasia, impaired intellectual development, and dysequilibrium syndrome 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 USP9X Lauren Rogers reviewed gene: USP9X: Rating: ; Mode of pathogenicity: None; Publications: 31443933, 26833328; Phenotypes: Intellectual developmental disorder, X-linked 99, MIM#300919; Mode of inheritance: None
Prepair 1000+ v1.65 TUFM Lauren Rogers changed review comment from: Features are lactic acidosis, progressive encephalopathy, dysplastic leukoencephalopathy due to abberant mitochondrial DNA translation.

Congenital onset; to: Features are lactic acidosis, progressive encephalopathy, dysplastic leukoencephalopathy due to abberant mitochondrial DNA translation.

Congenital onset
Prepair 1000+ v1.65 TUFM Lauren Rogers changed review comment from: Features are lactic acidosis, progressive encephalopathy, dysplastic leukoencephalopathy due to abberant mitochondrial DNA translation.

Co ngenital onset; to: Features are lactic acidosis, progressive encephalopathy, dysplastic leukoencephalopathy due to abberant mitochondrial DNA translation.

Congenital onset
Prepair 1000+ v1.65 TUFM Lauren Rogers reviewed gene: TUFM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 4, OMIM #610678; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 TUBGCP4 Lauren Rogers reviewed gene: TUBGCP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25817018; Phenotypes: Microcephaly and chorioretinopathy, autosomal recessive, 3, 616335; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 TPK1 Lauren Rogers reviewed gene: TPK1: Rating: GREEN; Mode of pathogenicity: None; Publications: Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type) MIM#614458; Phenotypes: 33086386, 32679198, 22152682, 33231275; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.328 SYCP2L Elena Tucker reviewed gene: SYCP2L: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38521400, PMID: 32303603; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 SURF1 Lauren Rogers commented on gene: SURF1: Established gene-disease association.

Childhood onset, variable age, multi-system disorder characterised by rapidly progressive neurodegeneration and encephalopathy
Prepair 1000+ v1.65 SURF1 Lauren Rogers reviewed gene: SURF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23829769; Phenotypes: Charcot-Marie-Tooth disease, type 4K MIM#616684, Mitochondrial complex IV deficiency, nuclear type 1 MIM#220110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 SUCLG1 Lauren Rogers reviewed gene: SUCLG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20693550; Phenotypes: Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) MIM#245400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 SLC46A1 Lauren Rogers reviewed gene: SLC46A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301716; Phenotypes: Folate malabsorption, hereditary, MIM# 229050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 SGCG Lauren Rogers reviewed gene: SGCG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 5 MIM#253700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 RNASEH2C Lauren Rogers reviewed gene: RNASEH2C: Rating: GREEN; Mode of pathogenicity: None; Publications: 32877590; Phenotypes: Aicardi-Goutieres syndrome 3, MIM# 610329; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 RMRP Lauren Rogers edited their review of gene: RMRP: Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 RMRP Lauren Rogers reviewed gene: RMRP: Rating: ; Mode of pathogenicity: None; Publications: 16244706, 21396580, 22420014, 11940090, 16252239; Phenotypes: Cartilage-hair hypoplasia MIM#250250, Anauxetic dysplasia 1, MIM#607095, Metaphyseal dysplasia without hypotrichosis MIM#250460; Mode of inheritance: None
Prepair 1000+ v1.65 RIN2 Lauren Rogers reviewed gene: RIN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19631308, 20424861, 23963297, 24449201; Phenotypes: Macrocephaly, alopecia, cutis laxa, and scoliosis, MIM#613075; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 RAB3GAP1 Lauren Rogers reviewed gene: RAB3GAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15696165, 20512159, 23420520, 30730599; Phenotypes: Warburg micro syndrome 1, MIM# 600118, Martsolf syndrome 2, MIM# 619420; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 PMM2 Lauren Rogers edited their review of gene: PMM2: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 PMM2 Lauren Rogers reviewed gene: PMM2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type Ia (MIM#212065); Mode of inheritance: None
Prepair 1000+ v1.65 PLPBP Lauren Rogers reviewed gene: PLPBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 30668673, 31741821; Phenotypes: Epilepsy, early-onset, vitamin B6-dependent, MIM#617290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 PIGA Lauren Rogers reviewed gene: PIGA: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM#300868, Neurodevelopmental disorder with epilepsy and hemochromatosis, MIM#301072; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.65 PGM3 Lauren Rogers reviewed gene: PGM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31231132, 33098103; Phenotypes: Immunodeficiency 23, MIM# 615816; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 PGM1 Lauren Rogers reviewed gene: PGM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24499211, 33342467; Phenotypes: Congenital disorder of glycosylation, type It (MIM#614921); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 ORC1 Lauren Rogers reviewed gene: ORC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21358633, 21358632, 21358631, 23023959; Phenotypes: Meier-Gorlin syndrome 1, MIM# 224690; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 CLDN1 Andrew Coventry reviewed gene: CLDN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11889141 12164927 35304779 36779798; Phenotypes: Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis MIM#607626; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 OBSL1 Lauren Rogers reviewed gene: OBSL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21737058, 19481195, 23018678, 19877176; Phenotypes: 3-M syndrome 2 (MIM#612921); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 OBSL1 Lauren Rogers Deleted their review
Prepair 1000+ v1.65 OBSL1 Lauren Rogers reviewed gene: OBSL1: Rating: ; Mode of pathogenicity: None; Publications: 21737058, 19481195, 23018678, 19877176; Phenotypes: 3-M syndrome 2, MIM #612921; Mode of inheritance: None
Prepair 1000+ v1.65 NTNG2 Lauren Rogers reviewed gene: NTNG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31668703, 31692205; Phenotypes: Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia, MIM# 618718; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 NKX3-2 Lauren Rogers reviewed gene: NKX3-2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20004766, 29704686; Phenotypes: Spondylo-megaepiphyseal-metaphyseal dysplasia (MIM#613330); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 CLCN4 Andrew Coventry reviewed gene: CLCN4: Rating: GREEN; Mode of pathogenicity: None; Publications: 27550844 33951195 25644381 34479510 37409888; Phenotypes: Raynaud-Claes syndrome MIM#300114; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.65 CIITA Andrew Coventry reviewed gene: CIITA: Rating: GREEN; Mode of pathogenicity: None; Publications: 8402893 9099848 11862382 28676232 24789686 20197681 11466404 15821736 12910265; Phenotypes: MHC class II deficiency 1 MIM#209920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 CDK10 Andrew Coventry reviewed gene: CDK10: Rating: GREEN; Mode of pathogenicity: None; Publications: 28886341 29130579 34974531; Phenotypes: Al Kaissi syndrome MIM#617694; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 NGLY1 Lauren Rogers reviewed gene: NGLY1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24651605, 27388694; Phenotypes: Congenital disorder of deglycosylation, MIM# 615273; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 MOGS Lauren Rogers reviewed gene: MOGS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31925597, 30587846, 33058492, 38498292, 33261925; Phenotypes: Congenital disorder of glycosylation, type IIb, MIM# 606056; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 C19orf12 Andrew Coventry reviewed gene: C19orf12: Rating: GREEN; Mode of pathogenicity: None; Publications: 21981780 31087512 23269600 33688131 22508347 31804703 30088953 20039086 24586779 35182730; Phenotypes: Neurodegeneration with brain iron accumulation 4 MIM#614298; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 MOCS2 Lauren Rogers reviewed gene: MOCS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10053004, 31848698, 16021469, 30900395; Phenotypes: Molybdenum cofactor deficiency B (MIM#252160); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 MMADHC Lauren Rogers reviewed gene: MMADHC: Rating: ; Mode of pathogenicity: None; Publications: 33552904; Phenotypes: Homocystinuria, cblD type, variant 1 MIM#277410, Methylmalonic aciduria and homocystinuria, cblD type MIM#277410, Methylmalonic aciduria, cblD type, variant 2 MIM#277410, Disorders of cobalamin absorption, transport and metabolism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 MEGF8 Lauren Rogers reviewed gene: MEGF8: Rating: ; Mode of pathogenicity: None; Publications: 23063620; Phenotypes: Carpenter syndrome, MIM#614976; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 MAN2B1 Lauren Rogers reviewed gene: MAN2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mannosidosis, alpha-, types I and II, MIM# 248500, MONDO:0009561; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 BCAP31 Andrew Coventry reviewed gene: BCAP31: Rating: GREEN; Mode of pathogenicity: None; Publications: 24011989 33603160 32681719; Phenotypes: Deafness, dystonia, and cerebral hypomyelination MIM#300475, Severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome MONDO:0010334; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.65 ISPD Lauren Rogers reviewed gene: ISPD: Rating: GREEN; Mode of pathogenicity: None; Publications: 28688748, 30060766, 22522420; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, MIM#614643; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1894 BBS4 Andrew Coventry reviewed gene: BBS4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11381270 12016587 10874630; Phenotypes: Bardet-Biedl syndrome 4 MIM#615982; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Susceptibility to Viral Infections v0.117 IKBKE Peter McNaughton gene: IKBKE was added
gene: IKBKE was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: IKBKE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IKBKE were set to PMID: 37937644
Phenotypes for gene: IKBKE were set to Recurrent HSV encephalitis
Review for gene: IKBKE was set to AMBER
Added comment: Single patient with recurrent HSV meningitis with supportive functional data.
Sources: Literature
Prepair 1000+ v1.65 ABCC8 Andrew Coventry reviewed gene: ABCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 17919176 1950816 21716120 38791571 36034573; Phenotypes: Diabetes mellitus, permanent neonatal 3, with or without neurologic features MIM#618857, Hyperinsulinemic hypoglycemia, familial, 1 MIM#256450; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Susceptibility to Viral Infections v0.117 RNASEL Peter McNaughton gene: RNASEL was added
gene: RNASEL was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: RNASEL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEL were set to PMID: 36538032
Phenotypes for gene: RNASEL were set to MIS-C
Review for gene: RNASEL was set to AMBER
Added comment: Single patient presenting with similar presentation and functional findings to OAS1 and OAS2
Sources: Literature
Susceptibility to Viral Infections v0.117 OAS2 Peter McNaughton gene: OAS2 was added
gene: OAS2 was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: OAS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OAS2 were set to PMID: 36538032
Phenotypes for gene: OAS2 were set to MIS-C
Review for gene: OAS2 was set to GREEN
Added comment: 3x unrelated patients with MIS-C after COVID infection. Patients displayed excessive inflammatory responses to intracellular dsRNA, SARS-CoV-2, SARS-CoV-2–infected cells, and their RNA, providing a plausible mechanism for MIS-C. Similar presentation to OAS1 and RNASEL.
Sources: Literature
Pulmonary Fibrosis_Interstitial Lung Disease v0.73 FBN1 Zornitza Stark Marked gene: FBN1 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.73 FBN1 Zornitza Stark Gene: fbn1 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.73 FBN1 Zornitza Stark Classified gene: FBN1 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.73 FBN1 Zornitza Stark Gene: fbn1 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.72 FBN1 Zornitza Stark gene: FBN1 was added
gene: FBN1 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert list
Mode of inheritance for gene: FBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBN1 were set to 31238364; 27138491; 17701892
Phenotypes for gene: FBN1 were set to Marfan syndrome, MIM# 154700; neonatal
Review for gene: FBN1 was set to GREEN
Added comment: Sources: Expert list
Pulmonary Fibrosis_Interstitial Lung Disease v0.71 FBLN5 Zornitza Stark Marked gene: FBLN5 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.71 FBLN5 Zornitza Stark Gene: fbln5 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.71 FBLN5 Zornitza Stark Classified gene: FBLN5 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.71 FBLN5 Zornitza Stark Gene: fbln5 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.70 FBLN5 Zornitza Stark gene: FBLN5 was added
gene: FBLN5 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert list
Mode of inheritance for gene: FBLN5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FBLN5 were set to Cutis laxa, autosomal recessive, type IA, MIM# 219100; childhood-onset emphysema
Review for gene: FBLN5 was set to GREEN
Added comment: Sources: Expert list
Pulmonary Fibrosis_Interstitial Lung Disease v0.69 FAT4 Zornitza Stark Marked gene: FAT4 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.69 FAT4 Zornitza Stark Gene: fat4 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.69 FAT4 Zornitza Stark Classified gene: FAT4 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.69 FAT4 Zornitza Stark Gene: fat4 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.68 FAT4 Zornitza Stark gene: FAT4 was added
gene: FAT4 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert list
Mode of inheritance for gene: FAT4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAT4 were set to 24913602; 14564208
Phenotypes for gene: FAT4 were set to Hennekam Syndrome, MIM# 235510; childhood pulmonary lymphangiectasia
Review for gene: FAT4 was set to GREEN
Added comment: Sources: Expert list
Prepair 1000+ v1.65 CLCNKB Lucy Spencer changed review comment from: Is the phenotype(s) severe and onset <18yo? YES. CLCNKB mutations cause Bartter syndrome type 3 also called classic Bartter syndrome with renal salt wasting, hypokalemia, metabolic alkalosis, polyuria, polydipsia, and failure to thrive. It typically manifests in early childhood but late childhood or adulthood onset cases have been reported. Classic Bartter syndrome has a heterogeneous presentation from severe to very mild (PMIDs: 25810436, 24965226)

There is also a digenic inheritance known for this gene with variants in CLCNKA causing Bartter syndrome type 4b.; to: Is the phenotype(s) severe and onset <18yo? YES. CLCNKB mutations cause Bartter syndrome type 3 also called classic Bartter syndrome with renal salt wasting, hypokalemia, metabolic alkalosis, polyuria, polydipsia, and failure to thrive. It typically manifests in early childhood but late childhood or adulthood onset cases have been reported. Classic Bartter syndrome has a heterogeneous presentation from severe to very mild (PMIDs: 25810436, 24965226)

There is also a digenic inheritance known for this gene with variants in CLCNKA causing Bartter syndrome type 4b.
Prepair 1000+ v1.65 CLCNKB Lucy Spencer reviewed gene: CLCNKB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25810436, 24965226; Phenotypes: Bartter syndrome, type 3 MIM#607364, Bartter syndrome, type 4b, digenic MIM#613090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dilated Cardiomyopathy v1.33 LDB3 Bryony Thompson reviewed gene: LDB3: Rating: AMBER; Mode of pathogenicity: None; Publications: 14662268, 14660611, 35284542, 32041989; Phenotypes: dilated cardiomyopathy MONDO:0005021; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1894 LDB3 Bryony Thompson Deleted their comment
Mendeliome v1.1894 LDB3 Bryony Thompson Classified gene: LDB3 as Green List (high evidence)
Mendeliome v1.1894 LDB3 Bryony Thompson Added comment: Comment on list classification: Monoallelic DCM association is still Amber
Mendeliome v1.1894 LDB3 Bryony Thompson Gene: ldb3 has been classified as Green List (High Evidence).
Mendeliome v1.1893 LDB3 Bryony Thompson Added comment: Comment on mode of inheritance: AD missense variants in LDB3 that affect only short isoforms are associated with skeletal myopathies, while AR LoF variants cause paediatric cardiomyopathy
Mendeliome v1.1893 LDB3 Bryony Thompson Mode of inheritance for gene: LDB3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1892 LDB3 Bryony Thompson reviewed gene: LDB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 36253531, 32922198; Phenotypes: dilated cardiomyopathy MONDO:0005021; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pulmonary Fibrosis_Interstitial Lung Disease v0.67 ELN Zornitza Stark Marked gene: ELN as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.67 ELN Zornitza Stark Gene: eln has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.67 ELN Zornitza Stark Classified gene: ELN as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.67 ELN Zornitza Stark Gene: eln has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.66 ELN Zornitza Stark gene: ELN was added
gene: ELN was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature
Mode of inheritance for gene: ELN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ELN were set to Cutis laxa, autosomal dominant, MIM# 123700
Review for gene: ELN was set to GREEN
Added comment: Sources: Literature
Pulmonary Fibrosis_Interstitial Lung Disease v0.65 EFEMP2 Zornitza Stark Marked gene: EFEMP2 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.65 EFEMP2 Zornitza Stark Gene: efemp2 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.65 EFEMP2 Zornitza Stark Classified gene: EFEMP2 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.65 EFEMP2 Zornitza Stark Gene: efemp2 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.64 EFEMP2 Zornitza Stark gene: EFEMP2 was added
gene: EFEMP2 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert list
Mode of inheritance for gene: EFEMP2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EFEMP2 were set to Cutis laxa, autosomal recessive, type IB MIM# 614437
Review for gene: EFEMP2 was set to GREEN
Added comment: Sources: Expert list
Pulmonary Fibrosis_Interstitial Lung Disease v0.63 DOCK8 Zornitza Stark Marked gene: DOCK8 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.63 DOCK8 Zornitza Stark Gene: dock8 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.63 DOCK8 Zornitza Stark Classified gene: DOCK8 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.63 DOCK8 Zornitza Stark Gene: dock8 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.62 DOCK8 Zornitza Stark gene: DOCK8 was added
gene: DOCK8 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert list
Mode of inheritance for gene: DOCK8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DOCK8 were set to Hyper-IgE recurrent infection syndrome, autosomal recessive, MIM# 243700; Childhood bronchiectasis
Review for gene: DOCK8 was set to GREEN
Added comment: Sources: Expert list
Pulmonary Fibrosis_Interstitial Lung Disease v0.61 CFTR Zornitza Stark Marked gene: CFTR as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.61 CFTR Zornitza Stark Gene: cftr has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.61 CFTR Zornitza Stark Classified gene: CFTR as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.61 CFTR Zornitza Stark Gene: cftr has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.60 CFTR Zornitza Stark gene: CFTR was added
gene: CFTR was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature
Mode of inheritance for gene: CFTR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CFTR were set to Cystic fibrosis, MIM# 219700
Review for gene: CFTR was set to GREEN
Added comment: Sources: Literature
Pulmonary Fibrosis_Interstitial Lung Disease v0.59 CCBE1 Zornitza Stark Marked gene: CCBE1 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.59 CCBE1 Zornitza Stark Gene: ccbe1 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.59 CCBE1 Zornitza Stark Classified gene: CCBE1 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.59 CCBE1 Zornitza Stark Gene: ccbe1 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.58 CCBE1 Zornitza Stark gene: CCBE1 was added
gene: CCBE1 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert list
Mode of inheritance for gene: CCBE1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CCBE1 were set to Hennekam lymphangiectasia- lymphoedema syndrome MIM# 235510
Review for gene: CCBE1 was set to GREEN
Added comment: Sources: Expert list
Autoinflammatory Disorders v1.48 TBK1 Zornitza Stark Phenotypes for gene: TBK1 were changed from Immunodeficiency, MONDO:0021094, TBK1-related, AR; Autoinflammation to Autoinflammation with arthritis and vasculitis, MIM# 620880
Autoinflammatory Disorders v1.47 TBK1 Zornitza Stark reviewed gene: TBK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoinflammation with arthritis and vasculitis, MIM# 620880; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.28 SNUPN Zornitza Stark Phenotypes for gene: SNUPN were changed from autosomal recessive limb-girdle muscular dystrophy MONDO:0015152 to Muscular dystrophy, limb-girdle, autosomal recessive 29, MIM# 620793
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.27 SNUPN Zornitza Stark reviewed gene: SNUPN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 29, MIM# 620793; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v1.34 SNUPN Zornitza Stark Phenotypes for gene: SNUPN were changed from autosomal recessive limb-girdle muscular dystrophy MONDO:0015152, SNUPN-related to Muscular dystrophy, limb-girdle, autosomal recessive 29, MIM# 620793
Muscular dystrophy and myopathy_Paediatric v1.33 SNUPN Zornitza Stark reviewed gene: SNUPN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 29, MIM# 620793; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1892 SNUPN Zornitza Stark Phenotypes for gene: SNUPN were changed from autosomal recessive limb-girdle muscular dystrophy MONDO:0015152 to Muscular dystrophy, limb-girdle, autosomal recessive 29, MIM# 620793
Mendeliome v1.1891 SNUPN Zornitza Stark reviewed gene: SNUPN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 29, MIM# 620793; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.186 NBEAL2 Peter McNaughton gene: NBEAL2 was added
gene: NBEAL2 was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: NBEAL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NBEAL2 were set to PMID: 37349339
Phenotypes for gene: NBEAL2 were set to Immune dysregulation
Review for gene: NBEAL2 was set to GREEN
Added comment: Patients with NBEAL2 deficiency present with ALPS-like disease with autoimmune manifestations including Evans syndrome, chill blain lupus, autoimmune thyroiditis, and/or antiplatelet autoantibodies. Functional data demonstrating that NBEAL2 affects CTLA4 expression regulation.
Sources: Literature
Susceptibility to Viral Infections v0.117 NFATC2 Peter McNaughton gene: NFATC2 was added
gene: NFATC2 was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: NFATC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFATC2 were set to PMID: 38427060
Phenotypes for gene: NFATC2 were set to EBV associated lymphoproliferative disease
Review for gene: NFATC2 was set to RED
Added comment: 12yo girl born to consanguineous parents with EBV associated lymphoproliferation. Initially presented with recurrent chest infections, lung deterioration, chronic wet cough and failure to thrive at the age of 9 and severe hypogammaglobulinaemia. Her elder brother died of lymphoma when he was 5 years old, otherwise family history was unremarkable.
Sources: Literature
Disorders of immune dysregulation v0.186 SH2B3 Peter McNaughton gene: SH2B3 was added
gene: SH2B3 was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: SH2B3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SH2B3 were set to PMID: 37206266
Phenotypes for gene: SH2B3 were set to Immune
Review for gene: SH2B3 was set to GREEN
Added comment: 2x unrelated patients with haematopoietic manifestations with predominantly myeloproliferative features. Both patients developed clinically significant extra‐haematopoietic multi‐organ autoimmune manifestations throughout life including autoimmune hypothyroidism, autoimmune hepatitis, alopecia areata and autoimmune diabetes mellitus.
Sources: Literature
Disorders of immune dysregulation v0.186 CD274 Peter McNaughton gene: CD274 was added
gene: CD274 was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: CD274 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD274 were set to PMID: 38634869
Phenotypes for gene: CD274 were set to Immune dysregulation
Review for gene: CD274 was set to AMBER
Added comment: Two siblings, born to second-degree consanguineous parents of Moroccan descent,
both developed neonatal-onset T1D (diagnosed at the ages of 1 day and 7 wk, respectively). One sibling was subsequently diagnosed with asthma at the age of 5 mo, auto-immune hypothyroidism at the age of 3 years, and growth hormone (GH) deficiency at the age of 10 years. He also had mild intellectual disability with delayed language development. By
contrast, his sister had no clinical manifestations other than T1D.
Sources: Literature
Combined Immunodeficiency v1.66 ITPR3 Peter McNaughton gene: ITPR3 was added
gene: ITPR3 was added to Combined Immunodeficiency. Sources: Literature
Mode of inheritance for gene: ITPR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITPR3 were set to PMID: 36302985
Phenotypes for gene: ITPR3 were set to Combined Immune deficiency, immune dysregulation
Review for gene: ITPR3 was set to GREEN
Added comment: Three different variants in two unrelated compound heterozygous patients demonstrated impaired IP3-mediated Ca2+ responses in vitro, translating into deficient T-cell activation and
proliferation. P1 was a 12-year-old male patient who presented with combined immunodeficiency with profoundly low numbers of B and T cells and required hematopoietic stem cell transplantation (HSCT) at the age of 6 years. P2 was a 36-year-old male
who presented with recurring immune thrombocytopenia (ITP), requiring splenectomy at the age of 19 years. He subsequently suffered from autoimmune hemolytic anemia, susceptibility to infections, and enteropathy. Hypogammaglobulinemia and low numbers of switched memory B cells led to a diagnosis of CVID and monthly treatment with intravenous
immunoglobulin. The patient did not show signs of neuromuscular disorder.
Authors suggest a partially recessive mode of inheritance with complete defects in these causing embryonic lethality.
Sources: Literature
Disorders of immune dysregulation v0.186 UNC93B1 Peter McNaughton gene: UNC93B1 was added
gene: UNC93B1 was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: UNC93B1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: UNC93B1 were set to PMID: 38869500
Phenotypes for gene: UNC93B1 were set to SLE, chilblain lupus
Mode of pathogenicity for gene: UNC93B1 was set to Other
Review for gene: UNC93B1 was set to GREEN
Added comment: Rare missense substitutions in UNC93B1 in probands from five unrelated kindreds presenting with early onset SLE (two probands) or CBL (three probands). Clinical, genetic, and functional in vitro and ex vivo data demonstrating changes in TLR7/8 signalling and trafficking.
Sources: Literature
Cerebral Palsy v1.364 TRPM3 Clare van Eyk gene: TRPM3 was added
gene: TRPM3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TRPM3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRPM3 were set to PMID: 37684057
Phenotypes for gene: TRPM3 were set to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures (NEDFSS), MIM#620224)
Review for gene: TRPM3 was set to RED
Added comment: Single case report of child with a likely pathogenic de novo missense variant in the ion transport domain of TRPM3 and neurodevelopmental delay with CP (PMID: 37684057). Cerebral palsy has not previously been reported.
Sources: Literature
Prepair 1000+ v1.65 CEP290 Lucy Spencer reviewed gene: CEP290: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 17345604, 16909394, 24807808, 16682970, 16682973, 27434533, 20690115, 32208788; Phenotypes: CEP290-related ciliopathy MONDO:0100451, Bardet-Biedl syndrome 14, MIM# 615991, Joubert syndrome 5 610188, Leber congenital amaurosis 10, MIM# 611755, Meckel syndrome 4, MIM# 611134, Senior-Loken syndrome 6, MIM# 610189; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 CDT1 Lucy Spencer reviewed gene: CDT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11992493, 21358631; Phenotypes: Meier-Gorlin syndrome 4 MIM#613804; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 CD55 Lucy Spencer reviewed gene: CD55: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28657829; Phenotypes: Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy, MIM# 226300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 CARD11 Lucy Spencer reviewed gene: CARD11: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36729250, 23561803, 23374270; Phenotypes: Immunodeficiency 11A MIM#615206; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 B3GAT3 Lucy Spencer reviewed gene: B3GAT3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31988067; Phenotypes: Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects, MIM#245600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 ATM Lauren Rogers reviewed gene: ATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 30137827; Phenotypes: Ataxia-telangiectasia, MIM# 208900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 ACY1 Zornitza Stark Tag for review tag was added to gene: ACY1.
Prepair 1000+ v1.65 CD81 Zornitza Stark Marked gene: CD81 as ready
Prepair 1000+ v1.65 CD81 Zornitza Stark Gene: cd81 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.65 CD81 Zornitza Stark Publications for gene: CD81 were set to 20237408
Prepair 1000+ v1.64 AIFM1 Zornitza Stark Marked gene: AIFM1 as ready
Prepair 1000+ v1.64 AIFM1 Zornitza Stark Gene: aifm1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.64 AIFM1 Zornitza Stark Phenotypes for gene: AIFM1 were changed from Cowchock syndrome, 310490 (3) to Combined oxidative phosphorylation deficiency 6, MIM#300816
Prepair 1000+ v1.63 AK2 Zornitza Stark Marked gene: AK2 as ready
Prepair 1000+ v1.63 AK2 Zornitza Stark Gene: ak2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.63 AK2 Zornitza Stark Phenotypes for gene: AK2 were changed from Reticular dysgenesis, 267500 (3) to Reticular dysgenesis MIM# 267500
Prepair 1000+ v1.62 AK2 Zornitza Stark Publications for gene: AK2 were set to
Prepair 1000+ v1.61 ALDH3A2 Zornitza Stark Marked gene: ALDH3A2 as ready
Prepair 1000+ v1.61 ALDH3A2 Zornitza Stark Gene: aldh3a2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.61 ALDH3A2 Zornitza Stark Phenotypes for gene: ALDH3A2 were changed from Sjogren-Larsson syndrome, 270200 (3) to Sjogren-Larsson syndrome (MIM#270200)
Prepair 1000+ v1.60 ALDH3A2 Zornitza Stark reviewed gene: ALDH3A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Sjogren-Larsson syndrome (MIM#270200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.60 ALDH7A1 Zornitza Stark Marked gene: ALDH7A1 as ready
Prepair 1000+ v1.60 ALDH7A1 Zornitza Stark Gene: aldh7a1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.60 ALDH7A1 Zornitza Stark Phenotypes for gene: ALDH7A1 were changed from Epilepsy, pyridoxine-dependent, 266100 (3) to Epilepsy, early-onset, 4, vitamin B6-dependent MIM #266100
Prepair 1000+ v1.59 ALDH7A1 Zornitza Stark Publications for gene: ALDH7A1 were set to
Prepair 1000+ v1.58 ALG12 Zornitza Stark Marked gene: ALG12 as ready
Prepair 1000+ v1.58 ALG12 Zornitza Stark Gene: alg12 has been classified as Green List (High Evidence).
Prepair 1000+ v1.58 ALG12 Zornitza Stark Phenotypes for gene: ALG12 were changed from Congenital disorder of glycosylation, type Ig, 607143 (3) to Congenital disorder of glycosylation, type Ig MIM# 607143
Prepair 1000+ v1.57 ALG12 Zornitza Stark Publications for gene: ALG12 were set to
Prepair 1000+ v1.56 ALG3 Zornitza Stark Marked gene: ALG3 as ready
Prepair 1000+ v1.56 ALG3 Zornitza Stark Gene: alg3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.56 ALG3 Zornitza Stark Publications for gene: ALG3 were set to
Prepair 1000+ v1.55 ALMS1 Zornitza Stark Marked gene: ALMS1 as ready
Prepair 1000+ v1.55 ALMS1 Zornitza Stark Gene: alms1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.55 ALMS1 Zornitza Stark Phenotypes for gene: ALMS1 were changed from Alstrom syndrome, 203800 (3) to Alstrom syndrome, MIM# 203800
Prepair 1000+ v1.54 ALOX12B Zornitza Stark Marked gene: ALOX12B as ready
Prepair 1000+ v1.54 ALOX12B Zornitza Stark Gene: alox12b has been classified as Green List (High Evidence).
Prepair 1000+ v1.54 ALOX12B Zornitza Stark Phenotypes for gene: ALOX12B were changed from Ichthyosis, congenital, autosomal recessive 2, 242100 (3) to Ichthyosis, congenital, autosomal recessive 2, MIM# 242100
Prepair 1000+ v1.53 ALOX12B Zornitza Stark Publications for gene: ALOX12B were set to
Prepair 1000+ v1.52 ALOX12B Zornitza Stark reviewed gene: ALOX12B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, congenital, autosomal recessive 2, MIM# 242100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.52 ALOXE3 Zornitza Stark Marked gene: ALOXE3 as ready
Prepair 1000+ v1.52 ALOXE3 Zornitza Stark Gene: aloxe3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.52 ALOXE3 Zornitza Stark Phenotypes for gene: ALOXE3 were changed from Ichthyosis, congenital, autosomal recessive 3, 606545 (3) to Ichthyosis, congenital, autosomal recessive 3 (MIM#606545)
Prepair 1000+ v1.51 ALOXE3 Zornitza Stark reviewed gene: ALOXE3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, congenital, autosomal recessive 3 (MIM#606545); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.51 ANTXR1 Zornitza Stark Marked gene: ANTXR1 as ready
Prepair 1000+ v1.51 ANTXR1 Zornitza Stark Gene: antxr1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.51 ANTXR1 Zornitza Stark Phenotypes for gene: ANTXR1 were changed from GAPO syndrome, 230740 (3) to GAPO syndrome (MIM#230740)
Prepair 1000+ v1.50 ANTXR2 Zornitza Stark Marked gene: ANTXR2 as ready
Prepair 1000+ v1.50 ANTXR2 Zornitza Stark Gene: antxr2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.50 ANTXR2 Zornitza Stark Phenotypes for gene: ANTXR2 were changed from Hyaline fibromatosis syndrome, 228600 (3) to Hyaline fibromatosis syndrome, MIM# 228600; MONDO:0009229
Prepair 1000+ v1.49 ANTXR2 Zornitza Stark Publications for gene: ANTXR2 were set to
Prepair 1000+ v1.48 AP4B1 Zornitza Stark Marked gene: AP4B1 as ready
Prepair 1000+ v1.48 AP4B1 Zornitza Stark Gene: ap4b1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.48 AP4B1 Zornitza Stark Publications for gene: AP4B1 were set to
Prepair 1000+ v1.47 AQP2 Zornitza Stark Marked gene: AQP2 as ready
Prepair 1000+ v1.47 AQP2 Zornitza Stark Gene: aqp2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.47 AQP2 Zornitza Stark Phenotypes for gene: AQP2 were changed from Diabetes insipidus, nephrogenic, 125800 (3) to Diabetes insipidus, nephrogenic, type 2 MIM# 125800
Prepair 1000+ v1.46 AQP2 Zornitza Stark Publications for gene: AQP2 were set to
Prepair 1000+ v1.45 ARG1 Zornitza Stark Marked gene: ARG1 as ready
Prepair 1000+ v1.45 ARG1 Zornitza Stark Gene: arg1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.45 ARG1 Zornitza Stark Phenotypes for gene: ARG1 were changed from Argininemia, 207800 (3) to Argininemia MIM# 207800
Prepair 1000+ v1.44 ARG1 Zornitza Stark Publications for gene: ARG1 were set to
Prepair 1000+ v1.43 CD40 Zornitza Stark Marked gene: CD40 as ready
Prepair 1000+ v1.43 CD40 Zornitza Stark Gene: cd40 has been classified as Green List (High Evidence).
Prepair 1000+ v1.43 COQ4 Zornitza Stark Marked gene: COQ4 as ready
Prepair 1000+ v1.43 COQ4 Zornitza Stark Gene: coq4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.43 DBT Zornitza Stark Marked gene: DBT as ready
Prepair 1000+ v1.43 DBT Zornitza Stark Gene: dbt has been classified as Green List (High Evidence).
Prepair 1000+ v1.43 DBT Zornitza Stark reviewed gene: DBT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.43 ARL6 Lauren Rogers edited their review of gene: ARL6: Changed phenotypes: Bardet-Biedl syndrome 3, MIM# 600151, Retinitis pigmentosa 55, MIM#613575
Prepair 1000+ v1.43 CRB1 Lauren Rogers edited their review of gene: CRB1: Changed phenotypes: Leber congenital amaurosis 8 MIM#613835, Retinitis pigmentosa-12, MIM#600105
Prepair 1000+ v1.43 COQ4 Lauren Rogers edited their review of gene: COQ4: Changed phenotypes: Coenzyme Q10 deficiency, primary, 7, MIM# 616276, Spastic ataxia 10, MIM#620666
Prepair 1000+ v1.43 COQ4 Lauren Rogers changed review comment from: At least 9 unrelated families reported.

