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Hereditary ataxia v1.321 SPG7 Sarah Leigh Mode of inheritance for gene: SPG7 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic, autosomal or pseudoautosomal.; to: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form).
Mitochondrial DNA maintenance disorder v3.3 SPG7 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic, autosomal or pseudoautosomal.; to: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form).
Mitochondrial DNA maintenance disorder v3.3 SPG7 Sarah Leigh edited their review of gene: SPG7: Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh edited their review of gene: SPG7: Changed publications to: 9635427, 16534102, 17646629, 18200586, 20186691, 22571692; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.307 SPG7 Sarah Leigh Mode of inheritance for gene: SPG7 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.306 SPG7 Sarah Leigh Publications for gene: SPG7 were set to Casari et al (1998)
Hereditary spastic paraplegia v1.305 SPG7 Sarah Leigh reviewed gene: SPG7: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial DNA maintenance disorder v3.3 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 24727571
Mitochondrial DNA maintenance disorder v3.2 SPG7 Sarah Leigh Tag Q2_23_MOI tag was added to gene: SPG7.
Mitochondrial DNA maintenance disorder v3.2 SPG7 Sarah Leigh reviewed gene: SPG7: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Inherited white matter disorders v1.172 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 22571692, 17646629
Inherited white matter disorders v1.171 SPG7 Sarah Leigh commented on gene: SPG7: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Inherited white matter disorders v1.171 SPG7 Sarah Leigh edited their review of gene: SPG7: Changed rating: GREEN; Changed publications to: 9635427, 16534102, 17646629, 18200586, 20186691, 22571692; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Inherited white matter disorders v1.171 SPG7 Sarah Leigh Classified gene: SPG7 as Green List (high evidence)
Inherited white matter disorders v1.171 SPG7 Sarah Leigh Gene: spg7 has been classified as Green List (High Evidence).
Hereditary ataxia v1.320 SPG7 Sarah Leigh Publications for gene: SPG7 were set to PMID: 25681447
Hereditary ataxia v1.319 SPG7 Sarah Leigh Mode of inheritance for gene: SPG7 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia v1.318 SPG7 Sarah Leigh reviewed gene: SPG7: Rating: ; Mode of pathogenicity: None; Publications: 9635427, 16534102, 17646629, 18200586, 20186691, 22571692; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be both monoallelic and biallelic, autosomal or pseudoautosomal.; to: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh Tag Q2_23_MOI tag was added to gene: SPG7.
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh reviewed gene: SPG7: Rating: ; Mode of pathogenicity: None; Publications: 9635427, 16534102, 17646629, 18200586, 20186691, 22571692; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 25681447; 32893728; 33774748; 32161564; 31068484; 23065789; 9635427; 16534102; 17646629; 18200586, 20186691; 22571692
Ataxia and cerebellar anomalies - narrow panel v4.6 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 25681447; 32893728
White matter disorders and cerebral calcification - narrow panel v3.3 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 22571692, 17646629
Adult onset neurodegenerative disorder v4.8 SPG7 Sarah Leigh edited their review of gene: SPG7: Changed publications to: 9635427, 16534102, 17646629, 18200586, 20186691, 22571692
Adult onset neurodegenerative disorder v4.8 SPG7 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be both monoallelic and biallelic, autosomal or pseudoautosomal.; to: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be both monoallelic and biallelic, autosomal or pseudoautosomal.
Adult onset neurodegenerative disorder v4.8 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 25681447; 16765570; 19364936; 9635427; 18200586
Adult onset neurodegenerative disorder v4.7 SPG7 Sarah Leigh Tag Q2_23_promote_green tag was added to gene: SPG7.
Tag Q2_23_MOI tag was added to gene: SPG7.
Adult onset neurodegenerative disorder v4.7 SPG7 Sarah Leigh edited their review of gene: SPG7: Added comment: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be both monoallelic and biallelic, autosomal or pseudoautosomal.; Changed rating: GREEN; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v4.7 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 25681447; 16765570; 19364936; 9635427
Adult onset neurodegenerative disorder v4.6 SPG7 Sarah Leigh Classified gene: SPG7 as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v4.6 SPG7 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Adult onset neurodegenerative disorder v4.6 SPG7 Sarah Leigh Gene: spg7 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.2 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, 607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Hereditary neuropathy or pain disorder v3.7 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Hereditary Neuropathies; Spastic paraplegia, optic atrophy, ataxia and sensory-motor axonal neuropathy in some patients to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Retinal disorders v4.5 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Hereditary ataxia with onset in adulthood v4.7 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7 (#607259) complex forms of the disease. Actually associated with a range of phenotypes including adult-onset ataxia; Autosomal recessive spastic paraplegia 7, 607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Mitochondrial disorders v4.2 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Disorders of mitochondrial DNA maintenance and integrity; Spastic paraplegia 7, autosomal recessive, 607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Intellectual disability v5.17 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive, 607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Likely inborn error of metabolism v4.2 SPG7 Sarah Leigh Added comment: Comment on phenotypes: Miscellaneous disorders/unknown function (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Spastic paraplegia 7, autosomal recessive, 607259;Disorders of mitochondrial DNA maintenance and integrity
Likely inborn error of metabolism v4.2 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Miscellaneous disorders/unknown function (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Spastic paraplegia 7, autosomal recessive, 607259; Disorders of mitochondrial DNA maintenance and integrity to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Hereditary neuropathy v1.463 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Hereditary Neuropathies; Spastic paraplegia, optic atrophy, ataxia and sensory-motor axonal neuropathy in some patients to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Possible mitochondrial disorder - nuclear genes v3.2 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Progressive external ophthalmoplegia with mitochondrial DNA deletions to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Undiagnosed metabolic disorders v1.573 SPG7 Sarah Leigh Added comment: Comment on phenotypes: Miscellaneous disorders/unknown function (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Disorders of mitochondrial DNA maintenance and integrity
Undiagnosed metabolic disorders v1.573 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Miscellaneous disorders/unknown function (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity; Spastic paraplegia 7, autosomal recessive, 607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Adult onset hereditary spastic paraplegia v3.2 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive, 607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Childhood onset hereditary spastic paraplegia v4.3 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive, 607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Hereditary spastic paraplegia v1.305 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Mitochondrial DNA maintenance disorder v3.2 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Progressive external ophthalmoplegia with mitochondrial DNA deletions to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Inherited white matter disorders v1.170 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive, MIM#607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Hereditary ataxia v1.318 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7 (#607259) complex forms of the disease. Actually associated with a range of phenotypes including adult-onset ataxia to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Ataxia and cerebellar anomalies - narrow panel v4.5 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive, OMIM:607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
White matter disorders and cerebral calcification - narrow panel v3.2 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive, MIM#607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Adult onset neurodegenerative disorder v4.5 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7 (#607259) complex forms of the disease. Actually associated with a range of phenotypes including adult-onset ataxia; Spastic paraplegia 7, autosomal recessive to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Adult onset neurodegenerative disorder v4.4 SPG7 Sarah Leigh Publications for gene: SPG7 were set to PMID: 25681447; Casari et al (1998)
Paediatric or syndromic cardiomyopathy v3.4 RRAGC Hannah Robinson gene: RRAGC was added
gene: RRAGC was added to Paediatric or syndromic cardiomyopathy. Sources: NHS GMS,Literature
Mode of inheritance for gene: RRAGC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RRAGC were set to 27234373
Penetrance for gene: RRAGC were set to unknown
Review for gene: RRAGC was set to GREEN
gene: RRAGC was marked as current diagnostic
Added comment: Newborn patient reported with syndromic DCM ventricular dilation and systolic dysfunction, bilateral cataracts, and mild facial dysmorphisms with de novo missense variant in RRAGC (PMID: 27234373). Subsequently, three unrelated patients reported with de novo variants in this gene displayed DCM and hepatopathy, plus brain anomalies including pachygyria,
polymicrogyria, and septo-optic dysplasia (https://doi.org/10.1016/j.gim.2023.100838, PMID not yet available). Additional patient identified through R14 WGS in Exeter Genomics Laboratory.
Sources: NHS GMS, Literature
Hypertrophic cardiomyopathy v4.1 TULP3 John Sayer gene: TULP3 was added
gene: TULP3 was added to Hypertrophic cardiomyopathy. Sources: Expert list
Mode of inheritance for gene: TULP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TULP3 were set to 35397207
Phenotypes for gene: TULP3 were set to hypertrophic cardiomyopathy; cystic kidney disease; congenital hepatic fibrosis
Penetrance for gene: TULP3 were set to Complete
Review for gene: TULP3 was set to RED
Added comment: 3 cases of hypertrophic cardiomyopathy reported by Devane et al. PMID 35397207
Sources: Expert list
Ductal plate malformation v1.19 TULP3 John Sayer gene: TULP3 was added
gene: TULP3 was added to Ductal plate malformation. Sources: Expert list
Mode of inheritance for gene: TULP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TULP3 were set to 36460032; 36276950; 35397207
Phenotypes for gene: TULP3 were set to cystic kidney disease; ductal plate malformation; congentital hepatic fibrosis; cardiomyopathy
Penetrance for gene: TULP3 were set to Complete
Review for gene: TULP3 was set to GREEN
Added comment: Congenital hepatic fibrosis and ductal plate malformation is a common phenotype
See OMIM 604730
Sources: Expert list
Cystic kidney disease v4.1 TULP3 John Sayer gene: TULP3 was added
gene: TULP3 was added to Cystic kidney disease. Sources: Expert list
Mode of inheritance for gene: TULP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TULP3 were set to 36460032; 36276950; 35397207
Phenotypes for gene: TULP3 were set to cystic kidney disease; ductal plate malformation; congentital hepatic fibrosis; cardiomyopathy
Penetrance for gene: TULP3 were set to Complete
Review for gene: TULP3 was set to GREEN
Added comment: TULP3 is a novel human cilipathy gene (OMIM 604730)
Hepatorenocardiac degenerative fibrosis is OMIM pehnotype
Cystic kidney disease is a typical feature
Sources: Expert list
Adult onset neurodegenerative disorder v4.3 SPG21 Sarah Leigh edited their review of gene: SPG21: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least three variants have been reported in three unrelated cases (PMIDs: 14564668, 24451228, 28752238), together with a supportive mouse model (PMID: 26978163).; Changed rating: GREEN
Adult onset leukodystrophy v3.2 SPG21 Sarah Leigh edited their review of gene: SPG21: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least three variants have been reported in three unrelated cases (PMIDs: 14564668, 24451228, 28752238), together with a supportive mouse model (PMID: 26978163).; Changed rating: GREEN
Adult onset leukodystrophy v3.2 SPG21 Sarah Leigh Tag Q2_23_promote_green tag was added to gene: SPG21.
Adult onset neurodegenerative disorder v4.3 SPG21 Sarah Leigh Tag Q2_23_promote_green tag was added to gene: SPG21.
Adult onset leukodystrophy v3.2 SPG21 Sarah Leigh Classified gene: SPG21 as Amber List (moderate evidence)
Adult onset leukodystrophy v3.2 SPG21 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Adult onset leukodystrophy v3.2 SPG21 Sarah Leigh Gene: spg21 has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v4.3 SPG21 Sarah Leigh Classified gene: SPG21 as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v4.3 SPG21 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Adult onset neurodegenerative disorder v4.3 SPG21 Sarah Leigh Gene: spg21 has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v4.2 SPG21 Sarah Leigh Publications for gene: SPG21 were set to 14564668; 28752238; 24451228
Paediatric or syndromic cardiomyopathy v3.4 TBX20 Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: TBX20.
Paediatric or syndromic cardiomyopathy v3.4 TBX20 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TBX20.
Paediatric or syndromic cardiomyopathy v3.4 TBX20 Achchuthan Shanmugasundram changed review comment from: One of the patients reported in PMID:30384889 was identified with an autosomal dominant variant in TBX20 (p.M224V) and was presented with left ventricular noncompaction (LVNC) cardiomyopathy and IgA deficiency. The age of onset of LVNC in this patient was 9 years of age.

PMID:35282022 reported a 6 year old patient with LVNC identified with a de novo variant (p.Arg287Trp) in TBX20 gene.

PMID:17668378 reported two families with congenital heart defects, in which affected individuals carried heterozygous variants in TBX20 gene. Individuals from one of these families (with p.Gln195Ter variant) presented with dilated cardiomyopathy in addition to congenital heart defects.; to: One of the patients reported in PMID:30384889 was identified with an autosomal dominant variant in TBX20 (p.M224V) and was presented with left ventricular noncompaction (LVNC) cardiomyopathy and IgA deficiency. The age of onset of LVNC in this patient was 9 years of age. PMID:35282022 reported a 6 year old patient with LVNC identified with a de novo variant (p.Arg287Trp) in TBX20 gene. These two cases fit well with paediatric cardiomyopathy as both cases are of childhood onset (<12 years of age at onset).

In addition to cases reviewed by Matthew Edwards, PMID:17668378 also reported two families with congenital heart defects, in which affected individuals carried heterozygous variants in TBX20 gene. Individuals from one of these families (with p.Gln195Ter variant) presented with dilated cardiomyopathy in addition to congenital heart defects. All these cases with wide spectrum of phenotypes including cardiomyopathy and congenital hart defects fits well with syndromic cardiomyopathy.
Intellectual disability v5.16 SPTAN1 Sarah Leigh Phenotypes for gene: SPTAN1 were changed from Epileptic encephalopathy, early infantile, 5, 613477; EPILEPTIC ENCEPHALOPATHY EARLY INFANTILE TYPE 5 (EIEE5) to Developmental and epileptic encephalopathy 5, OMIM:613477; developmental and epileptic encephalopathy, 5, MONDO:0013277
Paediatric or syndromic cardiomyopathy v3.4 TBX20 Achchuthan Shanmugasundram Classified gene: TBX20 as Amber List (moderate evidence)
Paediatric or syndromic cardiomyopathy v3.4 TBX20 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be associated with paediatric or syndromic cardiomyopathy and hence should be promoted to green at the next major review.
Paediatric or syndromic cardiomyopathy v3.4 TBX20 Achchuthan Shanmugasundram Gene: tbx20 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.15 SPTAN1 Sarah Leigh Publications for gene: SPTAN1 were set to
Paediatric or syndromic cardiomyopathy v3.3 TBX20 Achchuthan Shanmugasundram Publications for gene: TBX20 were set to PMID: 33585493; PMID: 275101702, PMID: 28798025; PMID: 32600061, PMID: 22080862
Paediatric or syndromic cardiomyopathy v3.2 TBX20 Achchuthan Shanmugasundram Phenotypes for gene: TBX20 were changed from Cardiomyopathy, dilated with or without LVNC; Atrial septal defect, congential heart disease to Atrial septal defect 4, OMIM:611363; Cardiomyopathy, dilated with or without LVNC; Atrial septal defect, congential heart disease
Paediatric or syndromic cardiomyopathy v3.1 TBX20 Achchuthan Shanmugasundram edited their review of gene: TBX20: Changed phenotypes to: Atrial septal defect 4, OMIM:611363
Paediatric or syndromic cardiomyopathy v3.1 TBX20 Achchuthan Shanmugasundram edited their review of gene: TBX20: Changed rating: GREEN
Paediatric or syndromic cardiomyopathy v3.1 TBX20 Achchuthan Shanmugasundram reviewed gene: TBX20: Rating: ; Mode of pathogenicity: None; Publications: 17668378, 30384889, 35282022; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v3.1 AARS2 Patrick Campbell gene: AARS2 was added
gene: AARS2 was added to Fetal anomalies. Sources: NHS GMS
Mode of inheritance for gene: AARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AARS2 were set to 30819764
Phenotypes for gene: AARS2 were set to fetal hydrops; polyhydramnios; pulmonary effusion; cardiomyopathy
Penetrance for gene: AARS2 were set to Complete
Mode of pathogenicity for gene: AARS2 was set to Other
Review for gene: AARS2 was set to GREEN
Added comment: This gene is not on R21. It can cause fetal phenotype and early neonatal death with bi-allelic variants. We had a fetus present locally with fetal hydrops from around 28 weeks. The result was discovered on whole genome sequencing after miscarriage (R14). It would not have been identified on R21 for fetal anomalies. The local finding of presentation antenatally is corroborated by recent publication (PMID 30819764) with a case showing polyhydramnios and nonimmune hydrops, with small pulmonary effusions and significant ascites first detected at 35 wk of pregnancy.
Consideration should be given to adding the gene to R21.
Sources: NHS GMS
Retinal disorders v4.4 SGSH Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major review. These include at least four cases with retinal disorders in literature and additional two cases reported by Siying Lin (Moorfields Eye Hospital).; to: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major review. These include at least four unrelated cases with retinal disorders in literature and additional two cases reported by Siying Lin (Moorfields Eye Hospital).
Retinal disorders v4.4 SGSH Achchuthan Shanmugasundram Classified gene: SGSH as Amber List (moderate evidence)
Retinal disorders v4.4 SGSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major review. These include at least four cases with retinal disorders in literature and additional two cases reported by Siying Lin (Moorfields Eye Hospital).
Retinal disorders v4.4 SGSH Achchuthan Shanmugasundram Gene: sgsh has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.3 SGSH Achchuthan Shanmugasundram Phenotypes for gene: SGSH were changed from to Retinal dystrophy, HP:0000556; retinitis pigmentosa, MONDO:0019200
Retinal disorders v4.2 SGSH Achchuthan Shanmugasundram Publications for gene: SGSH were set to PMID 31718697
Retinal disorders v4.1 SGSH Achchuthan Shanmugasundram edited their review of gene: SGSH: Changed publications to: 31718697, 32195255
Retinal disorders v4.1 SGSH Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: SGSH.
Tag Q2_23_NHS_review tag was added to gene: SGSH.
Retinal disorders v4.1 SGSH Achchuthan Shanmugasundram changed review comment from: PMID:31718697 reported that patients from three unrelated families with Mucopolysaccharidosis type III (MPS-III) presented with retinal dystrophy and another unrelated patient was presented with retinitis pigmentosa. They were identified with compound heterozygous variants in SGSH gene.

In addition, MPS-IIIA mice exhibited a progressive retinal dystrophy characterized by significant alterations in visual function (PMID:32195255).

Although SGSH gene has already been associated with MPS-IIIA in both OMIM and Gene2Phenotype, retinal phenotypes have not yet been included in these records.; to: PMID:31718697 reported that patients from three unrelated families with Mucopolysaccharidosis type III (MPS-III) presented with retinal dystrophy and another unrelated patient was presented with retinitis pigmentosa. They were identified with compound heterozygous variants in SGSH gene.

Siying Lin (Moorfields Eye Hospital) also reviewed about two additional cases of retinal dystrophy identified with biallelic SGSH variants in their patient cohort.

In addition, MPS-IIIA mice exhibited a progressive retinal dystrophy characterized by significant alterations in visual function (PMID:32195255).

Although SGSH gene has already been associated with MPS-IIIA in both OMIM and Gene2Phenotype, retinal phenotypes have not yet been included in these records.
Retinal disorders v4.1 SGSH Achchuthan Shanmugasundram reviewed gene: SGSH: Rating: GREEN; Mode of pathogenicity: None; Publications: 31718697; Phenotypes: Retinal dystrophy, HP:0000556, retinitis pigmentosa, MONDO:0019200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.6 TDP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.; to: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

There are a number of functional studies characterising the function of H493R variant in vitro (PMIDs:15920477, 17948061 & 31723605).

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.
Hereditary ataxia with onset in adulthood v4.6 TDP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

There are a number of functional studies characterising the function of H493R variant in vitro (PMIDs:15920477, 17948061 & 31723605)

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.; to: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

There are a number of functional studies characterising the function of H493R variant in vitro (PMIDs:15920477, 17948061 & 31723605).