Primary coenzyme Q10 deficiency-7 (COQ10D7) is an autosomal recessive disorder resulting from mitochondrial dysfunction. Most patients have onset of severe cardiac or neurologic symptoms soon after birth. IUGR reported.

Treatment: CoQ10 supplementation can limit disease progression and reverse some clinical manifestations.; to: At least 9 unrelated families reported.

Primary coenzyme Q10 deficiency-7 (COQ10D7) is an autosomal recessive disorder resulting from mitochondrial dysfunction. Most patients have onset of severe cardiac or neurologic symptoms soon after birth. IUGR reported.

Treatment: CoQ10 supplementation can limit disease progression and reverse some clinical manifestations.
Intellectual disability syndromic and non-syndromic v0.6063 SLC39A14 Kushani Jayasinghe reviewed gene: SLC39A14: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27231142, 29685658; Phenotypes: Hypermanganesemia with dystonia 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.43 ALOXE3 Lucy Spencer edited their review of gene: ALOXE3: Added comment: Discussed 25/07/24- this can be a very severe form of ichthyosis, should be green and remain on this panel; Changed rating: GREEN
Prepair 1000+ v1.43 ALOXE3 Lucy Spencer changed review comment from: HGNC approved symbol/name: ALOXE3

Is the phenotype(s) severe and onset <18yo ? Yes early onset; babyscreen review notes its congenital onset. However this gene causes ichthyosis and OMIM says "Affected individuals have a relatively mild ichthyosis phenotype". Im not sure its severe enough to include here.

Discussed 25/07/24- this can be a very severe form of ichthyosis, should be green and remain on this panel

Treatments available: No specific treatment available (from babyscreen); to: HGNC approved symbol/name: ALOXE3

Is the phenotype(s) severe and onset <18yo ? Yes early onset; babyscreen review notes its congenital onset. However this gene causes ichthyosis and OMIM says "Affected individuals have a relatively mild ichthyosis phenotype". Im not sure its severe enough to include here.

Treatments available: No specific treatment available (from babyscreen)
Prepair 1000+ v1.43 ALOXE3 Lucy Spencer changed review comment from: HGNC approved symbol/name: ALOXE3

Is the phenotype(s) severe and onset <18yo ? Yes early onset; babyscreen review notes its congenital onset. However this gene causes ichthyosis and OMIM says "Affected individuals have a relatively mild ichthyosis phenotype". Im not sure its severe enough to include here.

Treatments available: No specific treatment available (from babyscreen); to: HGNC approved symbol/name: ALOXE3

Is the phenotype(s) severe and onset <18yo ? Yes early onset; babyscreen review notes its congenital onset. However this gene causes ichthyosis and OMIM says "Affected individuals have a relatively mild ichthyosis phenotype". Im not sure its severe enough to include here.

Discussed 25/07/24- this can be a very severe form of ichthyosis, should be green and remain on this panel

Treatments available: No specific treatment available (from babyscreen)
Prepair 1000+ v1.43 ALOXE3 Lucy Spencer changed review comment from: HGNC approved symbol/name: ALOXE3

Is the phenotype(s) severe and onset <18yo ? Yes early onset; babyscreen review notes its congenital onset. However this gene causes ichthyosis and OMIM says "Affected individuals have a relatively mild ichthyosis phenotype". Im not sure its severe enough to include here.

Treatments available: No specific treatment available (from babyscreen)

Known technical challenges? Y; to: HGNC approved symbol/name: ALOXE3

Is the phenotype(s) severe and onset <18yo ? Yes early onset; babyscreen review notes its congenital onset. However this gene causes ichthyosis and OMIM says "Affected individuals have a relatively mild ichthyosis phenotype". Im not sure its severe enough to include here.

Treatments available: No specific treatment available (from babyscreen)
Prepair 1000+ v1.43 COL2A1 Lauren Rogers reviewed gene: COL2A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31755234, 32896647; Phenotypes: Spondyloperipheral dysplasia, MIM #271700; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v1.43 COQ4 Lauren Rogers changed review comment from: At least 9 unrelated families reported.

Primary coenzyme Q10 deficiency-7 (COQ10D7) is an autosomal recessive disorder resulting from mitochondrial dysfunction. Most patients have onset of severe cardiac or neurologic symptoms soon after birth. IUGR reported.

Treatment: CoQ10 supplementation can limit disease progression and reverse some clinical manifestations.; to: At least 9 unrelated families reported.

Primary coenzyme Q10 deficiency-7 (COQ10D7) is an autosomal recessive disorder resulting from mitochondrial dysfunction. Most patients have onset of severe cardiac or neurologic symptoms soon after birth. IUGR reported.

Treatment: CoQ10 supplementation can limit disease progression and reverse some clinical manifestations.
Prepair 1000+ v1.43 AP4M1 Zornitza Stark Marked gene: AP4M1 as ready
Prepair 1000+ v1.43 AP4M1 Zornitza Stark Gene: ap4m1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.43 AP4S1 Zornitza Stark Marked gene: AP4S1 as ready
Prepair 1000+ v1.43 AP4S1 Zornitza Stark Gene: ap4s1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.43 ARHGEF9 Zornitza Stark Marked gene: ARHGEF9 as ready
Prepair 1000+ v1.43 ARHGEF9 Zornitza Stark Gene: arhgef9 has been classified as Green List (High Evidence).
Prepair 1000+ v1.43 ARHGEF9 Zornitza Stark Phenotypes for gene: ARHGEF9 were changed from Epileptic encephalopathy, early infantile, 8, 300607 (3) to Developmental and epileptic encephalopathy 8, MIM# 300607
Prepair 1000+ v1.42 ARHGEF9 Zornitza Stark Publications for gene: ARHGEF9 were set to
Prepair 1000+ v1.41 ARHGEF9 Zornitza Stark Tag SV/CNV tag was added to gene: ARHGEF9.
Prepair 1000+ v1.41 ARL6 Zornitza Stark Marked gene: ARL6 as ready
Prepair 1000+ v1.41 ARL6 Zornitza Stark Gene: arl6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.41 ARL6 Zornitza Stark Phenotypes for gene: ARL6 were changed from Bardet-Biedl syndrome 3, 600151 (3) to Bardet-Biedl syndrome 3, MIM# 600151
Prepair 1000+ v1.40 AIFM1 Lilian Downie Publications for gene: AIFM1 were set to
Prepair 1000+ v1.40 ARL6 Zornitza Stark Publications for gene: ARL6 were set to
Prepair 1000+ v1.39 ARL6 Zornitza Stark changed review comment from: Usually associated with multi-system ciliopathy, ID is a feature.; to: Usually associated with multi-system ciliopathy, ID is usually, though not always, a feature. Note gene is also associated with isolated RP.
Prepair 1000+ v1.39 ARL6 Zornitza Stark reviewed gene: ARL6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 3, MIM# 600151; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.39 ARSB Zornitza Stark Marked gene: ARSB as ready
Prepair 1000+ v1.39 ARSB Zornitza Stark Gene: arsb has been classified as Green List (High Evidence).
Prepair 1000+ v1.39 ARSB Zornitza Stark Publications for gene: ARSB were set to
Prepair 1000+ v1.38 AGXT Lilian Downie Marked gene: AGXT as ready
Prepair 1000+ v1.38 AGXT Lilian Downie Gene: agxt has been classified as Green List (High Evidence).
Prepair 1000+ v1.38 AGXT Lilian Downie Publications for gene: AGXT were set to
Prepair 1000+ v1.37 ASAH1 Zornitza Stark Marked gene: ASAH1 as ready
Prepair 1000+ v1.37 ASAH1 Zornitza Stark Gene: asah1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.37 ASAH1 Zornitza Stark Phenotypes for gene: ASAH1 were changed from Farber lipogranulomatosis, 228000 (3) to Spinal muscular atrophy with progressive myoclonic epilepsy, MIM#159950; Farber lipogranulomatosis, MIM#228000
Prepair 1000+ v1.36 AGA Lilian Downie Marked gene: AGA as ready
Prepair 1000+ v1.36 AGA Lilian Downie Gene: aga has been classified as Green List (High Evidence).
Prepair 1000+ v1.36 ASAH1 Zornitza Stark reviewed gene: ASAH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy with progressive myoclonic epilepsy, MIM#159950, Farber lipogranulomatosis, MIM#228000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.36 AGA Lilian Downie Publications for gene: AGA were set to
Prepair 1000+ v1.35 ATP6V1B1 Zornitza Stark Marked gene: ATP6V1B1 as ready
Prepair 1000+ v1.35 ATP6V1B1 Zornitza Stark Gene: atp6v1b1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.35 ATP6V1B1 Zornitza Stark Phenotypes for gene: ATP6V1B1 were changed from Renal tubular acidosis with deafness, 267300 (3) to Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM# 267300
Prepair 1000+ v1.34 AGL Lilian Downie Marked gene: AGL as ready
Prepair 1000+ v1.34 AGL Lilian Downie Gene: agl has been classified as Green List (High Evidence).
Prepair 1000+ v1.34 AGL Lilian Downie Publications for gene: AGL were set to
Prepair 1000+ v1.33 ATRX Zornitza Stark Marked gene: ATRX as ready
Prepair 1000+ v1.33 ATRX Zornitza Stark Gene: atrx has been classified as Green List (High Evidence).
Prepair 1000+ v1.33 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from ATR-X-related syndrome MONDO:0016980; Mental retardation-hypotonic facies syndrome, X-linked, 309580 (3) to ATR-X-related syndrome MONDO:0016980
Prepair 1000+ v1.32 ATRX Zornitza Stark Publications for gene: ATRX were set to
Prepair 1000+ v1.31 BBS1 Zornitza Stark Marked gene: BBS1 as ready
Prepair 1000+ v1.31 BBS1 Zornitza Stark Gene: bbs1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.31 BBS1 Zornitza Stark Phenotypes for gene: BBS1 were changed from Bardet-Biedl syndrome 1, 209900 (3) to Bardet-Biedl syndrome 1, MIM# 209900
Prepair 1000+ v1.30 ADSL Lilian Downie Marked gene: ADSL as ready
Prepair 1000+ v1.30 ADSL Lilian Downie Gene: adsl has been classified as Green List (High Evidence).
Prepair 1000+ v1.30 ADSL Lilian Downie Publications for gene: ADSL were set to
Prepair 1000+ v1.30 BBS1 Zornitza Stark Publications for gene: BBS1 were set to
Prepair 1000+ v1.29 BBS1 Zornitza Stark reviewed gene: BBS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 1, MIM# 209900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.29 BBS12 Zornitza Stark Marked gene: BBS12 as ready
Prepair 1000+ v1.29 BBS12 Zornitza Stark Gene: bbs12 has been classified as Green List (High Evidence).
Prepair 1000+ v1.29 ACTA1 Lilian Downie Marked gene: ACTA1 as ready
Prepair 1000+ v1.29 ACTA1 Lilian Downie Gene: acta1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.29 ACTA1 Lilian Downie Publications for gene: ACTA1 were set to 19562689
Prepair 1000+ v1.28 BBS12 Zornitza Stark reviewed gene: BBS12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 12, MIM# 615989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.28 ACTA1 Lilian Downie Publications for gene: ACTA1 were set to
Prepair 1000+ v1.27 C1QA Zornitza Stark Marked gene: C1QA as ready
Prepair 1000+ v1.27 C1QA Zornitza Stark Gene: c1qa has been classified as Green List (High Evidence).
Prepair 1000+ v1.27 C1QA Zornitza Stark Publications for gene: C1QA were set to
Prepair 1000+ v1.26 C1QA Zornitza Stark reviewed gene: C1QA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: C1q deficiency, MIM# 613652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.26 ACAD9 Lilian Downie Marked gene: ACAD9 as ready
Prepair 1000+ v1.26 ACAD9 Lilian Downie Gene: acad9 has been classified as Green List (High Evidence).
Prepair 1000+ v1.26 ACAD9 Lilian Downie Publications for gene: ACAD9 were set to
Prepair 1000+ v1.25 CD3D Zornitza Stark Marked gene: CD3D as ready
Prepair 1000+ v1.25 CD3D Zornitza Stark Gene: cd3d has been classified as Green List (High Evidence).
Prepair 1000+ v1.25 CD3D Zornitza Stark Phenotypes for gene: CD3D were changed from Immunodeficiency 19, 615617 (3) to Immunodeficiency 19, severe combined MIM# 615617
Prepair 1000+ v1.24 ACO2 Lilian Downie Marked gene: ACO2 as ready
Prepair 1000+ v1.24 ACO2 Lilian Downie Gene: aco2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.24 ACO2 Lilian Downie Publications for gene: ACO2 were set to
Prepair 1000+ v1.23 CLN5 Zornitza Stark Marked gene: CLN5 as ready
Prepair 1000+ v1.23 CLN5 Zornitza Stark Gene: cln5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.23 CLN5 Zornitza Stark Phenotypes for gene: CLN5 were changed from Ceroid lipofuscinosis, neuronal, 5, 256731 (3) to Ceroid lipofuscinosis, neuronal, 5, MIM# 256731; MONDO:0009745
Prepair 1000+ v1.22 CRB1 Zornitza Stark Marked gene: CRB1 as ready
Prepair 1000+ v1.22 CRB1 Zornitza Stark Gene: crb1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.22 CRB1 Zornitza Stark Publications for gene: CRB1 were set to
Prepair 1000+ v1.21 CRB1 Zornitza Stark reviewed gene: CRB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leber congenital amaurosis 8, MIM#613835; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.21 ACADVL Lilian Downie Marked gene: ACADVL as ready
Prepair 1000+ v1.21 ACADVL Lilian Downie Gene: acadvl has been classified as Green List (High Evidence).
Prepair 1000+ v1.21 GFM1 Lauren Rogers changed review comment from: Well established gene-disease association.
Onset at birth with death within first months of life
No treatment available

Non-genetic confirmatory test: - Fibroblasts show decreased activity of mitochondrial respiratory complex I, complex III, complex IV, and complex V
; to: Well established gene-disease association.
Onset at birth with death within first months of life
No treatment available
Prepair 1000+ v1.21 ACADVL Lilian Downie Publications for gene: ACADVL were set to
Prepair 1000+ v1.20 ECHS1 Lauren Rogers changed review comment from: Well established gene-disease association.

Usually presents in infancy.

Treatable-ID – level 4 evidence: valine restriction improves psychomotor/cognitive development/IQ; improves neurological manifestations (incl. neuro-imaging); improves systemic manifestations (PMID: 32642440); to: Well established gene-disease association.

Usually presents in infancy.
Prepair 1000+ v1.20 CTSD Zornitza Stark Marked gene: CTSD as ready
Prepair 1000+ v1.20 CTSD Zornitza Stark Gene: ctsd has been classified as Green List (High Evidence).
Prepair 1000+ v1.20 CTSD Zornitza Stark reviewed gene: CTSD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 10, MIM# 610127; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.20 ABHD5 Lilian Downie Marked gene: ABHD5 as ready
Prepair 1000+ v1.20 ABHD5 Lilian Downie Gene: abhd5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.20 ABHD5 Lilian Downie Phenotypes for gene: ABHD5 were changed from Chanarin-Dorfman syndrome, 275630 (3) to Chanarin-Dorfman syndrome, MIM#275630
Prepair 1000+ v1.19 DIS3L2 Zornitza Stark Marked gene: DIS3L2 as ready
Prepair 1000+ v1.19 DIS3L2 Zornitza Stark Gene: dis3l2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.19 DIS3L2 Zornitza Stark Phenotypes for gene: DIS3L2 were changed from Perlman syndrome, 267000 (3) to Perlman syndrome MIM# 267000
Prepair 1000+ v1.18 ABHD5 Lilian Downie Publications for gene: ABHD5 were set to
Prepair 1000+ v1.17 DIS3L2 Zornitza Stark Publications for gene: DIS3L2 were set to
Prepair 1000+ v1.16 GFM1 Zornitza Stark Marked gene: GFM1 as ready
Prepair 1000+ v1.16 GFM1 Zornitza Stark Gene: gfm1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.16 GFM1 Lauren Rogers changed review comment from: Well established gene-disease association.
Onset at birth with death within first months of life
No treatment available

Non-genetic confirmatory test: - Fibroblasts show decreased activity of mitochondrial respiratory complex I, complex III, complex IV, and complex V

Detection on NBS would establish diagnosis early and allow palliative treatment; to: Well established gene-disease association.
Onset at birth with death within first months of life
No treatment available

Non-genetic confirmatory test: - Fibroblasts show decreased activity of mitochondrial respiratory complex I, complex III, complex IV, and complex V
Prepair 1000+ v1.16 ABCB7 Lilian Downie Marked gene: ABCB7 as ready
Prepair 1000+ v1.16 ABCB7 Lilian Downie Gene: abcb7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.16 ABCB7 Lilian Downie Phenotypes for gene: ABCB7 were changed from Anemia, sideroblastic, with ataxia, 301310 (3) to Anemia, sideroblastic, with ataxia, MIM# 301310
Prepair 1000+ v1.15 ABCB7 Lilian Downie Publications for gene: ABCB7 were set to
Prepair 1000+ v1.14 ABCA12 Lilian Downie Marked gene: ABCA12 as ready
Prepair 1000+ v1.14 ABCA12 Lilian Downie Gene: abca12 has been classified as Green List (High Evidence).
Prepair 1000+ v1.14 HPGD Zornitza Stark Marked gene: HPGD as ready
Prepair 1000+ v1.14 HPGD Zornitza Stark Gene: hpgd has been classified as Green List (High Evidence).
Prepair 1000+ v1.14 HPGD Zornitza Stark Publications for gene: HPGD were set to
Prepair 1000+ v1.13 HPGD Zornitza Stark reviewed gene: HPGD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertrophic osteoarthropathy, primary, autosomal recessive 1 MIM#259100, Cranioosteoarthropathy MIM#259100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.13 AARS2 Lilian Downie Marked gene: AARS2 as ready
Prepair 1000+ v1.13 AARS2 Lilian Downie Gene: aars2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.13 HPSE2 Zornitza Stark Marked gene: HPSE2 as ready
Prepair 1000+ v1.13 HPSE2 Zornitza Stark Gene: hpse2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.13 HPSE2 Zornitza Stark Phenotypes for gene: HPSE2 were changed from Urofacial syndrome 1, 236730 (3) to Urofacial syndrome 1 MIM#236730
Prepair 1000+ v1.12 HPSE2 Zornitza Stark Publications for gene: HPSE2 were set to
Prepair 1000+ v1.11 HPSE2 Zornitza Stark reviewed gene: HPSE2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Urofacial syndrome 1 MIM#236730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.11 AAAS Lilian Downie Marked gene: AAAS as ready
Prepair 1000+ v1.11 AAAS Lilian Downie Gene: aaas has been classified as Green List (High Evidence).
Prepair 1000+ v1.11 AAAS Lilian Downie Publications for gene: AAAS were set to
Prepair 1000+ v1.10 HSD17B4 Zornitza Stark Marked gene: HSD17B4 as ready
Prepair 1000+ v1.10 HSD17B4 Zornitza Stark Gene: hsd17b4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.10 HSD17B4 Zornitza Stark reviewed gene: HSD17B4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: D-bifunctional protein deficiency, AR (MIM#261515); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.10 IL1RN Zornitza Stark Marked gene: IL1RN as ready
Prepair 1000+ v1.10 IL1RN Zornitza Stark Gene: il1rn has been classified as Green List (High Evidence).
Prepair 1000+ v1.10 IL1RN Zornitza Stark Phenotypes for gene: IL1RN were changed from Interleukin 1 receptor antagonist deficiency, 612852 (3) to Interleukin 1 receptor antagonist deficiency, MIM# 612852; Chronic recurrent multifocal osteomyelitis 2, with periostitis and pustulosis, MIM# 61285
Prepair 1000+ v1.9 IL2RG Zornitza Stark Marked gene: IL2RG as ready
Prepair 1000+ v1.9 IL2RG Zornitza Stark Gene: il2rg has been classified as Green List (High Evidence).
Prepair 1000+ v1.9 IL7R Zornitza Stark Marked gene: IL7R as ready
Prepair 1000+ v1.9 IL7R Zornitza Stark Gene: il7r has been classified as Green List (High Evidence).
Prepair 1000+ v1.9 VPS11 Zornitza Stark reviewed gene: VPS11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukodystrophy, hypomyelinating, 12 (MIM#616683); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ARSB Kate Scarff reviewed gene: ARSB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11668612, 31142378; Phenotypes: Mucopolysaccharidosis type VI (Maroteaux-Lamy), MIM# 253200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ACTA1 Michelle Torres reviewed gene: ACTA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19562689; Phenotypes: Congenital myopathy 2B, severe infantile, autosomal recessive (MIM#620265); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ARHGEF9 Kate Scarff reviewed gene: ARHGEF9: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31942680, 30048823, 29130122, 28620718; Phenotypes: Developmental and epileptic encephalopathy 8, MIM# 300607; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.9 ACO2 Michelle Torres changed review comment from: Is the phenotype(s) severe and onset <18yo ? Y

NB: Optic atrophy 9 may also be AD.; to: Is the phenotype(s) severe and onset <18yo ? Y

*No clear genotype-phenotype correlation (Fig 1a, PMID: 34056600)

NB: Optic atrophy 9 may also be AD.
Prepair 1000+ v1.9 ARG1 Kate Scarff reviewed gene: ARG1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26467175, 2365823, 1598908, 29726057; Phenotypes: Argininemia MIM# 207800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ACO2 Michelle Torres changed review comment from: Is the phenotype(s) severe and onset <18yo ? Y

NB: Optic atrophy 9 may also be AD.; to: Is the phenotype(s) severe and onset <18yo ? Y

NB: Optic atrophy 9 may also be AD.
Prepair 1000+ v1.9 ACO2 Michelle Torres edited their review of gene: ACO2: Changed rating: GREEN
Prepair 1000+ v1.9 ACO2 Michelle Torres reviewed gene: ACO2: Rating: ; Mode of pathogenicity: None; Publications: 34056600; Phenotypes: Infantile cerebellar-retinal degeneration (MIM#614559), Optic atrophy 9 (MIM#616289); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ALG12 Kate Scarff changed review comment from: HGNC approved symbol/name: ALG12
Is the phenotype(s) severe and onset <18yo ? Yes
Features include impaired psychomotor development, dysmorphic features, failure to thrive, male genital hypoplasia, coagulation abnormalities, and immune deficiency. More variable features include skeletal dysplasia, cardiac anomalies, ocular abnormalities, and sensorineural hearing loss. Some patients die in the early neonatal or infantile period, whereas others are mildly affected and live to adulthood; to: HGNC approved symbol/name: ALG12
Is the phenotype(s) severe and onset <18yo ? Yes
Features include impaired psychomotor development, dysmorphic features, failure to thrive, male genital hypoplasia, coagulation abnormalities, and immune deficiency. More variable features include skeletal dysplasia, cardiac anomalies, ocular abnormalities, and sensorineural hearing loss. Some patients die in the early neonatal or infantile period, whereas others are mildly affected and live to adulthood.
No specific treatment at present.
Prepair 1000+ v1.9 AQP2 Kate Scarff reviewed gene: AQP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 7537761, 11536078; Phenotypes: Diabetes insipidus, nephrogenic, type 2 MIM# 125800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v1.9 AP4B1 Kate Scarff reviewed gene: AP4B1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21620353, 22290197, 24700674, 24781758; Phenotypes: Spastic paraplegia 47, autosomal recessive MIM# 614066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ALG12 Kate Scarff reviewed gene: ALG12: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31481313; Phenotypes: Congenital disorder of glycosylation, type Ig MIM# 607143; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.47 PIGA Zornitza Stark Marked gene: PIGA as ready
Bleeding and Platelet Disorders v1.47 PIGA Zornitza Stark Gene: piga has been classified as Red List (Low Evidence).
Bleeding and Platelet Disorders v1.47 PIGA Zornitza Stark Phenotypes for gene: PIGA were changed from PAROXYSMAL NOCTURNAL HEMOGLOBINURIA 1 OMIM# 300818 to Paroxysmal nocturnal hemoglobinuria, somatic, MIM# 300818
Bleeding and Platelet Disorders v1.46 PIGA Zornitza Stark Classified gene: PIGA as Red List (low evidence)
Bleeding and Platelet Disorders v1.46 PIGA Zornitza Stark Gene: piga has been classified as Red List (Low Evidence).
Bleeding and Platelet Disorders v1.45 PIGA Zornitza Stark Tag somatic tag was added to gene: PIGA.
Bleeding and Platelet Disorders v1.45 PROC Zornitza Stark Marked gene: PROC as ready
Bleeding and Platelet Disorders v1.45 PROC Zornitza Stark Gene: proc has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.45 PROC Zornitza Stark Phenotypes for gene: PROC were changed from THROMBOPHILIA DUE TO PROTEIN C DEFICIENCY, AUTOSOMAL DOMINANT # 176860; THROMBOPHILIA DUE TO PROTEIN C DEFICIENCY, AUTOSOMAL RECESSIVE, # 612304 to Thrombophilia 3 due to protein C deficiency MIM#176860; Thrombophilia 3 due to protein C deficiency MIM#612304
Bleeding and Platelet Disorders v1.44 PROC Zornitza Stark Classified gene: PROC as Green List (high evidence)
Bleeding and Platelet Disorders v1.44 PROC Zornitza Stark Gene: proc has been classified as Green List (High Evidence).
Cerebral Palsy v1.364 KDM3B Zornitza Stark Marked gene: KDM3B as ready
Cerebral Palsy v1.364 KDM3B Zornitza Stark Gene: kdm3b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.364 KDM3B Zornitza Stark Classified gene: KDM3B as Red List (low evidence)
Cerebral Palsy v1.364 KDM3B Zornitza Stark Gene: kdm3b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.363 ERLIN2 Zornitza Stark Marked gene: ERLIN2 as ready
Cerebral Palsy v1.363 ERLIN2 Zornitza Stark Gene: erlin2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.363 ERLIN2 Zornitza Stark Classified gene: ERLIN2 as Red List (low evidence)
Cerebral Palsy v1.363 ERLIN2 Zornitza Stark Gene: erlin2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.362 GCH1 Zornitza Stark Marked gene: GCH1 as ready
Cerebral Palsy v1.362 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.362 GCH1 Zornitza Stark Classified gene: GCH1 as Green List (high evidence)
Cerebral Palsy v1.362 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.361 GFAP Zornitza Stark Marked gene: GFAP as ready
Cerebral Palsy v1.361 GFAP Zornitza Stark Gene: gfap has been classified as Red List (Low Evidence).
Cerebral Palsy v1.361 GFAP Zornitza Stark Classified gene: GFAP as Red List (low evidence)
Cerebral Palsy v1.361 GFAP Zornitza Stark Gene: gfap has been classified as Red List (Low Evidence).
Cerebral Palsy v1.360 DHPS Zornitza Stark Marked gene: DHPS as ready
Cerebral Palsy v1.360 DHPS Zornitza Stark Gene: dhps has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.360 DHPS Zornitza Stark Classified gene: DHPS as Amber List (moderate evidence)
Cerebral Palsy v1.360 DHPS Zornitza Stark Gene: dhps has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.359 CYFIP2 Zornitza Stark Marked gene: CYFIP2 as ready
Cerebral Palsy v1.359 CYFIP2 Zornitza Stark Gene: cyfip2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.359 CYFIP2 Zornitza Stark Classified gene: CYFIP2 as Red List (low evidence)
Cerebral Palsy v1.359 CYFIP2 Zornitza Stark Gene: cyfip2 has been classified as Red List (Low Evidence).
Mendeliome v1.1891 SPATA5 Zornitza Stark commented on gene: SPATA5: DEFINITIVE by ClinGen.
Prepair 500+ v1.1 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Prepair 1000+ v1.9 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Fetal anomalies v1.255 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Fetal anomalies v1.255 SPATA5 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is AFG2A
Fetal anomalies v1.255 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Fetal anomalies v1.255 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Intellectual disability syndromic and non-syndromic v0.6063 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Intellectual disability syndromic and non-syndromic v0.6063 SPATA5 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is AFG2A
Intellectual disability syndromic and non-syndromic v0.6063 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6063 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Deafness_IsolatedAndComplex v1.194 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Deafness_IsolatedAndComplex v1.194 SPATA5 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is AFG2A
Deafness_IsolatedAndComplex v1.194 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.194 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Prepair 1000+ v1.9 ADSL Kate Scarff reviewed gene: ADSL: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25112391, 1302001, 22180458, 18524658; Phenotypes: Adenylosuccinase deficiency MIM#103050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.358 ACADM Zornitza Stark Publications for gene: ACADM were set to 11263545; 35076175
Cerebral Palsy v1.357 ACADM Zornitza Stark Classified gene: ACADM as Green List (high evidence)
Cerebral Palsy v1.357 ACADM Zornitza Stark Gene: acadm has been classified as Green List (High Evidence).
Cerebral Palsy v1.356 ACADM Clare van Eyk reviewed gene: ACADM: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38843839; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.356 CYFIP2 Clare van Eyk gene: CYFIP2 was added
gene: CYFIP2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CYFIP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CYFIP2 were set to PMID: 38843839
Phenotypes for gene: CYFIP2 were set to Developmental and epileptic encephalopathy 65, MIM#618008
Review for gene: CYFIP2 was set to RED
Added comment: One individual with a complex neurodevelopmental disorder including cerebral palsy reported with a de novo missense variant in CYFIP2 (PMID: 38843839).
Sources: Literature
Cerebral Palsy v1.356 DHPS Clare van Eyk gene: DHPS was added
gene: DHPS was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DHPS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHPS were set to PMID: 30661771; 38843839
Phenotypes for gene: DHPS were set to Neurodevelopmental disorder with seizures and speech and walking impairment (NEDSSWI), MIM#618480
Review for gene: DHPS was set to AMBER
Added comment: NEDSSWI is an autosomal recessive disorder with onset in infancy. In the first case series of 5 patients from 4 families, pregnancy complications including pregnancy-induced hypertension, preeclampsia, oligohydramnios, low blood pressure and premature birth were reported (PMID: 30661771). Patients show global developmental delay and hypotonia, hypertonia, spasticity, or poor coordination. 2 individuals have been reported with a cerebral palsy diagnosis (PMID: 30661771;38843839).
Sources: Literature
Cerebral Palsy v1.356 GFAP Clare van Eyk gene: GFAP was added
gene: GFAP was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GFAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GFAP were set to PMID: 38843839
Phenotypes for gene: GFAP were set to Alexander disease, MIM#203450
Review for gene: GFAP was set to RED
Added comment: One individual with a complex neurodevelopmental disorder including cerebral palsy reported with a de novo missense variant in GFAP (PMID: 38843839). Alexander disease has variable onset and progression, with frequent spasticity and ataxia reported.
Sources: Literature
Cerebral Palsy v1.356 GCH1 Clare van Eyk gene: GCH1 was added
gene: GCH1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GCH1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: GCH1 were set to PMID: 21935284; 1899474; 33875303; 34908184
Phenotypes for gene: GCH1 were set to Dystonia, DOPA-responsive, MIM#128230; Hyperphenylalaninemia, BH4-deficient, B, MIM#233910
Review for gene: GCH1 was set to GREEN
Added comment: Mutations in the GTP cyclohydrolase I gene (GCH1) are associated with early onset dopa-responsive dystonia with or without hyperphenylalaninemia which is frequently clinically diagnosed as cerebral palsy (PMID: 21935284; 1899474; 33875303; 34908184).
Sources: Literature
Mitochondrial disease v0.927 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Mitochondrial disease v0.927 SPATA5 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is AFG2A
Mitochondrial disease v0.927 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Mitochondrial disease v0.927 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Genetic Epilepsy v1.33 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Genetic Epilepsy v1.33 SPATA5 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is AFG2A
Genetic Epilepsy v1.33 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.33 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Microcephaly v1.269 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Microcephaly v1.269 SPATA5 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is AFG2A
Microcephaly v1.269 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Microcephaly v1.269 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Cerebral Palsy v1.356 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Cerebral Palsy v1.356 SPATA5 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is AFG2A
Cerebral Palsy v1.356 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Cerebral Palsy v1.356 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Mendeliome v1.1891 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Mendeliome v1.1891 SPATA5 Zornitza Stark Added comment: Comment when marking as ready: New gene name is AFG2A
Mendeliome v1.1891 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Mendeliome v1.1891 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Prepair 1000+ v1.9 AGA Lana Giameos reviewed gene: AGA: Rating: GREEN; Mode of pathogenicity: None; Publications: 1703489, 1904874, 8064811, 8946839; Phenotypes: Aspartylglucosaminuria, MIM# 208400, MONDO:0008830; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 AGL Marta Cifuentes Ochoa commented on gene: AGL: Current Treatment high-fat, high-protein and low-carbohydrate diet with cornstarch supplementation
Bleeding and Platelet Disorders v1.43 PROC Jane Lin gene: PROC was added
gene: PROC was added to Bleeding and Platelet Disorders. Sources: Expert list
Mode of inheritance for gene: PROC was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PROC were set to PMID: 2437584; PMID: 7670104; PMID: 10942114; PMID: 28265398
Phenotypes for gene: PROC were set to THROMBOPHILIA DUE TO PROTEIN C DEFICIENCY, AUTOSOMAL DOMINANT # 176860; THROMBOPHILIA DUE TO PROTEIN C DEFICIENCY, AUTOSOMAL RECESSIVE, # 612304
Review for gene: PROC was set to GREEN
gene: PROC was marked as current diagnostic
Added comment: Has well established gene-disease association with thrombosis. Biallelic inheritance is rare and there is evidence it is more severe but data is complicated by findings that some patients also have changes in Factor V Leiden so have not selected the option where biallelic inheritance is more severe.
Sources: Expert list
Bleeding and Platelet Disorders v1.43 PIGA Jane Lin gene: PIGA was added
gene: PIGA was added to Bleeding and Platelet Disorders. Sources: Expert list
Mode of inheritance for gene: PIGA was set to Unknown
Publications for gene: PIGA were set to PMID: 9019395; PMID: 28516949
Phenotypes for gene: PIGA were set to PAROXYSMAL NOCTURNAL HEMOGLOBINURIA 1 OMIM# 300818
Review for gene: PIGA was set to RED
gene: PIGA was marked as current diagnostic
Added comment: PIGA variants linked to Paroxysmal nocturnal hemoglobinuria (PNH), clinical features which include thrombosis, but as somatic changes.
Sources: Expert list
Prepair 1000+ v1.9 ATRX Andrew Coventry reviewed gene: ATRX: Rating: GREEN; Mode of pathogenicity: None; Publications: 16813605, 16955409, 15350606, 23681356; Phenotypes: Alpha thalassemia X-linked intellectual disability syndrome MONDO:0010519; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.9 AARS2 Clare Hunt reviewed gene: AARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 8, 614096 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 IL7R Lauren Rogers reviewed gene: IL7R: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Severe combined immunodeficiency 104 MIM# 608971; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ASAH1 Lucy Spencer reviewed gene: ASAH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy with progressive myoclonic epilepsy, MIM#159950, Farber lipogranulomatosis, MIM#; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 IL2RG Lauren Rogers reviewed gene: IL2RG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Severe combined immunodeficiency, X-linked MIM# 300400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.9 IL1RN Lauren Rogers reviewed gene: IL1RN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Interleukin 1 receptor antagonist deficiency, MIM# 612852, Chronic recurrent multifocal osteomyelitis 2, with periostitis and pustulosis, MIM# 61285; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 CRB1 Lauren Rogers reviewed gene: CRB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11231775, 11389483, 16543197; Phenotypes: Leber congenital amaurosis 8 MIM#613835; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 AP4S1 Lucy Spencer reviewed gene: AP4S1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 52, autosomal recessive, MIM#614067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 HSD17B4 Lauren Rogers reviewed gene: HSD17B4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: D-bifunctional protein deficiency, AR (MIM#261515); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 HPSE2 Lauren Rogers reviewed gene: HPSE2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25145936, 23313374, 33558177; Phenotypes: Urofacial syndrome 1 MIM#236730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 AP4M1 Lucy Spencer reviewed gene: AP4M1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 50, autosomal recessive (MIM#612936); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ANTXR1 Lucy Spencer reviewed gene: ANTXR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: GAPO syndrome (MIM#230740); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 HPGD Lauren Rogers reviewed gene: HPGD: Rating: GREEN; Mode of pathogenicity: None; Publications: 20406614, 32282352, 31878983, 29282707; Phenotypes: Hypertrophic osteoarthropathy, primary, autosomal recessive 1 MIM#259100, Cranioosteoarthropathy MIM#259100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ALOXE3 Lucy Spencer reviewed gene: ALOXE3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, congenital, autosomal recessive 3 (MIM#606545); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ALDH3A2 Lucy Spencer reviewed gene: ALDH3A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Sjogren-Larsson syndrome (MIM#270200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ACADVL Lucy Spencer reviewed gene: ACADVL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: VLCAD deficiency (MIM#201475); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 GFM1 Lauren Rogers reviewed gene: GFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 1, MIM#609060; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 CD81 Lauren Rogers reviewed gene: CD81: Rating: AMBER; Mode of pathogenicity: None; Publications: 20237408, 35849269; Phenotypes: Immunodeficiency, common variable, 6, OMIM:613496; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1891 CRNKL1 Zornitza Stark Marked gene: CRNKL1 as ready
Mendeliome v1.1891 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Mendeliome v1.1891 CRNKL1 Zornitza Stark Classified gene: CRNKL1 as Green List (high evidence)
Mendeliome v1.1891 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.9 C1QA Lauren Rogers reviewed gene: C1QA: Rating: GREEN; Mode of pathogenicity: None; Publications: 21654842, 9225968, 9590289; Phenotypes: C1q deficiency, MIM# 613652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1890 DCC Zornitza Stark Publications for gene: DCC were set to 20431009; 31697046; 21242494; 28250454; 28250456; 25763452
Mendeliome v1.1889 DCC Zornitza Stark commented on gene: DCC: Third family reported with biallelic variants and scoliosis, PMID 33141514; novel homozygous frameshift variant (p.Asn800Lysfs*11) in three individuals.
Skeletal dysplasia v0.285 DCC Zornitza Stark Marked gene: DCC as ready
Skeletal dysplasia v0.285 DCC Zornitza Stark Gene: dcc has been classified as Green List (High Evidence).
Skeletal dysplasia v0.285 DCC Zornitza Stark Phenotypes for gene: DCC were changed from Gaze palsy, familial horizontal, with progressive scoliosis, 2, MIM# 617542 to Gaze palsy, familial horizontal, with progressive scoliosis, 2, MIM# 617542
Skeletal dysplasia v0.284 DCC Zornitza Stark Phenotypes for gene: DCC were changed from Gaze palsy, familial horizontal, with progressive scoliosis, 2 617542; Gaze palsy, familial horizontal, with progressive scoliosis, 2 617542 to Gaze palsy, familial horizontal, with progressive scoliosis, 2, MIM# 617542
Skeletal dysplasia v0.283 DCC Zornitza Stark Publications for gene: DCC were set to 28250456
Skeletal dysplasia v0.282 DCC Zornitza Stark Classified gene: DCC as Green List (high evidence)
Skeletal dysplasia v0.282 DCC Zornitza Stark Gene: dcc has been classified as Green List (High Evidence).
Mendeliome v1.1889 SLC7A5 Zornitza Stark Marked gene: SLC7A5 as ready
Mendeliome v1.1889 SLC7A5 Zornitza Stark Gene: slc7a5 has been classified as Red List (Low Evidence).
Mendeliome v1.1889 SLC7A5 Zornitza Stark Classified gene: SLC7A5 as Red List (low evidence)
Mendeliome v1.1889 SLC7A5 Zornitza Stark Gene: slc7a5 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.128 SLC6A20 Zornitza Stark Marked gene: SLC6A20 as ready
Aminoacidopathy v1.128 SLC6A20 Zornitza Stark Gene: slc6a20 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.128 SLC6A20 Zornitza Stark Classified gene: SLC6A20 as Red List (low evidence)
Aminoacidopathy v1.128 SLC6A20 Zornitza Stark Gene: slc6a20 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.127 SLC25A22 Zornitza Stark Marked gene: SLC25A22 as ready
Aminoacidopathy v1.127 SLC25A22 Zornitza Stark Gene: slc25a22 has been classified as Green List (High Evidence).
Aminoacidopathy v1.127 SLC25A22 Zornitza Stark Classified gene: SLC25A22 as Green List (high evidence)
Aminoacidopathy v1.127 SLC25A22 Zornitza Stark Gene: slc25a22 has been classified as Green List (High Evidence).
Aminoacidopathy v1.126 SLC25A13 Zornitza Stark Marked gene: SLC25A13 as ready
Aminoacidopathy v1.126 SLC25A13 Zornitza Stark Gene: slc25a13 has been classified as Green List (High Evidence).
Aminoacidopathy v1.126 SLC25A13 Zornitza Stark Classified gene: SLC25A13 as Green List (high evidence)
Aminoacidopathy v1.126 SLC25A13 Zornitza Stark Gene: slc25a13 has been classified as Green List (High Evidence).
Aminoacidopathy v1.125 SLC7A5 Zornitza Stark Marked gene: SLC7A5 as ready
Aminoacidopathy v1.125 SLC7A5 Zornitza Stark Gene: slc7a5 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.125 SLC7A5 Zornitza Stark Classified gene: SLC7A5 as Red List (low evidence)
Aminoacidopathy v1.125 SLC7A5 Zornitza Stark Gene: slc7a5 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.124 XPNPEP3 Zornitza Stark Marked gene: XPNPEP3 as ready
Aminoacidopathy v1.124 XPNPEP3 Zornitza Stark Gene: xpnpep3 has been classified as Green List (High Evidence).
Aminoacidopathy v1.124 XPNPEP3 Zornitza Stark Classified gene: XPNPEP3 as Green List (high evidence)
Aminoacidopathy v1.124 XPNPEP3 Zornitza Stark Gene: xpnpep3 has been classified as Green List (High Evidence).
Aminoacidopathy v1.123 SLC1A4 Zornitza Stark Marked gene: SLC1A4 as ready
Aminoacidopathy v1.123 SLC1A4 Zornitza Stark Gene: slc1a4 has been classified as Green List (High Evidence).
Aminoacidopathy v1.123 SLC1A4 Zornitza Stark Classified gene: SLC1A4 as Green List (high evidence)
Aminoacidopathy v1.123 SLC1A4 Zornitza Stark Gene: slc1a4 has been classified as Green List (High Evidence).
Aminoacidopathy v1.122 PYCR2 Zornitza Stark Marked gene: PYCR2 as ready
Aminoacidopathy v1.122 PYCR2 Zornitza Stark Gene: pycr2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.122 PYCR2 Zornitza Stark Classified gene: PYCR2 as Green List (high evidence)
Aminoacidopathy v1.122 PYCR2 Zornitza Stark Gene: pycr2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.121 PEPD Zornitza Stark Marked gene: PEPD as ready
Aminoacidopathy v1.121 PEPD Zornitza Stark Gene: pepd has been classified as Green List (High Evidence).
Aminoacidopathy v1.121 PEPD Zornitza Stark Classified gene: PEPD as Green List (high evidence)
Aminoacidopathy v1.121 PEPD Zornitza Stark Gene: pepd has been classified as Green List (High Evidence).
Aminoacidopathy v1.120 OPLAH Zornitza Stark Marked gene: OPLAH as ready
Aminoacidopathy v1.120 OPLAH Zornitza Stark Gene: oplah has been classified as Red List (Low Evidence).
Aminoacidopathy v1.120 OPLAH Zornitza Stark Classified gene: OPLAH as Red List (low evidence)
Aminoacidopathy v1.120 OPLAH Zornitza Stark Gene: oplah has been classified as Red List (Low Evidence).
Aminoacidopathy v1.119 NFE2L2 Zornitza Stark Marked gene: NFE2L2 as ready
Aminoacidopathy v1.119 NFE2L2 Zornitza Stark Gene: nfe2l2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.119 NFE2L2 Zornitza Stark Classified gene: NFE2L2 as Green List (high evidence)
Aminoacidopathy v1.119 NFE2L2 Zornitza Stark Gene: nfe2l2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.118 GSR Zornitza Stark Marked gene: GSR as ready
Aminoacidopathy v1.118 GSR Zornitza Stark Gene: gsr has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.118 GSR Zornitza Stark Classified gene: GSR as Amber List (moderate evidence)
Aminoacidopathy v1.118 GSR Zornitza Stark Gene: gsr has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.117 GRHPR Zornitza Stark Marked gene: GRHPR as ready
Aminoacidopathy v1.117 GRHPR Zornitza Stark Gene: grhpr has been classified as Green List (High Evidence).
Aminoacidopathy v1.117 GRHPR Zornitza Stark Classified gene: GRHPR as Green List (high evidence)
Aminoacidopathy v1.117 GRHPR Zornitza Stark Gene: grhpr has been classified as Green List (High Evidence).
Aminoacidopathy v1.116 GPX4 Zornitza Stark Marked gene: GPX4 as ready
Aminoacidopathy v1.116 GPX4 Zornitza Stark Gene: gpx4 has been classified as Green List (High Evidence).
Aminoacidopathy v1.116 GPX4 Zornitza Stark Classified gene: GPX4 as Green List (high evidence)
Aminoacidopathy v1.116 GPX4 Zornitza Stark Gene: gpx4 has been classified as Green List (High Evidence).
Aminoacidopathy v1.115 GCLC Zornitza Stark Marked gene: GCLC as ready
Aminoacidopathy v1.115 GCLC Zornitza Stark Gene: gclc has been classified as Green List (High Evidence).
Aminoacidopathy v1.115 GCLC Zornitza Stark Classified gene: GCLC as Green List (high evidence)
Aminoacidopathy v1.115 GCLC Zornitza Stark Gene: gclc has been classified as Green List (High Evidence).
Aminoacidopathy v1.114 GRM6 Zornitza Stark Marked gene: GRM6 as ready
Aminoacidopathy v1.114 GRM6 Zornitza Stark Gene: grm6 has been classified as Green List (High Evidence).
Aminoacidopathy v1.114 GRM6 Zornitza Stark Classified gene: GRM6 as Green List (high evidence)
Aminoacidopathy v1.114 GRM6 Zornitza Stark Gene: grm6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.9 ABHD5 Lauren Thomas reviewed gene: ABHD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 30795549; Phenotypes: Chanarin-Dorfman syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.113 GRM6 Sangavi Sivagnanasundram gene: GRM6 was added
gene: GRM6 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: GRM6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM6 were set to 22008250
Phenotypes for gene: GRM6 were set to GRM6-related retinopathy MONDO:0800397
Review for gene: GRM6 was set to GREEN
Added comment: GRM6-related retinopathy is a glutamate neurotransmitter disorders affecting the ON-centre of the retinal ganglion cells.