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.
Hereditary neuropathy or pain disorder v3.6 TDP1 Achchuthan Shanmugasundram edited their review of gene: TDP1: Changed publications to: 12244316, 15920477, 17948061, 31182267, 31723605
Hereditary ataxia with onset in adulthood v4.6 TDP1 Achchuthan Shanmugasundram Publications for gene: TDP1 were set to 12244316; 31182267
Hereditary ataxia with onset in adulthood v4.5 TDP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.; to: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

There are a number of functional studies characterising the function of H493R variant in vitro (PMIDs:15920477, 17948061 & 31723605)

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.
Hereditary ataxia with onset in adulthood v4.5 TDP1 Achchuthan Shanmugasundram edited their review of gene: TDP1: Changed publications to: 12244316, 15920477, 17948061, 31182267, 31723605
Hereditary neuropathy or pain disorder v3.6 TDP1 Achchuthan Shanmugasundram Classified gene: TDP1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.6 TDP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene can now be promoted to AMBER as there are three unrelated cases. The "founder-effect" tag has been added as they are all of Middle Eastern descent and harboured the same homozygous variant. Hence, it cannot be promoted to green rating.
Hereditary neuropathy or pain disorder v3.6 TDP1 Achchuthan Shanmugasundram Gene: tdp1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.5 TDP1 Achchuthan Shanmugasundram Publications for gene: TDP1 were set to 12244316; 31182267
Hereditary neuropathy or pain disorder v3.4 TDP1 Achchuthan Shanmugasundram Tag founder-effect tag was added to gene: TDP1.
Hereditary neuropathy or pain disorder v3.4 TDP1 Achchuthan Shanmugasundram Phenotypes for gene: TDP1 were changed from Hereditary Neuropathies to ?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250
Hereditary neuropathy or pain disorder v3.3 TDP1 Achchuthan Shanmugasundram Publications for gene: TDP1 were set to 12244316
Hereditary neuropathy or pain disorder v3.2 TDP1 Achchuthan Shanmugasundram reviewed gene: TDP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 12244316, 31182267; Phenotypes: ?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v4.5 TDP1 Achchuthan Shanmugasundram Classified gene: TDP1 as Amber List (moderate evidence)
Hereditary ataxia with onset in adulthood v4.5 TDP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene can now be promoted to AMBER as there are three unrelated cases. The "founder-effect" tag has been added as they are all of Middle Eastern descent and harboured the same homozygous variant. Hence, it cannot be promoted to green rating.
Hereditary ataxia with onset in adulthood v4.5 TDP1 Achchuthan Shanmugasundram Gene: tdp1 has been classified as Amber List (Moderate Evidence).
Hereditary ataxia with onset in adulthood v4.4 TDP1 Achchuthan Shanmugasundram Tag founder-effect tag was added to gene: TDP1.
Hereditary ataxia with onset in adulthood v4.4 TDP1 Achchuthan Shanmugasundram Phenotypes for gene: TDP1 were changed from Autosomal recessive spinocerebellar ataxia with axonal neuropathy, 607250; Spinocerebellar ataxia, autosomal recessive with axonal neuropathy to ?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250
Hereditary ataxia with onset in adulthood v4.3 TDP1 Achchuthan Shanmugasundram Publications for gene: TDP1 were set to 12244316; 31182267
Hereditary ataxia with onset in adulthood v4.2 TDP1 Achchuthan Shanmugasundram Publications for gene: TDP1 were set to
Hereditary ataxia with onset in adulthood v4.1 TDP1 Achchuthan Shanmugasundram reviewed gene: TDP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 12244316, 31182267; Phenotypes: ?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram Deleted their comment
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence (>3 unrelated cases) with childhood-onset dystrophy for this gene to be promoted to GREEN in this panel in the next major review.; to: Comment on list classification: There is sufficient evidence (>3 unrelated cases) with childhood-onset muscular dystrophy for this gene to be promoted to GREEN in this panel in the next major review.
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: PYROXD1.
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PYROXD1.
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram Classified gene: PYROXD1 as Amber List (moderate evidence)
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) with childhood-onset dystrophy for this gene to be promoted to GREEN in this panel in the next major review.
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram Gene: pyroxd1 has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram Classified gene: PYROXD1 as Amber List (moderate evidence)
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) with childhood-onset dystrophy for this gene to be promoted to GREEN in this panel in the next major review.
Congenital muscular dystrophy v4.9 PYROXD1 Achchuthan Shanmugasundram Gene: pyroxd1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.4 NFASC Sarah Leigh Deleted their comment
Ataxia and cerebellar anomalies - narrow panel v4.4 NFASC Sarah Leigh Deleted their comment
Ataxia and cerebellar anomalies - narrow panel v4.4 NFASC Sarah Leigh Classified gene: NFASC as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.4 NFASC Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v4.4 NFASC Sarah Leigh Gene: nfasc has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v4.8 PYROXD1 Achchuthan Shanmugasundram Publications for gene: PYROXD1 were set to 33694278; 30515627
Ataxia and cerebellar anomalies - narrow panel v4.3 NFASC Sarah Leigh Tag Q2_23_promote_green tag was added to gene: NFASC.
Congenital muscular dystrophy v4.8 PYROXD1 Achchuthan Shanmugasundram Publications for gene: PYROXD1 were set to 33694278; 30515627
Congenital muscular dystrophy v4.8 PYROXD1 Achchuthan Shanmugasundram Publications for gene: PYROXD1 were set to PMID: 33694278; 30515627
Ataxia and cerebellar anomalies - narrow panel v4.3 NFASC Sarah Leigh Classified gene: NFASC as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.3 NFASC Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v4.3 NFASC Sarah Leigh Gene: nfasc has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v4.7 PYROXD1 Achchuthan Shanmugasundram reviewed gene: PYROXD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33694278; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.2 NFASC Sarah Leigh Entity copied from Hereditary ataxia v1.317
Ataxia and cerebellar anomalies - narrow panel v4.2 NFASC Sarah Leigh gene: NFASC was added
gene: NFASC was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature,Expert Review Green
Mode of inheritance for gene: NFASC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFASC were set to 30850329; 31608123; 31501903
Phenotypes for gene: NFASC were set to Neurodevelopmental disorder with central and peripheral motor dysfunction, OMIM:618356; neurodevelopmental disorder with central and peripheral motor dysfunction, MONDO:0032698
Penetrance for gene: NFASC were set to Complete
Hereditary ataxia v1.317 NFASC Sarah Leigh edited their review of gene: NFASC: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least three variants have been reported in three cases of OMIM:618356, where early onset ataxia is part of the phenotype (PMID: 30850329, 31608123, 31501903).; Changed rating: GREEN
Hereditary ataxia v1.317 NFASC Sarah Leigh Classified gene: NFASC as Green List (high evidence)
Hereditary ataxia v1.317 NFASC Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Hereditary ataxia v1.317 NFASC Sarah Leigh Gene: nfasc has been classified as Green List (High Evidence).
Hereditary ataxia v1.316 NFASC Sarah Leigh Publications for gene: NFASC were set to PMID: 30850329, 31608123, 31501903
Hereditary ataxia v1.315 NFASC Sarah Leigh Phenotypes for gene: NFASC were changed from Cerebellar ataxia, Demyelinating neuropathy to Neurodevelopmental disorder with central and peripheral motor dysfunction, OMIM:618356; neurodevelopmental disorder with central and peripheral motor dysfunction, MONDO:0032698
Intellectual disability v5.14 NFASC Sarah Leigh Phenotypes for gene: NFASC were changed from Neurodevelopmental disorder with central and peripheral motor dysfunction 618356 to Neurodevelopmental disorder with central and peripheral motor dysfunction, OMIM:618356; neurodevelopmental disorder with central and peripheral motor dysfunction, MONDO:003269
Early onset dystonia v1.133 VPS11 Sarah Leigh Classified gene: VPS11 as Amber List (moderate evidence)
Early onset dystonia v1.133 VPS11 Sarah Leigh Gene: vps11 has been classified as Amber List (Moderate Evidence).
Early onset dystonia v1.132 VPS11 Sarah Leigh reviewed gene: VPS11: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early onset dystonia v1.132 VPS11 Sarah Leigh Phenotypes for gene: VPS11 were changed from Neurodevelopmental disorder; Hypomyelination; Microcephaly; Infantile-onset dystonia; Adult-onset dystonia; Spasticity to ?Dystonia 32, OMIM:619637; dystonia 32, MONDO:0030486
Early onset dystonia v1.131 VPS11 Sarah Leigh Publications for gene: VPS11 were set to PMID: 33452836; 27120463; 27473128; 33871597
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.3 PYROXD1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PYROXD1.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.3 PYROXD1 Achchuthan Shanmugasundram changed review comment from: PMID:30345904 reported a Sudanese patient of Arab descent identified with homozygous variant (p.Asn155Ser) in PYROXD1 gene and presented with limb-girdle-type muscular dystrophy (LGMD). The variant was present in heterozygous state in unaffected sister, unaffected son and unaffected daughter and absent in unaffected brother.

PMID:30515627 reported four patients from three Finnish families with biallelic variants (three with homozygous p.Asn155Ser variant and one with compound heterozygous p.Asn155Ser/ p.Tyr354Cys variants). All of them presented with an adult-onset slowly-progressive LGMD phenotype of symmetric muscle weakness and wasting.

PMID:33694278 reported three patients from two consanguineous Turkish families with biallelic variants (homozygous missense variant (p.Asn155Ser) in family 1 with two affected females and compound heterozygous variants (p.Asn155Ser/ p.Leu112Valfs*8) in affected male of family 2). They presented with mild LGMD, facial weakness, normal CK levels, and slow progress. Authors report that their data suggest that c.464A>G is a Turkish founder mutation.; to: PMID:30345904 reported a Sudanese patient of Arab descent identified with homozygous variant (p.Asn155Ser) in PYROXD1 gene and presented with limb-girdle-type muscular dystrophy (LGMD). The variant was present in heterozygous state in unaffected sister, unaffected son and unaffected daughter and absent in unaffected brother.

PMID:30515627 reported four patients from three Finnish families with biallelic variants (three with homozygous p.Asn155Ser variant and one with compound heterozygous p.Asn155Ser/ p.Tyr354Cys variants). All of them presented with an adult-onset slowly-progressive LGMD phenotype of symmetric muscle weakness and wasting.

PMID:33694278 reported three patients from two consanguineous Turkish families with biallelic variants (homozygous missense variant (p.Asn155Ser) in family 1 with two affected females and compound heterozygous variants (p.Asn155Ser/ p.Leu112Valfs*8) in affected male of family 2). They presented with mild LGMD, facial weakness, normal CK levels, and slow progress. Authors report that their data suggest that c.464A>G is a Turkish founder mutation.

This gene has not yet been associated with LGMD either in OMIM or in Gene2Phenotype.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.3 PYROXD1 Achchuthan Shanmugasundram changed review comment from: PMID:30515627 reported four patients from three Finnish families with biallelic variants (three with homozygous p.Asn155Ser variant and one with compound heterozygous p.Asn155Ser/ p.Tyr354Cys variants). All of them presented with an adult-onset slowly-progressive limb-girdle-type muscular dystrophy (LGMD) phenotype of symmetric muscle weakness and wasting.

PMID:33694278 reported three patients from two consanguineous Turkish families with biallelic variants (homozygous missense variant (p.Asn155Ser) in family 1 with two affected females and compound heterozygous variants (p.Asn155Ser/ p.Leu112Valfs*8) in affected male of family 2). They presented with mild LGMD, facial weakness, normal CK levels, and slow progress. Authors report that their data suggest that c.464A>G is a Turkish founder mutation.; to: PMID:30345904 reported a Sudanese patient of Arab descent identified with homozygous variant (p.Asn155Ser) in PYROXD1 gene and presented with limb-girdle-type muscular dystrophy (LGMD). The variant was present in heterozygous state in unaffected sister, unaffected son and unaffected daughter and absent in unaffected brother.

PMID:30515627 reported four patients from three Finnish families with biallelic variants (three with homozygous p.Asn155Ser variant and one with compound heterozygous p.Asn155Ser/ p.Tyr354Cys variants). All of them presented with an adult-onset slowly-progressive LGMD phenotype of symmetric muscle weakness and wasting.

PMID:33694278 reported three patients from two consanguineous Turkish families with biallelic variants (homozygous missense variant (p.Asn155Ser) in family 1 with two affected females and compound heterozygous variants (p.Asn155Ser/ p.Leu112Valfs*8) in affected male of family 2). They presented with mild LGMD, facial weakness, normal CK levels, and slow progress. Authors report that their data suggest that c.464A>G is a Turkish founder mutation.
Severe microcephaly v4.3 MED11 Sarah Leigh edited their review of gene: MED11: Changed rating: AMBER
Severe microcephaly v4.3 MED11 Sarah Leigh Tag Q2_23_promote_green was removed from gene: MED11.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.3 PYROXD1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient number of cases (5 unrelated cases) to promote this gene to GREEN at the next major review.

Although the same variant has been identified in all patients reported with homozygous variants, the two patients with compound heterozygous variants harboured this variant together with novel variants.; to: Comment on list classification: There is sufficient number of cases (6 unrelated cases) to promote this gene to GREEN at the next major review.

Although the same variant (p.Asn155Ser) has been identified in all patients reported with homozygous variants, two patients with compound heterozygous variants harboured p.Asn155Ser together with novel variants.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.3 PYROXD1 Achchuthan Shanmugasundram edited their review of gene: PYROXD1: Changed publications to: 30345904, 30515627, 33694278
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.3 PYROXD1 Achchuthan Shanmugasundram Publications for gene: PYROXD1 were set to 30345904; 30515627; 27745833
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.2 PYROXD1 Achchuthan Shanmugasundram Deleted their comment
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.2 PYROXD1 Achchuthan Shanmugasundram Classified gene: PYROXD1 as Amber List (moderate evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.2 PYROXD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient number of cases (5 unrelated cases) to promote this gene to GREEN at the next major review.

Although the same variant has been identified in all patients reported with homozygous variants, the two patients with compound heterozygous variants harboured this variant together with novel variants.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.2 PYROXD1 Achchuthan Shanmugasundram Gene: pyroxd1 has been classified as Amber List (Moderate Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.2 PYROXD1 Achchuthan Shanmugasundram Classified gene: PYROXD1 as Amber List (moderate evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.2 PYROXD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient number of cases (5 unrelated cases) to promote this gene to GREEN at the next major review.

Although the same variant has been identified in all patients reported with homozygous variants, the two patients with compound heterozygous variants harboured this variant together with novel variants.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.2 PYROXD1 Achchuthan Shanmugasundram Gene: pyroxd1 has been classified as Amber List (Moderate Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.1 PYROXD1 Achchuthan Shanmugasundram reviewed gene: PYROXD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30515627, 33694278; Phenotypes: limb-girdle muscular dystrophy, MONDO:0016971; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.13 MED11 Sarah Leigh Classified gene: MED11 as Amber List (moderate evidence)
Intellectual disability v5.13 MED11 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.13 MED11 Sarah Leigh Gene: med11 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.6 MED11 Sarah Leigh Classified gene: MED11 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.6 MED11 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v4.6 MED11 Sarah Leigh Gene: med11 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v4.3 MED11 Sarah Leigh Classified gene: MED11 as Amber List (moderate evidence)
Severe microcephaly v4.3 MED11 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be amber on the Severe microcephaly panel.
Severe microcephaly v4.3 MED11 Sarah Leigh Gene: med11 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v4.2 MED11 Sarah Leigh gene: MED11 was added
gene: MED11 was added to Severe microcephaly. Sources: Literature
Q2_23_promote_green tags were added to gene: MED11.
Mode of inheritance for gene: MED11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED11 were set to 36001086
Phenotypes for gene: MED11 were set to MED11-associated neurodevelopmental disorder
Review for gene: MED11 was set to GREEN
Added comment: Not associated with a phenotype in OMIM, but is associated with MED11-associated neurodevelopmental disorder in Gen2Phen. PMID: 36001086 reports a single MED11 variant (NM_001001683.4: c.325C>T, p.Arg109*), that segregates with the condition in five unrelated families, however, there is homozygosity between two of these families, idicating that they may be related. Global delay was observed in three individuals from three unrelated familes and seizures were evident in four individuals from four unrelated families. Severe microcephaly was apparent in the two unrelated familes where this parameter was recorded. Overall, the MED11-associated neurodevelopmental disorder appeared to result in profound effects and proved fatal at birth and 10 days in two of the cases reported.
Sources: Literature
Early onset or syndromic epilepsy v4.5 MED11 Sarah Leigh gene: MED11 was added
gene: MED11 was added to Early onset or syndromic epilepsy. Sources: Literature
Q2_23_promote_green tags were added to gene: MED11.
Mode of inheritance for gene: MED11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED11 were set to 36001086
Phenotypes for gene: MED11 were set to MED11-associated neurodevelopmental disorder
Review for gene: MED11 was set to GREEN
Added comment: Not associated with a phenotype in OMIM, but is associated with MED11-associated neurodevelopmental disorder in Gen2Phen. PMID: 36001086 reports a single MED11 variant (NM_001001683.4: c.325C>T, p.Arg109*), that segregates with the condition in five unrelated families, however, there is homozygosity between two of these families, idicating that they may be related. Global delay was observed in three individuals from three unrelated familes and seizures were evident in four individuals from four unrelated families. Severe microcephaly was apparent in the two unrelated familes where this parameter was recorded. Overall, the MED11-associated neurodevelopmental disorder appeared to result in profound effects and proved fatal at birth and 10 days in two of the cases reported.
Sources: Literature
Intellectual disability v5.12 MED11 Sarah Leigh gene: MED11 was added
gene: MED11 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Q2_23_promote_green tags were added to gene: MED11.
Mode of inheritance for gene: MED11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED11 were set to 36001086
Phenotypes for gene: MED11 were set to MED11-associated neurodevelopmental disorder
Review for gene: MED11 was set to GREEN
Added comment: Not associated with a phenotype in OMIM, but is associated with MED11-associated neurodevelopmental disorder in Gen2Phen. PMID: 36001086 reports a single MED11 variant (NM_001001683.4: c.325C>T, p.Arg109*), that segregates with the condition in five unrelated families, however, there is homozygosity between two of these families, idicating that they may be related. Global delay was observed in three individuals from three unrelated familes and seizures were evident in four individuals from four unrelated families. Severe microcephaly was apparent in the two unrelated familes where this parameter was recorded. Overall, the MED11-associated neurodevelopmental disorder appeared to result in profound effects and proved fatal at birth and 10 days in two of the cases reported.
Sources: Literature
Congenital muscular dystrophy v4.7 EMD Achchuthan Shanmugasundram changed review comment from: EDMD1 is a rare X-linked recessive disease characterised by early childhood joint contractures, progressive weakness in muscles and cardiac involvement and can result in sudden death.

PMID:21697856 reported18 patients and three carriers identified with variants in EMD gene. The patients presented with EDMD and the Age at diagnosis was reported for all, but age of onset was only reported for only a few. The youngest patient was 5 days old but asymptomatic, eldest was 55 years. Of those with age of onset reported, 3 had progressive muscle weakness onset from neonatal to 5 years of age.

PMID:31645980 reported a male patient that began having difficulty moving his limb gridle and cervical vertebrae at the age of 5 years. The condition worsened when he was 13 years, and normal exercise was limited, with serious elbow contracture and mild scapular winging contracture.

PMID:31802929 reported one family with 10 affected males with serious cardiac conduction abnormalities at an early age and a high incidence of sudden cardiac death (SCD) along with mild skeletal muscular atrophy, joint contracture and elevated CK levels. and mild skeletal muscular dystrophy.

PMID:34026875 reported three unrelated patients with EDMD, who had cardiac manifestation in childhood without any skeletal muscle phenotypes.

This gene has been associated with phenotypes in OMIM (MIM #310300), which also describes the disorder as primarily of childhood onset. It has not yet been reported in Gene2Phenotype.; to: EDMD1 is a rare X-linked recessive disease characterised by early childhood joint contractures, progressive weakness in muscles and cardiac involvement and can result in sudden death.

PMID:21697856 reported18 patients and three carriers identified with variants in EMD gene. The patients presented with EDMD and the age at diagnosis was reported for all, but age of onset was only reported for only a few. The youngest patient was 5 days old but asymptomatic, eldest was 55 years. Of those with age of onset reported, 3 had progressive muscle weakness onset from neonatal to 5 years of age.

PMID:31645980 reported a male patient that began having difficulty moving his limb gridle and cervical vertebrae at the age of 5 years. The condition worsened when he was 13 years, and normal exercise was limited, with serious elbow contracture and mild scapular winging contracture.

PMID:31802929 reported one family with 10 affected males with serious cardiac conduction abnormalities at an early age and a high incidence of sudden cardiac death (SCD) along with mild skeletal muscular atrophy, joint contracture and elevated CK levels. and mild skeletal muscular dystrophy.

PMID:34026875 reported three unrelated patients with EDMD, who had cardiac manifestation in childhood without any skeletal muscle phenotypes.

This gene has been associated with phenotypes in OMIM (MIM #310300), which also describes the disorder as primarily of childhood onset. It has not yet been reported in Gene2Phenotype.
Congenital myopathy v4.26 BIN1 Achchuthan Shanmugasundram Tag watchlist_moi tag was added to gene: BIN1.
Congenital myopathy v4.26 BIN1 Achchuthan Shanmugasundram Publications for gene: BIN1 were set to 17676042; 27854204; 25260562
Congenital myopathy v4.25 BIN1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: Only one case with monoallelic BIN1 variant has been reported with childhood-onset myopathy. As there are not sufficient cases, the MOI should remain as "BIALLELIC, autosomal or pseudoautosomal" for now.

"watchlist_moi" tag has been added to review the MOI when new evidence becomes available.
Congenital myopathy v4.25 BIN1 Achchuthan Shanmugasundram Mode of inheritance for gene: BIN1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v4.24 BIN1 Achchuthan Shanmugasundram reviewed gene: BIN1: Rating: ; Mode of pathogenicity: None; Publications: 29103045; Phenotypes: ; Mode of inheritance: None
Congenital myopathy v4.24 TPM2 Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: TPM2.
Congenital myopathy v4.24 TPM2 Achchuthan Shanmugasundram Tag Q2_23_MOI tag was added to gene: TPM2.
Congenital myopathy v4.24 TPM2 Achchuthan Shanmugasundram changed review comment from: Comment on mode of inheritance: Three unrelated cases are reported with biallelic variants in TPM2. This is sufficient evidence to update the MOI from "MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next major review.; to: Comment on mode of inheritance: Three unrelated cases are reported with biallelic variants in TPM2. This is sufficient evidence to update the MOI from "MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next major review.
Congenital myopathy v4.24 TPM2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: Three unrelated cases are reported with biallelic variants in TPM2. This is sufficient evidence to update the MOI from "MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next major review.
Congenital myopathy v4.24 TPM2 Achchuthan Shanmugasundram Mode of inheritance for gene: TPM2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital myopathy v4.23 TPM2 Achchuthan Shanmugasundram changed review comment from: PMID:19155175 reported the identification of a homozygous null variant in TPM2 gene in a patient presented with nemaline myopathy associated with a non-lethal multiple pterygium syndrome.

Among 28 patients from 27 families reported in PMID:24692096, only one patient presenting with nemaline myopathy and pterygia was identified with recessive TPM2 variant.

A homozygous intronic sequence variant was identified in the patient reported with Escobar variant of multiple pterygium syndrome and congenital myopathy in PMID:33558124.

Only phenotypes associated with monoallelic variants (and NOT biallelic variants) are currently reported in OMIM and in Gene2Phenotype.

; to: PMID:19155175 reported the identification of a homozygous null variant in TPM2 gene in a patient presented with nemaline myopathy associated with a non-lethal multiple pterygium syndrome.

Among 28 patients from 27 families reported in PMID:24692096, only one patient presenting with nemaline myopathy and pterygia was identified with recessive TPM2 variant.

A homozygous intronic sequence variant was identified in the patient reported with Escobar variant of multiple pterygium syndrome and congenital myopathy in PMID:33558124.

Only phenotypes associated with monoallelic variants (and NOT biallelic variants) are currently reported in OMIM and in Gene2Phenotype.
Congenital myopathy v4.23 TPM2 Achchuthan Shanmugasundram changed review comment from: Three unrelated cases were reported with biallelic variants in TPM2.; to: PMID:19155175 reported the identification of a homozygous null variant in TPM2 gene in a patient presented with nemaline myopathy associated with a non-lethal multiple pterygium syndrome.

Among 28 patients from 27 families reported in PMID:24692096, only one patient presenting with nemaline myopathy and pterygia was identified with recessive TPM2 variant.

A homozygous intronic sequence variant was identified in the patient reported with Escobar variant of multiple pterygium syndrome and congenital myopathy in PMID:33558124.

Only phenotypes associated with monoallelic variants (and NOT biallelic variants) are currently reported in OMIM and in Gene2Phenotype.
Congenital myopathy v4.23 TNNT1 Achchuthan Shanmugasundram Tag Q2_23_MOI tag was added to gene: TNNT1.
Tag Q2_23_NHS_review tag was added to gene: TNNT1.
Congenital myopathy v4.23 TNNT1 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: TNNT1.
Tag Q2_23_NHS_review was removed from gene: TNNT1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.3 ALPK1 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: ALPK1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.3 ALPK1 Arina Puzriakova Classified gene: ALPK1 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.3 ALPK1 Arina Puzriakova Added comment: Comment on list classification: This gene is associated with a phenotype in OMIM and Gene2Phenotype (Strong). There is enough evidence to support a gene-disease association - recurrent infections present in some. This gene should be rated Green at the next review.