>5 unrelated families with a night blindness phenotype due to a defective signal transmission at the ON-centre.
Sources: Other
Aminoacidopathy v1.113 SLC25A22 Sangavi Sivagnanasundram gene: SLC25A22 was added
gene: SLC25A22 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: SLC25A22 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A22 were set to 15592994; 19780765; 24596948
Phenotypes for gene: SLC25A22 were set to Developmental and epileptic encephalopathy MONDO:0100062
Review for gene: SLC25A22 was set to GREEN
Added comment: Established gene-disease association with reported individuals having impaired mitochondrial glutamate transport.
Three unrelated families reported with three different rare missense variants.
Sources: Other
Aminoacidopathy v1.113 XPNPEP3 Sangavi Sivagnanasundram gene: XPNPEP3 was added
gene: XPNPEP3 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: XPNPEP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPNPEP3 were set to 32660933; 20179356
Phenotypes for gene: XPNPEP3 were set to Nephronophthisis-like nephropathy 1 MONDO:0013163
Review for gene: XPNPEP3 was set to GREEN
Added comment: XPNPEP3 is member of the X-pro-aminopeptidases family.

A total of 3 unrelated families (with different variants) reported with abnormal renal function due to an inborn error of peptide metabolism

32660933 - individual case with a rare frameshift variant p.Q241Tfs*13 who also had evidence of an inborn error of peptide metabolism.
Sources: Other
Aminoacidopathy v1.113 PEPD Sangavi Sivagnanasundram gene: PEPD was added
gene: PEPD was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: PEPD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEPD were set to 2365824; 19308961; 16470701
Phenotypes for gene: PEPD were set to Prolidase deficiency MONDO:0008221
Review for gene: PEPD was set to GREEN
Added comment: Well established gene-disease association with >10 individuals reported with variants in PEPD and a clinical phenotype associated with prolidase deficiency.
Prolidase deficiency is a classified inborn error of amino acid metabolism.
LoF appears to be the mechanism of disease (https://search.clinicalgenome.org/CCID:007640)
Sources: Other
Aminoacidopathy v1.113 PYCR2 Sangavi Sivagnanasundram edited their review of gene: PYCR2: Changed rating: GREEN
Aminoacidopathy v1.113 PYCR2 Sangavi Sivagnanasundram changed review comment from: Has been reported in 10 consanguineous families with different variants (frameshift, missense, splice). The affected individuals all had neurological clinical presentation however upon biochemical assessment, plasma proline levels were normal (showed no depletion). There is not enough evidence to indicate that these individuals have a phenotype consistent with an inborn error of amino acid metabolism.
Sources: Other; to: Has been reported in 10 consanguineous families with different variants (frameshift, missense, splice). The affected individuals all had neurological clinical presentation along with other phenotypes including failure to thrive.

Sources: Other
Aminoacidopathy v1.113 PYCR2 Sangavi Sivagnanasundram gene: PYCR2 was added
gene: PYCR2 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: PYCR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYCR2 were set to 25865492; 27130255
Phenotypes for gene: PYCR2 were set to Hypomyelinating leukodystrophy 10 MONDO:0014632; Disorders of ornithine, proline and hydroxyproline metabolism
Review for gene: PYCR2 was set to RED
Added comment: Has been reported in 10 consanguineous families with different variants (frameshift, missense, splice). The affected individuals all had neurological clinical presentation however upon biochemical assessment, plasma proline levels were normal (showed no depletion). There is not enough evidence to indicate that these individuals have a phenotype consistent with an inborn error of amino acid metabolism.
Sources: Other
Mendeliome v1.1888 SLC7A5 Sangavi Sivagnanasundram gene: SLC7A5 was added
gene: SLC7A5 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: SLC7A5 was set to Unknown
Publications for gene: SLC7A5 were set to 29884839
Phenotypes for gene: SLC7A5 were set to Large neutral amino acid transporter deficiency (MIM#600182)
Review for gene: SLC7A5 was set to RED
Added comment: Classified an inborn error of amino acid metabolism by IEMbase however more evidence is required to support the gene-disease association.
Sources: Other
Aminoacidopathy v1.113 SLC7A5 Sangavi Sivagnanasundram gene: SLC7A5 was added
gene: SLC7A5 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: SLC7A5 was set to Unknown
Publications for gene: SLC7A5 were set to 29884839
Phenotypes for gene: SLC7A5 were set to Large neutral amino acid transporter deficiency (MIM#600182)
Review for gene: SLC7A5 was set to RED
Added comment: Classified an inborn error of amino acid metabolism by IEMbase however more evidence is required to support the gene-disease association.
Sources: Other
Aminoacidopathy v1.113 SLC6A20 Sangavi Sivagnanasundram gene: SLC6A20 was added
gene: SLC6A20 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: SLC6A20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC6A20 were set to 36820062; 19033659; 24816252
Phenotypes for gene: SLC6A20 were set to Hyperglycinuria MONDO:0007677
Review for gene: SLC6A20 was set to RED
Added comment: Only one family reported with a rare missense variant and a clinical phenotype consistent with an inborn error of amino acid metabolism.

Cases have been reported in 19033659 and 24816252 however the variant is too common for a mendelian disease.

No other new publications have been released supporting the gene-disease association with relation to evidence of a biochemical abnormality.
Sources: Other
Skeletal dysplasia v0.281 DCC Achchuthan Shanmugasundram reviewed gene: DCC: Rating: GREEN; Mode of pathogenicity: None; Publications: 33141514; Phenotypes: Gaze palsy, familial horizontal, with progressive scoliosis, 2, OMIM:617542; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Speech apraxia v1.0 KDM5C Thomas Scerri changed review comment from: First reported CAS case with a de novo HNRNPK frameshift variant (Kaspi et al., 2022; PMID: 36117209).

Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of speech/verbal apraxia or dyspraxia though.

Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes.
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo KDM5C frameshift variant (Kaspi et al., 2022; PMID: 36117209).

Leonardi et al. (2023; PMID: 36434256) report 30 individuals with KDM5C variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of speech/verbal apraxia or dyspraxia though.

Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes.
Sources: Expert list, Expert Review
Aminoacidopathy v1.113 NFE2L2 Sangavi Sivagnanasundram gene: NFE2L2 was added
gene: NFE2L2 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: NFE2L2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFE2L2 were set to 29018201
Phenotypes for gene: NFE2L2 were set to Immunodeficiency, developmental delay, and hypohomocysteinemia MONDO:0060591; Disorders of glutathione metabolism
Review for gene: NFE2L2 was set to GREEN
Added comment: 4 unrelated patients with de novo missense variants affected with a multisystem disorder with failure to thrive, immunodeficiency and neurological symptoms including an inborn error of amino acid metabolism.
Sources: Other
Aminoacidopathy v1.113 GPX4 Sangavi Sivagnanasundram gene: GPX4 was added
gene: GPX4 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: GPX4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPX4 were set to 24706940; 32827718
Phenotypes for gene: GPX4 were set to Spondylometaphyseal dysplasia, Sedaghatian type MONDO:0009593; Disorders of glutathione metabolism
Review for gene: GPX4 was set to GREEN
Added comment: SSMD is an inborn error of gluthathione metabolism. Reports of four children (two were siblings from a consanguineous family) with SSMD. Parents were unaffected carriers.
LoF is the mechanism of disease.
Sources: Other
Aminoacidopathy v1.113 GSR Sangavi Sivagnanasundram gene: GSR was added
gene: GSR was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: GSR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GSR were set to 17185460; 31122244
Phenotypes for gene: GSR were set to Hemolytic anemia due to glutathione reductase deficiency MONDO:0019531; Disorders of glutathione metabolism
Review for gene: GSR was set to AMBER
Added comment: Not an established gene-disease association however there have been reports of two families reported with GR deficiency and there has been a report of functional evidence as well. More concrete evidence of biochemical abnormalities is required to promote the gene to green.
Sources: Other
Aminoacidopathy v1.113 OPLAH Sangavi Sivagnanasundram gene: OPLAH was added
gene: OPLAH was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: OPLAH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OPLAH were set to 27477828; 27604308
Phenotypes for gene: OPLAH were set to 5-oxoprolinase deficiency MONDO:0009825; Disorders of glutathione metabolism
Review for gene: OPLAH was set to RED
Added comment: Variants have been reported in individuals however it appears that this inborn error of glutathione metabolism appears to be of benign nature.
Sources: Other
Mendeliome v1.1888 CRNKL1 Mark Cleghorn gene: CRNKL1 was added
gene: CRNKL1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: CRNKL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CRNKL1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CRNKL1 was set to GREEN
Added comment: Unpublished, presented at ESHG June 2024 - Louise Bicknell, University of Otago NZ
8 unrelated families via gene matcher with rare, de novo, missense variants in CRNKL1
severe microcephaly (all, -8 to -11 SD)
ID/epilepsy
pontocerebellar hypoplasia (6/8)
simplified gyration (8/8)
7 variants are missense at p.Arg267 residue
1 variant missense at p.Arg301
RNA-seq on patient fibroblasts - no alteration in gene expression
Zebrafish homolog of Arg267 and Arg301 - mimics observed phenotype (reduced brain development), increased in embryo apoptosis
RNA seq on affected zebrafish embryos - transcriptome strongly disrupted
Splicing analysis in progress

CRKNL1 supports U6 structure in spliceosome
Sources: Other
Aminoacidopathy v1.113 GCLC Sangavi Sivagnanasundram gene: GCLC was added
gene: GCLC was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: GCLC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GCLC were set to 28571779; 10515893; 18024385
Phenotypes for gene: GCLC were set to Gamma-glutamylcysteine synthetase deficiency MONDO:0009259; Disorders of glutathione metabolism
Review for gene: GCLC was set to GREEN
Added comment: Established gene-disease association with >3 unrelated probands reported with GCLC deficiency which is an inborn error of amino acid metabolism.
Sources: Other
Aminoacidopathy v1.113 SLC25A15 Zornitza Stark Marked gene: SLC25A15 as ready
Aminoacidopathy v1.113 SLC25A15 Zornitza Stark Gene: slc25a15 has been classified as Green List (High Evidence).
Aminoacidopathy v1.113 SLC25A15 Zornitza Stark Classified gene: SLC25A15 as Green List (high evidence)
Aminoacidopathy v1.113 SLC25A15 Zornitza Stark Gene: slc25a15 has been classified as Green List (High Evidence).
Aminoacidopathy v1.112 SLC36A2 Zornitza Stark Marked gene: SLC36A2 as ready
Aminoacidopathy v1.112 SLC36A2 Zornitza Stark Gene: slc36a2 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.112 SLC36A2 Zornitza Stark Classified gene: SLC36A2 as Red List (low evidence)
Aminoacidopathy v1.112 SLC36A2 Zornitza Stark Gene: slc36a2 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.111 SLC38A8 Zornitza Stark Marked gene: SLC38A8 as ready
Aminoacidopathy v1.111 SLC38A8 Zornitza Stark Gene: slc38a8 has been classified as Green List (High Evidence).
Aminoacidopathy v1.111 SLC38A8 Zornitza Stark Classified gene: SLC38A8 as Green List (high evidence)
Aminoacidopathy v1.111 SLC38A8 Zornitza Stark Gene: slc38a8 has been classified as Green List (High Evidence).
Aminoacidopathy v1.110 SLC3A1 Zornitza Stark Marked gene: SLC3A1 as ready
Aminoacidopathy v1.110 SLC3A1 Zornitza Stark Gene: slc3a1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.110 SLC3A1 Zornitza Stark Classified gene: SLC3A1 as Green List (high evidence)
Aminoacidopathy v1.110 SLC3A1 Zornitza Stark Gene: slc3a1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.109 SLC6A19 Zornitza Stark Marked gene: SLC6A19 as ready
Aminoacidopathy v1.109 SLC6A19 Zornitza Stark Gene: slc6a19 has been classified as Green List (High Evidence).
Aminoacidopathy v1.109 SLC6A19 Zornitza Stark Classified gene: SLC6A19 as Green List (high evidence)
Aminoacidopathy v1.109 SLC6A19 Zornitza Stark Gene: slc6a19 has been classified as Green List (High Evidence).
Aminoacidopathy v1.108 SLC6A6 Zornitza Stark Marked gene: SLC6A6 as ready
Aminoacidopathy v1.108 SLC6A6 Zornitza Stark Gene: slc6a6 has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.108 SLC6A6 Zornitza Stark Classified gene: SLC6A6 as Amber List (moderate evidence)
Aminoacidopathy v1.108 SLC6A6 Zornitza Stark Gene: slc6a6 has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.107 SLC6A8 Zornitza Stark Marked gene: SLC6A8 as ready
Aminoacidopathy v1.107 SLC6A8 Zornitza Stark Gene: slc6a8 has been classified as Green List (High Evidence).
Aminoacidopathy v1.107 SLC6A8 Zornitza Stark Classified gene: SLC6A8 as Green List (high evidence)
Aminoacidopathy v1.107 SLC6A8 Zornitza Stark Gene: slc6a8 has been classified as Green List (High Evidence).
Aminoacidopathy v1.106 SLC7A7 Zornitza Stark Marked gene: SLC7A7 as ready
Aminoacidopathy v1.106 SLC7A7 Zornitza Stark Gene: slc7a7 has been classified as Green List (High Evidence).
Aminoacidopathy v1.106 SLC7A7 Zornitza Stark Classified gene: SLC7A7 as Green List (high evidence)
Aminoacidopathy v1.106 SLC7A7 Zornitza Stark Gene: slc7a7 has been classified as Green List (High Evidence).
Aminoacidopathy v1.105 SLC7A9 Zornitza Stark Marked gene: SLC7A9 as ready
Aminoacidopathy v1.105 SLC7A9 Zornitza Stark Gene: slc7a9 has been classified as Green List (High Evidence).
Aminoacidopathy v1.105 SLC7A9 Zornitza Stark Classified gene: SLC7A9 as Green List (high evidence)
Aminoacidopathy v1.105 SLC7A9 Zornitza Stark Gene: slc7a9 has been classified as Green List (High Evidence).
Aminoacidopathy v1.104 SPR Zornitza Stark Marked gene: SPR as ready
Aminoacidopathy v1.104 SPR Zornitza Stark Gene: spr has been classified as Green List (High Evidence).
Aminoacidopathy v1.104 SPR Zornitza Stark Classified gene: SPR as Green List (high evidence)
Aminoacidopathy v1.104 SPR Zornitza Stark Gene: spr has been classified as Green List (High Evidence).
Aminoacidopathy v1.103 SUGCT Zornitza Stark Marked gene: SUGCT as ready
Aminoacidopathy v1.103 SUGCT Zornitza Stark Gene: sugct has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.103 SUGCT Zornitza Stark Classified gene: SUGCT as Amber List (moderate evidence)
Aminoacidopathy v1.103 SUGCT Zornitza Stark Gene: sugct has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.102 SUOX Zornitza Stark Marked gene: SUOX as ready
Aminoacidopathy v1.102 SUOX Zornitza Stark Gene: suox has been classified as Green List (High Evidence).
Aminoacidopathy v1.102 SUOX Zornitza Stark Classified gene: SUOX as Green List (high evidence)
Aminoacidopathy v1.102 SUOX Zornitza Stark Gene: suox has been classified as Green List (High Evidence).
Aminoacidopathy v1.101 TAT Zornitza Stark Marked gene: TAT as ready
Aminoacidopathy v1.101 TAT Zornitza Stark Gene: tat has been classified as Green List (High Evidence).
Aminoacidopathy v1.101 TAT Zornitza Stark Classified gene: TAT as Green List (high evidence)
Aminoacidopathy v1.101 TAT Zornitza Stark Gene: tat has been classified as Green List (High Evidence).
Aminoacidopathy v1.100 TDO2 Zornitza Stark Marked gene: TDO2 as ready
Aminoacidopathy v1.100 TDO2 Zornitza Stark Gene: tdo2 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.100 TDO2 Zornitza Stark Classified gene: TDO2 as Red List (low evidence)
Aminoacidopathy v1.100 TDO2 Zornitza Stark Gene: tdo2 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.99 TH Zornitza Stark Marked gene: TH as ready
Aminoacidopathy v1.99 TH Zornitza Stark Gene: th has been classified as Green List (High Evidence).
Aminoacidopathy v1.99 TH Zornitza Stark Classified gene: TH as Green List (high evidence)
Aminoacidopathy v1.99 TH Zornitza Stark Gene: th has been classified as Green List (High Evidence).
Aminoacidopathy v1.98 TYR Zornitza Stark Marked gene: TYR as ready
Aminoacidopathy v1.98 TYR Zornitza Stark Gene: tyr has been classified as Green List (High Evidence).
Aminoacidopathy v1.98 TYR Zornitza Stark Classified gene: TYR as Green List (high evidence)
Aminoacidopathy v1.98 TYR Zornitza Stark Gene: tyr has been classified as Green List (High Evidence).
Aminoacidopathy v1.97 GRHPR Sangavi Sivagnanasundram gene: GRHPR was added
gene: GRHPR was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: GRHPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRHPR were set to 24116921
Phenotypes for gene: GRHPR were set to primary hyperoxaluria type 2 MONDO:0009824; Disorders of glyoxylate and oxalate metabolism
Review for gene: GRHPR was set to GREEN
Added comment: Well established gene - disease association with reported individuals having abnormal biochemical function.
Sources: Other
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.328 ZNF483 Zornitza Stark Marked gene: ZNF483 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.328 ZNF483 Zornitza Stark Gene: znf483 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.328 ZNF483 Zornitza Stark Mode of inheritance for gene: ZNF483 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.327 ZNF483 Zornitza Stark Classified gene: ZNF483 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.327 ZNF483 Zornitza Stark Gene: znf483 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1888 ZNF483 Zornitza Stark Marked gene: ZNF483 as ready
Mendeliome v1.1888 ZNF483 Zornitza Stark Gene: znf483 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1888 ZNF483 Zornitza Stark Mode of inheritance for gene: ZNF483 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1887 ZNF483 Zornitza Stark Classified gene: ZNF483 as Amber List (moderate evidence)
Mendeliome v1.1887 ZNF483 Zornitza Stark Gene: znf483 has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.97 UROC1 Zornitza Stark Marked gene: UROC1 as ready
Aminoacidopathy v1.97 UROC1 Zornitza Stark Gene: uroc1 has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.97 UROC1 Zornitza Stark Classified gene: UROC1 as Amber List (moderate evidence)
Aminoacidopathy v1.97 UROC1 Zornitza Stark Gene: uroc1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6063 CRNKL1 Zornitza Stark Marked gene: CRNKL1 as ready
Intellectual disability syndromic and non-syndromic v0.6063 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6063 CRNKL1 Zornitza Stark Classified gene: CRNKL1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6063 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Microcephaly v1.269 CRNKL1 Zornitza Stark Marked gene: CRNKL1 as ready
Microcephaly v1.269 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Microcephaly v1.269 CRNKL1 Zornitza Stark Classified gene: CRNKL1 as Green List (high evidence)
Microcephaly v1.269 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.65 CRNKL1 Zornitza Stark Marked gene: CRNKL1 as ready
Cerebellar and Pontocerebellar Hypoplasia v1.65 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.65 CRNKL1 Zornitza Stark Classified gene: CRNKL1 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.65 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.96 HOGA1 Zornitza Stark Marked gene: HOGA1 as ready
Aminoacidopathy v1.96 HOGA1 Zornitza Stark Gene: hoga1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.96 HOGA1 Zornitza Stark Classified gene: HOGA1 as Green List (high evidence)
Aminoacidopathy v1.96 HOGA1 Zornitza Stark Gene: hoga1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.95 HOGA1 Sangavi Sivagnanasundram gene: HOGA1 was added
gene: HOGA1 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: HOGA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HOGA1 were set to 26401545; 21896830; 20797690
Phenotypes for gene: HOGA1 were set to primary hyperoxaluria type 3 MONDO:0013327; Disorders of ornithine, proline and hydroxyproline metabolism
Review for gene: HOGA1 was set to GREEN
Added comment: Established gene-disease association with >4 unrelated individuals having evidence of abnormal biochemical function.
Sources: Other
Cerebellar and Pontocerebellar Hypoplasia v1.64 CRNKL1 Mark Cleghorn gene: CRNKL1 was added
gene: CRNKL1 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Other
Mode of inheritance for gene: CRNKL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CRNKL1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CRNKL1 was set to GREEN
Added comment: Unpublished, presented at ESHG June 2024 - Louise Bicknell, University of Otago NZ
8 unrelated families via gene matcher with rare, de novo, missense variants in CRNKL1
severe microcephaly (all, -8 to -11 SD)
ID/epilepsy
pontocerebellar hypoplasia (6/8)
simplified gyration (8/8)
7 variants are missense at p.Arg267 residue
1 variant missense at p.Arg301
RNA-seq on patient fibroblasts - no alteration in gene expression
Zebrafish homolog of Arg267 and Arg301 - mimics observed phenotype (reduced brain development), increased in embryo apoptosis
RNQ seq on affected zebrafish embryos - transcriptome strongly disrupted
Splicing analysis in progress

CRKNL1 supports U6 structure in spliceosome
Sources: Other
Microcephaly v1.268 CRNKL1 Mark Cleghorn gene: CRNKL1 was added
gene: CRNKL1 was added to Microcephaly. Sources: Other
Mode of inheritance for gene: CRNKL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CRNKL1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CRNKL1 was set to GREEN
Added comment: Unpublished, presented at ESHG June 2024 - Louise Bicknell, University of Otago NZ
8 unrelated families via gene matcher with rare, de novo, missense variants in CRNKL1
severe microcephaly (all, -8 to -11 SD)
ID/epilepsy
pontocerebellar hypoplasia (6/8)
simplified gyration (8/8)
7 variants are missense at p.Arg267 residue
1 variant missense at p.Arg301
RNA-seq on patient fibroblasts - no alteration in gene expression
Zebrafish homolog of Arg267 and Arg301 - mimics observed phenotype (reduced brain development), increased in embryo apoptosis
RNQ seq on affected zebrafish embryos - transcriptome strongly disrupted
Splicing analysis in progress

CRKNL1 supports U6 structure in spliceosome
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6062 CRNKL1 Mark Cleghorn gene: CRNKL1 was added
gene: CRNKL1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: CRNKL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CRNKL1 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: CRNKL1 were set to Complete
Review for gene: CRNKL1 was set to GREEN
Added comment: Unpublished, presented at ESHG June 2024 - Louise Bicknell, University of Otago NZ
8 unrelated families via gene matcher with rare, de novo, missense variants in CRNKL1
severe microcephaly (all, -8 to -11 SD)
ID/epilepsy
pontocerebellar hypoplasia (6/8)
simplified gyration (8/8)
7 variants are missense at p.Arg267 residue
1 variant missense at p.Arg301
RNA-seq on patient fibroblasts - no alteration in gene expression
Zebrafish homolog of Arg267 and Arg301 - mimics observed phenotype (reduced brain development), increased in embryo apoptosis
RNQ seq on affected zebrafish embryos - transcriptome strongly disrupted
Splicing analysis in progress

CRKNL1 supports U6 structure in spliceosome
Sources: Other
Aminoacidopathy v1.95 UROC1 Sangavi Sivagnanasundram gene: UROC1 was added
gene: UROC1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: UROC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UROC1 were set to 19304569; 30619714; 32439973; 27391121
Phenotypes for gene: UROC1 were set to urocanic aciduria MONDO:0010167
Review for gene: UROC1 was set to AMBER
Added comment: The relationship between the phenotypes and evidence of biochemical abnormality remains unclear for this gene-disease association.