PMID: 35868845 - 27 patients with ROSAH syndrome, in vitro assays and systematic analysis demonstrated inflammatory features establishing ROSAH as autoinflammatory disease.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.3 ALPK1 Arina Puzriakova Gene: alpk1 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.2 ALPK1 Arina Puzriakova Phenotypes for gene: ALPK1 were changed from ROSAH syndrome to ROSAH syndrome, OMIM:614979
Congenital myopathy v4.23 TPM2 Achchuthan Shanmugasundram reviewed gene: TPM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19155175, 24692096, 33558124; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.23 TNNT1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TNNT1.
Tag Q2_23_NHS_review tag was added to gene: TNNT1.
Congenital myopathy v4.23 TNNT1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As reviewed by Anna Sarkozy, monoallelic variants in TNNT1 have been reported in two unrelated families with nemaline myopathy and supported by in vitro functional studies. There is sufficient evidence available for updating the MOI from "BIALLELIC, autosomal or pseudoautosomal" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next GMS review.
Congenital myopathy v4.23 TNNT1 Achchuthan Shanmugasundram Mode of inheritance for gene: TNNT1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v4.22 TNNT1 Achchuthan Shanmugasundram reviewed gene: TNNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29178646, 35510366; Phenotypes: Nemaline myopathy 5, Amish type, OMIM:605355; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.22 NEB Achchuthan Shanmugasundram Tag watchlist_moi tag was added to gene: NEB.
Congenital myopathy v4.22 NEB Achchuthan Shanmugasundram commented on gene: NEB
Congenital myopathy v4.22 MYH7 Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: MYH7.
Congenital myopathy v4.22 MYH3 Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: MYH3.
Congenital myopathy v4.22 MYH3 Achchuthan Shanmugasundram Tag Q2_23_MOI tag was added to gene: MYH3.
Congenital myopathy v4.22 MYH3 Achchuthan Shanmugasundram Phenotypes for gene: MYH3 were changed from Arthrogryposis, distal, type 2A (Freeman-Sheldon), OMIM:193700; Arthrogryposis, distal, type 2B3 (Sheldon-Hall), OMIM:618436 to Arthrogryposis, distal, type 2A (Freeman-Sheldon), OMIM:193700; Arthrogryposis, distal, type 2B3 (Sheldon-Hall), OMIM:618436; Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A, OMIM:178110; Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B, OMIM:618469
Congenital myopathy v4.21 MYH3 Achchuthan Shanmugasundram Publications for gene: MYH3 were set to 18695058; 26578207; 29805041; 32902138
Congenital myopathy v4.21 MYH3 Achchuthan Shanmugasundram Publications for gene: MYH3 were set to 18695058; 26578207
Congenital myopathy v4.20 MYH3 Achchuthan Shanmugasundram Mode of inheritance for gene: MYH3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital myopathy v4.19 MYH3 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As reviewed by Anna Sarkozy, there is sufficient evidence for updating the MOI of this gene from "MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next major review.
Congenital myopathy v4.19 MYH3 Achchuthan Shanmugasundram Mode of inheritance for gene: MYH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.18 MYH3 Achchuthan Shanmugasundram reviewed gene: MYH3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29805041, 32902138; Phenotypes: Arthrogryposis, distal, type 2A (Freeman-Sheldon), OMIM:193700, Arthrogryposis, distal, type 2B3 (Sheldon-Hall), OMIM:618436, Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A, OMIM:178110, Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B, OMIM:618469; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.18 DNM2 Achchuthan Shanmugasundram commented on gene: DNM2: The "watchlist_moi" tag is added to this gene to review the MOI in light of any new evidence as there is one family reported with biallelic inheritance.
Congenital myopathy v4.18 DNM2 Achchuthan Shanmugasundram Tag watchlist_moi tag was added to gene: DNM2.
Congenital myopathy v4.18 DNM2 Achchuthan Shanmugasundram Phenotypes for gene: DNM2 were changed from Centronuclear myopathy 1, OMIM:160150; Lethal congenital contracture syndrome 5, OMIM:615368 to Centronuclear myopathy 1, OMIM:160150; Lethal congenital contracture syndrome 5, OMIM:615368
Congenital myopathy v4.17 DNM2 Achchuthan Shanmugasundram Phenotypes for gene: DNM2 were changed from Centronuclear myopathy 1, OMIM:160150 to Centronuclear myopathy 1, OMIM:160150; Lethal congenital contracture syndrome 5, OMIM:615368
Congenital myopathy v4.16 DNM2 Achchuthan Shanmugasundram Publications for gene: DNM2 were set to 22396310
Congenital myopathy v4.15 DNM2 Achchuthan Shanmugasundram reviewed gene: DNM2: Rating: ; Mode of pathogenicity: None; Publications: 23092955; Phenotypes: Lethal congenital contracture syndrome 5, OMIM:615368; Mode of inheritance: None
Congenital muscular dystrophy v4.7 EMD Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: EMD.
Congenital muscular dystrophy v4.7 EMD Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Anna Sarkozy, patients with Emery-Dreifuss muscular dystrophy 1(EDMD1) present symptoms (skeletal muscle and/ or cardiac manifestations) in childhood./ There is sufficient evidence (>3 cases) for this gene to be promoted to green in the next major review.; to: Comment on list classification: As reviewed by Anna Sarkozy, patients with Emery-Dreifuss muscular dystrophy 1(EDMD1) present symptoms (skeletal muscle and/ or cardiac manifestations) in childhood. There is sufficient evidence (>3 cases) for this gene to be promoted to green in the next major review.
Congenital muscular dystrophy v4.7 DTNA Achchuthan Shanmugasundram Tag Q1_23_NHS_review tag was added to gene: DTNA.
Congenital muscular dystrophy v4.7 BET1 Achchuthan Shanmugasundram Tag Q1_23_NHS_review tag was added to gene: BET1.
Congenital muscular dystrophy v4.7 GOSR2 Achchuthan Shanmugasundram Tag Q1_23_NHS_review tag was added to gene: GOSR2.
Congenital myopathy v4.15 GBE1 Achchuthan Shanmugasundram Tag Q1_23_NHS_review tag was added to gene: GBE1.
Congenital myopathy v4.15 DNAJB4 Achchuthan Shanmugasundram Tag Q1_23_NHS_review tag was added to gene: DNAJB4.
Congenital myopathy v4.15 COL25A1 Achchuthan Shanmugasundram Tag Q1_23_NHS_review tag was added to gene: COL25A1.
Congenital myopathy v4.15 COL13A1 Achchuthan Shanmugasundram Tag Q1_23_NHS_review tag was added to gene: COL13A1.
Congenital myopathy v4.15 ASCC1 Achchuthan Shanmugasundram Tag Q1_23_NHS_review tag was added to gene: ASCC1.
Congenital muscular dystrophy v4.7 DAG1 Achchuthan Shanmugasundram changed review comment from: "watchlist_moi" tag added to review this gene for MOI change when more monoallelic cases are reported in the literature.; to: "watchlist_moi" tag added to review this gene for MOI change with new evidence.
Paediatric or syndromic cardiomyopathy v3.1 TBX20 Matthew Edwards gene: TBX20 was added
gene: TBX20 was added to Paediatric or syndromic cardiomyopathy. Sources: Other
Mode of inheritance for gene: TBX20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBX20 were set to PMID: 33585493; PMID: 275101702, PMID: 28798025; PMID: 32600061, PMID: 22080862
Phenotypes for gene: TBX20 were set to Cardiomyopathy, dilated with or without LVNC; Atrial septal defect, congential heart disease
Penetrance for gene: TBX20 were set to unknown
Review for gene: TBX20 was set to GREEN
Added comment: TBX20 encodes transcription factors involved in the regulation of several important aspects of cardiac development and homeostasis and heart function. Pathogenic variants in TBX20 are widely associated with the complex spectrum of congenital heart defects and it has also been reported in association with dilated cardiomyopathies and heart arrhythmia (PMID: 33585493)
Although loss of function (LoF) has not been clearly established as a disease mechanism for TBX20 in dilated cardiomyopathy (DCM) and left ventricular non-compaction (LVNC), several LoF alterations have been reported in individuals with these conditions, segregating with disease in several families (PMID: 275101702, PMID: 28798025). In addition mouse model studies have shown that mutant mice with conditional Tbx20 ablation in adult cardiomyocytes have dilated hearts with a rapid loss of systolic function and slower conduction and severe arrhythmia (PMID: 32600061, PMID: 22080862). A functional study ofa truncating variant identified in a DCM case, revealed that the truncated TBX20 protein had no transcriptional activity in contrast to its wild-type counterpart, which further supports the previous mouse model findings and LoF as a disease mechanism for DCM/LVNC (PMID: 275101702).
Sources: Other
Congenital muscular dystrophy v4.7 DAG1 Achchuthan Shanmugasundram commented on gene: DAG1: "watchlist_moi" tag added to review this gene for MOI change when more monoallelic cases are reported in the literature.
Congenital muscular dystrophy v4.7 DAG1 Achchuthan Shanmugasundram Tag watchlist_moi tag was added to gene: DAG1.
Congenital muscular dystrophy v4.7 DAG1 Achchuthan Shanmugasundram reviewed gene: DAG1: Rating: ; Mode of pathogenicity: None; Publications: 35082294; Phenotypes: ; Mode of inheritance: None
Congenital muscular dystrophy v4.7 EMD Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: EMD.
Congenital muscular dystrophy v4.7 EMD Achchuthan Shanmugasundram changed review comment from: As reviewed by Anna Sarkozy, patients with Emery-Dreifuss muscular dystrophy 1(EDMD1) present symptoms (skeletal muscle and/ or cardiac manifestations) in childhood.

EDMD1 is a rare X-linked recessive disease characterised by early childhood joint contractures, progressive weakness in muscles and cardiac involvement and can result in sudden death.

PMID:21697856 reported18 patients and three carriers identified with variants in EMD gene. The patients presented with EDMD and the Age at diagnosis was reported for all, but age of onset was only reported for only a few. The youngest patient was 5 days old but asymptomatic, eldest was 55 years. Of those with age of onset reported, 3 had progressive muscle weakness onset from neonatal to 5 years of age.

PMID:31645980 reported a male patient that began having difficulty moving his limb gridle and cervical vertebrae at the age of 5 years. The condition worsened when he was 13 years, and normal exercise was limited, with serious elbow contracture and mild scapular winging contracture.

PMID:31802929 reported one family with 10 affected males with serious cardiac conduction abnormalities at an early age and a high incidence of sudden cardiac death (SCD) along with mild skeletal muscular atrophy, joint contracture and elevated CK levels. and mild skeletal muscular dystrophy.

PMID:34026875 reported three unrelated patients with EDMD, who had cardiac manifestation in childhood without any skeletal muscle phenotypes.

This gene has been associated with phenotypes in OMIM (MIM #310300), which also describes the disorder as primarily of childhood onset. It has not yet been reported in Gene2Phenotype.; to: EDMD1 is a rare X-linked recessive disease characterised by early childhood joint contractures, progressive weakness in muscles and cardiac involvement and can result in sudden death.

PMID:21697856 reported18 patients and three carriers identified with variants in EMD gene. The patients presented with EDMD and the Age at diagnosis was reported for all, but age of onset was only reported for only a few. The youngest patient was 5 days old but asymptomatic, eldest was 55 years. Of those with age of onset reported, 3 had progressive muscle weakness onset from neonatal to 5 years of age.

PMID:31645980 reported a male patient that began having difficulty moving his limb gridle and cervical vertebrae at the age of 5 years. The condition worsened when he was 13 years, and normal exercise was limited, with serious elbow contracture and mild scapular winging contracture.

PMID:31802929 reported one family with 10 affected males with serious cardiac conduction abnormalities at an early age and a high incidence of sudden cardiac death (SCD) along with mild skeletal muscular atrophy, joint contracture and elevated CK levels. and mild skeletal muscular dystrophy.

PMID:34026875 reported three unrelated patients with EDMD, who had cardiac manifestation in childhood without any skeletal muscle phenotypes.

This gene has been associated with phenotypes in OMIM (MIM #310300), which also describes the disorder as primarily of childhood onset. It has not yet been reported in Gene2Phenotype.
Congenital muscular dystrophy v4.7 EMD Achchuthan Shanmugasundram Classified gene: EMD as Amber List (moderate evidence)
Congenital muscular dystrophy v4.7 EMD Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Anna Sarkozy, patients with Emery-Dreifuss muscular dystrophy 1(EDMD1) present symptoms (skeletal muscle and/ or cardiac manifestations) in childhood./ There is sufficient evidence (>3 cases) for this gene to be promoted to green in the next major review.
Congenital muscular dystrophy v4.7 EMD Achchuthan Shanmugasundram Gene: emd has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v4.6 EMD Achchuthan Shanmugasundram edited their review of gene: EMD: Changed publications to: 21697856, 31645980, 31802929, 34026875
Congenital muscular dystrophy v4.6 EMD Achchuthan Shanmugasundram Publications for gene: EMD were set to 21697856; 31645980; 31802929; 34026875
Congenital muscular dystrophy v4.6 EMD Achchuthan Shanmugasundram Publications for gene: EMD were set to
Congenital muscular dystrophy v4.5 EMD Achchuthan Shanmugasundram reviewed gene: EMD: Rating: GREEN; Mode of pathogenicity: None; Publications: 21697856, 31645980, 31802929, :34026875; Phenotypes: Emery-Dreifuss muscular dystrophy 1, X-linked, OMIM:310300; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Severe early-onset obesity v4.1 DYRK1B Tracy Lester gene: DYRK1B was added
gene: DYRK1B was added to Severe early-onset obesity. Sources: NHS GMS
Mode of inheritance for gene: DYRK1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DYRK1B were set to 34193236; 34786696; 24827035
Phenotypes for gene: DYRK1B were set to obesity; diabetes
Penetrance for gene: DYRK1B were set to unknown
Review for gene: DYRK1B was set to GREEN
Added comment: This gene is green on the diabetes panel but there are cases in the literature who also have early-onset obesity
34193236: performed whole-exome sequencing in the probands from 2 of 3 multigenerational Iranian families with metabolic syndrome and early-onset coronary artery disease and identified a heterozygous missense mutation in the DYRK1B gene (R102C; 604556.0001) that segregated with disease in all 3 families.
34786696: report a splice variant in a 5yr old with severe ID, autism, obesity and seizures, inherited from affected father and also segregates in 2 affected sisters. RNA studies confimed aberrant splicing leading to LOF
24827035: patients with type 2 diabetes and obesity, identified 2 missense that co-segregated with full penetrance (R252H and K68Q). Age-dependent variable expressivity described with central obesity and insulin resistance apparent in childhood and morbid obesity, severe triglyceridemia and labile type 2 diabetes before age 40. Youngest aged 11.
Sources: NHS GMS
Congenital muscular dystrophy v4.5 DTNA Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: DTNA.
Congenital muscular dystrophy v4.5 DTNA Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital), there is sufficient evidence for this gene to be promoted to GREEN at the next major review.

This gene has not yet been associated with muscular dystrophy phenotype either in OMIM or in G2P.; to: Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital), there is sufficient evidence for this gene to be promoted to GREEN at the next major review.

This gene has not yet been associated with muscular dystrophy phenotype either in OMIM or in Gene2Phenotype.
Congenital muscular dystrophy v4.5 DTNA Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital), there is sufficient evidence for this gene to be promoted to GREEN at the next major review.; to: Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital), there is sufficient evidence for this gene to be promoted to GREEN at the next major review.

This gene has not yet been associated with muscular dystrophy phenotype either in OMIM or in G2P.
Congenital muscular dystrophy v4.5 DTNA Achchuthan Shanmugasundram Classified gene: DTNA as Amber List (moderate evidence)
Congenital muscular dystrophy v4.5 DTNA Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital), there is sufficient evidence for this gene to be promoted to GREEN at the next major review.
Congenital muscular dystrophy v4.5 DTNA Achchuthan Shanmugasundram Gene: dtna has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v4.4 DTNA Achchuthan Shanmugasundram reviewed gene: DTNA: Rating: GREEN; Mode of pathogenicity: None; Publications: 36799992; Phenotypes: muscular dystrophy, MONDO:0020121; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital muscular dystrophy v4.4 DTNA Achchuthan Shanmugasundram Phenotypes for gene: DTNA were changed from muscular dystrophy to muscular dystrophy, MONDO:0020121
Congenital muscular dystrophy v4.3 DTNA Achchuthan Shanmugasundram Publications for gene: DTNA were set to 36799992
Congenital muscular dystrophy v4.3 DTNA Achchuthan Shanmugasundram Publications for gene: DTNA were set to 36799992
Congenital muscular dystrophy v4.2 DTNA Achchuthan Shanmugasundram Publications for gene: DTNA were set to 36799992
Congenital muscular dystrophy v4.2 DTNA Achchuthan Shanmugasundram Publications for gene: DTNA were set to PMID: 36799992
Congenital muscular dystrophy v4.1 GOSR2 Achchuthan Shanmugasundram edited their review of gene: GOSR2: Changed phenotypes to: Muscular dystrophy, congenital, with or without seizures, OMIM:620166
Congenital myopathy v4.15 GBE1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: GBE1.
Congenital myopathy v4.15 GBE1 Achchuthan Shanmugasundram Classified gene: GBE1 as Amber List (moderate evidence)
Congenital myopathy v4.15 GBE1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital), biallelic variants in GBE1 has been reported in sufficient number of cases presenting with fetal akinesia/hypokinesia, arthrogryposis multiplex congenita and severe congenital myopathies. Hence, this gene can be promoted to GREEN rating at the next major review.

This gene has been associated with phenotypes in both OMIM and Gene2Phenotype (with 'definitive' rating).
Congenital myopathy v4.15 GBE1 Achchuthan Shanmugasundram Gene: gbe1 has been classified as Amber List (Moderate Evidence).
Congenital myopathy v4.14 GBE1 Achchuthan Shanmugasundram reviewed gene: GBE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23218673, 26578207, 30303820, 30569318; Phenotypes: Glycogen storage disease IV, OMIM:232500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v4.14 GBE1 Achchuthan Shanmugasundram Publications for gene: GBE1 were set to PMID: 23218673; 30303820; PMID: 26578207
Congenital myopathy v4.13 DNAJB4 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: DNAJB4.
Congenital myopathy v4.13 DNAJB4 Achchuthan Shanmugasundram Publications for gene: DNAJB4 were set to PMID: 36264506
Congenital myopathy v4.12 DNAJB4 Achchuthan Shanmugasundram Classified gene: DNAJB4 as Amber List (moderate evidence)
Congenital myopathy v4.12 DNAJB4 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital), there is sufficient evidence (three unrelated cases and functional evidence from mouse models) for promoting this gene to GREEN at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with 'limited' rating.
Congenital myopathy v4.12 DNAJB4 Achchuthan Shanmugasundram Gene: dnajb4 has been classified as Amber List (Moderate Evidence).
Congenital myopathy v4.11 COL25A1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: COL25A1.
Congenital myopathy v4.11 COL25A1 Achchuthan Shanmugasundram Phenotypes for gene: COL25A1 were changed from rthrogryposis multiplex congenita with or without ocular congenital cranial dysinnervation disorder to Arthrogryposis multiplex congenita with or without ocular congenital cranial dysinnervation disorder
Congenital myopathy v4.10 COL25A1 Achchuthan Shanmugasundram Publications for gene: COL25A1 were set to PMID: 35077597
Congenital myopathy v4.9 COL25A1 Achchuthan Shanmugasundram Classified gene: COL25A1 as Amber List (moderate evidence)
Congenital myopathy v4.9 COL25A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As per expert review by Anna Sarkozy (Great Ormond Street Hospital), the condition caused by biallelic variants in this gene has overlap in clinical presentations with other forms of myopathies. Hence, this gene should be considered for promotion to green at the next major review.
Congenital myopathy v4.9 COL25A1 Achchuthan Shanmugasundram Gene: col25a1 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.3 COL25A1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: COL25A1.
Arthrogryposis v5.3 COL25A1 Achchuthan Shanmugasundram Classified gene: COL25A1 as Amber List (moderate evidence)
Arthrogryposis v5.3 COL25A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated cases) for promoting this gene to GREEN rating at the next major review.
Arthrogryposis v5.3 COL25A1 Achchuthan Shanmugasundram Gene: col25a1 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.2 COL25A1 Achchuthan Shanmugasundram gene: COL25A1 was added
gene: COL25A1 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: COL25A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL25A1 were set to 35077597
Phenotypes for gene: COL25A1 were set to Arthrogryposis multiplex congenita with or without an ocular congenital cranial dysinnervation disorder
Review for gene: COL25A1 was set to GREEN
Added comment: PMID:35077597 reported five patients from three unrelated families identified with biallelic variants in COL25A1 gene presented with a phenotype characterized by arthrogryposis with or without an ocular congenital cranial dysinnervation disorder. The severity of arthrogryposis varied, ranging from mild distal upper limb involvement to arthrogryposis multiplex congenita.

Although the extraocular muscle phenotype has been reported in OMIM (MIM # 616219) and Gene2Phenotype, arthrogryposis has not yet been included in these records.
Sources: Literature
Congenital fibrosis of the extraocular muscles v1.13 COL25A1 Achchuthan Shanmugasundram changed review comment from: PMID:35077597 reported five patients from three unrelated families identified with biallelic variants in COL25A1 gene. Of these four patients from three families had ocular congenital cranial dysinnervation disorder phenotype.

This gene has been associated with this phenotype in both OMIM and Gene2Phenotype (with 'strong' rating).; to: Comment on gene classification: There is sufficient evidence (five unrelated cases) for promoting this gene to GREEN at the next major review.

PMID:35077597 reported five patients from three unrelated families identified with biallelic variants in COL25A1 gene. Of these four patients from three families had ocular congenital cranial dysinnervation disorder phenotype.