Variants have been reported in 4 unrelated individuals however one individual was reported to be phenotypically asymptomatic except for evidence of urocanase deficiency in a biochemical assay (PMID: 30619714).

Classified Moderate by Aminoacidopathy GCEP on 26/04/2024 - https://search.clinicalgenome.org/CCID:006504
Sources: ClinGen
Mendeliome v1.1886 ZNF483 Mark Cleghorn gene: ZNF483 was added
gene: ZNF483 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNF483 was set to Unknown
Publications for gene: ZNF483 were set to 38951643
Phenotypes for gene: ZNF483 were set to primary ovarian failure MONDO:0005387
Review for gene: ZNF483 was set to AMBER
Added comment: PMID: 38951643, ESHG 2024 presentation
Large cohort assessing PRS for age of menarche
Noted rare PTVs in ZNF483 assoc w earlier menarche
No individual case information in this study
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.326 ZNF483 Mark Cleghorn gene: ZNF483 was added
gene: ZNF483 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature
Mode of inheritance for gene: ZNF483 was set to Unknown
Publications for gene: ZNF483 were set to 38951643
Phenotypes for gene: ZNF483 were set to primary ovarian failure MONDO:0005387
Penetrance for gene: ZNF483 were set to unknown
Review for gene: ZNF483 was set to AMBER
Added comment: PMID: 38951643, ESHG 2024 presentation
Large cohort assessing PRS for age of menarche
Noted rare PTVs in ZNF483 assoc w earlier menarche
No individual case information in this study
Sources: Literature
Aminoacidopathy v1.95 TYR Sangavi Sivagnanasundram gene: TYR was added
gene: TYR was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: TYR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TYR were set to 2511845; 32411182; 31199599; 29052256
Phenotypes for gene: TYR were set to oculocutaneous albinism type 1 MONDO:0018135
Review for gene: TYR was set to GREEN
Added comment: TYR encodes tyrosinase which vital in melanin synthesis. Reported individuals have an error in tyrosinase metabolism thus affecting melanin synthesis. >5 probands have been reported with errors in tyrosinase metabolism.

Classified Definitive by Aminoacidopathy GCEP on 28/08/2020 - https://search.clinicalgenome.org/CCID:006490
Sources: ClinGen
Aminoacidopathy v1.95 TH Sangavi Sivagnanasundram gene: TH was added
gene: TH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: TH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TH were set to 30383639; 29225908; 22264700; 12891655
Phenotypes for gene: TH were set to tyrosine hydroxylase deficiency MONDO:0100064
Review for gene: TH was set to GREEN
Added comment: >10 unrelated probands reported with an inborn error in tyrosine metabolism.

Classified Definitive by Aminoacidopathy GCEP on 22/03/2019 - https://search.clinicalgenome.org/CCID:006363
Sources: ClinGen
Aminoacidopathy v1.95 TDO2 Sangavi Sivagnanasundram gene: TDO2 was added
gene: TDO2 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: TDO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TDO2 were set to 28285122
Phenotypes for gene: TDO2 were set to familial hypertryptophanemia MONDO:0010907
Review for gene: TDO2 was set to RED
Added comment: Reported in one individual to date however there is evidence that this is a benign biochemical variant with no clinical significance.

Classified Limitied by Aminoacidopathy GCEP on 17/11/2023 - https://search.clinicalgenome.org/CCID:006345
Sources: ClinGen
Aminoacidopathy v1.95 TAT Sangavi Sivagnanasundram gene: TAT was added
gene: TAT was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: TAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAT were set to 9544843; 16917729
Phenotypes for gene: TAT were set to tyrosinemia type II MONDO:0010160
Review for gene: TAT was set to GREEN
Added comment: Well reported gene-disease association with affected individuals having reports of a deficiency in hepatic tyrosine aminotransferase (TAT).

Classified Definitive by Aminoacidopathy GCEP on 29/06/2020 - https://search.clinicalgenome.org/CCID:006320
Sources: ClinGen
Aminoacidopathy v1.95 SUOX Sangavi Sivagnanasundram gene: SUOX was added
gene: SUOX was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SUOX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUOX were set to 28980090
Phenotypes for gene: SUOX were set to isolated sulfite oxidase deficiency MONDO:0010089
Review for gene: SUOX was set to GREEN
Added comment: Well established gene-disease association (reported in >40 patients).

Classified Definitive by Aminoacidopathy GCEP on 22/03/2019 - https://search.clinicalgenome.org/CCID:006301
Sources: ClinGen
Aminoacidopathy v1.95 SUGCT Sangavi Sivagnanasundram gene: SUGCT was added
gene: SUGCT was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SUGCT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUGCT were set to 18926513; 28766179; 29421601
Phenotypes for gene: SUGCT were set to glutaric acidemia type 3 MONDO:0009283
Review for gene: SUGCT was set to AMBER
Added comment: There is uncertain clinical relevance for this gene-disease association - reports of different clinical phenotypes between affected individuals and potentially a benign condition. Variants have been reported in >3 unrelated affected probands however their clinical presentations vary.

Classified Moderate by Aminoacidopathy GCEP on 12/12/2022- https://search.clinicalgenome.org/CCID:006299
Sources: ClinGen
Aminoacidopathy v1.95 SPR Sangavi Sivagnanasundram gene: SPR was added
gene: SPR was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPR were set to 33903016
Phenotypes for gene: SPR were set to dopa-responsive dystonia due to sepiapterin reductase deficiency MONDO:0012994
Review for gene: SPR was set to GREEN
Added comment: Well-established gene-disease association with reported individuals having an inborn error of amino acid metabolism.

Classified Definitive by Aminoacidopathy GCEP on 04/06/2021- https://search.clinicalgenome.org/CCID:006266
Sources: ClinGen
Aminoacidopathy v1.95 SLC7A9 Sangavi Sivagnanasundram gene: SLC7A9 was added
gene: SLC7A9 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC7A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC7A9 were set to 23532419; 16609684; 25296721; 11157794; 10471498
Phenotypes for gene: SLC7A9 were set to cystinuria MONDO:0009067
Review for gene: SLC7A9 was set to GREEN
Added comment: Established gene-disease association with reported individuals having errors in amino acid transport and metabolism.

Classified Definitive by Aminoacidopathy GCEP on 29/06/2020 - https://search.clinicalgenome.org/CCID:006202
Sources: ClinGen
Aminoacidopathy v1.95 SLC7A7 Sangavi Sivagnanasundram gene: SLC7A7 was added
gene: SLC7A7 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC7A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC7A7 were set to 10080182; 10080183; 15776247
Phenotypes for gene: SLC7A7 were set to lysinuric protein intolerance MONDO:0009109
Review for gene: SLC7A7 was set to GREEN
Added comment: Reported in at least 8 probands all having an error in amino acid transport. LoF is the mechanism of disease.

Classified Definitive by Aminoacidopathy GCEP on 08/11/2019 - https://search.clinicalgenome.org/CCID:006201
Sources: ClinGen
Aminoacidopathy v1.95 SLC6A8 Sangavi Sivagnanasundram gene: SLC6A8 was added
gene: SLC6A8 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC6A8 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SLC6A8 were set to 27604308; 16738945
Phenotypes for gene: SLC6A8 were set to creatine transporter deficiency MONDO:0010305
Review for gene: SLC6A8 was set to GREEN
Added comment: Well-established gene disease association with reported individuals having error in creatine transport.

Classified Definitive by Aminoacidopathy GCEP on 10/02/2020 - https://search.clinicalgenome.org/CCID:006200
Sources: ClinGen
Aminoacidopathy v1.95 SLC6A6 Sangavi Sivagnanasundram gene: SLC6A6 was added
gene: SLC6A6 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC6A6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC6A6 were set to 31903486; 31345061
Phenotypes for gene: SLC6A6 were set to hypotaurinemic retinal degeneration and cardiomyopathy MONDO:0007777
Review for gene: SLC6A6 was set to AMBER
Added comment: 4 individuals reported with retinal degeneration while 2 (who are siblings) also reported cardiomyopathy. The proband (one of the siblings) was given oral taurine supplementation that reversed their phenotype (cardiomyopathy was reversed and the retinal degeneration was halted) (PMID: 31903486).

Classified Limited by Aminoacidopathy GCEP on 10/03/2023 - https://search.clinicalgenome.org/CCID:006199
Sources: ClinGen
Prepair 1000+ v1.9 ETFDH Lilian Downie Marked gene: ETFDH as ready
Prepair 1000+ v1.9 ETFDH Lilian Downie Gene: etfdh has been classified as Green List (High Evidence).
Prepair 1000+ v1.9 ETFDH Lilian Downie Publications for gene: ETFDH were set to 31904027
Prepair 1000+ v1.8 ETFDH Lilian Downie Publications for gene: ETFDH were set to
Aminoacidopathy v1.95 SLC6A19 Sangavi Sivagnanasundram gene: SLC6A19 was added
gene: SLC6A19 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC6A19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC6A19 were set to 15286787; 15286788; 18484095
Phenotypes for gene: SLC6A19 were set to Hartnup disease MONDO:0009324
Review for gene: SLC6A19 was set to GREEN
Added comment: Established gene-disease association with >10 probands reported with clinical symptoms assocation with Hartnup disease. Mechanism of disease is LoF with affected individuals having a defect in amino acid transportation.

Classified Definitive by Aminoacidopathy GCEP on 07/05/2020 - https://search.clinicalgenome.org/CCID:006196
Sources: ClinGen
Aminoacidopathy v1.95 SLC3A1 Sangavi Sivagnanasundram gene: SLC3A1 was added
gene: SLC3A1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC3A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC3A1 were set to 8054986; 16374432; 8486766
Phenotypes for gene: SLC3A1 were set to cystinuria MONDO:0009067
Review for gene: SLC3A1 was set to GREEN
Added comment: Established gene-disease association with reported individuals having biochemical abnormalities affecting cystine transportation.

Classified Definitive by Aminoacidopathy GCEP on 29/06/2020 - https://search.clinicalgenome.org/CCID:006188
Sources: ClinGen
Aminoacidopathy v1.95 SLC38A8 Sangavi Sivagnanasundram gene: SLC38A8 was added
gene: SLC38A8 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC38A8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC38A8 were set to 32744312; 24290379; 24045842; 25451601; 24290379
Phenotypes for gene: SLC38A8 were set to foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome MONDO:0012216
Review for gene: SLC38A8 was set to GREEN
Added comment: Reported in >5 unrelated probands with reported errors in glutamate/glutamine transport.

Classified Definitive by Aminoacidopathy GCEP on 10/02/2023 - https://search.clinicalgenome.org/CCID:006184
Sources: ClinGen
Aminoacidopathy v1.95 SLC36A2 Sangavi Sivagnanasundram gene: SLC36A2 was added
gene: SLC36A2 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC36A2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SLC36A2 were set to 19033659; 26141664
Phenotypes for gene: SLC36A2 were set to iminoglycinuria MONDO:0009448
Review for gene: SLC36A2 was set to RED
Added comment: IG phenotype is due to excess urinary excretion of proline, hydroxyproline and glycine which is thought to be benign. Variants have been reported in individuals with varying phenotypes - One homozygous individual reported with an IG phenotype while some heterozygous individuals reported to have hyperglycinuria. Biochemical abnormalities result in an IG phenotype is not a common clinical feature in the reported individuals.

Classified Limitied by Aminoacidopathy GCEP on 11/04/2024 - https://search.clinicalgenome.org/CCID:006183
Sources: ClinGen
Aminoacidopathy v1.95 SLC25A15 Sangavi Sivagnanasundram gene: SLC25A15 was added
gene: SLC25A15 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC25A15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A15 were set to 25874378
Phenotypes for gene: SLC25A15 were set to ornithine translocase deficiency MONDO:0009393 (HHH Syndrome)
Review for gene: SLC25A15 was set to GREEN
Added comment: Well established gene-disease association with reported individuals presenting with a biochemical triad of abnormalities - hyperornithinemia, hyperammonemia, and homocitrullinuria (severity of the clinical symptoms can vary).

Common variants in individuals with HHH syndrome
p.Phe188del
French Canadian Founder - NFE GrpMax AF - 0.004% (reported in 62 hets globally)

p.Arg179X
Commonly seen in Japanese patients - EAS GrpMax AF - 0.017% (reported in 26 hets globally)

Classified Definitive by Aminoacidopathy GCEP on 04/12/2019 -https://search.clinicalgenome.org/CCID:006162
Sources: ClinGen
Aminoacidopathy v1.95 SLC25A13 Sangavi Sivagnanasundram gene: SLC25A13 was added
gene: SLC25A13 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC25A13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A13 were set to 18367750; 10369257; 19036621; 18392553; 11343053; 31607264
Phenotypes for gene: SLC25A13 were set to citrin deficiency MONDO:0016602
Review for gene: SLC25A13 was set to GREEN
Added comment: Established gene-disease association with variants reported in >10 probands with reported biochemical abnormalities. Variants in this gene have been reported in both adult onset citrullinemia type 2 but also in individuals with neonatal intrahepatic cholestasis.

Mechanism of disease is biallelic loss of function - significantly reduced or absent glutamate transport in and aspartate transport out of mitochondria depriving argininosuccinate synthetase leading to the accumulation of citrulline and ammonia.

Classified Definitive by Aminoacidopathy GCEP on 23/07/2021 - https://search.clinicalgenome.org/CCID:006161
Sources: ClinGen
Aminoacidopathy v1.95 SLC1A4 Sangavi Sivagnanasundram gene: SLC1A4 was added
gene: SLC1A4 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC1A4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC1A4 were set to 25930971, 27711071, 29989513, 29652076, 26041762, 27193218, 30125339
Phenotypes for gene: SLC1A4 were set to spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome MONDO:0014725
Review for gene: SLC1A4 was set to GREEN
Added comment: Reported in at least 9 individuals with reported biochemical abnormalities involving the L-serine transporter.

Classified Definitive by Aminoacidopathy GCEP on 14/05/2021 - https://search.clinicalgenome.org/CCID:006155
Sources: ClinGen
Intellectual disability syndromic and non-syndromic v0.6062 B9D1 Achchuthan Shanmugasundram reviewed gene: B9D1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 32622957; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v1.44 DDOST Achchuthan Shanmugasundram changed review comment from: PMID:34462534 reported the identification of homozygous DDOST variant (c.1187G>A) in a Chinese patient who presented with feeding difficulty, lactose intolerance, facial dysmorphism, failure to thrive, strabismus, high myopia, astigmatism, hypotonia, developmental delay and situs inversus totalis. Serum transferrin isoelectrofocusing demonstrated defective glycosylation in the patient. T; to: PMID:34462534 reported the identification of homozygous DDOST variant (c.1187G>A) in a Chinese patient who presented with feeding difficulty, lactose intolerance, facial dysmorphism, failure to thrive, strabismus, high myopia, astigmatism, hypotonia, developmental delay and situs inversus totalis. Serum transferrin isoelectrofocusing demonstrated defective glycosylation in the patient.
Congenital Disorders of Glycosylation v1.44 DDOST Achchuthan Shanmugasundram reviewed gene: DDOST: Rating: GREEN; Mode of pathogenicity: None; Publications: 34462534; Phenotypes: Congenital disorder of glycosylation, type Ir, OMIM:614507; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1886 DDOST Achchuthan Shanmugasundram reviewed gene: DDOST: Rating: GREEN; Mode of pathogenicity: None; Publications: 34462534; Phenotypes: Congenital disorder of glycosylation, type Ir, OMIM:614507; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ETFDH Lauren Rogers reviewed gene: ETFDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 31904027; Phenotypes: Glutaric acidemia IIC, MIM# 231680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ECHS1 Lauren Rogers reviewed gene: ECHS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32642440; Phenotypes: Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency MIM# 616277; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 DIS3L2 Lauren Rogers reviewed gene: DIS3L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22306653, 28328139, 29950491; Phenotypes: Perlman syndrome MIM# 267000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 DBT Lauren Rogers reviewed gene: DBT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Maple syrup urine disease, type II (MIM#248600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ATP7B Andrew Coventry reviewed gene: ATP7B: Rating: GREEN; Mode of pathogenicity: None; Publications: 35042319 8298639 9554743 10790207 7626145 16133174 28433102; Phenotypes: Wilson disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ALG3 Andrew Coventry reviewed gene: ALG3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31067009, 10581255, 15840742; Phenotypes: Congenital disorder of glycosylation, type Id; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Speech apraxia v1.0 SETD1A Thomas Scerri edited their review of gene: SETD1A: Changed rating: GREEN; Changed publications: 29463886, 32346159, 36117209
Speech apraxia v1.0 SETD1A Thomas Scerri changed review comment from: First reported CAS case with a de novo SETD1A frameshift variant (Eising et al., 2019; PMID: 29463886)

Fifteen further independent probands with loss-of-function SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1).

Sources: Expert list, Expert Review; to: First reported CAS case with a de novo SETD1A frameshift variant (Eising et al., 2019; PMID: 29463886)

Kaspi et al. (2022; PMID: 36117209) report a CAS proband with a de novo SETD1A splice acceptor variant.

An independent (unpublished) in-house CAS proband has a de novo SETD1A frameshift variant.

Fifteen further independent probands with loss-of-function SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1).

Sources: Expert list, Expert Review
Predominantly Antibody Deficiency v0.135 FNIP1 Zornitza Stark Marked gene: FNIP1 as ready
Predominantly Antibody Deficiency v0.135 FNIP1 Zornitza Stark Gene: fnip1 has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.135 FNIP1 Zornitza Stark Classified gene: FNIP1 as Green List (high evidence)
Predominantly Antibody Deficiency v0.135 FNIP1 Zornitza Stark Gene: fnip1 has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.134 SENP7 Zornitza Stark Marked gene: SENP7 as ready
Predominantly Antibody Deficiency v0.134 SENP7 Zornitza Stark Gene: senp7 has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.134 SENP7 Zornitza Stark Classified gene: SENP7 as Green List (high evidence)
Predominantly Antibody Deficiency v0.134 SENP7 Zornitza Stark Gene: senp7 has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.133 SENP7 Zornitza Stark gene: SENP7 was added
gene: SENP7 was added to Predominantly Antibody Deficiency. Sources: Literature
Mode of inheritance for gene: SENP7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SENP7 were set to 38972567
Phenotypes for gene: SENP7 were set to Arthrogryposis multiplex congenita, MONDO:0015168, SENP7-related
Review for gene: SENP7 was set to GREEN
Added comment: 4 individuals from three unrelated families reported with biallelic variants and neurodevelopmental abnormalities, dysmorphism, and immunodeficiency, including hypogammaglobulinaemia.
Sources: Literature
Mendeliome v1.1886 SENP7 Zornitza Stark Publications for gene: SENP7 were set to PMID: 37460201
Mendeliome v1.1885 SENP7 Zornitza Stark Classified gene: SENP7 as Green List (high evidence)
Mendeliome v1.1885 SENP7 Zornitza Stark Gene: senp7 has been classified as Green List (High Evidence).
Mendeliome v1.1884 SENP7 Zornitza Stark reviewed gene: SENP7: Rating: GREEN; Mode of pathogenicity: None; Publications: 38972567, 37460201; Phenotypes: Arthrogryposis multiplex congenita, MONDO:0015168, SENP7-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v1.29 SENP7 Zornitza Stark Publications for gene: SENP7 were set to PMID: 37460201; 38972567
Phagocyte Defects v1.28 SENP7 Zornitza Stark Publications for gene: SENP7 were set to PMID: 37460201
Phagocyte Defects v1.27 SENP7 Zornitza Stark Classified gene: SENP7 as Green List (high evidence)
Phagocyte Defects v1.27 SENP7 Zornitza Stark Gene: senp7 has been classified as Green List (High Evidence).
Phagocyte Defects v1.26 SENP7 Zornitza Stark reviewed gene: SENP7: Rating: GREEN; Mode of pathogenicity: None; Publications: 38972567; Phenotypes: Arthrogryposis multiplex congenita, MONDO:0015168, SENP7-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1884 MYZAP Zornitza Stark changed review comment from: 10 individuals from four unrelated families with bi-allelic variants in this gene with DCM. Supportive zebrafish model. Note the MYZAP and GCOM1 genes are part of the GRINL1A complex transcription unit. Some of the reported variants affect GCOM1 with postulated effect on MYZAP due to read through transcription (two families), and in the rest of the families MYZAP was affected directly.
Sources: Literature; to: 10 individuals from four unrelated families with bi-allelic variants in this gene with DCM. Supportive zebrafish model.

The MYZAP gene is part of the GRINL1A complex transcription unit (CTU), or GCOM1, which also includes the downstream POLR2M gene, or GRINL1A.. Some of the reported variants affect GCOM1 with postulated effect on MYZAP due to read through transcription (two families), and in the rest of the families MYZAP was affected directly.

Transcription from an upstream promoter within the GRINL1A CTU produces 2 types of alternatively spliced transcripts: MYZAP transcripts, also called GRINL1A upstream (GUP) transcripts, which include only exons from the MYZAP gene, and GRINL1A combined (GCOM) transcripts, which include exons from both the MYZAP gene and the downstream POLR2M gene. Transcription of the POLR2M gene initiates at a downstream promoter within the GRINL1A CTU and produces alternatively spliced POLR2M transcripts, also called GRINL1A downstream (GDOWN) transcripts, which include only exons from the POLR2M gene
Sources: Literature
Dilated Cardiomyopathy v1.33 MYZAP Zornitza Stark changed review comment from: 10 individuals from four unrelated families with bi-allelic variants in this gene with DCM. Supportive zebrafish model.

Note the MYZAP and GCOM1 genes are part of the GRINL1A complex transcription unit. Some of the reported variants affect GCOM1 with postulated effect on MYZAP due to read through transcription (two families), and in the rest of the families MYZAP was affected directly.
Sources: Literature; to: 10 individuals from four unrelated families with bi-allelic variants in this gene with DCM. Supportive zebrafish model.

The MYZAP gene is part of the GRINL1A complex transcription unit (CTU), or GCOM1, which also includes the downstream POLR2M gene, or GRINL1A.. Some of the reported variants affect GCOM1 with postulated effect on MYZAP due to read through transcription (two families), and in the rest of the families MYZAP was affected directly.

Transcription from an upstream promoter within the GRINL1A CTU produces 2 types of alternatively spliced transcripts: MYZAP transcripts, also called GRINL1A upstream (GUP) transcripts, which include only exons from the MYZAP gene, and GRINL1A combined (GCOM) transcripts, which include exons from both the MYZAP gene and the downstream POLR2M gene. Transcription of the POLR2M gene initiates at a downstream promoter within the GRINL1A CTU and produces alternatively spliced POLR2M transcripts, also called GRINL1A downstream (GDOWN) transcripts, which include only exons from the POLR2M gene
Sources: Literature
Mendeliome v1.1884 MYZAP Zornitza Stark Marked gene: MYZAP as ready
Mendeliome v1.1884 MYZAP Zornitza Stark Gene: myzap has been classified as Green List (High Evidence).
Mendeliome v1.1884 MYZAP Zornitza Stark Classified gene: MYZAP as Green List (high evidence)
Mendeliome v1.1884 MYZAP Zornitza Stark Gene: myzap has been classified as Green List (High Evidence).
Mendeliome v1.1883 MYZAP Zornitza Stark gene: MYZAP was added
gene: MYZAP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MYZAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYZAP were set to 34899865; 35840178; 38436102; 20093627
Phenotypes for gene: MYZAP were set to Cardiomyopathy, dilated, 2K, MIM# 620894
Review for gene: MYZAP was set to GREEN
Added comment: 10 individuals from four unrelated families with bi-allelic variants in this gene with DCM. Supportive zebrafish model. Note the MYZAP and GCOM1 genes are part of the GRINL1A complex transcription unit. Some of the reported variants affect GCOM1 with postulated effect on MYZAP due to read through transcription (two families), and in the rest of the families MYZAP was affected directly.
Sources: Literature
Dilated Cardiomyopathy v1.33 MYZAP Zornitza Stark Marked gene: MYZAP as ready
Dilated Cardiomyopathy v1.33 MYZAP Zornitza Stark Gene: myzap has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.33 MYZAP Zornitza Stark Classified gene: MYZAP as Green List (high evidence)
Dilated Cardiomyopathy v1.33 MYZAP Zornitza Stark Gene: myzap has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.32 MYZAP Zornitza Stark gene: MYZAP was added
gene: MYZAP was added to Dilated Cardiomyopathy. Sources: Literature
Mode of inheritance for gene: MYZAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYZAP were set to 34899865; 35840178; 38436102; 20093627
Phenotypes for gene: MYZAP were set to Cardiomyopathy, dilated, 2K, MIM# 620894
Review for gene: MYZAP was set to GREEN
Added comment: 10 individuals from four unrelated families with bi-allelic variants in this gene with DCM. Supportive zebrafish model.