This gene has been associated with this phenotype in both OMIM and Gene2Phenotype (with 'strong' rating).
Congenital fibrosis of the extraocular muscles v1.13 COL25A1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: COL25A1.
Congenital fibrosis of the extraocular muscles v1.13 COL25A1 Achchuthan Shanmugasundram Publications for gene: COL25A1 were set to 25500261
Congenital fibrosis of the extraocular muscles v1.12 COL25A1 Achchuthan Shanmugasundram reviewed gene: COL25A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35077597; Phenotypes: Fibrosis of extraocular muscles, congenital, 5, OMIM:616219; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.11 KDM5A Tracy Lester reviewed gene: KDM5A: Rating: AMBER; Mode of pathogenicity: None; Publications: 33350388; Phenotypes: ASD, lack of speech; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myaesthenic syndrome v4.1 COL13A1 Achchuthan Shanmugasundram reviewed gene: COL13A1: Rating: ; Mode of pathogenicity: None; Publications: 31449669; Phenotypes: ; Mode of inheritance: None
Congenital myaesthenic syndrome v4.1 COL13A1 Achchuthan Shanmugasundram Tag treatable tag was added to gene: COL13A1.
Congenital myopathy v4.8 COL13A1 Achchuthan Shanmugasundram Classified gene: COL13A1 as Amber List (moderate evidence)
Congenital myopathy v4.8 COL13A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for the association of this gene with myopathy and hence it can be promoted to GREEN rating in the next major review.
Congenital myopathy v4.8 COL13A1 Achchuthan Shanmugasundram Gene: col13a1 has been classified as Amber List (Moderate Evidence).
Congenital myopathy v4.7 COL13A1 Achchuthan Shanmugasundram commented on gene: COL13A1: The 'treatable' tag has been added as salbutamol alone or in combination with 3,4-DAP was reported effective in all tested patients (PMID:31449669).
Congenital myopathy v4.7 COL13A1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: COL13A1.
Congenital myopathy v4.7 COL13A1 Achchuthan Shanmugasundram Tag treatable tag was added to gene: COL13A1.
Congenital myopathy v4.7 COL13A1 Achchuthan Shanmugasundram Phenotypes for gene: COL13A1 were changed from to Myasthenic syndrome, congenital, 19, OMIM:616720
Congenital myopathy v4.6 COL13A1 Achchuthan Shanmugasundram Publications for gene: COL13A1 were set to PMID: 30767057; 31081514
Congenital myopathy v4.5 COL13A1 Achchuthan Shanmugasundram reviewed gene: COL13A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30767057, 31018245, 31449669; Phenotypes: Myasthenic syndrome, congenital, 19, OMIM:616720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v4.5 ASCC1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence (>3 unrelated cases and functional evidence from zebrafish model) for this gene to be promoted to GREEN rating at the next major review.

This gene has already been associated with relevant phenotypes in both OMIM and Gene2Phenotype.; to: Comment on list classification: There is sufficient evidence (>3 unrelated cases and functional evidence from zebrafish model) for this gene to be promoted to GREEN rating at the next major review.

This gene has already been associated with relevant phenotypes in both OMIM and Gene2Phenotype.
Congenital myopathy v4.5 ASCC1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: ASCC1.
Congenital myopathy v4.5 ASCC1 Achchuthan Shanmugasundram Classified gene: ASCC1 as Amber List (moderate evidence)
Congenital myopathy v4.5 ASCC1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases and functional evidence from zebrafish model) for this gene to be promoted to GREEN rating at the next major review.

This gene has already been associated with relevant phenotypes in both OMIM and Gene2Phenotype.
Congenital myopathy v4.5 ASCC1 Achchuthan Shanmugasundram Gene: ascc1 has been classified as Amber List (Moderate Evidence).
Congenital myopathy v4.4 ASCC1 Achchuthan Shanmugasundram Phenotypes for gene: ASCC1 were changed from prenatal-onset muscle weakness; congenital onset myopathy; arthrogryposis; congenital bone fractures to Spinal muscular atrophy with congenital bone fractures 2, OMIM:616867
Congenital myopathy v4.3 ASCC1 Achchuthan Shanmugasundram Publications for gene: ASCC1 were set to PMID: 35838082; 30327447; 35690317
Congenital myopathy v4.2 ASCC1 Achchuthan Shanmugasundram reviewed gene: ASCC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26924529, 28218388, 30327447, 35276412, 35690317, 35838082; Phenotypes: Spinal muscular atrophy with congenital bone fractures 2, OMIM:616867; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.4 UBAP2L Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Konstantinos Varvagiannis, 7 out of 12 unrelated cases from PMID:35977029 had seizures, while 3 of them had a formal diagnosis of epilepsy. This is sufficient evidence to promote this gene to GREEN at the next major review.

This gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate rating'.; to: Comment on list classification: As reviewed by Konstantinos Varvagiannis, 7 out of 12 unrelated cases from PMID:35977029 had seizures, while 3 of them had a formal diagnosis of epilepsy. This is sufficient evidence to promote this gene to GREEN at the next major review.

This gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.
Early onset or syndromic epilepsy v4.4 UBAP2L Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: UBAP2L.
Early onset or syndromic epilepsy v4.4 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.4 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, 7 out of 12 unrelated cases from PMID:35977029 had seizures, while 3 of them had a formal diagnosis of epilepsy. This is sufficient evidence to promote this gene to GREEN at the next major review.

This gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate rating'.
Early onset or syndromic epilepsy v4.4 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.; to: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and the association is supported by functional studies from mouse models. This gene therefore has sufficient evidence for promotion to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.; to: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: UBAP2L.
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.9 CAPRIN1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As indicated by the previous reviewers, there is sufficient evidence (>10 unrelated cases) for this gene to be promoted to GREEN at the next major review.

However, this gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.; to: Comment on list classification: As indicated by the previous reviewers, there is sufficient evidence (>10 unrelated cases and supporting functional evidence) for this gene to be promoted to GREEN at the next major review.

However, this gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.
Intellectual disability v5.9 CAPRIN1 Achchuthan Shanmugasundram Mode of inheritance for gene: CAPRIN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.9 CAPRIN1 Achchuthan Shanmugasundram Mode of inheritance for gene: CAPRIN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.9 CAPRIN1 Achchuthan Shanmugasundram Mode of inheritance for gene: CAPRIN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.9 CAPRIN1 Achchuthan Shanmugasundram Mode of inheritance for gene: CAPRIN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.9 CAPRIN1 Achchuthan Shanmugasundram Mode of inheritance for gene: CAPRIN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.8 CAPRIN1 Achchuthan Shanmugasundram Publications for gene: CAPRIN1 were set to 23849776; 35979925; 36136249
Intellectual disability v5.8 CAPRIN1 Achchuthan Shanmugasundram Publications for gene: CAPRIN1 were set to 23849776; 35979925; 36136249
Intellectual disability v5.8 CAPRIN1 Achchuthan Shanmugasundram Publications for gene: CAPRIN1 were set to 23849776; 35979925; 36136249
Intellectual disability v5.8 CAPRIN1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.8 CAPRIN1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.8 CAPRIN1 Achchuthan Shanmugasundram Publications for gene: CAPRIN1 were set to 23849776; 35979925; 36136249
Intellectual disability v5.7 CAPRIN1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.7 CAPRIN1 Achchuthan Shanmugasundram Publications for gene: CAPRIN1 were set to 23849776; 35979925; 36136249
Intellectual disability v5.7 CAPRIN1 Achchuthan Shanmugasundram Publications for gene: CAPRIN1 were set to 23849776
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Classified gene: CAPRIN1 as Amber List (moderate evidence)
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As indicated by the previous reviewers, there is sufficient evidence (>10 unrelated cases) for this gene to be promoted to GREEN at the next major review.

However, this gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Gene: caprin1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Classified gene: CAPRIN1 as Amber List (moderate evidence)
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As indicated by the previous reviewers, there is sufficient evidence (>10 unrelated cases) for this gene to be promoted to GREEN at the next major review.

However, this gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Gene: caprin1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: CAPRIN1.
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Classified gene: CAPRIN1 as Amber List (moderate evidence)
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As indicated by the previous reviewers, there is sufficient evidence (>10 unrelated cases) for this gene to be promoted to GREEN at the next major review.

However, this gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Gene: caprin1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Classified gene: CAPRIN1 as Amber List (moderate evidence)
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As indicated by the previous reviewers, there is sufficient evidence (>10 unrelated cases) for this gene to be promoted to GREEN at the next major review.

However, this gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Gene: caprin1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.1 CAPRIN1 Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. The 'watchlist' tag has been added to look out for new evidence in order to promote this gene to green.

PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor & sensory axonal neuropathy) as the other two patients.

In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics.

These functional evidences also suggest a gain-of-function mechanism for P512L variant.; to: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. The 'watchlist' tag has been added to look out for new evidence in order to promote this gene to green.

PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor/ sensory axonal neuropathy) as the other two patients.

In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics.

These functional evidences also suggest a gain-of-function mechanism for P512L variant.
Ataxia and cerebellar anomalies - narrow panel v4.1 CAPRIN1 Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. The 'watchlist' tag has been added to look out for new evidence in order to promote this gene to green.

PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor > sensory axonal neuropathy) as the other two patients.

In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics.

These functional evidences also suggest a gain-of-function mechanism for P512L variant.; to: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. The 'watchlist' tag has been added to look out for new evidence in order to promote this gene to green.

PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor & sensory axonal neuropathy) as the other two patients.

In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics.

These functional evidences also suggest a gain-of-function mechanism for P512L variant.
Childhood onset hereditary spastic paraplegia v4.2 WASHC5 Achchuthan Shanmugasundram Publications for gene: WASHC5 were set to 17160902
Childhood onset hereditary spastic paraplegia v4.1 WASHC5 Achchuthan Shanmugasundram Tag Q1_23_expert_review tag was added to gene: WASHC5.
Childhood onset hereditary spastic paraplegia v4.1 WASHC5 Achchuthan Shanmugasundram Tag Q1_23_demote_red tag was added to gene: WASHC5.
Childhood onset hereditary spastic paraplegia v4.1 WASHC5 Achchuthan Shanmugasundram reviewed gene: WASHC5: Rating: RED; Mode of pathogenicity: None; Publications: 17160902, 23455931, 26572744, 31814071, 33662919; Phenotypes: Spastic paraplegia 8, autosomal dominant, OMIM:603563; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v3.2 TDP1 Ian Berry reviewed gene: TDP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 12244316, PMID: 31182267; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary ataxia with onset in adulthood v4.1 TDP1 Ian Berry reviewed gene: TDP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: PMID: 12244316, PMID: 31182267; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Multiple monogenic benign skin tumours v2.2 PRDM10 Achchuthan Shanmugasundram gene: PRDM10 was added
gene: PRDM10 was added to Multiple monogenic benign skin tumours. Sources: Literature
Mode of inheritance for gene: PRDM10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRDM10 were set to 36440963
Phenotypes for gene: PRDM10 were set to Fibrofolliculoma, HP:0030436; lipomatosis, MONDO:0006574; renal cell carcinoma, MONDO:0005086
Review for gene: PRDM10 was set to RED
Added comment: Comment on gene rating: This gene should be rated RED as it has only been identified with a variant in this gene from one family.

PMID:36440963 reported a family presenting with skin and mucosal lesions, extensive lipomatosis and renal cell carcinomas. The proband was initially diagnosed with Birt-Hogg-Dubé syndrome (BHD, MIM #135150) based on the presence of fibrofolliculomas, but no pathogenic germline variant was detected in FLCN, the gene associated with BHD. A heterozygous missense variant (p.Cys677Tyr) was identified, which co-segregated with the phenotype in the family.

Functional studies show that Cys677Tyr loses affinity for a regulatory binding motif in the FLCN promoter, abrogating cellular FLCN mRNA and protein levels. Overexpressing inducible PRDM10Cys677Tyr in renal epithelial cells altered the transcription of multiple genes, showing overlap but also differences with the effects of knocking out FLCN.

This gene has not yet been associated with phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Inherited renal cancer v1.24 PRDM10 Achchuthan Shanmugasundram gene: PRDM10 was added
gene: PRDM10 was added to Inherited renal cancer. Sources: Literature
Mode of inheritance for gene: PRDM10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRDM10 were set to 36440963
Phenotypes for gene: PRDM10 were set to Fibrofolliculoma, HP:0030436; lipomatosis, MONDO:0006574; renal cell carcinoma, MONDO:0005086
Review for gene: PRDM10 was set to RED
Added comment: Comment on gene rating: This gene should be rated RED as it has only been identified with a variant in this gene from one family.

PMID:36440963 reported a family presenting with skin and mucosal lesions, extensive lipomatosis and renal cell carcinomas. The proband was initially diagnosed with Birt-Hogg-Dubé syndrome (BHD, MIM #135150) based on the presence of fibrofolliculomas, but no pathogenic germline variant was detected in FLCN, the gene associated with BHD. A heterozygous missense variant (p.Cys677Tyr) was identified, which co-segregated with the phenotype in the family.

Functional studies show that Cys677Tyr loses affinity for a regulatory binding motif in the FLCN promoter, abrogating cellular FLCN mRNA and protein levels. Overexpressing inducible PRDM10Cys677Tyr in renal epithelial cells altered the transcription of multiple genes, showing overlap but also differences with the effects of knocking out FLCN.

This gene has not yet been associated with phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Congenital myopathy v4.2 DNAJB4 Anna Sarkozy gene: DNAJB4 was added
gene: DNAJB4 was added to Congenital myopathy. Sources: Literature
Mode of inheritance for gene: DNAJB4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJB4 were set to PMID: 36264506
Phenotypes for gene: DNAJB4 were set to congenital myopathy with early respiratory failure
Penetrance for gene: DNAJB4 were set to unknown
Mode of pathogenicity for gene: DNAJB4 was set to Other
Review for gene: DNAJB4 was set to GREEN
Added comment: biallelic variants in DNAJB4 gene have now been described in three unrelated families, in particular stop gain and missense variants. the phenotype is characterised by axial rigidity and early respiratory failure between the 1st and 4th decade of life. muscle pathology is myopathic with protein inclusions and occasional rimmed vacuoles.
Sources: Literature
Congenital muscular dystrophy v4.1 GOSR2 Anna Sarkozy reviewed gene: GOSR2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 33639315, 33639315; Phenotypes: congenital muscular dystrophy with secondary alpha-dystroglycanopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital muscular dystrophy v4.1 EMD Anna Sarkozy reviewed gene: EMD: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: Emery Dreifuss muscular dystrophy, X linked; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Congenital muscular dystrophy v4.1 BET1 Anna Sarkozy reviewed gene: BET1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 34779586; Phenotypes: congenital muscular dystrophy with epilepsy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital muscular dystrophy v4.1 PYROXD1 Anna Sarkozy gene: PYROXD1 was added
gene: PYROXD1 was added to Congenital muscular dystrophy. Sources: Literature
Mode of inheritance for gene: PYROXD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYROXD1 were set to PMID: 33694278; 30515627
Phenotypes for gene: PYROXD1 were set to muscular dystrophy
Penetrance for gene: PYROXD1 were set to unknown
Mode of pathogenicity for gene: PYROXD1 was set to Other
Review for gene: PYROXD1 was set to GREEN
Added comment: this gene is already included as green gene in the CM panel. there is body of evidence that the clinical spectrum of this gene is wider and also includes dystrophic presentations with raised CK. thus this gene should also be included in the CMD R79 panel
Sources: Literature
Congenital muscular dystrophy v4.1 DAG1 Anna Sarkozy reviewed gene: DAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35082294; Phenotypes: muscular dystrophy, secondary alpha-dystroglycanopathy, hyper-CKemia; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.2 TPM2 Anna Sarkozy edited their review of gene: TPM2: Added comment: comment re inheritance: recessive TPM2 pathogenic variant has been described in a patient with multiple pterygium syndrome and congenital myopathy. heterozygous carrier parents were unaffected, supporting recessive inheritance of the variant.; Changed publications to: 33558124; Changed phenotypes to: CAP myopathy 2 609285, Nemaline myopathy 4, autosomal dominant 609285, recessively inherited Escobar variant of multiple pterygium syndrome and congenital myopathy; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.2 TNNT1 Anna Sarkozy edited their review of gene: TNNT1: Added comment: comment re inheritance: both dominant and recessive TNNT1 gene variants have now been reported in patients with congenital myopathies. Dominant mutations are likely acting via a dominant negative mechanism; Changed publications to: 26296490, 25430424, 35510366, 29178646; Changed phenotypes to: nemaline myopathy, Nemaline Myopathy, Recessive, Nemaline myopathy 5, Amish type, 605355, autpsomal dominant nemaline myopathy; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.2 NEB Anna Sarkozy edited their review of gene: NEB: Added comment: comment re inheritance: a large in frame deletion in the NEB gene have now been described in a three-generation family and was shown to cause the production of a smaller mutant nebulin protein. Thus, it was suggested that this novel mutant nebulin protein has a dominant-negative effect.; Changed publications to: 12207937, 30679003; Changed phenotypes to: nemaline myopathy, Nemaline Myopathy, Recessive, Nemaline myopathy 2, autosomal recessive, 256030, Dominantly inherited distal nemaline/cap myopathy; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.2 MYH7 Anna Sarkozy edited their review of gene: MYH7: Added comment: re inheritance mode: recessive variants in MYH7 are now well recognised in patients with congenital myopathies; Changed publications to: 15322983, 31130376, 31130376; Changed phenotypes to: Laing Distal Myopathy 160500, congenital myopathy
Congenital myopathy v4.2 MYH3 Anna Sarkozy edited their review of gene: MYH3: Added comment: Recessive MYH3 variants reported in patients with multiple pterygia and this disease entity is designated as "Contractures, pterygia, and variable skeletal fusions syndrome 1B," in OMIM.; Changed publications to: 18695058, 26578207, 32902138; Changed phenotypes to: Arthrogryposis, distal, type 2A 193700, Arthrogryposis, distal, type 2B 601680, Arthrogryposis, distal, type 8 178110, ontractures, pterygia, and variable skeletal fusions syndrome 1B; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v4.2 DNM2 Anna Sarkozy edited their review of gene: DNM2: Added comment: biallelic DNM2 variants were also described in three consanguineous patients with lethal congenital syndrome caractherised by akinesia, joint contractures, hypotonia, skeletal abnormalities, and brain and retinal hemorrhages. muscle biopsy and EMG showed myopathic features. in particular, muscle biopsy of one patient showed small rounded fibers with some centralized nuclei, suggestive of a congenital myopathy whereas biopsy of a 2nd patient showed atrophic fibers without obvious centralization of nuclei.; Changed publications to: 22396310, 23092955; Changed phenotypes to: Myopathy, centronuclear, 160150, Charcot-Marie-Tooth disease, axonal, type 2M, 606482, lethal congenital syndrome; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.2 BIN1 Anna Sarkozy edited their review of gene: BIN1: Added comment: Adult-onset autosomal dominant centronuclear myopathy, also with myalgia and CK elevation; Changed publications to: PMID: 25260562, 27854204; Changed phenotypes to: Centronuclear Myopathy, Recessive, Myopathy, centronuclear, autosomal recessive, 255200, dominant centronuclear myopathy; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v4.2 ASCC1 Anna Sarkozy gene: ASCC1 was added
gene: ASCC1 was added to Congenital myopathy. Sources: Literature
Mode of inheritance for gene: ASCC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASCC1 were set to PMID: 35838082; 30327447; 35690317
Phenotypes for gene: ASCC1 were set to prenatal-onset muscle weakness; congenital onset myopathy; arthrogryposis; congenital bone fractures
Penetrance for gene: ASCC1 were set to unknown
Mode of pathogenicity for gene: ASCC1 was set to Other
Review for gene: ASCC1 was set to GREEN
Added comment: recessive pathogenic variants in ASCC1 gene have now been described in a number of unrelated individuals presenting with a spectrum of phenotypes ranging from prenatal-onset muscle weakness with arthrogryposis and congenital bone fractures to milder presentations without fractures, in keeping with a diagnosis of congenital myopathy .
Sources: Literature
Congenital myopathy v4.2 COL13A1 Anna Sarkozy gene: COL13A1 was added
gene: COL13A1 was added to Congenital myopathy. Sources: Literature
Mode of inheritance for gene: COL13A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL13A1 were set to PMID: 30767057; 31081514
Penetrance for gene: COL13A1 were set to unknown
Mode of pathogenicity for gene: COL13A1 was set to Other
Added comment: Affected individuals may present mild non specific myopathic findings on muscle biopsy in addition to clinical features of congenital myasthenic syndrome thus strongly in differential with congenital myopathies.
Sources: Literature
Congenital myopathy v4.2 GBE1 Anna Sarkozy gene: GBE1 was added
gene: GBE1 was added to Congenital myopathy. Sources: Literature,Expert Review
Mode of inheritance for gene: GBE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBE1 were set to PMID: 23218673; 30303820; PMID: 26578207
Phenotypes for gene: GBE1 were set to arthrogryposis multiplex congenita; foetal akinesias; fetal akinesia deformation sequence; severe congenital myopathy; multiple pterygium syndrome
Penetrance for gene: GBE1 were set to unknown
Mode of pathogenicity for gene: GBE1 was set to Other
Review for gene: GBE1 was set to GREEN
Added comment: recessive pathogenic variants in GBE1 gene responsible for GSD IV, have now been identified in a relevant number of patients presenting with severe early onset neuromuscular conditions, ranging from fetal akinesia deformation sequence, to arthrogryposis multiplex congenita and severe forms of congenital onset myopathies. given the major clinical overlap with severe forms of congenital myopathies, this gene should be considered in differential and included in the R81 panel and tested in patients with possible congenital myopathy.
Sources: Literature, Expert Review
Congenital muscular dystrophy v4.1 DTNA Anna Sarkozy gene: DTNA was added
gene: DTNA was added to Congenital muscular dystrophy. Sources: Literature
Mode of inheritance for gene: DTNA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DTNA were set to PMID: 36799992
Phenotypes for gene: DTNA were set to muscular dystrophy
Penetrance for gene: DTNA were set to unknown
Mode of pathogenicity for gene: DTNA was set to Other
Review for gene: DTNA was set to GREEN
Added comment: Nascimento et al described four unrelated families (12 individuals in total) with monoallelic DTNA variants affecting the coiled-coil domain of α-dystrobrevin. the phenotype is characterised by myalgia, exercise intolerance with variable ages of onset, proximal lower limb weakness from first decade, raised CK levels and one report of rhabdomyolysis. Autism spectrum disorder and learning disabilities were also reported. Muscle biopsies showed mixed myopathic and dystrophic findings, with reduced α-dystrobrevin immunoreactivity and variably reduced immunoreactivity of other DGC proteins.
Sources: Literature
Congenital myopathy v4.2 COL25A1 Anna Sarkozy gene: COL25A1 was added
gene: COL25A1 was added to Congenital myopathy. Sources: Expert list,Literature,Expert Review,Research
Mode of inheritance for gene: COL25A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL25A1 were set to PMID: 35077597
Phenotypes for gene: COL25A1 were set to rthrogryposis multiplex congenita with or without ocular congenital cranial dysinnervation disorder
Penetrance for gene: COL25A1 were set to unknown
Mode of pathogenicity for gene: COL25A1 was set to Other
Review for gene: COL25A1 was set to GREEN
Added comment: pathogenic recessive variants (missense and splice site) in the COL25A1 gene have now been described in three unrelated families (5 patients in total) presenting with arthrogryposis multiplex congenita with or without an ocular congenital cranial dysinnervation disorder, normal CK and absence of abnormalities on EMG. Given similarities of presentations with other forms of myopathic contractural phenotypes and no/mild progression over time, this condition should be considered in differential for congenital myopathies, thus we would recommend to add this gene as green gene into the R81 panel.
Sources: Expert list, Literature, Expert Review, Research
Sarcoma cancer susceptibility v1.21 RECQL4 Dmitrijs Rots reviewed gene: RECQL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31604778; Phenotypes: Osteosarcoma; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Classified gene: STX4 as Amber List (moderate evidence)
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as it has been implicated in congenital hearing impairment, as identified from one family and supported by functional studies.
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Gene: stx4 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Classified gene: STX4 as Amber List (moderate evidence)
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as it has been implicated in congenital hearing impairment, as identified from one family and supported by functional studies.
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Gene: stx4 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Classified gene: STX4 as Amber List (moderate evidence)
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as it has been implicated in congenital hearing impairment, as identified from one family and supported by functional studies.
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Gene: stx4 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.4 STX4 Achchuthan Shanmugasundram gene: STX4 was added
gene: STX4 was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: STX4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STX4 were set to 36355422
Phenotypes for gene: STX4 were set to Hearing impairment, HP:0000365
Review for gene: STX4 was set to AMBER
Added comment: PMID:36355422 reported a large consanguineous Pakistani family with eight affected individuals showing bilateral severe-to-profound hearing impairment. A homozygous splice region variant was identified in STX4 (c.232 + 6T>C), which causes exon skipping and a frameshift, that segregated with hearing impairment in this family.