Note the MYZAP and GCOM1 genes are part of the GRINL1A complex transcription unit. Some of the reported variants affect GCOM1 with postulated effect on MYZAP due to read through transcription (two families), and in the rest of the families MYZAP was affected directly.
Sources: Literature
Prepair 1000+ v1.7 AFF2 Lauren Rogers reviewed gene: AFF2: Rating: AMBER; Mode of pathogenicity: None; Publications: 35431806, 8334699, 21739600, 22773736; Phenotypes: Intellectual disability, X-linked, FRAXE type 309548; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.7 ALDH7A1 Andrew Coventry reviewed gene: ALDH7A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16491085, 17068770, 32969477, 33200442, 17721876, 19142996, 22784480, 29053735; Phenotypes: Epilepsy, early-onset, 4, vitamin B6-dependent MIM #266100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 AK2 Andrew Coventry reviewed gene: AK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19043416, 19043417; Phenotypes: Reticular dysgenesis MIM# 267500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 AGXT Andrew Coventry reviewed gene: AGXT: Rating: GREEN; Mode of pathogenicity: None; Publications: 2039493, 19479957, 33789010; Phenotypes: Hyperoxaluria, primary, type 1 MIM #259900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.94 PCBD1 Zornitza Stark Marked gene: PCBD1 as ready
Aminoacidopathy v1.94 PCBD1 Zornitza Stark Gene: pcbd1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.94 PCBD1 Zornitza Stark Classified gene: PCBD1 as Green List (high evidence)
Aminoacidopathy v1.94 PCBD1 Zornitza Stark Gene: pcbd1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.93 PAH Zornitza Stark Marked gene: PAH as ready
Aminoacidopathy v1.93 PAH Zornitza Stark Gene: pah has been classified as Green List (High Evidence).
Aminoacidopathy v1.93 PAH Zornitza Stark Classified gene: PAH as Green List (high evidence)
Aminoacidopathy v1.93 PAH Zornitza Stark Gene: pah has been classified as Green List (High Evidence).
Aminoacidopathy v1.92 OTC Zornitza Stark Marked gene: OTC as ready
Aminoacidopathy v1.92 OTC Zornitza Stark Gene: otc has been classified as Green List (High Evidence).
Aminoacidopathy v1.92 OTC Zornitza Stark Classified gene: OTC as Green List (high evidence)
Aminoacidopathy v1.92 OTC Zornitza Stark Gene: otc has been classified as Green List (High Evidence).
Aminoacidopathy v1.91 OAT Zornitza Stark Marked gene: OAT as ready
Aminoacidopathy v1.91 OAT Zornitza Stark Gene: oat has been classified as Green List (High Evidence).
Aminoacidopathy v1.91 OAT Zornitza Stark Classified gene: OAT as Green List (high evidence)
Aminoacidopathy v1.91 OAT Zornitza Stark Gene: oat has been classified as Green List (High Evidence).
Aminoacidopathy v1.90 NAT8L Zornitza Stark Marked gene: NAT8L as ready
Aminoacidopathy v1.90 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Aminoacidopathy v1.90 NAT8L Zornitza Stark Classified gene: NAT8L as Red List (low evidence)
Aminoacidopathy v1.90 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Aminoacidopathy v1.89 NAGS Zornitza Stark Marked gene: NAGS as ready
Aminoacidopathy v1.89 NAGS Zornitza Stark Gene: nags has been classified as Green List (High Evidence).
Aminoacidopathy v1.89 NAGS Zornitza Stark Classified gene: NAGS as Green List (high evidence)
Aminoacidopathy v1.89 NAGS Zornitza Stark Gene: nags has been classified as Green List (High Evidence).
Aminoacidopathy v1.88 MTRR Zornitza Stark Marked gene: MTRR as ready
Aminoacidopathy v1.88 MTRR Zornitza Stark Gene: mtrr has been classified as Green List (High Evidence).
Aminoacidopathy v1.88 MTRR Zornitza Stark Classified gene: MTRR as Green List (high evidence)
Aminoacidopathy v1.88 MTRR Zornitza Stark Gene: mtrr has been classified as Green List (High Evidence).
Aminoacidopathy v1.87 MTR Zornitza Stark Marked gene: MTR as ready
Aminoacidopathy v1.87 MTR Zornitza Stark Gene: mtr has been classified as Green List (High Evidence).
Aminoacidopathy v1.87 MTR Zornitza Stark Classified gene: MTR as Green List (high evidence)
Aminoacidopathy v1.87 MTR Zornitza Stark Gene: mtr has been classified as Green List (High Evidence).
Aminoacidopathy v1.86 MTHFR Zornitza Stark Marked gene: MTHFR as ready
Aminoacidopathy v1.86 MTHFR Zornitza Stark Gene: mthfr has been classified as Green List (High Evidence).
Aminoacidopathy v1.86 MTHFR Zornitza Stark Classified gene: MTHFR as Green List (high evidence)
Aminoacidopathy v1.86 MTHFR Zornitza Stark Gene: mthfr has been classified as Green List (High Evidence).
Aminoacidopathy v1.85 MPST Zornitza Stark Marked gene: MPST as ready
Aminoacidopathy v1.85 MPST Zornitza Stark Gene: mpst has been classified as Red List (Low Evidence).
Aminoacidopathy v1.85 MPST Zornitza Stark Classified gene: MPST as Red List (low evidence)
Aminoacidopathy v1.85 MPST Zornitza Stark Gene: mpst has been classified as Red List (Low Evidence).
Aminoacidopathy v1.84 MMACHC Zornitza Stark Marked gene: MMACHC as ready
Aminoacidopathy v1.84 MMACHC Zornitza Stark Gene: mmachc has been classified as Green List (High Evidence).
Aminoacidopathy v1.84 MMACHC Zornitza Stark Classified gene: MMACHC as Green List (high evidence)
Aminoacidopathy v1.84 MMACHC Zornitza Stark Gene: mmachc has been classified as Green List (High Evidence).
Aminoacidopathy v1.83 MCEE Zornitza Stark Marked gene: MCEE as ready
Aminoacidopathy v1.83 MCEE Zornitza Stark Gene: mcee has been classified as Green List (High Evidence).
Aminoacidopathy v1.83 MCEE Zornitza Stark Classified gene: MCEE as Green List (high evidence)
Aminoacidopathy v1.83 MCEE Zornitza Stark Gene: mcee has been classified as Green List (High Evidence).
Aminoacidopathy v1.82 MAT1A Zornitza Stark Marked gene: MAT1A as ready
Aminoacidopathy v1.82 MAT1A Zornitza Stark Gene: mat1a has been classified as Green List (High Evidence).
Aminoacidopathy v1.82 MAT1A Zornitza Stark Classified gene: MAT1A as Green List (high evidence)
Aminoacidopathy v1.82 MAT1A Zornitza Stark Gene: mat1a has been classified as Green List (High Evidence).
Ataxia - adult onset v1.16 PNPT1 Zornitza Stark Publications for gene: PNPT1 were set to 35411967
Prepair 1000+ v1.7 CTSD Lauren Rogers reviewed gene: CTSD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 10, MIM# 610127; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ABCB7 Andrew Coventry reviewed gene: ABCB7: Rating: GREEN; Mode of pathogenicity: None; Publications: 10196363, 33157103, 31772327, 31511561, 26242992, 34354969, 22398176; Phenotypes: Anaemia, sideroblastic, with ataxia MIM# 301310; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.7 ABCB7 Andrew Coventry Deleted their review
Prepair 1000+ v1.7 ABCB7 Andrew Coventry changed review comment from: HGNC approved symbol/name: ABCB7
Reported cases of ataxia are typically childhood onset and progressive, anaemia reported to be mostly mild.; to: HGNC approved symbol/name: ABCB7
Reported cases of ataxia are typically childhood onset and progressive, anaemia reported to be mostly mild.
Prepair 1000+ v1.7 COQ4 Lauren Rogers reviewed gene: COQ4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coenzyme Q10 deficiency, primary, 7, MIM# 616276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ABCB7 Andrew Coventry reviewed gene: ABCB7: Rating: ; Mode of pathogenicity: None; Publications: 10196363, 33157103, 31772327, 31511561, 26242992, 34354969, 22398176; Phenotypes: Anaemia, sideroblastic, with ataxia MIM# 301310; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ataxia - adult onset v1.15 PNPT1 Chris Ciotta reviewed gene: PNPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 37935417; Phenotypes: Spinocerebellar ataxia 25 (MIM#608703); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.7 AGL Marta Cifuentes Ochoa reviewed gene: AGL: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26885414, 20301788, 35834487, 27106217; Phenotypes: Glycogen storage disease IIIa and IIIb, MIM#232400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ACY1 Marta Cifuentes Ochoa reviewed gene: ACY1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16274666, 16465618, 17562838, 24117009, 37523070, 29653693, 26686503; Phenotypes: Aminoacylase 1 deficiency, MIM# 609924; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.7 AIFM1 Karina Sandoval reviewed gene: AIFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20362274, 22019070, 26173962, 31523922, 31783324, 28299359, 25934856, 28842795, 28842795; Phenotypes: Combined oxidative phosphorylation deficiency 6, 300816, Cowchock syndrome, 310490, Deafness, X-linked 5, 300614, Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy, 300232; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral vascular malformations v0.39 BRCC3 Zornitza Stark Marked gene: BRCC3 as ready
Cerebral vascular malformations v0.39 BRCC3 Zornitza Stark Gene: brcc3 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.39 BRCC3 Zornitza Stark Publications for gene: BRCC3 were set to 21596366
Cerebral vascular malformations v0.38 BRCC3 Zornitza Stark changed review comment from: PMID 21596366: three unrelated families with multiple affected males segregating a deletion involving MTCP1 and BRCC3. Positional approach used. Supportive zebrafish model, knockdown of BRCC3; angiogenesis affected.

PMID 33868155, additional report of affected male, with similar deletion.; to: PMID 21596366: three unrelated families with multiple affected males segregating a deletion involving MTCP1 and BRCC3. Positional approach used. Supportive zebrafish model, knockdown of BRCC3; angiogenesis affected.

PMID 33868155, additional report of affected male, with similar deletion.

No reports of SNVs identified, including in ClinVar.
Cerebral vascular malformations v0.38 BRCC3 Zornitza Stark edited their review of gene: BRCC3: Changed rating: RED
Cerebral vascular malformations v0.38 BRCC3 Zornitza Stark reviewed gene: BRCC3: Rating: ; Mode of pathogenicity: None; Publications: 21596366, 33868155; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Deafness_IsolatedAndComplex v1.194 RAF1 Chirag Patel Classified gene: RAF1 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.194 RAF1 Chirag Patel Gene: raf1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.195 MAP2K1 Chirag Patel Classified gene: MAP2K1 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.195 MAP2K1 Chirag Patel Gene: map2k1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.194 BRAF Chirag Patel Classified gene: BRAF as Green List (high evidence)
Deafness_IsolatedAndComplex v1.194 BRAF Chirag Patel Gene: braf has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.194 RAF1 Chirag Patel Classified gene: RAF1 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.194 RAF1 Chirag Patel Gene: raf1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.194 RAF1 Chirag Patel Classified gene: RAF1 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.194 RAF1 Chirag Patel Gene: raf1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.193 PTPN11 Chirag Patel Classified gene: PTPN11 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.193 PTPN11 Chirag Patel Gene: ptpn11 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.193 MAP2K1 Chirag Patel gene: MAP2K1 was added
gene: MAP2K1 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: MAP2K1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP2K1 were set to PMID: 20301557
Phenotypes for gene: MAP2K1 were set to Noonan Syndrome with Multiple Lentigines, OMIM # 615279
Review for gene: MAP2K1 was set to GREEN
gene: MAP2K1 was marked as current diagnostic
Added comment: Established gene-disease association.
Sensorineural hearing loss is present in ~20% of 'Noonan Syndrome with Multiple Lentigines'
Sources: Literature
Deafness_IsolatedAndComplex v1.192 RAF1 Chirag Patel gene: RAF1 was added
gene: RAF1 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: RAF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAF1 were set to PMID: 20301557
Phenotypes for gene: RAF1 were set to Noonan Syndrome with Multiple Lentigines, OMIM # 611554
Review for gene: RAF1 was set to GREEN
gene: RAF1 was marked as current diagnostic
Added comment: Established gene-disease association.
Sensorineural hearing loss is present in ~20% of 'Noonan Syndrome with Multiple Lentigines'
Sources: Literature
Deafness_IsolatedAndComplex v1.191 PTPN11 Chirag Patel gene: PTPN11 was added
gene: PTPN11 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: PTPN11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN11 were set to PMID: 20301557, 32737134
Phenotypes for gene: PTPN11 were set to Noonan Syndrome with Multiple Lentigines, OMIM # 151100
Review for gene: PTPN11 was set to GREEN
gene: PTPN11 was marked as current diagnostic
Added comment: Established gene-disease association.
Sensorineural hearing loss is present in ~20% of 'Noonan Syndrome with Multiple Lentigines'
Sources: Literature
Deafness_IsolatedAndComplex v1.191 BRAF Chirag Patel gene: BRAF was added
gene: BRAF was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRAF were set to PMID: 20301557
Phenotypes for gene: BRAF were set to Noonan Syndrome with Multiple Lentigines, OMIM # 613707
Review for gene: BRAF was set to GREEN
gene: BRAF was marked as current diagnostic
Added comment: Established gene-disease association.
Sensorineural hearing loss is present in ~20% of 'Noonan Syndrome with Multiple Lentigines'
Sources: Literature
Aminoacidopathy v1.81 PHGDH Zornitza Stark Classified gene: PHGDH as Green List (high evidence)
Aminoacidopathy v1.81 PHGDH Zornitza Stark Gene: phgdh has been classified as Green List (High Evidence).
Aminoacidopathy v1.80 PHYKPL Zornitza Stark Marked gene: PHYKPL as ready
Aminoacidopathy v1.80 PHYKPL Zornitza Stark Gene: phykpl has been classified as Red List (Low Evidence).
Aminoacidopathy v1.80 PHYKPL Zornitza Stark Classified gene: PHYKPL as Red List (low evidence)
Aminoacidopathy v1.80 PHYKPL Zornitza Stark Gene: phykpl has been classified as Red List (Low Evidence).
Aminoacidopathy v1.79 PRODH Zornitza Stark Marked gene: PRODH as ready
Aminoacidopathy v1.79 PRODH Zornitza Stark Gene: prodh has been classified as Green List (High Evidence).
Aminoacidopathy v1.79 PRODH Zornitza Stark Classified gene: PRODH as Green List (high evidence)
Aminoacidopathy v1.79 PRODH Zornitza Stark Gene: prodh has been classified as Green List (High Evidence).
Aminoacidopathy v1.78 PRODH2 Zornitza Stark Marked gene: PRODH2 as ready
Aminoacidopathy v1.78 PRODH2 Zornitza Stark Gene: prodh2 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.78 PRODH2 Zornitza Stark Classified gene: PRODH2 as Red List (low evidence)
Aminoacidopathy v1.78 PRODH2 Zornitza Stark Gene: prodh2 has been classified as Red List (Low Evidence).
Mendeliome v1.1882 PRODH2 Zornitza Stark Marked gene: PRODH2 as ready
Mendeliome v1.1882 PRODH2 Zornitza Stark Gene: prodh2 has been classified as Red List (Low Evidence).
Mendeliome v1.1882 PRODH2 Zornitza Stark Classified gene: PRODH2 as Red List (low evidence)
Mendeliome v1.1882 PRODH2 Zornitza Stark Gene: prodh2 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.77 PSAT1 Zornitza Stark Marked gene: PSAT1 as ready
Aminoacidopathy v1.77 PSAT1 Zornitza Stark Gene: psat1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.77 PSAT1 Zornitza Stark Classified gene: PSAT1 as Green List (high evidence)
Aminoacidopathy v1.77 PSAT1 Zornitza Stark Gene: psat1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.76 PSPH Zornitza Stark Marked gene: PSPH as ready
Aminoacidopathy v1.76 PSPH Zornitza Stark Gene: psph has been classified as Green List (High Evidence).
Aminoacidopathy v1.76 PSPH Zornitza Stark Classified gene: PSPH as Green List (high evidence)
Aminoacidopathy v1.76 PSPH Zornitza Stark Gene: psph has been classified as Green List (High Evidence).
Aminoacidopathy v1.75 PTS Zornitza Stark Marked gene: PTS as ready
Aminoacidopathy v1.75 PTS Zornitza Stark Gene: pts has been classified as Green List (High Evidence).
Aminoacidopathy v1.75 PTS Zornitza Stark Classified gene: PTS as Green List (high evidence)
Aminoacidopathy v1.75 PTS Zornitza Stark Gene: pts has been classified as Green List (High Evidence).
Aminoacidopathy v1.74 PYCR1 Zornitza Stark Marked gene: PYCR1 as ready
Aminoacidopathy v1.74 PYCR1 Zornitza Stark Gene: pycr1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.74 PYCR1 Zornitza Stark Classified gene: PYCR1 as Green List (high evidence)
Aminoacidopathy v1.74 PYCR1 Zornitza Stark Gene: pycr1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.73 QDPR Zornitza Stark Marked gene: QDPR as ready
Aminoacidopathy v1.73 QDPR Zornitza Stark Gene: qdpr has been classified as Green List (High Evidence).
Aminoacidopathy v1.73 QDPR Zornitza Stark Classified gene: QDPR as Green List (high evidence)
Aminoacidopathy v1.73 QDPR Zornitza Stark Gene: qdpr has been classified as Green List (High Evidence).
Aminoacidopathy v1.72 SARDH Zornitza Stark Marked gene: SARDH as ready
Aminoacidopathy v1.72 SARDH Zornitza Stark Gene: sardh has been classified as Red List (Low Evidence).
Aminoacidopathy v1.72 SARDH Zornitza Stark Classified gene: SARDH as Red List (low evidence)
Aminoacidopathy v1.72 SARDH Zornitza Stark Gene: sardh has been classified as Red List (Low Evidence).
Aminoacidopathy v1.71 SELENBP1 Zornitza Stark Marked gene: SELENBP1 as ready
Aminoacidopathy v1.71 SELENBP1 Zornitza Stark Gene: selenbp1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.71 SELENBP1 Zornitza Stark Classified gene: SELENBP1 as Green List (high evidence)
Aminoacidopathy v1.71 SELENBP1 Zornitza Stark Gene: selenbp1 has been classified as Green List (High Evidence).
Mendeliome v1.1881 SELENBP1 Zornitza Stark Marked gene: SELENBP1 as ready
Mendeliome v1.1881 SELENBP1 Zornitza Stark Gene: selenbp1 has been classified as Green List (High Evidence).
Mendeliome v1.1881 SELENBP1 Zornitza Stark Classified gene: SELENBP1 as Green List (high evidence)
Mendeliome v1.1881 SELENBP1 Zornitza Stark Gene: selenbp1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.70 SHMT2 Zornitza Stark Marked gene: SHMT2 as ready
Aminoacidopathy v1.70 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.70 SHMT2 Zornitza Stark Classified gene: SHMT2 as Green List (high evidence)
Aminoacidopathy v1.70 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.69 SLC1A1 Zornitza Stark Marked gene: SLC1A1 as ready
Aminoacidopathy v1.69 SLC1A1 Zornitza Stark Gene: slc1a1 has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.69 SLC1A1 Zornitza Stark Classified gene: SLC1A1 as Amber List (moderate evidence)
Aminoacidopathy v1.69 SLC1A1 Zornitza Stark Gene: slc1a1 has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.68 SLC1A2 Zornitza Stark Marked gene: SLC1A2 as ready
Aminoacidopathy v1.68 SLC1A2 Zornitza Stark Gene: slc1a2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.68 SLC1A2 Zornitza Stark Classified gene: SLC1A2 as Green List (high evidence)
Aminoacidopathy v1.68 SLC1A2 Zornitza Stark Gene: slc1a2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.67 SLC1A3 Zornitza Stark Marked gene: SLC1A3 as ready
Aminoacidopathy v1.67 SLC1A3 Zornitza Stark Gene: slc1a3 has been classified as Green List (High Evidence).
Aminoacidopathy v1.67 SLC1A3 Zornitza Stark Classified gene: SLC1A3 as Green List (high evidence)
Aminoacidopathy v1.67 SLC1A3 Zornitza Stark Gene: slc1a3 has been classified as Green List (High Evidence).
Mendeliome v1.1880 RNU4-2 Zornitza Stark Publications for gene: RNU4-2 were set to 38645094
Mendeliome v1.1879 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Changed publications: 38991538
Intellectual disability syndromic and non-syndromic v0.6062 RNU4-2 Zornitza Stark Publications for gene: RNU4-2 were set to 38645094
Intellectual disability syndromic and non-syndromic v0.6061 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Changed publications: 38991538
Ataxia - adult onset v1.15 FDXR Zornitza Stark Marked gene: FDXR as ready
Ataxia - adult onset v1.15 FDXR Zornitza Stark Gene: fdxr has been classified as Amber List (Moderate Evidence).
Ataxia - paediatric v1.26 FDXR Zornitza Stark Marked gene: FDXR as ready
Ataxia - paediatric v1.26 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Ataxia - paediatric v1.26 FDXR Zornitza Stark Classified gene: FDXR as Green List (high evidence)
Ataxia - paediatric v1.26 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Ataxia - paediatric v1.25 FDXR Zornitza Stark gene: FDXR was added
gene: FDXR was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: FDXR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FDXR were set to 30250212; 28965846; 29040572; 33348459; 37046037; 37481223
Phenotypes for gene: FDXR were set to Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Review for gene: FDXR was set to GREEN
Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly. Ataxia reported in multiple individuals, largely paediatric.
Sources: Literature
Ataxia - adult onset v1.15 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, 617717 to Auditory neuropathy and optic atrophy, 617717; Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Ataxia - adult onset v1.14 FDXR Zornitza Stark Publications for gene: FDXR were set to
Ataxia - adult onset v1.13 FDXR Zornitza Stark Classified gene: FDXR as Amber List (moderate evidence)
Ataxia - adult onset v1.13 FDXR Zornitza Stark Gene: fdxr has been classified as Amber List (Moderate Evidence).
Ataxia - adult onset v1.12 FDXR Zornitza Stark changed review comment from: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly. Ataxia reported in multiple individuals.; to: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly. Ataxia reported in multiple individuals, though largely paediatric.
Ataxia - adult onset v1.12 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly. Ataxia reported in multiple individuals.; Changed rating: AMBER; Changed publications: 30250212, 28965846, 29040572, 33348459, 37046037, 37481223; Changed phenotypes: Auditory neuropathy and optic atrophy, MIM#617717, Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Regression v0.556 FDXR Zornitza Stark Publications for gene: FDXR were set to 30250212
Regression v0.555 FDXR Zornitza Stark Classified gene: FDXR as Green List (high evidence)
Regression v0.555 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Regression v0.554 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly.; Changed rating: GREEN; Changed publications: 30250212, 28965846, 29040572, 33348459, 37046037, 37481223; Changed phenotypes: Auditory neuropathy and optic atrophy, MIM# 617717, Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Mitochondrial disease v0.927 FDXR Zornitza Stark Marked gene: FDXR as ready
Mitochondrial disease v0.927 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Mitochondrial disease v0.927 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from to Auditory neuropathy and optic atrophy, MIM#617717; Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Mitochondrial disease v0.926 FDXR Zornitza Stark Publications for gene: FDXR were set to
Mitochondrial disease v0.925 FDXR Zornitza Stark Mode of inheritance for gene: FDXR was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.924 FDXR Zornitza Stark Mode of inheritance for gene: FDXR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.923 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly. Leigh-like presentation at the severe end of the spectrum.; Changed publications: 30250212, 28965846, 29040572, 33348459, 37046037, 37481223; Changed phenotypes: Auditory neuropathy and optic atrophy, MIM#617717, Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Microcephaly v1.268 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, MIM# 617717 to Auditory neuropathy and optic atrophy, MIM# 617717; Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Microcephaly v1.267 FDXR Zornitza Stark Publications for gene: FDXR were set to 30250212
Microcephaly v1.266 FDXR Zornitza Stark Classified gene: FDXR as Green List (high evidence)
Microcephaly v1.266 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Microcephaly v1.265 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly.; Changed rating: GREEN; Changed publications: 30250212, 28965846, 29040572, 33348459, 37046037, 37481223; Changed phenotypes: Auditory neuropathy and optic atrophy, MIM# 617717, Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Mendeliome v1.1879 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, MIM#617717 to Auditory neuropathy and optic atrophy, MIM#617717; Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Mendeliome v1.1878 FDXR Zornitza Stark Publications for gene: FDXR were set to 30250212; 28965846
Intellectual disability syndromic and non-syndromic v0.6061 FDXR Zornitza Stark Publications for gene: FDXR were set to 30250212
Mendeliome v1.1877 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression.; Changed publications: 30250212, 28965846, 29040572, 33348459, 37046037, 37481223; Changed phenotypes: Auditory neuropathy and optic atrophy, MIM#617717, Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Intellectual disability syndromic and non-syndromic v0.6060 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887; Auditory neuropathy and optic atrophy, MIM# 617717 to Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887; Auditory neuropathy and optic atrophy, MIM# 617717
Intellectual disability syndromic and non-syndromic v0.6059 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, MIM# 617717 to Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887; Auditory neuropathy and optic atrophy, MIM# 617717
Intellectual disability syndromic and non-syndromic v0.6058 FDXR Zornitza Stark Classified gene: FDXR as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6058 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6057 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression.; Changed rating: GREEN; Changed publications: 30250212, 29040572, 33348459, 37046037, 37481223; Changed phenotypes: Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887, Auditory neuropathy and optic atrophy, MIM# 617717
Prepair 1000+ v1.7 CLN5 Lauren Rogers reviewed gene: CLN5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 5, MIM# 256731, MONDO:0009745; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 CD40 Lauren Rogers reviewed gene: CD40: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency with hyper-IgM, type 3, MIM# 606843; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 CD3D Lauren Rogers reviewed gene: CD3D: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 19, severe combined MIM# 615617; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 BBS12 Lauren Rogers reviewed gene: BBS12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 12, MIM# 615989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 BBS1 Lauren Rogers reviewed gene: BBS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20177705, 15637713; Phenotypes: Bardet-Biedl syndrome 1, MIM# 209900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ATP6V1B1 Lauren Rogers reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM# 267300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ARL6 Lauren Rogers reviewed gene: ARL6: Rating: ; Mode of pathogenicity: None; Publications: 15258860, 32361989, 31888296, 25402481, 31736247, 19858128; Phenotypes: Bardet-Biedl syndrome 3, MIM# 600151; Mode of inheritance: None
Prepair 1000+ v1.7 ANTXR2 Lauren Rogers reviewed gene: ANTXR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 12973667, 14508707; Phenotypes: Hyaline fibromatosis syndrome, MIM# 228600, MONDO:0009229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ALOX12B Lauren Rogers reviewed gene: ALOX12B: Rating: GREEN; Mode of pathogenicity: None; Publications: 16116617, 11773004; Phenotypes: Ichthyosis, congenital, autosomal recessive 2, MIM# 242100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ADPRHL2 Karina Sandoval reviewed gene: ADPRHL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30100084, 30401461, 35664652; Phenotypes: Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures (MIM#618170); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ALMS1 Lauren Rogers reviewed gene: ALMS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alstrom syndrome, MIM# 203800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 AAAS Lauren Rogers reviewed gene: AAAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 29255950; Phenotypes: Achalasia-addisonianism-alacrimia syndrome, MIM#231550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ACAD9 Karina Sandoval reviewed gene: ACAD9: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:30025539, 26475292; Phenotypes: Mitochondrial complex I deficiency, nuclear type 20 (MIM#611126); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ABCA12 Karina Sandoval reviewed gene: ABCA12: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31168818, 19664001, 31489029; Phenotypes: Ichthyosis, congenital, autosomal recessive 4A (MIM#601277), Ichthyosis, congenital, autosomal recessive 4B (harlequin) (MIM#242500); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and Metabolic Myopathy v1.6 SLC25A32 Bryony Thompson Marked gene: SLC25A32 as ready
Rhabdomyolysis and Metabolic Myopathy v1.6 SLC25A32 Bryony Thompson Gene: slc25a32 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.6 SLC25A32 Bryony Thompson Classified gene: SLC25A32 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v1.6 SLC25A32 Bryony Thompson Gene: slc25a32 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.5 SLC25A32 Bryony Thompson gene: SLC25A32 was added
gene: SLC25A32 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Literature
Mode of inheritance for gene: SLC25A32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A32 were set to 26933868; 35727412; 34764427; 28443623
Phenotypes for gene: SLC25A32 were set to Exercise intolerance, riboflavin-responsive MONDO:0014795
Review for gene: SLC25A32 was set to GREEN
Added comment: 5 cases with MADD from 4 unrelated families (4 homozygotes & 1 chet) and a supporting mouse model. At least 2 cases and the mouse model had exercise intolerance.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6057 RNU4-2 Zornitza Stark Phenotypes for gene: RNU4-2 were changed from Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related to Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, MIM# 620851
Intellectual disability syndromic and non-syndromic v0.6056 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Changed phenotypes: Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, MIM# 620851
Mendeliome v1.1877 RNU4-2 Zornitza Stark Phenotypes for gene: RNU4-2 were changed from Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related to Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, MIM# 620851
Mendeliome v1.1876 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Changed phenotypes: Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, MIM# 620851
Speech apraxia v1.0 Zornitza Stark promoted panel to version 1.0
Aminoacidopathy v1.66 SLC1A3 Sangavi Sivagnanasundram gene: SLC1A3 was added
gene: SLC1A3 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC1A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC1A3 were set to 27829685, 16116111, 29062094, 19139306, 29208948, 29066757, 32754645, 25497598
Phenotypes for gene: SLC1A3 were set to episodic ataxia type 6 MONDO:0012982
Mode of pathogenicity for gene: SLC1A3 was set to Other
Review for gene: SLC1A3 was set to GREEN
Added comment: Variants reported in 8 unrelated probands with reported errors in glutamate metabolism. Mechanism of disease varies depending on the mutation. The most severe variants (p.M128R, p.P290R, and p.T318A) appear to have gain of function mechanism.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 09/10/2020
https://search.clinicalgenome.org/CCID:006154
Sources: ClinGen
Aminoacidopathy v1.66 SLC1A2 Sangavi Sivagnanasundram gene: SLC1A2 was added
gene: SLC1A2 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC1A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC1A2 were set to 23934111; 27476654; 28777935; 30937933
Phenotypes for gene: SLC1A2 were set to developmental and epileptic encephalopathy, 41 MONDO:0014916
Review for gene: SLC1A2 was set to GREEN
Added comment: Reported variants in 6 unrelated probands. The mechanism of disease is heterozygous dominant negative.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 29/10/2020
https://search.clinicalgenome.org/CCID:006153
Sources: ClinGen
Aminoacidopathy v1.66 SLC1A1 Sangavi Sivagnanasundram gene: SLC1A1 was added
gene: SLC1A1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC1A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC1A1 were set to 21123949
Phenotypes for gene: SLC1A1 were set to dicarboxylic aminoaciduria MONDO:0009110
Review for gene: SLC1A1 was set to AMBER
Added comment: Reported in 2 unrelated probands along with a mouse knockout model recapitulating human phenotype.