In silico analysis showed that murine Stx4a is highly and widespread expressed in the developing and adult inner ear. Knockdown of stx4 in zebrafish showed an abnormal startle response, morphological and developmental defects, and a disrupted mechanotransduction function in neuromast hair cells.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.5 ARF1 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:36345169 reported a paediatric patient identified with a monoallelic de novo missense variant (c.296 G > A; p.R99H) in the ARF1 gene, associated with developmental delay, hypotonia, intellectual disability and motor stereotypies. This patient did not exhibit periventricular heterotopias previously observed in other patients with ARF1 variants (including p.R99H). Functional analysis shows that the pathogenetic mechanism of the R99H-ARF1 variant involves constitutive activation with resultant Golgi and endosomal alterations.
Intellectual disability v5.5 ARF1 Achchuthan Shanmugasundram Publications for gene: ARF1 were set to 28868155; 34353862; 36345169
Intellectual disability v5.5 ARF1 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:36345169 reported a paediatric patient identified with a monoallelic de novo missense variant (c.296 G > A; p.R99H) in the ARF1 gene, associated with developmental delay, hypotonia, intellectual disability and motor stereotypies. This patient did not exhibit periventricular heterotopias previously observed in other patients with ARF1 variants (including p.R99H). Functional analysis shows that the pathogenetic mechanism of the R99H-ARF1 variant involves constitutive activation with resultant Golgi and endosomal alterations.
Intellectual disability v5.5 ARF1 Achchuthan Shanmugasundram Publications for gene: ARF1 were set to 28868155; 34353862; 36345169
Intellectual disability v5.4 ARF1 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:36345169 reported a paediatric patient identified with a monoallelic de novo missense variant (c.296 G > A; p.R99H) in the ARF1 gene, associated with developmental delay, hypotonia, intellectual disability and motor stereotypies. This patient did not exhibit periventricular heterotopias previously observed in other patients with ARF1 variants (including p.R99H). Functional analysis shows that the pathogenetic mechanism of the R99H-ARF1 variant involves constitutive activation with resultant Golgi and endosomal alterations.
Intellectual disability v5.4 ARF1 Achchuthan Shanmugasundram Publications for gene: ARF1 were set to 28868155; 34353862; 36345169
Intellectual disability v5.4 ARF1 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:36345169 reported a paediatric patient identified with a monoallelic de novo missense variant (c.296 G > A; p.R99H) in the ARF1 gene, associated with developmental delay, hypotonia, intellectual disability and motor stereotypies. This patient did not exhibit periventricular heterotopias previously observed in other patients with ARF1 variants (including p.R99H). Functional analysis shows that the pathogenetic mechanism of the R99H-ARF1 variant involves constitutive activation with resultant Golgi and endosomal alterations.
Intellectual disability v5.4 ARF1 Achchuthan Shanmugasundram Publications for gene: ARF1 were set to 28868155; 34353862
Intellectual disability v5.3 FEM1C Achchuthan Shanmugasundram Publications for gene: FEM1C were set to 36336956
Intellectual disability v5.2 FEM1C Achchuthan Shanmugasundram edited their review of gene: FEM1C: Changed publications to: 28135719, 36336956
Intellectual disability v5.2 FEM1C Achchuthan Shanmugasundram gene: FEM1C was added
gene: FEM1C was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: FEM1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FEM1C were set to 36336956
Phenotypes for gene: FEM1C were set to Intellectual disability, MONDO:0001071
Review for gene: FEM1C was set to RED
Added comment: This gene should be rated RED as there is only one clear case of intellectual disability reported in literature.

PMID:36336956 reported a 9 year-old boy with severe global developmental delay, lack of speech, pyramidal signs and limb ataxia and identified with a heterozygous de novo missense variant c.376G>C (p.Asp126His) in the FEM1C gene. Cognitive assessment performed at 9 years of age showed that he has moderate intellectual disability.

De novo variant in the same residue (p.Asp126Val) has also been associated with an uncharacterised developmental disorder in PMID:28135719.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature
Congenital myopathy v4.2 KLHL40 Achchuthan Shanmugasundram Publications for gene: KLHL40 were set to 23746549
Monogenic hearing loss v4.3 ATP11A Achchuthan Shanmugasundram Classified gene: ATP11A as Amber List (moderate evidence)
Monogenic hearing loss v4.3 ATP11A Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as it has been implicated in sensorineural hearing loss from four unrelated families, and supported by functional studies from mouse model.
Monogenic hearing loss v4.3 ATP11A Achchuthan Shanmugasundram Gene: atp11a has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.2 ATP11A Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: ATP11A.
Monogenic hearing loss v4.2 ATP11A Achchuthan Shanmugasundram gene: ATP11A was added
gene: ATP11A was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: ATP11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP11A were set to 35278131; 36300302
Phenotypes for gene: ATP11A were set to Deafness, autosomal dominant 84, OMIM:619810
Review for gene: ATP11A was set to GREEN
Added comment: A heterozygous cryptic donor splice site variant in ATP11A has been identified in a large 6-generation family from Newfoundland in which 16 individuals had progressive sensorineural hearing loss. In addition, several individuals with postlingual-onset progressive hearing loss from two unrelated multigenerational Jewish Israeli families with their origins in Uzbekistan and Afghanistan were also identified with a novel duplication in ATP11A (PMID:35278131).

5500 bp deletion involving the last coding exon of both ATP11A isoforms were identified in the large German multi-generational family that was first reported in PMID:28601886 with auditory synaptopathy/neuropathy, which is a distinct type of sensorineural hearing loss. The deletion is present in all affected individuals from the family and absent in two unaffected family members tested (PMID:36300302).

Functional studies in mice showed ATP11A protein is expressed in mouse inner ear and conditional Atp11a knockout mice showed age-progressive dysfunction or loss of spiral ganglion neurons, recapitulating the human phenotype of auditory neuropathy (PMID:36300302).

This gene has been associated with relevant phenotypes in OMIM, but not in Gene2Phenotype.
Sources: Literature
Long QT syndrome v3.3 KCNH2 Achchuthan Shanmugasundram Publications for gene: KCNH2 were set to 19716085; 31358886; 26888179; 7889573; 9927399
Hereditary ataxia v1.314 NFASC Edoardo Monfrini gene: NFASC was added
gene: NFASC was added to Hereditary ataxia. Sources: Literature
Mode of inheritance for gene: NFASC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFASC were set to PMID: 30850329, 31608123, 31501903
Phenotypes for gene: NFASC were set to Cerebellar ataxia, Demyelinating neuropathy
Penetrance for gene: NFASC were set to Complete
Review for gene: NFASC was set to GREEN
gene: NFASC was marked as current diagnostic
Added comment: Sources: Literature
Early onset dystonia v1.130 VPS11 Edoardo Monfrini gene: VPS11 was added
gene: VPS11 was added to Early onset dystonia. Sources: Literature
Mode of inheritance for gene: VPS11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS11 were set to PMID: 33452836; 27120463; 27473128; 33871597
Phenotypes for gene: VPS11 were set to Neurodevelopmental disorder; Hypomyelination; Microcephaly; Infantile-onset dystonia; Adult-onset dystonia; Spasticity
Penetrance for gene: VPS11 were set to Complete
Review for gene: VPS11 was set to GREEN
gene: VPS11 was marked as current diagnostic
Added comment: Early-onset patients present hypomyelination, developmental delay, spasticity and dystonia.