Classified as Limited by ClinGen Aminoacidopathy GCEP on 12/12/2022
https://search.clinicalgenome.org/CCID:006152
Sources: ClinGen
Aminoacidopathy v1.66 SHMT2 Sangavi Sivagnanasundram gene: SHMT2 was added
gene: SHMT2 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHMT2 were set to 33015733; 35398349; 29323231
Phenotypes for gene: SHMT2 were set to neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities MONDO:0030866
Review for gene: SHMT2 was set to GREEN
Added comment: Reported in 5 unrelated probands with abnormal biochemical function.

Classified as Moderate by ClinGen Aminoacidopathy GCEP on 11/11/2022
https://search.clinicalgenome.org/CCID:006136
Sources: ClinGen
Mendeliome v1.1876 SELENBP1 Sangavi Sivagnanasundram gene: SELENBP1 was added
gene: SELENBP1 was added to Mendeliome. Sources: ClinGen
Mode of inheritance for gene: SELENBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SELENBP1 were set to 29255262
Phenotypes for gene: SELENBP1 were set to extraoral halitosis due to methanethiol oxidase deficiency MONDO:0029144
Review for gene: SELENBP1 was set to GREEN
Added comment: 3 unrelated probands in one publication. All reported individuals had a “cabbage-like” breath odour due to the elevated levels of methanethiol and dimethylsulfide in their breath.
Knockout mouse model recapitulating the human phenotype including the biochemical characteristics.

Classified as Moderate by ClinGen Aminoacidopathy GCEP on 11/11/2022
https://search.clinicalgenome.org/CCID:006103
Sources: ClinGen
Aminoacidopathy v1.66 SELENBP1 Sangavi Sivagnanasundram gene: SELENBP1 was added
gene: SELENBP1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SELENBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SELENBP1 were set to 29255262
Phenotypes for gene: SELENBP1 were set to extraoral halitosis due to methanethiol oxidase deficiency MONDO:0029144
Review for gene: SELENBP1 was set to GREEN
Added comment: 3 unrelated probands in one publication. All reported individuals had a “cabbage-like” breath odour due to the elevated levels of methanethiol and dimethylsulfide in their breath.
Knockout mouse model recapitulating the human phenotype including the biochemical characteristics.

Classified as Moderate by ClinGen Aminoacidopathy GCEP on 11/11/2022
https://search.clinicalgenome.org/CCID:006103
Sources: ClinGen
Aminoacidopathy v1.66 SARDH Sangavi Sivagnanasundram gene: SARDH was added
gene: SARDH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SARDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARDH were set to 22825317
Phenotypes for gene: SARDH were set to sarcosinemia MONDO:0010008
Review for gene: SARDH was set to RED
Added comment: The clinical phenotypes vary and sarcosinemia is considered a benign condition.

Classified as Limited by ClinGen Aminoacidopathy GCEP on 12/12/2022
https://search.clinicalgenome.org/CCID:006052
Sources: ClinGen
Aminoacidopathy v1.66 QDPR Sangavi Sivagnanasundram gene: QDPR was added
gene: QDPR was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: QDPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: QDPR were set to 14114862; 3033643; 11153907; 9341885; 19099731
Phenotypes for gene: QDPR were set to dihydropteridine reductase deficiency MONDO:0009862
Review for gene: QDPR was set to GREEN
Added comment: Well established gene disease association. LoF is a mechanism of disease.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 18/06/2018
https://search.clinicalgenome.org/CCID:005939
Sources: ClinGen
Aminoacidopathy v1.66 PYCR1 Sangavi Sivagnanasundram gene: PYCR1 was added
gene: PYCR1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PYCR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYCR1 were set to 19576563; 19648921
Phenotypes for gene: PYCR1 were set to autosomal recessive cutis laxa type 2B MONDO:0013051
Review for gene: PYCR1 was set to GREEN
Added comment: Established gene disease association with reported individuals having an inborn error of proline metabolism.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 21/05/2020
https://search.clinicalgenome.org/CCID:005936
Sources: ClinGen
Aminoacidopathy v1.66 PTS Sangavi Sivagnanasundram gene: PTS was added
gene: PTS was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PTS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTS were set to 22729819; 21542064; 20059486
Phenotypes for gene: PTS were set to BH4-deficient hyperphenylalaninemia A MONDO:0009863
Review for gene: PTS was set to GREEN
Added comment: Well established gene-disease association. >5 unrelated individuals reported with a biochemical phenotype. LoF is the mechanism of disease.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 22/12/2017
https://search.clinicalgenome.org/CCID:005931
Sources: ClinGen
Aminoacidopathy v1.66 PSPH Sangavi Sivagnanasundram gene: PSPH was added
gene: PSPH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PSPH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSPH were set to 26589312, 25080166, 14673469; 27604308; 26888760; 25152457
Phenotypes for gene: PSPH were set to neurometabolic disorder due to serine deficiency MONDO:0018162
Review for gene: PSPH was set to GREEN
Added comment: Established gene disease assocation. Reported in >5 unrelated individuals with biochemical phenotypes.
Classified as Moderate by ClinGen Aminoacidopathy GCEP on 12/12/2022
https://search.clinicalgenome.org/CCID:005917
Sources: ClinGen
Aminoacidopathy v1.66 PSAT1 Sangavi Sivagnanasundram gene: PSAT1 was added
gene: PSAT1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PSAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSAT1 were set to 26610677; 12633500; 27626380; 32077105
Phenotypes for gene: PSAT1 were set to neurometabolic disorder due to serine deficiency MONDO:0018162
Review for gene: PSAT1 was set to GREEN
Added comment: Well established gene disease association with reported individuals having errors in serine deficiency. Severity of the condition depends on the residual enzyme activity.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 29/06/2020
https://search.clinicalgenome.org/CCID:005912
Sources: ClinGen
Mendeliome v1.1876 PRODH2 Sangavi Sivagnanasundram gene: PRODH2 was added
gene: PRODH2 was added to Mendeliome. Sources: ClinGen
Mode of inheritance for gene: PRODH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRODH2 were set to 27139199
Phenotypes for gene: PRODH2 were set to hydroxyprolinemia MONDO:0009374
Review for gene: PRODH2 was set to RED
Added comment: PMID: 27139199
Variants reported in 6 individuals however only 2 cases presented with intermittant biochemical phenotype however the cause remains unclear. The rest of the individuals were asymptomatic suggesting that hydroxyprolinemia is a benign condition.

Classified as Limited by ClinGen Aminoacidopathy GCEP on 12/12/2022
https://search.clinicalgenome.org/CCID:005893
Sources: ClinGen
Aminoacidopathy v1.66 PRODH2 Sangavi Sivagnanasundram gene: PRODH2 was added
gene: PRODH2 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PRODH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRODH2 were set to 27139199
Phenotypes for gene: PRODH2 were set to hydroxyprolinemia MONDO:0009374
Review for gene: PRODH2 was set to RED
Added comment: PMID: 27139199
Variants reported in 6 individuals however only 2 cases presented with intermittant biochemical phenotype however the cause remains unclear. The rest of the individuals were asymptomatic suggesting that hydroxyprolinemia is a benign condition.

Classified as Limited by ClinGen Aminoacidopathy GCEP on 12/12/2022
https://search.clinicalgenome.org/CCID:005893
Sources: ClinGen
Aminoacidopathy v1.66 PRODH Sangavi Sivagnanasundram gene: PRODH was added
gene: PRODH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PRODH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRODH were set to 12217952
Phenotypes for gene: PRODH were set to hyperprolinemia type 1 MONDO:0009400
Review for gene: PRODH was set to GREEN
Added comment: Well established gene disease association with reported individuals having an inborn error of proline metabolism.
Reported affected individuals have reported 2-10 times the normal plasma proline level.

Classified as Moderate by ClinGen Aminoacidopathy GCEP on 27/04/2021
https://search.clinicalgenome.org/CCID:005892
Sources: ClinGen
Aminoacidopathy v1.66 PHYKPL Sangavi Sivagnanasundram gene: PHYKPL was added
gene: PHYKPL was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PHYKPL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PHYKPL were set to 23242558
Phenotypes for gene: PHYKPL were set to phosphohydroxylysinuria MONDO:0014008
Review for gene: PHYKPL was set to RED
Added comment: Chet individual reported with variants in this gene and a phenotype similar to EDS. This individual was not reported to any metabolic phenotype. No other reports published at this stage to support gene-disease association.

Classified as Limitied by ClinGen Aminoacidopathy GCEP on 17/11/2023
https://search.clinicalgenome.org/CCID:005792
Sources: ClinGen
Aminoacidopathy v1.66 PHGDH Sangavi Sivagnanasundram gene: PHGDH was added
gene: PHGDH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PHGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PHGDH were set to 37347880; 19235232; 24836451; 28440900; 22393170; 25913727
Phenotypes for gene: PHGDH were set to neurometabolic disorder due to serine deficiency MONDO:0018162
Review for gene: PHGDH was set to GREEN
Added comment: Established gene-disease association. >10 unrelated probands reported with an inborn error of serine deficiency. LoF is the mechanism of disease (PMID: 37347880).

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 29/06/2020
https://search.clinicalgenome.org/CCID:005786
Sources: ClinGen
Aminoacidopathy v1.66 PCBD1 Sangavi Sivagnanasundram gene: PCBD1 was added
gene: PCBD1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PCBD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCBD1 were set to 19234759
Phenotypes for gene: PCBD1 were set to pterin-4 alpha-carbinolamine dehydratase 1 deficiency MONDO:0009908
Review for gene: PCBD1 was set to GREEN
Added comment: Well established gene disease association with affected individuals having a transient hyperphenylalaninemia phenotype.

Mechanism of disease appears to be a defect in BH4 regeneration leading to an excess build up of phenylalanine and primapterim levels in blood, urine and tissues (PMID: 19234759)

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 27/07/2021
https://search.clinicalgenome.org/CCID:005739
Sources: ClinGen
Aminoacidopathy v1.66 PAH Sangavi Sivagnanasundram gene: PAH was added
gene: PAH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PAH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAH were set to 1301187, 13138177
Phenotypes for gene: PAH were set to phenylketonuria MONDO:0009861
Review for gene: PAH was set to GREEN
Added comment: Well-established gene-disease association. Affected individuals reported to have an inborn error of phenylalanine metabolism. LoF is the established mechanism of disease (PMID:1301187).

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 24/04/2020
https://search.clinicalgenome.org/CCID:005722
Sources: ClinGen
Aminoacidopathy v1.66 OTC Sangavi Sivagnanasundram gene: OTC was added
gene: OTC was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: OTC 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: OTC were set to 26059767
Phenotypes for gene: OTC were set to ornithine carbamoyltransferase deficiency MONDO:0010703
Review for gene: OTC was set to GREEN
Added comment: Well established gene-disease association where affected individuals have a deficiency in carbamoyltransferase which affects the urea cycle.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 29/10/2019
https://search.clinicalgenome.org/CCID:005712
Sources: Other
Pulmonary Fibrosis_Interstitial Lung Disease v0.57 COPA Zornitza Stark Marked gene: COPA as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.57 COPA Zornitza Stark Gene: copa has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.57 COPA Zornitza Stark Phenotypes for gene: COPA were changed from COPA syndrome - autoimmune disorder associated with childhood interstitial lung disease and pulmonary haemorrhage, arthritis, and kidney disease to Autoimmune interstitial lung, joint, and kidney disease, MIM# 616414
Mendeliome v1.1876 GAS2 Zornitza Stark Marked gene: GAS2 as ready
Mendeliome v1.1876 GAS2 Zornitza Stark Gene: gas2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1876 GAS2 Zornitza Stark Classified gene: GAS2 as Amber List (moderate evidence)
Mendeliome v1.1876 GAS2 Zornitza Stark Gene: gas2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1875 GAS2 Zornitza Stark gene: GAS2 was added
gene: GAS2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GAS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAS2 were set to 33964205
Phenotypes for gene: GAS2 were set to Deafness, autosomal recessive 125, MIM#620877
Review for gene: GAS2 was set to AMBER
Added comment: Single family reported with four affected brothers and a splicing variant. Supportive mouse model.
Sources: Literature
Deafness_IsolatedAndComplex v1.190 GAS2 Zornitza Stark Marked gene: GAS2 as ready
Deafness_IsolatedAndComplex v1.190 GAS2 Zornitza Stark Gene: gas2 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.190 GAS2 Zornitza Stark Classified gene: GAS2 as Amber List (moderate evidence)
Deafness_IsolatedAndComplex v1.190 GAS2 Zornitza Stark Gene: gas2 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.189 GAS2 Zornitza Stark gene: GAS2 was added
gene: GAS2 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: GAS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAS2 were set to 33964205
Phenotypes for gene: GAS2 were set to Deafness, autosomal recessive 125, MIM#620877
Review for gene: GAS2 was set to AMBER
Added comment: Single family reported with four affected brothers and a splicing variant. Supportive mouse model.
Sources: Literature
Deafness_Isolated v1.63 GAS2 Zornitza Stark Marked gene: GAS2 as ready
Deafness_Isolated v1.63 GAS2 Zornitza Stark Gene: gas2 has been classified as Amber List (Moderate Evidence).
Deafness_Isolated v1.63 GAS2 Zornitza Stark Classified gene: GAS2 as Amber List (moderate evidence)
Deafness_Isolated v1.63 GAS2 Zornitza Stark Gene: gas2 has been classified as Amber List (Moderate Evidence).
Deafness_Isolated v1.62 GAS2 Zornitza Stark gene: GAS2 was added
gene: GAS2 was added to Deafness_Isolated. Sources: Literature
Mode of inheritance for gene: GAS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAS2 were set to 33964205
Phenotypes for gene: GAS2 were set to Deafness, autosomal recessive 125, MIM#620877
Review for gene: GAS2 was set to AMBER
Added comment: Single family reported with four affected brothers and a splicing variant. Supportive mouse model.
Sources: Literature
Mendeliome v1.1874 KIF1A Zornitza Stark Phenotypes for gene: KIF1A were changed from Neuropathy, hereditary sensory, type IIC, MIM# 614213; NESCAV syndrome, MIM# 614255; Spastic paraplegia 30, MIM# 610357 to Neuropathy, hereditary sensory, type IIC, MIM# 614213; NESCAV syndrome, MIM# 614255; Spastic paraplegia 30, autosomal dominant MIM# 610357; Spastic paraplegia 30, autosomal recessive 620607
Mendeliome v1.1873 KIF1A Zornitza Stark edited their review of gene: KIF1A: Changed phenotypes: Neuropathy, hereditary sensory, type IIC, MIM# 614213, NESCAV syndrome, MIM# 614255, Spastic paraplegia 30, autosomal dominant MIM# 610357, Spastic paraplegia 30, autosomal recessive 620607
Hereditary Spastic Paraplegia - adult onset v1.11 KIF1A Zornitza Stark Phenotypes for gene: KIF1A were changed from Spastic paraplegia 30, autosomal recessive, 610357 to Spastic paraplegia 30, autosomal dominant MIM# 610357; Spastic paraplegia 30, autosomal recessive 620607
Hereditary Spastic Paraplegia - adult onset v1.10 KIF1A Zornitza Stark edited their review of gene: KIF1A: Changed phenotypes: Spastic paraplegia 30, autosomal dominant MIM# 610357, Spastic paraplegia 30, autosomal recessive 620607
Hereditary Spastic Paraplegia - paediatric v1.76 KIF1A Zornitza Stark Phenotypes for gene: KIF1A were changed from Spastic paraplegia 30, MIM# 610357 to Spastic paraplegia 30, autosomal dominant MIM# 610357; Spastic paraplegia 30, autosomal recessive 620607
Hereditary Spastic Paraplegia - paediatric v1.75 KIF1A Zornitza Stark edited their review of gene: KIF1A: Changed phenotypes: Spastic paraplegia 30, autosomal dominant MIM# 610357, Spastic paraplegia 30, autosomal recessive 620607
Pulmonary Fibrosis_Interstitial Lung Disease v0.56 COPA Chirag Patel Classified gene: COPA as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.56 COPA Chirag Patel Gene: copa has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.55 COPA Chirag Patel gene: COPA was added
gene: COPA was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert list
Mode of inheritance for gene: COPA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COPA were set to PMID: 27048656, 30385646, 30804679, 29977900
Phenotypes for gene: COPA were set to COPA syndrome - autoimmune disorder associated with childhood interstitial lung disease and pulmonary haemorrhage, arthritis, and kidney disease
Review for gene: COPA was set to GREEN
gene: COPA was marked as current diagnostic
Added comment: Over 10 unrelated families reported.
Well-established gene-disease association.
Sources: Expert list
Ichthyosis v1.11 SREBF2 Zornitza Stark Marked gene: SREBF2 as ready
Ichthyosis v1.11 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Ichthyosis v1.11 SREBF2 Zornitza Stark Classified gene: SREBF2 as Amber List (moderate evidence)
Ichthyosis v1.11 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Ichthyosis v1.10 SREBF2 Zornitza Stark gene: SREBF2 was added
gene: SREBF2 was added to Ichthyosis. Sources: Literature
Mode of inheritance for gene: SREBF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SREBF2 were set to 38847193
Phenotypes for gene: SREBF2 were set to Neurocutaneous syndrome, MONDO:0042983, SREBF2-related
Review for gene: SREBF2 was set to AMBER
Added comment: Two individuals with de novo missense variants, presenting with neurological, cutaneous and skeletal features; supportive functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6056 SREBF2 Zornitza Stark Marked gene: SREBF2 as ready
Intellectual disability syndromic and non-syndromic v0.6056 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6056 SREBF2 Zornitza Stark Classified gene: SREBF2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6056 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6055 SREBF2 Zornitza Stark gene: SREBF2 was added
gene: SREBF2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SREBF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SREBF2 were set to 38847193
Phenotypes for gene: SREBF2 were set to Neurocutaneous syndrome, MONDO:0042983, SREBF2-related
Review for gene: SREBF2 was set to AMBER
Added comment: Two individuals with de novo missense variants, presenting with neurological, cutaneous and skeletal features; supportive functional data.
Sources: Literature
Mendeliome v1.1873 SREBF2 Zornitza Stark Marked gene: SREBF2 as ready
Mendeliome v1.1873 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1873 SREBF2 Zornitza Stark Classified gene: SREBF2 as Amber List (moderate evidence)
Mendeliome v1.1873 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1872 SREBF2 Zornitza Stark gene: SREBF2 was added
gene: SREBF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SREBF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SREBF2 were set to 38847193
Phenotypes for gene: SREBF2 were set to Neurocutaneous syndrome, MONDO:0042983, SREBF2-related
Review for gene: SREBF2 was set to AMBER
Added comment: Two individuals with de novo missense variants, presenting with neurological, cutaneous and skeletal features; supportive functional data.
Sources: Literature
Genetic Epilepsy v1.33 USP25 Zornitza Stark Classified gene: USP25 as Green List (high evidence)
Genetic Epilepsy v1.33 USP25 Zornitza Stark Gene: usp25 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.32 USP25 Zornitza Stark gene: USP25 was added
gene: USP25 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: USP25 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: USP25 were set to 38875478
Phenotypes for gene: USP25 were set to Epilepsy, idiopathic generalized, MONDO:0005579, USP25-related
Review for gene: USP25 was set to GREEN
Added comment: PMID: 38875478 5 heterozygous variants were identified in 8 individuals from 5 unrelated families all with clinical phenotypes associated with generalised epilepsy. Knock-out mouse model showed increased seizure susceptibility compared to the WT. Both loss of function and gain of function variants can be a mechanism of disease in individuals with USP25-related epilepsy.
Sources: Literature
Mendeliome v1.1871 USP25 Zornitza Stark Marked gene: USP25 as ready
Mendeliome v1.1871 USP25 Zornitza Stark Gene: usp25 has been classified as Green List (High Evidence).
Mendeliome v1.1871 USP25 Zornitza Stark Classified gene: USP25 as Green List (high evidence)
Mendeliome v1.1871 USP25 Zornitza Stark Gene: usp25 has been classified as Green List (High Evidence).
Mendeliome v1.1870 C10orf71 Zornitza Stark Marked gene: C10orf71 as ready
Mendeliome v1.1870 C10orf71 Zornitza Stark Gene: c10orf71 has been classified as Green List (High Evidence).
Mendeliome v1.1870 C10orf71 Zornitza Stark Classified gene: C10orf71 as Green List (high evidence)
Mendeliome v1.1870 C10orf71 Zornitza Stark Gene: c10orf71 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.31 C10orf71 Zornitza Stark Marked gene: C10orf71 as ready
Dilated Cardiomyopathy v1.31 C10orf71 Zornitza Stark Gene: c10orf71 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.31 C10orf71 Zornitza Stark Classified gene: C10orf71 as Green List (high evidence)
Dilated Cardiomyopathy v1.31 C10orf71 Zornitza Stark Gene: c10orf71 has been classified as Green List (High Evidence).
Mendeliome v1.1869 PSMC5 Zornitza Stark Phenotypes for gene: PSMC5 were changed from Developmental disorders to Neurodevelopmental disorder (MONDO#0700092), PSMC5-related
Mendeliome v1.1868 PSMC5 Zornitza Stark Publications for gene: PSMC5 were set to 33057194
Mendeliome v1.1867 PSMC5 Zornitza Stark Classified gene: PSMC5 as Green List (high evidence)
Mendeliome v1.1867 PSMC5 Zornitza Stark Gene: psmc5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6054 PSMC5 Zornitza Stark Phenotypes for gene: PSMC5 were changed from Developmental disorders to Neurodevelopmental disorder (MONDO#0700092), PSMC5-related
Intellectual disability syndromic and non-syndromic v0.6053 PSMC5 Zornitza Stark Classified gene: PSMC5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6053 PSMC5 Zornitza Stark Gene: psmc5 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v2.3 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Early-onset Parkinson disease v2.3 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v2.3 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Early-onset Parkinson disease v2.3 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v2.2 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: PSMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMF1 were set to https://www.medrxiv.org/content/10.1101/2024.06.19.24308302v1
Phenotypes for gene: PSMF1 were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PSMF1-related
Review for gene: PSMF1 was set to GREEN
Added comment: 22 individuals from 15 families reported with a range of neurological phenotypes ranging from early-onset Parkinson's disease; childhood conditions typified by ID and a range of movement disorders; through to perinatal lethal presentations with arthrogryposis multiplex. Genotype-phenotype correlation: biallelic missense variants resulted in the milder phenotypes, while bi-allelic LoF variants in the more severe phenotypes. Supportive functional data.
Sources: Literature
Fetal anomalies v1.255 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Fetal anomalies v1.255 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Fetal anomalies v1.255 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Fetal anomalies v1.255 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Fetal anomalies v1.254 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PSMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMF1 were set to https://www.medrxiv.org/content/10.1101/2024.06.19.24308302v1
Phenotypes for gene: PSMF1 were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PSMF1-related
Review for gene: PSMF1 was set to GREEN
Added comment: 22 individuals from 15 families reported with a range of neurological phenotypes ranging from early-onset Parkinson's disease; childhood conditions typified by ID and a range of movement disorders; through to perinatal lethal presentations with arthrogryposis multiplex. Genotype-phenotype correlation: biallelic missense variants resulted in the milder phenotypes, while bi-allelic LoF variants in the more severe phenotypes. Supportive functional data.
Sources: Literature
Arthrogryposis v0.411 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Arthrogryposis v0.411 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Arthrogryposis v0.411 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Arthrogryposis v0.411 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Arthrogryposis v0.410 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: PSMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMF1 were set to https://www.medrxiv.org/content/10.1101/2024.06.19.24308302v1
Phenotypes for gene: PSMF1 were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PSMF1-related
Review for gene: PSMF1 was set to GREEN
Added comment: 22 individuals from 15 families reported with a range of neurological phenotypes ranging from early-onset Parkinson's disease; childhood conditions typified by ID and a range of movement disorders; through to perinatal lethal presentations with arthrogryposis multiplex. Genotype-phenotype correlation: biallelic missense variants resulted in the milder phenotypes, while bi-allelic LoF variants in the more severe phenotypes. Supportive functional data.
Sources: Expert list
Mendeliome v1.1866 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Mendeliome v1.1866 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Mendeliome v1.1866 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Mendeliome v1.1866 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Mendeliome v1.1865 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMF1 were set to https://www.medrxiv.org/content/10.1101/2024.06.19.24308302v1
Phenotypes for gene: PSMF1 were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PSMF1-related
Review for gene: PSMF1 was set to GREEN
Added comment: 22 individuals from 15 families reported with a range of neurological phenotypes ranging from early-onset Parkinson's disease; childhood conditions typified by ID and a range of movement disorders; through to perinatal lethal presentations with arthrogryposis multiplex. Genotype-phenotype correlation: biallelic missense variants resulted in the milder phenotypes, while bi-allelic LoF variants in the more severe phenotypes. Supportive functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6052 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Intellectual disability syndromic and non-syndromic v0.6052 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6052 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6052 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6051 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PSMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMF1 were set to https://www.medrxiv.org/content/10.1101/2024.06.19.24308302v1
Phenotypes for gene: PSMF1 were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PSMF1-related
Review for gene: PSMF1 was set to GREEN
Added comment: 22 individuals from 15 families reported with a range of neurological phenotypes ranging from early-onset Parkinson's disease; childhood conditions typified by ID and a range of movement disorders; through to perinatal lethal presentations with arthrogryposis multiplex. Genotype-phenotype correlation: biallelic missense variants resulted in the milder phenotypes, while bi-allelic LoF variants in the more severe phenotypes. Supportive functional data.
Sources: Literature
Regression v0.554 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Regression v0.554 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Regression v0.553 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Regression v0.553 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Regression v0.552 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Regression v0.552 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Red List (Low Evidence).
Regression v0.552 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Regression. Sources: Literature
Mode of inheritance for gene: PSMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMF1 were set to https://www.medrxiv.org/content/10.1101/2024.06.19.24308302v1
Phenotypes for gene: PSMF1 were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PSMF1-related
Review for gene: PSMF1 was set to GREEN
Added comment: 22 individuals from 15 families reported with a range of neurological phenotypes ranging from early-onset Parkinson's disease; childhood conditions typified by ID and a range of movement disorders; through to perinatal lethal presentations with arthrogryposis multiplex.