A single adult-onset generalized dystonic patient without additional neurologic signs has been reported. This genetic association needs additional cases to be definitively confirmed.
Sources: Literature
Early onset or syndromic epilepsy v4.3 SPTAN1 Sarah Leigh Phenotypes for gene: SPTAN1 were changed from Epileptic encephalopathy, early infantile, 5 to Developmental and epileptic encephalopathy 5, OMIM:613477; developmental and epileptic encephalopathy, 5, MONDO:0013277
Early onset or syndromic epilepsy v4.2 SPTAN1 Sarah Leigh Publications for gene: SPTAN1 were set to Saitsu et al (2010) Am J Hum Genet 86: 881_891
Severe microcephaly v4.1 TRAPPC10 Aleš Maver edited their review of gene: TRAPPC10: Added comment: The study on biallelic TRAPPC10 variants in microcephaly has now been published in PMID: 35298461, reporting 8 individuals with a homozygous loss-of function variant in one family and two affected individuals from the second, unrelated family.; Changed publications to: PMID: 30167849, PMID: 35298461; Changed phenotypes to: Microcephaly, short stature, developmental delay
Corneal dystrophy v3.3 Eleanor Williams Panel version 3.2 has been signed off on 2023-03-22
Corneal dystrophy v3.2 Eleanor Williams Panel signed off version 3.0 has been removed
Mitochondrial disorder with complex II deficiency v2.3 Eleanor Williams Panel version 2.2 has been signed off on 2023-03-22
Mitochondrial disorder with complex II deficiency v2.2 Eleanor Williams Panel signed off version 2.0 has been removed
Ichthyosis and erythrokeratoderma v3.3 Eleanor Williams Panel version 3.2 has been signed off on 2023-03-22
Ichthyosis and erythrokeratoderma v3.2 Eleanor Williams Panel signed off version 3.0 has been removed
Intestinal failure or congenital diarrhoea v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2023-03-22
Intestinal failure or congenital diarrhoea v3.0 Sarah Leigh promoted panel to version 3.0
Cholestasis v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2023-03-22
Cholestasis v3.0 Sarah Leigh promoted panel to version 3.0
Epidermolysis bullosa and congenital skin fragility v2.3 Eleanor Williams Panel version 2.2 has been signed off on 2023-03-22
Epidermolysis bullosa and congenital skin fragility v2.2 Eleanor Williams Panel signed off version 2.0 has been removed
Severe early-onset obesity v4.1 Sarah Leigh Panel version 4.0 has been signed off on 2023-03-22
Severe early-onset obesity v4.0 Sarah Leigh promoted panel to version 4.0
Pituitary hormone deficiency v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2023-03-22
Pituitary hormone deficiency v3.0 Sarah Leigh promoted panel to version 3.0
Childhood onset leukodystrophy v14.3 Eleanor Williams Panel version 14.2 has been signed off on 2023-03-22
Severe insulin resistance and lipodystrophy syndromes v4.1 Sarah Leigh Panel version 4.0 has been signed off on 2023-03-22
Severe insulin resistance and lipodystrophy syndromes v4.0 Sarah Leigh promoted panel to version 4.0
Other rare neuromuscular disorders v19.2 Eleanor Williams Panel version 19.1 has been signed off on 2023-03-22
Differences in sex development v4.1 Sarah Leigh Panel version 4.0 has been signed off on 2023-03-22
Cystic renal disease v7.2 Arina Puzriakova Panel version 7.1 has been signed off on 2023-03-22
Differences in sex development v4.0 Sarah Leigh promoted panel to version 4.0
Lysosomal storage disorder v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Hereditary ataxia and cerebellar anomalies - childhood onset v12.2 Arina Puzriakova Panel version 12.1 has been signed off on 2023-03-22
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2023-03-22
Lysosomal storage disorder v3.0 Catherine Snow promoted panel to version 3.0
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome v3.0 Sarah Leigh promoted panel to version 3.0
Glycogen storage disease v2.1 Catherine Snow Panel version 2.0 has been signed off on 2023-03-22
Glycogen storage disease v2.0 Catherine Snow promoted panel to version 2.0
Rare genetic inflammatory skin disorders v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2023-03-22
Rare genetic inflammatory skin disorders v3.0 Sarah Leigh promoted panel to version 3.0
Cerebral malformation v10.2 Eleanor Williams Panel version 10.1 has been signed off on 2023-03-22
Rare multisystem ciliopathy Super panel v12.3 Arina Puzriakova Panel version 12.2 has been signed off on 2023-03-22
Primary immunodeficiency or monogenic inflammatory bowel disease v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Pigmentary skin disorders v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2023-03-22
Pigmentary skin disorders v3.0 Sarah Leigh promoted panel to version 3.0
Hypotonic infant v25.2 Arina Puzriakova Panel version 25.1 has been signed off on 2023-03-22
Paediatric disorders v35.3 Eleanor Williams Panel version 35.2 has been signed off on 2023-03-22
Palmoplantar keratodermas v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2023-03-22
Palmoplantar keratodermas v3.0 Sarah Leigh promoted panel to version 3.0
Primary immunodeficiency or monogenic inflammatory bowel disease v4.0 Catherine Snow promoted panel to version 4.0
Ichthyosis and erythrokeratoderma v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2022-03-22
Ichthyosis and erythrokeratoderma v3.0 Sarah Leigh promoted panel to version 3.0
Sudden unexplained death or survivors of a cardiac event v19.7 Arina Puzriakova Panel version 19.6 has been signed off on 2023-03-22
Inherited predisposition to acute myeloid leukaemia (AML) v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Inherited predisposition to acute myeloid leukaemia (AML) v3.0 Catherine Snow promoted panel to version 3.0
Epidermolysis bullosa and congenital skin fragility v2.1 Sarah Leigh Panel version 2.0 has been signed off on 2022-03-22
Hereditary Erythrocytosis v2.1 Catherine Snow Panel version 2.0 has been signed off on 2023-03-22
Hereditary Erythrocytosis v2.0 Catherine Snow promoted panel to version 2.0
Epidermolysis bullosa and congenital skin fragility v2.0 Sarah Leigh promoted panel to version 2.0
Unexplained death in infancy and sudden unexplained death in childhood v6.3 Eleanor Williams Panel version 6.2 has been signed off on 2023-03-22
Cytopenia - NOT Fanconi anaemia v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Cytopenia - NOT Fanconi anaemia v3.0 Catherine Snow promoted panel to version 3.0
Bleeding and platelet disorders v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Bleeding and platelet disorders v3.0 Catherine Snow promoted panel to version 3.0
Paediatric pseudo-obstruction syndrome v1.1 Catherine Snow Panel version 1.0 has been signed off on 2023-03-22
Paediatric pseudo-obstruction syndrome v1.0 Catherine Snow promoted panel to version 1.0
Neuronal ceroid lipofuscinosis v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2023-03-22
Neuronal ceroid lipofuscinosis v2.0 Arina Puzriakova promoted panel to version 2.0
Cardiac arrhythmias v13.5 Eleanor Williams Panel version 13.4 has been signed off on 2023-03-22
Haematological malignancies cancer susceptibility v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Mitochondrial disorder with complex I deficiency v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2023-03-22
Haematological malignancies cancer susceptibility v4.0 Catherine Snow promoted panel to version 4.0
Mitochondrial disorder with complex I deficiency v3.0 Arina Puzriakova promoted panel to version 3.0
Mitochondrial disorder with complex II deficiency v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2022-03-22
Breast cancer pertinent cancer susceptibility v2.1 Catherine Snow Panel version 2.0 has been signed off on 2023-03-22
Ectodermal dysplasia v3.1 Sarah Leigh Panel version 3.0 has been signed off on 2023-03-22
Mitochondrial disorder with complex II deficiency v2.0 Arina Puzriakova promoted panel to version 2.0
Breast cancer pertinent cancer susceptibility v2.0 Catherine Snow promoted panel to version 2.0
Ectodermal dysplasia v3.0 Sarah Leigh promoted panel to version 3.0
Cutaneous photosensitivity with a likely genetic cause v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2023-03-22
Multi locus imprinting disorders v1.3 Achchuthan Shanmugasundram Panel version 1.2 has been signed off on 2023-03-22
Malformations of cortical development v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2023-03-22
Cutaneous photosensitivity with a likely genetic cause v3.0 Arina Puzriakova promoted panel to version 3.0
Malformations of cortical development v4.0 Eleanor Williams promoted panel to version 4.0
Inherited ovarian cancer (without breast cancer) v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Inherited ovarian cancer (without breast cancer) v4.0 Arina Puzriakova promoted panel to version 4.0
Inherited breast cancer and ovarian cancer v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2023-03-22
Inherited breast cancer and ovarian cancer v2.0 Arina Puzriakova promoted panel to version 2.0
Li Fraumeni Syndrome v1.1 Achchuthan Shanmugasundram Panel version 1.0 has been signed off on 2023-03-22
Li Fraumeni Syndrome v1.0 Achchuthan Shanmugasundram promoted panel to version 1.0
Fetal anomalies v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2023-03-22
Severe microcephaly v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Severe microcephaly v4.0 Catherine Snow promoted panel to version 4.0
Fetal anomalies v3.0 Arina Puzriakova promoted panel to version 3.0
Hereditary diffuse gastric cancer v1.1 Catherine Snow Panel version 1.0 has been signed off on 2023-03-22
Hereditary diffuse gastric cancer v1.0 Catherine Snow promoted panel to version 1.0
Hereditary isolated diabetes insipidus v1.1 Achchuthan Shanmugasundram Panel version 1.0 has been signed off on 2023-03-22
Hereditary isolated diabetes insipidus v1.0 Achchuthan Shanmugasundram promoted panel to version 1.0
Unexplained young onset end-stage renal disease v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Unexplained young onset end-stage renal disease v3.0 Catherine Snow promoted panel to version 3.0
Ovarian cancer pertinent cancer susceptibility v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2023-03-22
Ovarian cancer pertinent cancer susceptibility v2.0 Arina Puzriakova promoted panel to version 2.0
Inherited prostate cancer v1.1 Achchuthan Shanmugasundram Panel version 1.0 has been signed off on 2023-03-22
Inherited prostate cancer v1.0 Achchuthan Shanmugasundram promoted panel to version 1.0
Membranoproliferative glomerulonephritis including C3 glomerulopathy v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Membranoproliferative glomerulonephritis including C3 glomerulopathy v3.0 Catherine Snow promoted panel to version 3.0
Respiratory ciliopathies including non-CF bronchiectasis v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Respiratory ciliopathies including non-CF bronchiectasis v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Corneal dystrophy v3.1 Catherine Snow Panel version 3.0 has been signed off on 2022-03-22
Corneal dystrophy v3.0 Catherine Snow promoted panel to version 3.0
Bilateral congenital or childhood onset cataracts v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Bilateral congenital or childhood onset cataracts v4.0 Catherine Snow promoted panel to version 4.0
Pneumothorax - familial v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Pneumothorax - familial v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Adult onset leukodystrophy v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Adult onset leukodystrophy v3.0 Catherine Snow promoted panel to version 3.0
Laterality disorders and isomerism v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Laterality disorders and isomerism v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Adult onset neurodegenerative disorder v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Adult onset neurodegenerative disorder v4.0 Catherine Snow promoted panel to version 4.0
Tubulointerstitial kidney disease v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Tubulointerstitial kidney disease v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Adult onset hereditary spastic paraplegia v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Renal tubulopathies v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2023-03-22
Adult onset hereditary spastic paraplegia v3.0 Catherine Snow promoted panel to version 3.0
Renal tubulopathies v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Hereditary ataxia with onset in adulthood v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Hereditary ataxia with onset in adulthood v4.0 Catherine Snow promoted panel to version 4.0
Childhood onset dystonia, chorea or related movement disorder v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Proteinuric renal disease v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2023-03-22
Childhood onset dystonia, chorea or related movement disorder v3.0 Catherine Snow promoted panel to version 3.0
Proteinuric renal disease v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Adult onset dystonia, chorea or related movement disorder v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Adult onset dystonia, chorea or related movement disorder v3.0 Catherine Snow promoted panel to version 3.0
Nephrocalcinosis or nephrolithiasis v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2023-03-22
Nephrocalcinosis or nephrolithiasis v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Ehlers Danlos syndrome with a likely monogenic cause v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Ehlers Danlos syndrome with a likely monogenic cause v3.0 Catherine Snow promoted panel to version 3.0
Atypical haemolytic uraemic syndrome v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Atypical haemolytic uraemic syndrome v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Structural eye disease v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.0 Catherine Snow promoted panel to version 4.0
Neurological segmental overgrowth v2.7 Eleanor Williams Panel version 2.6 has been signed off on 2023-03-22
Structural eye disease v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Familial chylomicronaemia syndrome (FCS) v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
DDG2P v3.2 Eleanor Williams Panel version 3.1 has been signed off on 2023-03-22
Familial chylomicronaemia syndrome (FCS) v3.0 Catherine Snow promoted panel to version 3.0
Stickler syndrome v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2023-03-22
Stickler syndrome v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Short QT syndrome v3.2 Eleanor Williams Panel version 3.1 has been signed off on 2023-03-22
Rare anaemia v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Rare anaemia v3.0 Catherine Snow promoted panel to version 3.0
Retinal disorders v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2023-03-22
Progressive cardiac conduction disease v2.3 Eleanor Williams Panel version 2.2 has been signed off on 2023-03-22
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Retinal disorders v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.0 Arina Puzriakova promoted panel to version 4.0
Long QT syndrome v3.2 Eleanor Williams Panel version 3.1 has been signed off on 2023-03-22
Iron metabolism disorders - NOT common HFE mutations v2.1 Catherine Snow Panel version 2.0 has been signed off on 2023-03-22
Iron metabolism disorders - NOT common HFE mutations v2.0 Catherine Snow promoted panel to version 2.0
Optic neuropathy v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2023-03-22
Optic neuropathy v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Brugada syndrome and cardiac sodium channel disease v3.3 Eleanor Williams Panel version 3.2 has been signed off on 2023-03-22
Confirmed Fanconi anaemia or Bloom syndrome v2.1 Catherine Snow Panel version 2.0 has been signed off on 2023-03-22
Confirmed Fanconi anaemia or Bloom syndrome v2.0 Catherine Snow promoted panel to version 2.0
Arrhythmogenic right ventricular cardiomyopathy v3.6 Eleanor Williams Panel version 3.5 has been signed off on 2023-03-22
Albinism or congenital nystagmus v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Clefting v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Clefting v4.0 Arina Puzriakova promoted panel to version 4.0
Albinism or congenital nystagmus v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Renal ciliopathies v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2023-03-22
Hypogonadotropic hypogonadism (GMS) v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Skeletal ciliopathies v3.2 Arina Puzriakova Panel version 3.1 has been signed off on 2023-03-22
Renal ciliopathies v3.0 Eleanor Williams promoted panel to version 3.0
Skeletal muscle channelopathy v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Hypogonadotropic hypogonadism (GMS) v3.0 Catherine Snow promoted panel to version 3.0
Skeletal muscle channelopathy v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Cystic kidney disease v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2023-03-22
Cystic kidney disease v4.0 Eleanor Williams promoted panel to version 4.0
Skeletal ciliopathies v3.0 Arina Puzriakova promoted panel to version 3.0
Limb disorders v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Ophthalmological ciliopathies v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2023-03-22
Limb disorders v4.0 Arina Puzriakova promoted panel to version 4.0
Ophthalmological ciliopathies v3.0 Eleanor Williams promoted panel to version 3.0
Mitochondrial disorders v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Paroxysmal central nervous system disorders v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Paroxysmal central nervous system disorders v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
White matter disorders and cerebral calcification - narrow panel v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2023-03-22
Mitochondrial disorders v4.0 Arina Puzriakova promoted panel to version 4.0
White matter disorders and cerebral calcification - narrow panel v3.0 Eleanor Williams promoted panel to version 3.0
Cerebral vascular malformations v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Congenital disorders of glycosylation v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Congenital disorders of glycosylation v4.0 Arina Puzriakova promoted panel to version 4.0
Cerebral vascular malformations v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Endocrine neoplasia v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Paediatric disorders - additional genes v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2023-03-22
Rhabdomyolysis and metabolic muscle disorders v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2023-03-22
Endocrine neoplasia v3.0 Catherine Snow promoted panel to version 3.0
Paediatric disorders - additional genes v3.0 Arina Puzriakova promoted panel to version 3.0
Rhabdomyolysis and metabolic muscle disorders v3.0 Eleanor Williams promoted panel to version 3.0
Catecholaminergic polymorphic VT v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Neonatal diabetes v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Paediatric motor neuronopathies v3.4 Eleanor Williams Panel version 3.3 has been signed off on 2023-03-22
Catecholaminergic polymorphic VT v4.0 Arina Puzriakova promoted panel to version 4.0
Paediatric motor neuronopathies v3.3 Eleanor Williams Panel signed off version 3.0 has been removed
Cardiac arrhythmias - additional genes v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2023-03-22
Neonatal diabetes v4.0 Catherine Snow promoted panel to version 4.0
Cardiac arrhythmias - additional genes v3.0 Arina Puzriakova promoted panel to version 3.0
Arthrogryposis v5.1 Achchuthan Shanmugasundram Panel version 5.0 has been signed off on 2023-03-22
Congenital myopathy v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Arthrogryposis v5.0 Achchuthan Shanmugasundram promoted panel to version 5.0
Congenital hyperinsulinism v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Congenital myopathy v4.0 Arina Puzriakova promoted panel to version 4.0
Congenital hyperinsulinism v3.0 Catherine Snow promoted panel to version 3.0
Paediatric motor neuronopathies v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2023-03-22
Congenital muscular dystrophy v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Paediatric motor neuronopathies v3.0 Eleanor Williams promoted panel to version 3.0
Congenital muscular dystrophy v4.0 Arina Puzriakova promoted panel to version 4.0
Holoprosencephaly v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Segmental overgrowth disorders - Deep sequencing v3.4 Catherine Snow Panel version 3.3 has been signed off on 2023-03-22
Holoprosencephaly v4.0 Arina Puzriakova promoted panel to version 4.0
Neurological ciliopathies v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2023-03-22
Likely inborn error of metabolism v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Osteogenesis imperfecta v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2023-03-22
Neurological ciliopathies v3.0 Eleanor Williams promoted panel to version 3.0
Likely inborn error of metabolism v4.0 Arina Puzriakova promoted panel to version 4.0
Osteogenesis imperfecta v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Hypertrophic cardiomyopathy v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Hypertrophic cardiomyopathy v4.0 Arina Puzriakova promoted panel to version 4.0
Dilated and arrhythmogenic cardiomyopathy v2.9 Arina Puzriakova Panel version 2.8 has been signed off on 2023-03-22
Familial hypercholesterolaemia (GMS) v2.1 Catherine Snow Panel version 2.0 has been signed off on 2023-03-22
Amelogenesis imperfecta v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Paediatric or syndromic cardiomyopathy v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2023-03-22
Familial hypercholesterolaemia (GMS) v2.0 Catherine Snow promoted panel to version 2.0
Paediatric or syndromic cardiomyopathy v3.0 Arina Puzriakova promoted panel to version 3.0
Amelogenesis imperfecta v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Hydrocephalus v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2023-03-22
Ataxia and cerebellar anomalies - narrow panel v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Hydrocephalus v4.0 Eleanor Williams promoted panel to version 4.0
Ataxia and cerebellar anomalies - narrow panel v4.0 Arina Puzriakova promoted panel to version 4.0
Early onset or syndromic epilepsy v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Thoracic aortic aneurysm or dissection (GMS) v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Possible mitochondrial disorder - nuclear genes v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Distal myopathies v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2023-03-22
Thoracic aortic aneurysm or dissection (GMS) v3.0 Catherine Snow promoted panel to version 3.0
Early onset or syndromic epilepsy v4.0 Arina Puzriakova promoted panel to version 4.0
Distal myopathies v3.0 Eleanor Williams promoted panel to version 3.0
Intellectual disability v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2023-03-22
Possible mitochondrial disorder - nuclear genes v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Childhood solid tumours v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Childhood solid tumours v4.0 Catherine Snow promoted panel to version 4.0
Mitochondrial DNA maintenance disorder v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Congenital myaesthenic syndrome v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2023-03-22
Mitochondrial DNA maintenance disorder v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Intellectual disability v5.0 Arina Puzriakova promoted panel to version 5.0
Congenital myaesthenic syndrome v4.0 Eleanor Williams promoted panel to version 4.0
Mitochondrial disorder with complex V deficiency v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2023-03-22
Monogenic hearing loss v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Thrombophilia with a likely monogenic cause v2.3 Eleanor Williams Panel version 2.2 has been signed off on 2023-03-22
Mitochondrial disorder with complex V deficiency v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Monogenic hearing loss v4.0 Arina Puzriakova promoted panel to version 4.0
Childhood onset hereditary spastic paraplegia v4.1 Catherine Snow Panel version 4.0 has been signed off on 2023-03-22
Monogenic hearing loss v3.17 Arina Puzriakova Panel signed off version 3.15 has been removed
Monogenic hearing loss v3.16 Arina Puzriakova Panel version 3.15 has been signed off on 2023-03-22
Childhood onset hereditary spastic paraplegia v4.0 Catherine Snow promoted panel to version 4.0
Hereditary systemic amyloidosis v1.19 Arina Puzriakova Panel version 1.18 has been signed off on 2023-03-22
Skeletal dysplasia v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2023-03-22
Mitochondrial disorder with complex IV deficiency v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2023-03-22
Skeletal dysplasia v4.0 Eleanor Williams promoted panel to version 4.0
Mitochondrial disorder with complex IV deficiency v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Sporadic aniridia v3.3 Arina Puzriakova Panel version 3.2 has been signed off on 2023-03-22
Mitochondrial liver disease, including transient infantile liver failure v1.10 Arina Puzriakova Panel version 1.9 has been signed off on 2023-03-22
Polycystic liver disease v1.27 Eleanor Williams Panel version 1.26 has been signed off on 2023-03-22
Mitochondrial disorder with complex III deficiency v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2023-03-22
Hereditary neuropathy or pain disorder v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Mitochondrial disorder with complex III deficiency v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Hereditary neuropathy or pain disorder v3.0 Catherine Snow promoted panel to version 3.0
Arrhythmogenic right ventricular cardiomyopathy v3.5 Eleanor Williams List of related panels changed from Arrythmogenic cardiomyopathy; R133 to Arrhythmogenic cardiomyopathy; R133
Neonatal diabetes v3.5 Eleanor Williams List of related panels changed from Neonatal diabetes (diagnosed less than 6 months); Neonatal diabetes; Neonatal diabetes diagnosed <6 months; Diabetes - neonatal onset; R143 to Neonatal diabetes (diagnosed less than 6 months); Neonatal diabetes diagnosed <6 months; Diabetes - neonatal onset; R143
Hereditary neuropathy or pain disorder v2.30 Eleanor Williams List of related panels changed from Hereditary neuropathy or pain disorder - NOT PMP22 copy number; Hereditary neuropathy NOT PMP22 copy number; R78 to Hereditary neuropathy NOT PMP22 copy number; R78
Hereditary ataxia with onset in adulthood v3.18 Eleanor Williams List of related panels changed from Hereditary ataxia with onset in adulthood; Hereditary ataxia - adult onset; R54 to Hereditary ataxia - adult onset; R54
Childhood onset dystonia, chorea or related movement disorder v2.13 Eleanor Williams List of related panels changed from Childhood onset dystonia; chorea or related movement disorder; Childhood onset dystonia or chorea or related movement disorder; R57 to Childhood onset dystonia or chorea or related movement disorder; R57
Cerebral malformation v8.25 Eleanor Williams List of related panels changed from Cerebral malformation; Cerebral malformations; R87 to Cerebral malformations; R87
Adult onset hereditary spastic paraplegia v2.26 Arina Puzriakova Panel name changed from Adult onset hereditary spastic paraplegia. to Adult onset hereditary spastic paraplegia
Adult onset hereditary spastic paraplegia v2.25 Eleanor Williams List of related panels changed from Adult onset hereditary spastic paraplegia; Hereditary spastic paraplegia - adult onset; R60 to Hereditary spastic paraplegia - adult onset; R60
Adult onset dystonia, chorea or related movement disorder v2.10 Eleanor Williams List of related panels changed from Adult onset dystonia; chorea or related movement disorder; Adult onset movement disorder; R56 to Adult onset movement disorder; R56
Adult onset leukodystrophy v2.48 Arina Puzriakova List of related panels changed from Adult onset leukodystrophy; White matter disorders - adult onset; R62 to White matter disorders - adult onset; R62
Iron metabolism disorders - NOT common HFE mutations v1.41 Eleanor Williams Panel name changed from Iron metabolism disorders to Iron metabolism disorders - NOT common HFE mutations
List of related panels changed from R96 to Iron metabolism disorders; R96
Other rare neuromuscular disorders v12.270 Arina Puzriakova List of related panels changed from Neuromuscular disorders; Other rare neuromuscular disorders; R381 to Neuromuscular disorders; R381
Polycystic liver disease v1.26 Eleanor Williams Panel name changed from Iron metabolism disorders - NOT common HFE mutations to Polycystic liver disease
List of related panels changed from Polycystic liver disease interim; Polycystic liver disease; R173 to Polycystic liver disease interim; R173
Adult onset neurodegenerative disorder v3.61 Arina Puzriakova List of related panels changed from Adult onset neurodegenerative disorder; Neurodegenerative disorders - adult onset; R58 to Neurodegenerative disorders - adult onset; R58
Holoprosencephaly v3.6 Arina Puzriakova List of related panels changed from Rhombencephalosynapsis; Holoprosencephaly - NOT chromosomal; Holoprosencephaly; R85 to Rhombencephalosynapsis; Holoprosencephaly; R85
Childhood onset hereditary spastic paraplegia v3.28 Arina Puzriakova List of related panels changed from Childhood onset hereditary spastic paraplegia; Hereditary spastic paraplegia - childhood onset; R61 to Hereditary spastic paraplegia - childhood onset; R61
Childhood onset leukodystrophy v10.374 Achchuthan Shanmugasundram List of related panels changed from White matter disorders - childhood onset; Childhood onset leukodystrophy; R109 to White matter disorders - childhood onset; R109
Bilateral congenital or childhood onset cataracts v3.5 Achchuthan Shanmugasundram List of related panels changed from Cataracts; Bilateral congenital or childhood onset cataracts; R31 to Cataracts; R31
Retinal disorders v3.34 SGSH Siying Lin gene: SGSH was added
gene: SGSH was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: SGSH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGSH were set to PMID 31718697
Mode of pathogenicity for gene: SGSH was set to Other
Review for gene: SGSH was set to GREEN
Added comment: Reports of late onset retinal dystrophy with mild systemic involvement (attenuated MPS phenotype) associated with biallelic genotypes which include likely hypomorphic alleles. Also two individuals identified in our clinical cohort with retinal dystrophy associated with biallelic SGSH variants.
Sources: Literature
Adult onset leukodystrophy v2.47 Eleanor Williams Panel name changed from White matter disorders - adult onset to Adult onset leukodystrophy
List of related panels changed from R62; Adult onset leukodystrophy to Adult onset leukodystrophy; White matter disorders - adult onset; R62
Childhood onset leukodystrophy v10.373 Achchuthan Shanmugasundram Panel name changed from White matter disorders - childhood onset to Childhood onset leukodystrophy
List of related panels changed from Childhood onset leukodystrophy; R109 to White matter disorders - childhood onset; Childhood onset leukodystrophy; R109
Other rare neuromuscular disorders v12.269 Eleanor Williams Panel name changed from Neuromuscular disorders to Other rare neuromuscular disorders
List of related panels changed from Other rare neuromuscular disorders; R381 to Neuromuscular disorders; Other rare neuromuscular disorders; R381
Sporadic aniridia v3.2 Achchuthan Shanmugasundram Panel name changed from Aniridia to Sporadic aniridia
List of related panels changed from R38 to Aniridia; R38
Adult onset neurodegenerative disorder v3.60 Eleanor Williams Panel name changed from Neurodegenerative disorders - adult onset to Adult onset neurodegenerative disorder
List of related panels changed from R58; Adult onset neurodegenerative disorder to Adult onset neurodegenerative disorder; Neurodegenerative disorders - adult onset; R58
Bilateral congenital or childhood onset cataracts v3.4 Achchuthan Shanmugasundram Panel name changed from Cataracts to Bilateral congenital or childhood onset cataracts
List of related panels changed from R31; Bilateral congenital or childhood onset cataracts to Cataracts; Bilateral congenital or childhood onset cataracts; R31
Likely inborn error of metabolism v3.21 Catherine Snow Panel name changed from Inborn errors of metabolism to Likely inborn error of metabolism - targeted testing not possible
List of related panels changed from Likely inborn error of metabolism - targeted testing not possible; Likely inborn error of metabolism; R98 to Likely inborn error of metabolism - targeted testing not possible; Likely inborn error of metabolism; Inborn errors of metabolism; R98
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.14 Eleanor Williams Panel name changed from Limb girdle muscular dystrophy to Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies
List of related panels changed from R82 to Limb girdle muscular dystrophy; R82
Thrombophilia with a likely monogenic cause v2.2 Catherine Snow Panel name changed from Thrombophilia to Thrombophilia with a likely monogenic cause
List of related panels changed from R97 to Thrombophilia; R97
Corneal dystrophy v2.4 Achchuthan Shanmugasundram Panel name changed from Corneal dystrophies to Corneal dystrophy
List of related panels changed from R262 to Corneal dystrophies; R262
Holoprosencephaly v3.5 Eleanor Williams Panel name changed from Holoprosencephaly to Holoprosencephaly - NOT chromosomal
List of related panels changed from Rhombencephalosynapsis; Holoprosencephaly - NOT chromosomal; R85 to Rhombencephalosynapsis; Holoprosencephaly - NOT chromosomal; Holoprosencephaly; R85
Polycystic liver disease v1.25 Catherine Snow Panel name changed from Polycystic liver disease to Iron metabolism disorders - NOT common HFE mutations
List of related panels changed from Polycystic liver disease interim; R173 to Polycystic liver disease interim; Polycystic liver disease; R173
Adult onset hereditary spastic paraplegia v2.24 Eleanor Williams List of related panels changed from R60; Adult onset hereditary spastic paraplegia; Hereditary spastic paraplegia - adult onset to Adult onset hereditary spastic paraplegia; Hereditary spastic paraplegia - adult onset; R60
Polycystic liver disease v1.24 Catherine Snow Panel name changed from Polycystic liver disease interim to Polycystic liver disease
List of related panels changed from R173 to Polycystic liver disease interim; R173
Childhood onset hereditary spastic paraplegia v3.27 Eleanor Williams Panel name changed from Hereditary spastic paraplegia - childhood onset to Childhood onset hereditary spastic paraplegia
List of related panels changed from Childhood onset hereditary spastic paraplegia; R61 to Childhood onset hereditary spastic paraplegia; Hereditary spastic paraplegia - childhood onset; R61
Adult onset hereditary spastic paraplegia v2.23 Eleanor Williams Panel name changed from Hereditary spastic paraplegia - adult onset to Adult onset hereditary spastic paraplegia.
Hereditary neuropathy or pain disorder v2.29 Sarah Leigh Panel name changed from Hereditary neuropathy NOT PMP22 copy number to Hereditary neuropathy or pain disorder - NOT PMP22 copy number
List of related panels changed from R78; Hereditary neuropathy or pain disorder - NOT PMP22 copy number to Hereditary neuropathy or pain disorder - NOT PMP22 copy number; Hereditary neuropathy NOT PMP22 copy number; R78
Adult onset hereditary spastic paraplegia v2.22 Eleanor Williams List of related panels changed from R60; Adult onset hereditary spastic paraplegia to R60; Adult onset hereditary spastic paraplegia; Hereditary spastic paraplegia - adult onset
Multi locus imprinting disorders v1.2 Catherine Snow List of related panels changed from R417 to R417.2
Hereditary ataxia with onset in adulthood v3.17 Sarah Leigh Panel name changed from Hereditary ataxia - adult onset to Hereditary ataxia with onset in adulthood
List of related panels changed from Hereditary ataxia with onset in adulthood; R54 to Hereditary ataxia with onset in adulthood; Hereditary ataxia - adult onset; R54
Early onset or syndromic epilepsy v3.115 Sarah Leigh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; Component Of Super Panel; GMS signed-off
Early onset or syndromic epilepsy v3.114 Sarah Leigh Panel name changed from Genetic epilepsy syndromes to Early onset or syndromic epilepsy
List of related panels changed from Epilepsy Plus; Epilepsy plus other features; Genetic Epilepsy Syndromes; Epileptic encephalopathy; Familial Focal Epilepsies; Familial Genetic Generalised Epilepsies; Genetic Epilepsies with Febrile Seizures Plus (GEFS+); Genetic Epilepsies with Febrile Seizures Plus; Early onset or syndromic epilepsy; R59 to Epilepsy Plus; Epilepsy plus other features; Genetic Epilepsy Syndromes; Epileptic encephalopathy; Familial Focal Epilepsies; Familial Genetic Generalised Epilepsies; Genetic Epilepsies with Febrile Seizures Plus (GEFS+); Genetic Epilepsies with Febrile Seizures Plus; Early onset or syndromic epilepsy; Genetic epilepsy syndromes; R59
Hypogonadotropic hypogonadism (GMS) v2.6 Catherine Snow Panel name changed from Hypogonadotropic hypogonadism idiopathic to Hypogonadotropic hypogonadism (GMS)
List of related panels changed from R148 to Hypogonadotropic hypogonadism idiopathic; R148
Intellectual disability v4.127 HIST1H4E Eleanor Williams commented on gene: HIST1H4E
Childhood onset dystonia, chorea or related movement disorder v2.12 Sarah Leigh Panel name changed from Childhood onset dystonia or chorea or related movement disorder to Childhood onset dystonia, chorea or related movement disorder
List of related panels changed from R57; Childhood onset dystonia; chorea or related movement disorder to Childhood onset dystonia; chorea or related movement disorder; Childhood onset dystonia or chorea or related movement disorder; R57
Endocrine neoplasia v2.4 Catherine Snow List of related panels changed from R217 to Endocrine neoplasms; R217
Endocrine neoplasia v2.3 Catherine Snow Panel name changed from Endocrine neoplasms to Endocrine neoplasia
Cerebral malformation v8.22 Sarah Leigh Panel name changed from Cerebral malformations to Cerebral malformation
List of related panels changed from Cerebral malformation; R87 to Cerebral malformation; Cerebral malformations; R87
Neonatal diabetes v3.4 Catherine Snow Panel name changed from Diabetes - neonatal onset to Neonatal diabetes
List of related panels changed from Neonatal diabetes (diagnosed less than 6 months); Neonatal diabetes; Neonatal diabetes diagnosed <6 months; R143 to Neonatal diabetes (diagnosed less than 6 months); Neonatal diabetes; Neonatal diabetes diagnosed <6 months; Diabetes - neonatal onset; R143
Adult onset dystonia, chorea or related movement disorder v2.9 Sarah Leigh Panel name changed from Adult onset movement disorder to Adult onset dystonia, chorea or related movement disorder
List of related panels changed from R56; Adult onset dystonia; chorea or related movement disorder to Adult onset dystonia; chorea or related movement disorder; Adult onset movement disorder; R56
Ehlers Danlos syndrome with a likely monogenic cause v2.70 Sarah Leigh Panel name changed from Ehlers Danlos syndromes to Ehlers Danlos syndrome with a likely monogenic cause
List of related panels changed from Classical Ehlers Danlos Syndrome; Classical Ehlers-Danlos Syndrome; Ehlers-Danlos Syndrome (unusual phenotypes e.g. absent pain sense); Ehlers-Danlos syndrome type 3; Kyphoscoliotic Ehlers-Danlos syndrome; EDS; Ehlers-Danlos syndromes; R101 to Classical Ehlers Danlos Syndrome; Classical Ehlers-Danlos Syndrome; Ehlers-Danlos Syndrome (unusual phenotypes e.g. absent pain sense); Ehlers-Danlos syndrome type 3; Kyphoscoliotic Ehlers-Danlos syndrome; EDS; Ehlers-Danlos syndromes; Ehlers Danlos syndromes; R101
Paediatric disorders v24.419 Arina Puzriakova List of related panels changed from Acutely unwell children with a likely monogenic disorder; Congenital malformation and dysmorphism syndromes - microarray and sequencing; Congenital malformation and dysmorphism syndromes; R14; R27 to Congenital malformation and dysmorphism syndromes - microarray and sequencing; Congenital malformation and dysmorphism syndromes; R27
Mitochondrial liver disease, including transient infantile liver failure v1.9 Sarah Leigh Panel name changed from Mitochondrial liver disease to Mitochondrial liver disease, including transient infantile liver failure
List of related panels changed from R317 to Mitochondrial liver disease; R317
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.5 Sarah Leigh Panel name changed from Craniosynostosis to Rare syndromic craniosynostosis or isolated multisuture synostosis
List of related panels changed from Craniosynostosis syndromes; Craniosynostosis syndromes phenotypes; Rare syndromic craniosynostosis or isolated multisuture synostosis; R100 to Craniosynostosis syndromes; Craniosynostosis syndromes phenotypes; Rare syndromic craniosynostosis or isolated multisuture synostosis; Craniosynostosis; R100
Segmental overgrowth disorders - Deep sequencing v3.3 Catherine Snow Panel name changed from Segmental overgrowth disorders to Segmental overgrowth disorders - Deep sequencing
List of related panels changed from Regional overgrowth disorders; R110 to Regional overgrowth disorders; Segmental overgrowth disorders; R110
Li Fraumeni Syndrome v0.9 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease; GMS signed-off
Familial chylomicronaemia syndrome (FCS) v2.5 Sarah Leigh List of related panels changed from Lipoprotein lipase deficiency;R324 to Lipoprotein lipase deficiency; R324
Hereditary isolated diabetes insipidus v0.4 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease; GMS signed-off
Intellectual disability v4.126 Arina Puzriakova Panel name changed from Intellectual disability to Intellectual disability - microarray and sequencing
List of related panels changed from Coarse facial features including Coffin-Siris-like disorders; ID; Moderate; severe or profound intellectual disability; Schizophrenia plus additional features; Intellectual disability - microarray; fragile X and sequencing; R29 to Coarse facial features including Coffin-Siris-like disorders; ID; Moderate; severe or profound intellectual disability; Schizophrenia plus additional features; Intellectual disability - microarray; fragile X and sequencing; Intellectual disability; R29
Inherited prostate cancer v0.5 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease; GMS signed-off
Familial hypercholesterolaemia (GMS) v1.13 Arina Puzriakova Panel name changed from Familial hypercholesterolaemia - targeted panel to Familial hypercholesterolaemia (GMS)
List of related panels changed from R134 to Familial hypercholesterolaemia - targeted panel; R134
Paediatric pseudo-obstruction syndrome v0.219 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease; GMS signed-off
Unexplained death in infancy and sudden unexplained death in childhood v3.195 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease Virtual; Super Panel; GMS signed-off
Thoracic aortic aneurysm or dissection (GMS) v2.4 Arina Puzriakova Panel name changed from Thoracic aortic aneurysm and dissection to Thoracic aortic aneurysm or dissection (GMS)
List of related panels changed from R125 to Thoracic aortic aneurysm and dissection; R125
Hypertrophic cardiomyopathy v3.5 Arina Puzriakova Panel name changed from Hypertrophic cardiomyopathy - teen and adult to Hypertrophic cardiomyopathy
List of related panels changed from Hypertrophic Cardiomyopathy; HCM; R131 to Hypertrophic cardiomyopathy - teen and adult; HCM; R131
Hereditary diffuse gastric cancer v0.8 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease; GMS signed-off
Dilated and arrhythmogenic cardiomyopathy v2.8 Arina Puzriakova Panel name changed from Dilated cardiomyopathy - adult and teen to Dilated and arrhythmogenic cardiomyopathy
List of related panels changed from R132 to Dilated cardiomyopathy - adult and teen; R132
Paediatric or syndromic cardiomyopathy v2.10 Arina Puzriakova Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Paediatric or syndromic cardiomyopathy v2.9 Arina Puzriakova Panel name changed from Cardiomyopathies - including childhood onset to Paediatric or syndromic cardiomyopathy
List of related panels changed from Paediatric or syndromic cardiomyopathy; R135 to Cardiomyopathies - including childhood onset; R135
Familial chylomicronaemia syndrome (FCS) v2.4 Sarah Leigh Panel name changed from Lipoprotein lipase deficiency to Familial chylomicronaemia syndrome (FCS)
List of related panels changed from R324 to Lipoprotein lipase deficiency;R324
Unexplained young onset end-stage renal disease v2.7 Achchuthan Shanmugasundram Panel name changed from Unexplained paediatric onset end-stage renal disease to Unexplained young onset end-stage renal disease
List of related panels changed from R257 to Unexplained paediatric onset end-stage renal disease; R257
Brugada syndrome and cardiac sodium channel disease v3.2 Arina Puzriakova Panel name changed from Brugada syndrome to Brugada syndrome and cardiac sodium channel disease
List of related panels changed from R128 to Brugada syndrome; R128
Arrhythmogenic right ventricular cardiomyopathy v3.4 Arina Puzriakova Panel name changed from Arrhythmogenic cardiomyopathy to Arrhythmogenic right ventricular cardiomyopathy
List of related panels changed from Arrhythmogenic Right Ventricular Cardiomyopathy; Arrythmogenic cardiomyopathy; R133 to Arrythmogenic cardiomyopathy; R133
Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.32 Achchuthan Shanmugasundram Panel name changed from Membranoproliferative glomerulonephritis to Membranoproliferative glomerulonephritis including C3 glomerulopathy
List of related panels changed from PMG; MPGN; Primary Membranoproliferative Glomerulonephritis; Primary membranoproliferative glomerulonephritis; R197 to PMG; MPGN; Primary Membranoproliferative Glomerulonephritis; Primary membranoproliferative glomerulonephritis; Membranoproliferative glomerulonephritis; R197
Childhood solid tumours v3.5 Arina Puzriakova Panel name changed from Tumour predisposition - childhood onset to Childhood solid tumours
List of related panels changed from Paediatric congenital malformation-dysmorphism-tumour syndrome; Paediatric congenital malformation-dysmorphism-tumour syndromes; Paediatric congenital malformation-dysmorphism-tumour sydromes; Paediatric congenital malformation-dysmorphism-tumour syndrome; R359 to Paediatric congenital malformation-dysmorphism-tumour syndrome; Paediatric congenital malformation-dysmorphism-tumour syndromes; Paediatric congenital malformation-dysmorphism-tumour sydromes; Paediatric congenital malformation-dysmorphism-tumour syndrome; Tumour predisposition - childhood onset; R359
Hereditary systemic amyloidosis v1.17 Achchuthan Shanmugasundram Panel name changed from Amyloidosis to Hereditary systemic amyloidosis
List of related panels changed from R204 to Amyloidosis; R204
Monogenic hearing loss v3.15 Arina Puzriakova Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Paediatric disorders v24.414 Arina Puzriakova Changed child panels to: Intellectual disability; Inborn errors of metabolism; Monogenic hearing loss; Skeletal dysplasia; Clefting; Limb disorders; DDG2P; Paediatric disorders - additional genes; Renal ciliopathies; Neurological ciliopathies; Ophthalmological ciliopathies; Skeletal ciliopathies
Primary immunodeficiency or monogenic inflammatory bowel disease v3.9 STAT6 Dmitrijs Rots reviewed gene: STAT6: Rating: GREEN; Mode of pathogenicity: None; Publications: 36884218; Phenotypes: Eosinophilia, severe allergy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset hereditary spastic paraplegia v2.21 RAB3GAP2 Achchuthan Shanmugasundram Classified gene: RAB3GAP2 as Amber List (moderate evidence)
Adult onset hereditary spastic paraplegia v2.21 RAB3GAP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene is rated AMBER as all the cases are of childhood-onset.
Adult onset hereditary spastic paraplegia v2.21 RAB3GAP2 Achchuthan Shanmugasundram Gene: rab3gap2 has been classified as Amber List (Moderate Evidence).
Adult onset hereditary spastic paraplegia v2.20 RAB3GAP2 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: RAB3GAP2.
Adult onset hereditary spastic paraplegia v2.20 RAB3GAP2 Achchuthan Shanmugasundram Deleted their comment
Childhood onset hereditary spastic paraplegia v3.26 RNF170 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: RNF170.
Childhood onset hereditary spastic paraplegia v3.26 RNF170 Achchuthan Shanmugasundram Classified gene: RNF170 as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v3.26 RNF170 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (6 unrelated cases) for this gene to be promoted to GREEN at the next major review.
Childhood onset hereditary spastic paraplegia v3.26 RNF170 Achchuthan Shanmugasundram Gene: rnf170 has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v3.25 RNF170 Achchuthan Shanmugasundram Phenotypes for gene: RNF170 were changed from Hereditary spastic paraplegia to Spastic paraplegia 85, autosomal recessive, OMIM:619686
Childhood onset hereditary spastic paraplegia v3.24 RNF170 Achchuthan Shanmugasundram Publications for gene: RNF170 were set to 31636353
Childhood onset hereditary spastic paraplegia v3.23 RNF170 Achchuthan Shanmugasundram changed review comment from: PMID:31636353 reported 9 patients from 4 unrelated families with childhood-onset spastic paraplegia. The age of onset of the condition ranged from 2 to 5 years of age and they were all identified with a homozygous variant in RNF170 gene. It is a neurological disorder characterised by the onset of motor symptoms in the first few years of life. Affected individuals have spasticity and hyperreflexia of the lower limbs resulting in gait abnormalities, with oilder patients also having upper limb involvement and axonal polyneuropathy.

PMID:33165979 reported four members from a single family carrying a homozygous stop gain variant in RNF170 and diagnosed with hereditary spastic paraplegia.

PMID:35041108 reported a 7 year old girl with novel homozygous missense variant in RNF170 and she presented with progressive difficulty in walking that started when she was 3 years old, lower limb predominant spastic paraparesis, and mild upper limbs involvement with slight tremor in the hands, all occurring in the absence of neurodevelopmental or growth delays.; to: PMID:31636353 reported 9 patients from 4 unrelated families with childhood-onset spastic paraplegia. The age of onset of the condition ranged from 2 to 5 years of age and they were all identified with a homozygous variant in RNF170 gene. It is a neurological disorder characterised by the onset of motor symptoms in the first few years of life. Affected individuals have spasticity and hyperreflexia of the lower limbs resulting in gait abnormalities, with oilder patients also having upper limb involvement and axonal polyneuropathy.

PMID:33165979 reported four members from a single family carrying a homozygous stop gain variant in RNF170 and diagnosed with hereditary spastic paraplegia.

PMID:35041108 reported a 7 year old girl with novel homozygous missense variant in RNF170 and she presented with progressive difficulty in walking that started when she was 3 years old, lower limb predominant spastic paraparesis, and mild upper limbs involvement with slight tremor in the hands, all occurring in the absence of neurodevelopmental or growth delays.

This gene has been associated with relevant phenotypes in OMIM (MIM #619686), but not yet in Gene2Phenotype.
Childhood onset hereditary spastic paraplegia v3.23 RNF170 Achchuthan Shanmugasundram reviewed gene: RNF170: Rating: GREEN; Mode of pathogenicity: None; Publications: 31636353, 33165979, 35041108; Phenotypes: Spastic paraplegia 85, autosomal recessive, OMIM:619686; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v3.23 RAB3GAP2 Achchuthan Shanmugasundram Publications for gene: RAB3GAP2 were set to 24482476
Adult onset hereditary spastic paraplegia v2.20 RAB3GAP2 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: RAB3GAP2.
Adult onset hereditary spastic paraplegia v2.20 RAB3GAP2 Achchuthan Shanmugasundram Phenotypes for gene: RAB3GAP2 were changed from Warburg micro syndrome 2, OMIM:614225 to Martsolf syndrome 1, OMIM:212720; Warburg micro syndrome 2, OMIM:614225
Adult onset hereditary spastic paraplegia v2.19 RAB3GAP2 Achchuthan Shanmugasundram Publications for gene: RAB3GAP2 were set to 24482476
Adult onset hereditary spastic paraplegia v2.18 RAB3GAP2 Achchuthan Shanmugasundram Classified gene: RAB3GAP2 as Amber List (moderate evidence)
Adult onset hereditary spastic paraplegia v2.18 RAB3GAP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) available for this gene to be considered for a green rating in the next major review.
Adult onset hereditary spastic paraplegia v2.18 RAB3GAP2 Achchuthan Shanmugasundram Gene: rab3gap2 has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v3.22 RAB3GAP2 Achchuthan Shanmugasundram changed review comment from: PMID:32740904 reported 9 cases identified with biallelic variants in RAB3GAP2 gene. Seven of them were diagnosed with Martsolf syndrome 1 (MIM #212720) and the remaining two with Warburg micro syndrome 2 (MIM #614225). All of them presented with spasticity (either paraparesis or quadriparesis) as one of the clinical manifestations. The age of patients ranged from 1 year 4 months to 14 years old, with six ion them under 10 years old.

This gene has been associated with phenotypes in both OMIM and Gene2Phenotype.; to: PMID:32740904 reported 9 cases identified with biallelic variants in RAB3GAP2 gene. Seven of them were diagnosed with Martsolf syndrome 1 (MIM #212720) and the remaining two with Warburg micro syndrome 2 (MIM #614225). All of them presented with spasticity (either paraparesis or quadriparesis) as one of the clinical manifestations. The age of patients ranged from 1 year 4 months to 14 years old, with six of them under 10 years old.

This gene has been associated with phenotypes in both OMIM and Gene2Phenotype.
Adult onset hereditary spastic paraplegia v2.17 RAB3GAP2 Achchuthan Shanmugasundram reviewed gene: RAB3GAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32740904; Phenotypes: Martsolf syndrome 1, OMIM:212720, Warburg micro syndrome 2, OMIM:614225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v3.22 RAB3GAP2 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: RAB3GAP2.
Childhood onset hereditary spastic paraplegia v3.22 RAB3GAP2 Achchuthan Shanmugasundram Classified gene: RAB3GAP2 as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v3.22 RAB3GAP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) available for this gene to be considered for a green rating in the next major review.
Childhood onset hereditary spastic paraplegia v3.22 RAB3GAP2 Achchuthan Shanmugasundram Gene: rab3gap2 has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v3.21 RAB3GAP2 Achchuthan Shanmugasundram Phenotypes for gene: RAB3GAP2 were changed from Martsolf syndrome 1, OMIM:212720 to Martsolf syndrome 1, OMIM:212720; Warburg micro syndrome 2, OMIM:614225
Childhood onset hereditary spastic paraplegia v3.20 RAB3GAP2 Achchuthan Shanmugasundram reviewed gene: RAB3GAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32740904; Phenotypes: Martsolf syndrome 1, OMIM:212720, Warburg micro syndrome 2, OMIM:614225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v2.17 SMARCC1 Eleanor Williams Added comment: Comment on phenotypes: Adding the OMIM phenotype and removing the gene-checked tag.
Fetal anomalies v2.17 SMARCC1 Eleanor Williams Phenotypes for gene: SMARCC1 were changed from Congenital hydrocephalus; Aqueductal stenosis; Septal agenesis; Corpus callosum abnormalities to Congenital hydrocephalus; Aqueductal stenosis; Septal agenesis; Corpus callosum abnormalities; {Hydrocephalus, congenital, 5, susceptibility to}, OMIM:620241
Fetal anomalies v2.16 SMARCC1 Eleanor Williams Tag gene-checked was removed from gene: SMARCC1.
Hydrocephalus v3.6 SMARCC1 Eleanor Williams Added comment: Comment on phenotypes: Adding the OMIM phenotype and removing the gene-checked tag.
Hydrocephalus v3.6 SMARCC1 Eleanor Williams Phenotypes for gene: SMARCC1 were changed from Congenital hydrocephalus; Aqueductal stenosis; Septal agenesis; Corpus callosum abnormalities to Congenital hydrocephalus; Aqueductal stenosis; Septal agenesis; Corpus callosum abnormalities; {Hydrocephalus, congenital, 5, susceptibility to}, OMIM:620241
Hydrocephalus v3.5 SMARCC1 Eleanor Williams Tag gene-checked was removed from gene: SMARCC1.
Severe microcephaly v3.12 ATP9A Eleanor Williams Phenotypes for gene: ATP9A were changed from Neurodevelopmental delay; Postnatal microcephaly; Failure to thrive; Gastrointestinal symptoms to Neurodevelopmental delay; Postnatal microcephaly; Failure to thrive; Gastrointestinal symptoms; Neurodevelopmental disorder with poor growth and behavioral abnormalities, OMIM:620242
Intellectual disability v4.125 ATP9A Eleanor Williams Tag gene-checked was removed from gene: ATP9A.
Intellectual disability v4.125 ATP9A Eleanor Williams Added comment: Comment on phenotypes: Adding the OMIM phenotype which was added to OMIM in Feb 2023.
Intellectual disability v4.125 ATP9A Eleanor Williams Phenotypes for gene: ATP9A were changed from Global developmental delay; Intellectual disability; Postnatal microcephaly; Failure to thrive; Abnormality of the abdomen to Global developmental delay; Intellectual disability; Postnatal microcephaly; Failure to thrive; Abnormality of the abdomen; Neurodevelopmental disorder with poor growth and behavioral abnormalities, OMIM:620242
Intellectual disability v4.124 TAB2 Achchuthan Shanmugasundram Publications for gene: TAB2 were set to 35971781
Intellectual disability v4.124 TAB2 Achchuthan Shanmugasundram Publications for gene: TAB2 were set to 35971781
Intellectual disability v4.123 TAB2 Achchuthan Shanmugasundram Publications for gene: TAB2 were set to 35971781
Intellectual disability v4.123 TAB2 Achchuthan Shanmugasundram Publications for gene: TAB2 were set to
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Classified gene: TAB2 as Amber List (moderate evidence)
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER. Although there are four unrelated cases reported with ID, ID is part of a broad spectrum of phenotypes and the majority of cases in PMID:35971781 and other previous studies were not reported with ID as part of the phenotype.

ID has not been reported as part of the phenotype either in OMIM or in Gene2Phenotype.
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Gene: tab2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Classified gene: TAB2 as Amber List (moderate evidence)
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER. Although there are four unrelated cases reported with ID, ID is part of a broad spectrum of phenotypes and the majority of cases in PMID:35971781 and other previous studies were not reported with ID as part of the phenotype.

ID has not been reported as part of the phenotype either in OMIM or in Gene2Phenotype.
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Gene: tab2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Classified gene: TAB2 as Amber List (moderate evidence)
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER. Although there are four unrelated cases reported with ID, ID is part of a broad spectrum of phenotypes and the majority of cases in PMID:35971781 and other previous studies were not reported with ID as part of the phenotype.

ID has not been reported as part of the phenotype either in OMIM or in Gene2Phenotype.
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Gene: tab2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Classified gene: TAB2 as Amber List (moderate evidence)
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER. Although there are four unrelated cases reported with ID, ID is part of a broad spectrum of phenotypes and the majority of cases in PMID:35971781 and other previous studies were not reported with ID as part of the phenotype.

ID has not been reported as part of the phenotype either in OMIM or in Gene2Phenotype.
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Gene: tab2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.120 TAB2 Achchuthan Shanmugasundram changed review comment from: 4 out of 14 patients identified with heterozygous variants in TAB2 gene in PMID:35971781 were reported with global developmental delay and intellectual disability (ID). Two other patients were reported with motor delay. Although developmental delay was reported in previous studies including the one reviewed by Andrea Haworth below, none of the previous studies reported cases with ID.

Although there are four unrelated cases reported with ID, ID is part of a broad spectrum of phenotypes and a majority of cases in this study and other previous studies did not report ID as part of the phenotype.