Genotype-phenotype correlation: biallelic missense variants resulted in the milder phenotypes, while bi-allelic LoF variants in the more severe phenotypes. Supportive functional data.
Sources: Literature
Severe Combined Immunodeficiency (absent T present B cells) v1.6 POLD3 Zornitza Stark Phenotypes for gene: POLD3 were changed from Severe combined immunodeficiency MONDO:0015974 to Immunodeficiency 122, MIM# 620869
Severe Combined Immunodeficiency (absent T present B cells) v1.5 POLD3 Zornitza Stark Publications for gene: POLD3 were set to 37030525; 36395985; 27524497
Severe Combined Immunodeficiency (absent T present B cells) v1.4 POLD3 Zornitza Stark Classified gene: POLD3 as Green List (high evidence)
Severe Combined Immunodeficiency (absent T present B cells) v1.4 POLD3 Zornitza Stark Gene: pold3 has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency (absent T present B cells) v1.3 POLD3 Zornitza Stark reviewed gene: POLD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38099988; Phenotypes: Immunodeficiency 122, MIM# 620869; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1864 POLD3 Zornitza Stark Phenotypes for gene: POLD3 were changed from Severe combined immunodeficiency MONDO:0015974 to Immunodeficiency 122, MIM# 620869
Mendeliome v1.1863 POLD3 Zornitza Stark Publications for gene: POLD3 were set to 37030525; 36395985; 27524497
Mendeliome v1.1862 POLD3 Zornitza Stark Classified gene: POLD3 as Green List (high evidence)
Mendeliome v1.1862 POLD3 Zornitza Stark Gene: pold3 has been classified as Green List (High Evidence).
Mendeliome v1.1861 POLD3 Zornitza Stark reviewed gene: POLD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38099988; Phenotypes: Immunodeficiency 122, MIM# 620869; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.418 ALDH1A2 Gina Ravenscroft commented on gene: ALDH1A2
Calcium and Phosphate disorders v1.24 SGK3 Bryony Thompson Marked gene: SGK3 as ready
Calcium and Phosphate disorders v1.24 SGK3 Bryony Thompson Gene: sgk3 has been classified as Red List (Low Evidence).
Calcium and Phosphate disorders v1.24 SGK3 Bryony Thompson gene: SGK3 was added
gene: SGK3 was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: SGK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGK3 were set to 31821448; 21451460
Phenotypes for gene: SGK3 were set to Hypophosphatemic rickets
Review for gene: SGK3 was set to RED
Added comment: SGK3 c.979-96T>A reported to segregate in the single family is more common in gnomAD v4.1 than expected for a dominant disease: global allele frequency of 0.004729 (0.5%, 5,882/1,243,870 alleles, 27 homozygotes in gnomAD v4.1).
A knockout mouse model had decreased bone density and increased phosphaturia.
Sources: Literature
Mendeliome v1.1861 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Mendeliome v1.1861 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Mendeliome v1.1860 TUBA4A Bryony Thompson reviewed gene: TUBA4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 38884572, 37418012; Phenotypes: Hereditary ataxia MONDO:0100309, TUBA4A-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v1.24 TUBA4A Bryony Thompson Publications for gene: TUBA4A were set to 25374358; 25893256; 28069311; 38463699; 38884572; 26675813
Motor Neurone Disease v1.23 TUBA4A Bryony Thompson Publications for gene: TUBA4A were set to 28069311; 25374358; 26675813
Motor Neurone Disease v1.22 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Motor Neurone Disease v1.22 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Motor Neurone Disease v1.21 TUBA4A Bryony Thompson edited their review of gene: TUBA4A: Added comment: At least 13 probands reported with ALS or phenotype including motor neurone involvement. Limited segregation evidence and mechanism of disease not established - toxic gain of function, dominant negative, or loss of function suggested
PMID: 25374358 - 7 rare TUBA4A variants OR = 36 [95% CI: 10–210], p = 4.3 × 10−7, Pcorrected = 4.2 × 10−3 in an FALS cohort. Included 1 nonsense (W407X in last exon) and 6 missense variants. FALS cases n=635, controls n=5,510. T145P variant segregated with disease within the family, while K430N was not detected in an affected first cousin of the sequenced proband (?phenocopy). Functional analyses revealed that TUBA4A mutants destabilize the microtubule network, diminishing its repolymerization capability - suggesting a dominant negative mechanism of disease.
PMID: 25893256 - 4 Italian sporadic ALS cases with rare TUBA4A variants (3 missense & 1 splice variant). Minigene assay demonstrates c.226+4A>G causes exon 2 skipping which is expected to a frameshift and NMD. Loss of function is not an established mechanism of ALS in relation to TUBA4A.
PMID: 28069311 - rare missense (Thr381Met) detected in 2 siblings with ALS, but both had the C9orf72 expansion
PMID: 38463699 - reduced TUBA4A protein expression in familial and sporadic ALS brain tissue. Knockout zebrafish has a motor axonopathy and motor behavior defects reflecting a motor neuron disease phenotype
PMID: 38884572 - Multicentre cohort of 12 patients from 11 unrelated families presenting with ataxia age of onset 2-60 yrs (9 different missense variants). Amyotrophy or upper limb muscular weakness in 2/12, 16.6%.; Changed rating: GREEN; Changed publications: 25374358, 25893256, 28069311, 38463699, 38884572; Changed phenotypes: amyotrophic lateral sclerosis type 22 MONDO:0014531; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v1.24 TUBA4A Bryony Thompson Publications for gene: TUBA4A were set to 28069311; 25374358; 26675813
Early-onset Dementia v1.23 TUBA4A Bryony Thompson edited their review of gene: TUBA4A: Changed phenotypes: Inherited neurodegenerative disorder MONDO:0024237, TUBA4A-related
Early-onset Dementia v1.23 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Early-onset Dementia v1.23 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Early-onset Dementia v1.22 TUBA4A Bryony Thompson reviewed gene: TUBA4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 25374358, 28069311, 35327632, 34169147, 38884572, 33760283; Phenotypes: amyotrophic lateral sclerosis type 22 MONDO:0014531; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Speech apraxia v0.39 KAT6A Thomas Scerri changed review comment from: First reported CAS case with a KAT6A splice acceptor variant (Eising et al., 2019; PMID: 29463886).

Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with KAT6A variants and found speech delay was a core feature, and report 1 case diagnosed with oromotor dyspraxia.

St John et al. (2022; PMID: 35892268) examined 49 cases with KAT6A variants and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. "


Sources: Expert list, Expert Review; to: First reported CAS case with a KAT6A splice acceptor variant (Eising et al., 2019; PMID: 29463886).

Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with KAT6A variants and found speech delay was a core feature.

St John et al. (2022; PMID: 35892268) examined 49 cases with KAT6A variants and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. "


Sources: Expert list, Expert Review
Hereditary Spastic Paraplegia - paediatric v1.75 TUBA4A Bryony Thompson Marked gene: TUBA4A as ready
Hereditary Spastic Paraplegia - paediatric v1.75 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.75 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v1.75 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.74 TUBA4A Bryony Thompson gene: TUBA4A was added
gene: TUBA4A was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to 38884572; 37418012
Phenotypes for gene: TUBA4A were set to Hereditary ataxia MONDO:0100309, TUBA4A-related
Mode of pathogenicity for gene: TUBA4A was set to Other
Review for gene: TUBA4A was set to GREEN
Added comment: PMID: 38884572 - Multicentre cohort of 12 patients from 11 unrelated families presenting with ataxia age of onset 2-60 yrs (9 different missense variants). Spasticity was present in 7/12, 58.3%, cognitive decline in 4/12, 33,3%, and amyotrophy or upper limb muscular weakness in 2/12, 16.6%. 2 patients with p.Pro173Arg also had learning disabilities. 5 cases were confirmed de novo for the variants. Enrichment of rare missense in an ataxia cohort from UK 100k genomes - 6/1103 cases vs 2/20,904 controls, OR = 57.0847 [10.2- 576.7], p = 4.02e-7. Cultured fibroblasts from 3 patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organisation and dynamics, suggestive of a dominant negative mechanism of disease.

PMID: 37418012 - 2 Italian spastic ataxia families with p.Glu415Lys, one family segregating the variant in 11 affected individuals and one de novo.
Sources: Literature
Hereditary Spastic Paraplegia - adult onset v1.10 TUBA4A Bryony Thompson Marked gene: TUBA4A as ready
Hereditary Spastic Paraplegia - adult onset v1.10 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - adult onset v1.10 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Hereditary Spastic Paraplegia - adult onset v1.10 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - adult onset v1.9 TUBA4A Bryony Thompson gene: TUBA4A was added
gene: TUBA4A was added to Hereditary Spastic Paraplegia - adult onset. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to 38884572; 37418012
Phenotypes for gene: TUBA4A were set to Hereditary ataxia MONDO:0100309, TUBA4A-related
Mode of pathogenicity for gene: TUBA4A was set to Other
Review for gene: TUBA4A was set to GREEN
Added comment: PMID: 38884572 - Multicentre cohort of 12 patients from 11 unrelated families presenting with ataxia age of onset 2-60 yrs (9 different missense variants). Spasticity was present in 7/12, 58.3%, cognitive decline in 4/12, 33,3%, and amyotrophy or upper limb muscular weakness in 2/12, 16.6%. 2 patients with p.Pro173Arg also had learning disabilities. 5 cases were confirmed de novo for the variants. Enrichment of rare missense in an ataxia cohort from UK 100k genomes - 6/1103 cases vs 2/20,904 controls, OR = 57.0847 [10.2- 576.7], p = 4.02e-7. Cultured fibroblasts from 3 patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organisation and dynamics, suggestive of a dominant negative mechanism of disease.

PMID: 37418012 - 2 Italian spastic ataxia families with p.Glu415Lys, one family segregating the variant in 11 affected individuals and one de novo.
Sources: Literature
Ataxia - paediatric v1.24 TUBA4A Bryony Thompson Marked gene: TUBA4A as ready
Ataxia - paediatric v1.24 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Ataxia - paediatric v1.24 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Ataxia - paediatric v1.24 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Ataxia - paediatric v1.23 TUBA4A Bryony Thompson gene: TUBA4A was added
gene: TUBA4A was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to 38884572; 37418012
Phenotypes for gene: TUBA4A were set to Hereditary ataxia MONDO:0100309, TUBA4A-related
Mode of pathogenicity for gene: TUBA4A was set to Other
Review for gene: TUBA4A was set to GREEN
Added comment: PMID: 38884572 - Multicentre cohort of 12 patients from 11 unrelated families presenting with ataxia age of onset 2-60 yrs (9 different missense variants). Spasticity was present in 7/12, 58.3%, cognitive decline in 4/12, 33,3%, and amyotrophy or upper limb muscular weakness in 2/12, 16.6%. 2 patients with p.Pro173Arg also had learning disabilities. 5 cases were confirmed de novo for the variants. Enrichment of rare missense in an ataxia cohort from UK 100k genomes - 6/1103 cases vs 2/20,904 controls, OR = 57.0847 [10.2- 576.7], p = 4.02e-7. Cultured fibroblasts from 3 patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organisation and dynamics, suggestive of a dominant negative mechanism of disease.

PMID: 37418012 - 2 Italian spastic ataxia families with p.Glu415Lys, one family segregating the variant in 11 affected individuals and one de novo.
Sources: Literature
Ataxia - adult onset v1.12 TUBA4A Bryony Thompson edited their review of gene: TUBA4A: Changed mode of pathogenicity: Other
Ataxia - adult onset v1.12 TUBA4A Bryony Thompson Marked gene: TUBA4A as ready
Ataxia - adult onset v1.12 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Ataxia - adult onset v1.12 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Ataxia - adult onset v1.12 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Ataxia - adult onset v1.11 TUBA4A Bryony Thompson gene: TUBA4A was added
gene: TUBA4A was added to Ataxia - adult onset. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to 38884572; 37418012
Phenotypes for gene: TUBA4A were set to Hereditary ataxia MONDO:0100309, TUBA4A-related
Review for gene: TUBA4A was set to GREEN
Added comment: PMID: 38884572 - Multicentre cohort of 12 patients from 11 unrelated families presenting with ataxia age of onset 2-60 yrs (9 different missense variants). Spasticity was present in 7/12, 58.3%, cognitive decline in 4/12, 33,3%, and amyotrophy or upper limb muscular weakness in 2/12, 16.6%. 2 patients with p.Pro173Arg also had learning disabilities. 5 cases were confirmed de novo for the variants. Enrichment of rare missense in an ataxia cohort from UK 100k genomes - 6/1103 cases vs 2/20,904 controls, OR = 57.0847 [10.2- 576.7], p = 4.02e-7. Cultured fibroblasts from 3 patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organisation and dynamics, suggestive of a dominant negative mechanism of disease.

PMID: 37418012 - 2 Italian spastic ataxia families with p.Glu415Lys, one family segregating the variant in 11 affected individuals and one de novo.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6050 PSMC5 Rylee Peters reviewed gene: PSMC5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38776958, 38293138; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), PSMC5-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1860 PSMC5 Rylee Peters reviewed gene: PSMC5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38776958, 38293138; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), PSMC5-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.253 VPS50 Ain Roesley Publications for gene: VPS50 were set to PMID: 34037727
Fetal anomalies v1.252 VPS50 Ain Roesley reviewed gene: VPS50: Rating: AMBER; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v1.31 VPS50 Ain Roesley Publications for gene: VPS50 were set to 34037727; 38876772
Genetic Epilepsy v1.30 VPS50 Ain Roesley Publications for gene: VPS50 were set to 34037727; 38876772
Intellectual disability syndromic and non-syndromic v0.6050 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6050 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.30 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Genetic Epilepsy v1.30 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6050 VPS50 Ain Roesley Publications for gene: VPS50 were set to 34037727
Genetic Epilepsy v1.30 VPS50 Ain Roesley Publications for gene: VPS50 were set to 34037727
Genetic Epilepsy v1.30 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Genetic Epilepsy v1.30 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6049 VPS50 Ain Roesley reviewed gene: VPS50: Rating: GREEN; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis MIM#619685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v1.29 VPS50 Ain Roesley commented on gene: VPS50: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
severe ID, muscular hypotonia, sensorineural hearing impairment, microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive
Genetic Epilepsy v1.29 VPS50 Ain Roesley reviewed gene: VPS50: Rating: GREEN; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis MIM#619685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Cholestasis v0.240 VPS50 Ain Roesley changed review comment from: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive; to: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
severe ID, muscular hypotonia, sensorineural hearing impairment, microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive
Microcephaly v1.265 VPS50 Ain Roesley changed review comment from: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive; to: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
severe ID, muscular hypotonia, sensorineural hearing impairment, microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive
Mendeliome v1.1860 VPS50 Ain Roesley changed review comment from: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive; to: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
severe ID, muscular hypotonia, sensorineural hearing impairment, microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive
Fetal anomalies v1.252 SERPINA11 Ain Roesley Marked gene: SERPINA11 as ready
Fetal anomalies v1.252 SERPINA11 Ain Roesley Gene: serpina11 has been classified as Red List (Low Evidence).
Mendeliome v1.1860 SERPINA11 Ain Roesley Marked gene: SERPINA11 as ready
Mendeliome v1.1860 SERPINA11 Ain Roesley Gene: serpina11 has been classified as Red List (Low Evidence).
Fetal anomalies v1.252 SERPINA11 Ain Roesley gene: SERPINA11 was added
gene: SERPINA11 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SERPINA11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERPINA11 were set to 38831697
Phenotypes for gene: SERPINA11 were set to pericardial effusion; pleural effusion
Review for gene: SERPINA11 was set to RED
gene: SERPINA11 was marked as current diagnostic
Added comment: 1 family with 2 fetuses.

1st fetus presented with isolated pericardial effusion and a TOP was opted.
post mortem:
mild subcutaneous edema with subtle facial dysmorphic features
small gelatinous glistening cyst on the right pericardium. Bilateral pleural effusion and multiple similar cysts were noted on the lung surfaces

2nd fetus also presented with pleural and pericardial effusion and a TOP was opted
post mortem findings were similar to fetus#1

homozygous nonsense variant in SERPINA11 was found p.(Tyr224*)

Immunofluorescence of lung sections from fetus#1 and a gestation-matched fetus as a control demonstrated undetectable levels of SERPINA11 in the bronchiolar epithelium
Sources: Literature
Mendeliome v1.1860 SERPINA11 Ain Roesley Phenotypes for gene: SERPINA11 were changed from to pericardial effusion; pleural effusion
Mendeliome v1.1859 SERPINA11 Ain Roesley edited their review of gene: SERPINA11: Changed phenotypes: pericardial effusion, pleural effusion
Intellectual disability syndromic and non-syndromic v0.6049 PSMD11 Bryony Thompson Marked gene: PSMD11 as ready
Intellectual disability syndromic and non-syndromic v0.6049 PSMD11 Bryony Thompson Gene: psmd11 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6049 PSMD11 Bryony Thompson Classified gene: PSMD11 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6049 PSMD11 Bryony Thompson Gene: psmd11 has been classified as Green List (High Evidence).
Mendeliome v1.1859 SERPINA11 Ain Roesley gene: SERPINA11 was added
gene: SERPINA11 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SERPINA11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERPINA11 were set to 38831697
Review for gene: SERPINA11 was set to RED
gene: SERPINA11 was marked as current diagnostic
Added comment: 1 family with 2 fetuses.

1st fetus presented with isolated pericardial effusion and a TOP was opted.
post mortem:
mild subcutaneous edema with subtle facial dysmorphic features
small gelatinous glistening cyst on the right pericardium. Bilateral pleural effusion and multiple similar cysts were noted on the lung surfaces

2nd fetus also presented with pleural and pericardial effusion and a TOP was opted
post mortem findings were similar to fetus#1

homozygous nonsense variant in SERPINA11 was found p.(Tyr224*)

Immunofluorescence of lung sections from fetus#1 and a gestation-matched fetus as a control demonstrated undetectable levels of SERPINA11 in the bronchiolar epithelium
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6048 PSMD11 Bryony Thompson gene: PSMD11 was added
gene: PSMD11 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PSMD11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMD11 were set to 38866022; 30733659
Phenotypes for gene: PSMD11 were set to Neurodevelopmental disorder, MONDO:0700092, PSMD11-related
Review for gene: PSMD11 was set to GREEN
Added comment: PMID: 38866022 - 10 unrelated children with early-onset syndromic intellectual disability and neurodevelopmental delay with recurrent obesity. Cognitive impairment is recapitulated in a drosophila model. Loss of function is the mechanism of disease

PMID: 30733659 - 4 probands with ID and different 17q11.2 deletions spanning PSMD11
Sources: Literature
Mendeliome v1.1858 PSMD11 Bryony Thompson Marked gene: PSMD11 as ready
Mendeliome v1.1858 PSMD11 Bryony Thompson Gene: psmd11 has been classified as Green List (High Evidence).
Mendeliome v1.1858 PSMD11 Bryony Thompson Classified gene: PSMD11 as Green List (high evidence)
Mendeliome v1.1858 PSMD11 Bryony Thompson Gene: psmd11 has been classified as Green List (High Evidence).
Mendeliome v1.1857 PSMD11 Bryony Thompson gene: PSMD11 was added
gene: PSMD11 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMD11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMD11 were set to 38866022; 30733659
Phenotypes for gene: PSMD11 were set to Neurodevelopmental disorder, MONDO:0700092, PSMD11-related
Review for gene: PSMD11 was set to GREEN
Added comment: PMID: 38866022 - 10 unrelated children with early-onset syndromic intellectual disability and neurodevelopmental delay with recurrent obesity. Cognitive impairment is recapitulated in a drosophila model. Loss of function is the mechanism of disease

PMID: 30733659 - 4 probands with ID and different 17q11.2 deletions spanning PSMD11
Sources: Literature
Microcephaly v1.265 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Microcephaly v1.265 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Cholestasis v0.240 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Cholestasis v0.240 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Mendeliome v1.1856 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Mendeliome v1.1856 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Microcephaly v1.264 VPS50 Ain Roesley reviewed gene: VPS50: Rating: GREEN; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis MIM#619685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1855 VPS50 Ain Roesley changed review comment from: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive; to: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive
Cholestasis v0.239 VPS50 Ain Roesley changed review comment from: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive; to: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive
Cholestasis v0.239 VPS50 Ain Roesley reviewed gene: VPS50: Rating: GREEN; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis MIM#619685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1855 VPS50 Ain Roesley reviewed gene: VPS50: Rating: GREEN; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis MIM#619685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6047 PAK2 Ain Roesley Marked gene: PAK2 as ready
Intellectual disability syndromic and non-syndromic v0.6047 PAK2 Ain Roesley Gene: pak2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6047 PAK2 Ain Roesley Classified gene: PAK2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6047 PAK2 Ain Roesley Gene: pak2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6046 PAK2 Ain Roesley gene: PAK2 was added
gene: PAK2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PAK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAK2 were set to 33693784; 38894571; 38712026
Phenotypes for gene: PAK2 were set to Knobloch 2 syndrome MIM#618458
Review for gene: PAK2 was set to GREEN
gene: PAK2 was marked as current diagnostic
Added comment: total of 3 families including 2 siblings with intra-familial variability

Siblings' phenotypes:
Both had retinal detachment and interstitial parenchymal pulmonary changes on chest X-rays, but only one child had additional significant features such as cataract, posterior encephalocele, severe DD/ID with ASD, and epilepsy.

Other 2 pro bands:
GDD, delayed motor (but normal verbal) skills, hypotonia

Missense variants with in vitro functional demonstrating reduction in PAK2 auto phosphorylation
Sources: Literature