ID has not been reported as part of the phenotype either in OMIM or in Gene2Phenotype.; to: 4 out of 14 patients identified with heterozygous variants in TAB2 gene in PMID:35971781 were reported with global developmental delay and intellectual disability (ID). Two other patients were reported with motor delay. Although developmental delay was reported in previous studies including the one reviewed by Andrea Haworth below, none of the previous studies reported cases with ID.
Intellectual disability v4.120 TAB2 Achchuthan Shanmugasundram reviewed gene: TAB2: Rating: AMBER; Mode of pathogenicity: None; Publications: 35971781; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v3.113 SATB2 Sarah Leigh edited their review of gene: SATB2: Added comment: Associated with Glass syndrome, OMIM:612313 and as definitive Gen2Phen gene for the same condition. Table 2 in PMID: 32446642 presents a clincal review of SATB2 variant carriers. Amongst the 35 cases carrying intragenic variants, 14 did not have clinical seizures, 19 had seizures (10 well controlled, 9 somewhat controlled) and the diagnosis was uncertain in two other cases.; Changed rating: GREEN
Early onset or syndromic epilepsy v3.113 SATB2 Sarah Leigh Phenotypes for gene: SATB2 were changed from Glass syndrome, MIM# 612313 to Glass syndrome, OMIM:612313
Intellectual disability v4.120 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.120 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.119 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.120 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.119 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.119 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.119 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.119 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587
Early onset or syndromic epilepsy v3.112 SATB2 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: SATB2.
Early onset or syndromic epilepsy v3.112 SATB2 Sarah Leigh Classified gene: SATB2 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.112 SATB2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v3.112 SATB2 Sarah Leigh Gene: satb2 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v3.111 KPTN Sarah Leigh Tag watchlist was removed from gene: KPTN.
Tag Q1_23_promote_green tag was added to gene: KPTN.
Early onset or syndromic epilepsy v3.111 KPTN Sarah Leigh edited their review of gene: KPTN: Added comment: Associated with relevant phenotype in OMIM and as strong Gen2Phen gene. At least five KPTN variants have been reported in four unrelated cases of OMIM: 615637, seizures were evident in three unrelated cases (PMID: 24239382;25847626;32358097;32808430).; Changed rating: GREEN
Early onset or syndromic epilepsy v3.111 KPTN Sarah Leigh Classified gene: KPTN as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.111 KPTN Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v3.111 KPTN Sarah Leigh Gene: kptn has been classified as Amber List (Moderate Evidence).
Fetal anomalies v2.16 KPTN Sarah Leigh Phenotypes for gene: KPTN were changed from MACROCEPHALY, NEURODEVELOPMENTAL DELAY, AND SEIZURES to Intellectual developmental disorder, autosomal recessive 41, OMIM:615637; macrocephaly-developmental delay syndrome, MONDO:0014289
Intellectual disability v4.118 KPTN Sarah Leigh Phenotypes for gene: KPTN were changed from MACROCEPHALY, NEURODEVELOPMENTAL DELAY, AND SEIZURES to Intellectual developmental disorder, autosomal recessive 41, OMIM:615637; macrocephaly-developmental delay syndrome, MONDO:0014289
Early onset or syndromic epilepsy v3.110 KPTN Sarah Leigh Phenotypes for gene: KPTN were changed from Mental retardation, autosomal recessive 4,1615637; seizures to Intellectual developmental disorder, autosomal recessive 41, OMIM:615637; macrocephaly-developmental delay syndrome, MONDO:0014289
Early onset or syndromic epilepsy v3.109 KPTN Sarah Leigh Publications for gene: KPTN were set to 24239382; 25847626
Skeletal dysplasia v3.13 EXT2 Sarah Leigh changed review comment from: Biallelic EXT2 variants are also reported in Seizures, scoliosis, and macrocephaly syndrome, OMIM:616682. Table 2 in PMID: 30997052 highlights the phenotypic features of OMIM:616682. Scoliosis, which is relevant to this panel, is seen in 2/4 families reviewed in PMID: 30997052. If scoliosis is observed in more cases of OMIM:616682, then it would be appropriate to change the mode of inheritance of EXT2 to BOTH monoallelic and biallelic. The Watchlist tag has been added to this gene to reflect this situation.; to: Biallelic EXT2 variants are also reported in Seizures, scoliosis, and macrocephaly syndrome, OMIM:616682. Table 2 in PMID: 30997052 highlights the phenotypic features of OMIM:616682. Scoliosis, which is relevant to this panel, is seen in 2/4 families reviewed in PMID: 30997052. If scoliosis is observed in more cases of OMIM:616682, then it would be appropriate to change the mode of inheritance of EXT2 to BOTH monoallelic and biallelic. The Watchlist_moi tag has been added to this gene to reflect this situation.
Skeletal dysplasia v3.13 EXT2 Sarah Leigh Tag watchlist_moi tag was added to gene: EXT2.
Skeletal dysplasia v3.13 EXT2 Sarah Leigh Phenotypes for gene: EXT2 were changed from Exostoses, multiple, type 2 133701 to Exostoses, multiple, type 2, OMIM:133701
Skeletal dysplasia v3.12 EXT2 Sarah Leigh edited their review of gene: EXT2: Added comment: Biallelic EXT2 variants are also reported in Seizures, scoliosis, and macrocephaly syndrome, OMIM:616682. Table 2 in PMID: 30997052 highlights the phenotypic features of OMIM:616682. Scoliosis, which is relevant to this panel, is seen in 2/4 families reviewed in PMID: 30997052. If scoliosis is observed in more cases of OMIM:616682, then it would be appropriate to change the mode of inheritance of EXT2 to BOTH monoallelic and biallelic. The Watchlist tag has been added to this gene to reflect this situation.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v3.12 EXT2 Sarah Leigh Added comment: Comment on phenotypes: EXT2 variants are also reported in: Seizures, scoliosis, and macrocephaly syndrome, OMIM:616682
Skeletal dysplasia v3.12 EXT2 Sarah Leigh Phenotypes for gene: EXT2 were changed from Exostoses, multiple, type 2 133701 to Exostoses, multiple, type 2 133701
Amyotrophic lateral sclerosis/motor neuron disease v1.67 SPAST Sarah Leigh Publications for gene: SPAST were set to 16832076; 18401025; 33589474
Amyotrophic lateral sclerosis/motor neuron disease v1.66 SPAST Sarah Leigh reviewed gene: SPAST: Rating: GREEN; Mode of pathogenicity: None; Publications: 16240363, 18401025, 33589474; Phenotypes: ; Mode of inheritance: None
Amyotrophic lateral sclerosis/motor neuron disease v1.66 SPAST Sarah Leigh Classified gene: SPAST as Green List (high evidence)
Amyotrophic lateral sclerosis/motor neuron disease v1.66 SPAST Sarah Leigh Gene: spast has been classified as Green List (High Evidence).
Hereditary neuropathy or pain disorder v2.28 SPAST Sarah Leigh Phenotypes for gene: SPAST were changed from Hereditary Neuropathies; Spastic paraplegia 4, autosomal dominant; Spasticity to Spastic paraplegia 4, autosomal dominant, OMIM:182601; hereditary spastic paraplegia 4, MONDO:0008438
Hereditary neuropathy v1.462 SPAST Sarah Leigh Phenotypes for gene: SPAST were changed from Hereditary Neuropathies; Spastic paraplegia 4, autosomal dominant; Spasticity to Spastic paraplegia 4, autosomal dominant, OMIM:182601; hereditary spastic paraplegia 4, MONDO:0008438
Adult onset neurodegenerative disorder v3.59 SPAST Sarah Leigh Phenotypes for gene: SPAST were changed from Spastic paraplegia 4, autosomal dominant, OMIM:182601 to Spastic paraplegia 4, autosomal dominant, OMIM:182601; hereditary spastic paraplegia 4, MONDO:0008438
Adult onset hereditary spastic paraplegia v2.17 SPAST Sarah Leigh Phenotypes for gene: SPAST were changed from Spastic paraplegia 4, autosomal dominant, 182601 to Spastic paraplegia 4, autosomal dominant, OMIM:182601; hereditary spastic paraplegia 4, MONDO:0008438
Childhood onset hereditary spastic paraplegia v3.20 SPAST Sarah Leigh Phenotypes for gene: SPAST were changed from Spastic paraplegia 4, autosomal dominant, 182601 to Spastic paraplegia 4, autosomal dominant, OMIM:182601; hereditary spastic paraplegia 4, MONDO:0008438
Amyotrophic lateral sclerosis/motor neuron disease v1.65 SPAST Sarah Leigh Phenotypes for gene: SPAST were changed from Spastic paraplegia 4, autosomal dominant to Spastic paraplegia 4, autosomal dominant, OMIM:182601; hereditary spastic paraplegia 4, MONDO:0008438
Hereditary spastic paraplegia v1.304 SPAST Sarah Leigh Phenotypes for gene: SPAST were changed from Spastic paraplegia 4, autosomal dominant to Spastic paraplegia 4, autosomal dominant, OMIM:182601; hereditary spastic paraplegia 4, MONDO:0008438
Adult onset neurodegenerative disorder v3.58 NEK1 Sarah Leigh changed review comment from: Associated with Amyotrophic lateral sclerosis, susceptibility to, 24 (OMIM:617892), but not associated with a relevant phenotype in Gen2Phen. At least 12 NEK1 variants have been reported in amyotrophic lateral sclerosis cases (PMID: 30093141; 31768050; 26945885; 27455347), together with supportive functional studies (PMID: 2992911).; to: Associated with Amyotrophic lateral sclerosis, susceptibility to, 24 (OMIM:617892), but not associated with a relevant phenotype in Gen2Phen. At least 12 NEK1 variants have been reported in amyotrophic lateral sclerosis cases (PMID: 30093141; 31768050; 26945885; 27455347), together with supportive functional studies (PMID: 2992911).
ClinGen Definitive gene - disease classification (29/04/2022): https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_bb4f311c-df33-4d9e-8ac6-731b43b93615-2022-04-29T192526.542Z?page=1&size=25&search=
Amyotrophic lateral sclerosis/motor neuron disease v1.64 NEK1 Sarah Leigh Phenotypes for gene: NEK1 were changed from Amyotrophic lateral sclerosis, susceptibility to, 24 to Amyotrophic lateral sclerosis, susceptibility to, 24, OMIM:617892; amyotrophic lateral sclerosis, susceptibility to, 24, MONDO:0054750
Amyotrophic lateral sclerosis/motor neuron disease v1.63 NEK1 Sarah Leigh reviewed gene: NEK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Amyotrophic lateral sclerosis/motor neuron disease v1.63 NEK1 Sarah Leigh Classified gene: NEK1 as Green List (high evidence)
Amyotrophic lateral sclerosis/motor neuron disease v1.63 NEK1 Sarah Leigh Gene: nek1 has been classified as Green List (High Evidence).
Familial hypoparathyroidism v2.10 TBX1 Arina Puzriakova Classified gene: TBX1 as Amber List (moderate evidence)
Familial hypoparathyroidism v2.10 TBX1 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green on this panel (at least three cases of parathyroid dysfunction, including a patient with isolated hypoparathyroidism) at the next GMS panel update.
Familial hypoparathyroidism v2.10 TBX1 Arina Puzriakova Gene: tbx1 has been classified as Amber List (Moderate Evidence).
Familial hypoparathyroidism v2.9 TBX1 Arina Puzriakova Phenotypes for gene: TBX1 were changed from to DiGeorge syndrome, OMIM:188400; Conotruncal anomaly face syndrome, OMIM:217095; Velocardiofacial syndrome, OMIM:192430
Familial hypoparathyroidism v2.8 TBX1 Arina Puzriakova Publications for gene: TBX1 were set to 30137364
Familial hypoparathyroidism v2.7 TBX1 Arina Puzriakova Tag Q1_23_promote_green tag was added to gene: TBX1.
Familial hypoparathyroidism v2.7 TBX1 Arina Puzriakova reviewed gene: TBX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 14585638, 17273972, 30137364; Phenotypes: DiGeorge syndrome, OMIM:188400, Conotruncal anomaly face syndrome, OMIM:217095, Velocardiofacial syndrome, OMIM:192430; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v4.117 TBX1 Arina Puzriakova reviewed gene: TBX1: Rating: ; Mode of pathogenicity: None; Publications: 14585638, 17273972, 30137364; Phenotypes: ; Mode of inheritance: None
Primary immunodeficiency or monogenic inflammatory bowel disease v3.9 TBX1 Arina Puzriakova Publications for gene: TBX1 were set to 11242110; 32048120; 32086639; 14585638; 24198816; 12548732
Primary immunodeficiency or monogenic inflammatory bowel disease v3.8 TBX1 Arina Puzriakova Classified gene: TBX1 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v3.8 TBX1 Arina Puzriakova Added comment: Comment on list classification: Following consultation with Helen Brittain (Genomics England Clinical Team) it was agreed that there is sufficient evidence to promote this gene to Green on this panel (at least three cases of immune involvement) at the next GMS panel update.
Primary immunodeficiency or monogenic inflammatory bowel disease v3.8 TBX1 Arina Puzriakova Gene: tbx1 has been classified as Amber List (Moderate Evidence).
Clefting v3.9 TBX1 Arina Puzriakova Classified gene: TBX1 as Amber List (moderate evidence)
Clefting v3.9 TBX1 Arina Puzriakova Added comment: Comment on list classification: Following consultation with Helen Brittain (Genomics England Clinical Team) it was agreed that there is sufficient evidence to promote this gene to Green on this panel (at least three cases of palatal involvement) at the next GMS panel update.
Clefting v3.9 TBX1 Arina Puzriakova Gene: tbx1 has been classified as Amber List (Moderate Evidence).
Clefting v3.8 TBX1 Arina Puzriakova Phenotypes for gene: TBX1 were changed from CONOTRUNCAL HEART MALFORMATIONS; CTHM; Cleft palate to DiGeorge syndrome, OMIM:188400; Conotruncal anomaly face syndrome, OMIM:217095; Velocardiofacial syndrome, OMIM:192430
Clefting v3.7 TBX1 Arina Puzriakova Publications for gene: TBX1 were set to
Clefting v3.6 TBX1 Arina Puzriakova Tag Q1_23_promote_green tag was added to gene: TBX1.
Clefting v3.6 TBX1 Arina Puzriakova reviewed gene: TBX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 14585638, 17273972, 30137364; Phenotypes: DiGeorge syndrome, OMIM:188400, Conotruncal anomaly face syndrome, OMIM:217095, Velocardiofacial syndrome, OMIM:192430; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary immunodeficiency or monogenic inflammatory bowel disease v3.7 TBX1 Arina Puzriakova Phenotypes for gene: TBX1 were changed from Hypoparathyroidism, conotruncal cardiac malformation, velopalatal insufficiency, abnormal facies, intellectual disability; Di George syndrome; Severe combined immunodeficiency (SCID); DiGeorge syndrome 188400; T-B+ SCID; Combined immunodeficiencies with associated or syndromic features to DiGeorge syndrome, OMIM:188400; Conotruncal anomaly face syndrome, OMIM:217095; Velocardiofacial syndrome, OMIM:192430
Primary immunodeficiency or monogenic inflammatory bowel disease v3.6 TBX1 Arina Puzriakova Tag Q1_23_promote_green tag was added to gene: TBX1.
Primary immunodeficiency or monogenic inflammatory bowel disease v3.6 TBX1 Arina Puzriakova reviewed gene: TBX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 14585638, 17273972, 30137364; Phenotypes: DiGeorge syndrome, OMIM:188400, Conotruncal anomaly face syndrome, OMIM:217095, Velocardiofacial syndrome, OMIM:192430; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.20 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.19 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: GCSH.
Early onset or syndromic epilepsy v3.108 GCSH Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: GCSH.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: GCSH.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.116 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.116 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.116 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.116 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.116 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.115 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to 36190515
Intellectual disability v4.116 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.116 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.116 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.115 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to 36190515
Intellectual disability v4.115 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to 36190515
Intellectual disability v4.116 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from Glycine encephalopathy to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.115 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to 36190515
Intellectual disability v4.115 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to 36190515
Intellectual disability v4.115 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to 36190515
Intellectual disability v4.115 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to 36190515
Intellectual disability v4.115 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to
Intellectual disability v4.114 GCSH Achchuthan Shanmugasundram reviewed gene: GCSH: Rating: GREEN; Mode of pathogenicity: None; Publications: 36190515; Phenotypes: ?Glycine encephalopathy, OMIM:605899, Neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.17 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.17 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.17 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.18 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.17 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.17 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.17 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.17 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.17 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.17 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.17 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.17 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.17 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.17 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.17 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to green at the next NHS GMS review.
Likely inborn error of metabolism v3.17 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.17 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism v3.17 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism v3.17 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.17 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Likely inborn error of metabolism v3.16 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Likely inborn error of metabolism v3.16 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Likely inborn error of metabolism v3.16 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Likely inborn error of metabolism v3.16 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Likely inborn error of metabolism v3.16 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Likely inborn error of metabolism v3.15 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Likely inborn error of metabolism v3.15 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Likely inborn error of metabolism v3.16 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Likely inborn error of metabolism v3.15 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Likely inborn error of metabolism v3.15 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Likely inborn error of metabolism v3.15 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Likely inborn error of metabolism v3.15 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from Glycine encephalopathy to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Likely inborn error of metabolism v3.15 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to 27604308; 16450403; 36190515
Likely inborn error of metabolism v3.15 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to 27604308; 16450403; 36190515
Likely inborn error of metabolism v3.14 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to 27604308; 16450403; 36190515
Likely inborn error of metabolism v3.14 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to 27604308; 16450403
Likely inborn error of metabolism v3.13 GCSH Achchuthan Shanmugasundram reviewed gene: GCSH: Rating: GREEN; Mode of pathogenicity: None; Publications: 36190515; Phenotypes: ?Glycine encephalopathy, OMIM:605899, Neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v3.108 GCSH Achchuthan Shanmugasundram changed review comment from: PMID:36190515 reported six unrelated individuals with biallelic variants in GCSH. They presented with a broad clinical spectrum with three cases with an early-onset severe fatal glycine encephalopathy and the other three cases displaying an attenuated phenotype of developmental delay, behavioural problems, epilepsy and variable movement problems and they had long-term survival. The three early-onset and fatal cases displayed compound heterozygous variants, while the cases with attenuated phenotype harboured homozygous variants.

All three individuals with the early-onset severe fatal glycine encephalopathy had epilepsy/ seizures as part of the presenting phenotypes. Only patient (patient 6) from the three cases with the attenuated phenotype had left-sided partial seizures, while other two had no seizures/ epilepsy.

Functional studies in patient's fibroblasts, molecular modeling, expression analysis in GCSH knockdown COS7 cells and yeast, and in vitro protein studies demonstrated that most variants identified in this cohort produced a hypomorphic effect on both protein lipoylation and glycine metabolism, causing combined deficiency, whereas some missense variants affected primarily one function only.

This gene has also been associated with Glycine encephalopathy in both OMIM and Gene2Phenotype.;; to: PMID:36190515 reported six unrelated individuals with biallelic variants in GCSH. They presented with a broad clinical spectrum with three cases with an early-onset severe fatal glycine encephalopathy and the other three cases displaying an attenuated phenotype of developmental delay, behavioural problems, epilepsy and variable movement problems and they had long-term survival. The three early-onset and fatal cases displayed compound heterozygous variants, while the cases with attenuated phenotype harboured homozygous variants.

All three individuals with the early-onset severe fatal glycine encephalopathy had epilepsy/ seizures as part of the presenting phenotypes. Only patient (patient 6) from the three cases with the attenuated phenotype had left-sided partial seizures, while other two had no seizures/ epilepsy.

Functional studies in patient's fibroblasts, molecular modeling, expression analysis in GCSH knockdown COS7 cells and yeast, and in vitro protein studies demonstrated that most variants identified in this cohort produced a hypomorphic effect on both protein lipoylation and glycine metabolism, causing combined deficiency, whereas some missense variants affected primarily one function only.

This gene has also been associated with Glycine encephalopathy in both OMIM and Gene2Phenotype.
Early onset or syndromic epilepsy v3.108 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.108 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are five unrelated cases identified with biallelic variants in GCSH and reported with seizures/ epilepsy as part of the phenotype. one case was reported in PMID:1671321 and four in PMID:36190515 (three with severe neonatal/ infantile phenotype and one with attenuated phenotype).
Early onset or syndromic epilepsy v3.108 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v3.107 GCSH Achchuthan Shanmugasundram changed review comment from: PMID:36190515 reported six unrelated individuals with biallelic variants in GCSH. They presented with a broad clinical spectrum with three cases with an early-onset severe fatal glycine encephalopathy and the other three cases displaying an attenuated phenotype of developmental delay, behavioural problems, epilepsy and variable movement problems and they had long-term survival. The three early-onset and fatal cases displayed compound heterozygous variants, while the cases with attenuated phenotype harboured homozygous variants.

All three individuals with the early-onset severe fatal glycine encephalopathy had epilepsy/ seizures as part of the presenting phenotypes. Only patient (patient 6) from the three cases with the attenuated phenotype had left-sided partial seizures, while other two had no seizures/ epilepsy.

Functional studies in patient's fibroblasts, molecular modeling, expression analysis in GCSH knockdown COS7 cells and yeast, and in vitro protein studies demonstrated that most variants identified in this cohort produced a hypomorphic effect on both protein lipoylation and glycine metabolism, causing combined deficiency, whereas some missense variants affected primarily one function only.; to: PMID:36190515 reported six unrelated individuals with biallelic variants in GCSH. They presented with a broad clinical spectrum with three cases with an early-onset severe fatal glycine encephalopathy and the other three cases displaying an attenuated phenotype of developmental delay, behavioural problems, epilepsy and variable movement problems and they had long-term survival. The three early-onset and fatal cases displayed compound heterozygous variants, while the cases with attenuated phenotype harboured homozygous variants.

All three individuals with the early-onset severe fatal glycine encephalopathy had epilepsy/ seizures as part of the presenting phenotypes. Only patient (patient 6) from the three cases with the attenuated phenotype had left-sided partial seizures, while other two had no seizures/ epilepsy.

Functional studies in patient's fibroblasts, molecular modeling, expression analysis in GCSH knockdown COS7 cells and yeast, and in vitro protein studies demonstrated that most variants identified in this cohort produced a hypomorphic effect on both protein lipoylation and glycine metabolism, causing combined deficiency, whereas some missense variants affected primarily one function only.

This gene has also been associated with Glycine encephalopathy in both OMIM and Gene2Phenotype.;
Early onset or syndromic epilepsy v3.107 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Early onset or syndromic epilepsy v3.106 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to
Early onset or syndromic epilepsy v3.105 GCSH Achchuthan Shanmugasundram Mode of inheritance for gene: GCSH was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v3.105 GCSH Achchuthan Shanmugasundram Mode of inheritance for gene: GCSH was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v3.105 GCSH Achchuthan Shanmugasundram Mode of inheritance for gene: GCSH was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v3.104 GCSH Achchuthan Shanmugasundram reviewed gene: GCSH: Rating: GREEN; Mode of pathogenicity: None; Publications: 36190515; Phenotypes: ?Glycine encephalopathy, OMIM:605899, Neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.114 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587
Intellectual disability v4.113 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587
Intellectual disability v4.114 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587
Intellectual disability v4.114 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587
Intellectual disability v4.114 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587
Intellectual disability v4.114 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587
Intellectual disability v4.113 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587
Intellectual disability v4.112 SUPT16H Achchuthan Shanmugasundram Phenotypes for gene: SUPT16H were changed from Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum to Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum
Intellectual disability v4.113 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697
Intellectual disability v4.112 SUPT16H Achchuthan Shanmugasundram Phenotypes for gene: SUPT16H were changed from Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum to Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum
Intellectual disability v4.112 SUPT16H Achchuthan Shanmugasundram Phenotypes for gene: SUPT16H were changed from Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum to Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum
Intellectual disability v4.111 SUPT16H Achchuthan Shanmugasundram Phenotypes for gene: SUPT16H were changed from Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum to Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum
Intellectual disability v4.111 SUPT16H Achchuthan Shanmugasundram Phenotypes for gene: SUPT16H were changed from Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum to Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum
Intellectual disability v4.111 SUPT16H Achchuthan Shanmugasundram Phenotypes for gene: SUPT16H were changed from Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum to Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum
Intellectual disability v4.111 SUPT16H Achchuthan Shanmugasundram Phenotypes for gene: SUPT16H were changed from Global developmental delay; Intellectual disability; Abnormality of the corpus callosum to Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum
Primary immunodeficiency or monogenic inflammatory bowel disease v3.6 IL23R Dmitrijs Rots reviewed gene: IL23R: Rating: GREEN; Mode of pathogenicity: None; Publications: 36763636; Phenotypes: Mendelian susceptibility to mycobacterial disease (MSMD), chronic mucocutaneous candidiasis (CMC); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v3.11 PKDCC Alistair Pagnamenta reviewed gene: PKDCC: Rating: GREEN; Mode of pathogenicity: None; Publications: https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.14324; Phenotypes: rhizomelia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cystic kidney disease v3.9 ALG5 Arina Puzriakova Classified gene: ALG5 as Amber List (moderate evidence)
Cystic kidney disease v3.9 ALG5 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Cystic kidney disease v3.9 ALG5 Arina Puzriakova Gene: alg5 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v3.8 ALG5 Arina Puzriakova gene: ALG5 was added
gene: ALG5 was added to Cystic kidney disease. Sources: Literature
Q1_23_promote_green, Q1_23_NHS_review tags were added to gene: ALG5.
Mode of inheritance for gene: ALG5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ALG5 were set to 35896117
Phenotypes for gene: ALG5 were set to Polycystic kidney disease 7, OMIM:620056
Review for gene: ALG5 was set to GREEN
Added comment: New gene suggested for this panel by Prof John Sayer (Newcastle Hospitals NHS Foundation Trust). Associated with a relevant phenotype in OMIM (MIM# 620056) but is not yet listed in G2P.

Lemoine et al., 2022 (PMID: 35896117) reported 19 patients from 5 unrelated families with adult-onset polycystic kidney disease and monoallelic variants in this gene. Affected individuals had non-enlarged cystic kidneys and few or no liver cysts, and some patients reached end-stage kidney disease from 62 to 91 years of age.
Sources: Literature
Monogenic hearing loss v3.14 ATP2B2 Claire Walder reviewed gene: ATP2B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30535804, 33111345, 33105617; Phenotypes: Deafness, autosomal dominant 82; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v2.27 HARS Achchuthan Shanmugasundram Phenotypes for gene: HARS were changed from Charcot-Marie-Tooth disease, axonal, type 2W, OMIM: 616625 to Charcot-Marie-Tooth disease, axonal, type 2W, OMIM:616625
Hereditary neuropathy or pain disorder v2.26 HARS Achchuthan Shanmugasundram Phenotypes for gene: HARS were changed from to Charcot-Marie-Tooth disease, axonal, type 2W, OMIM: 616625
Monogenic hearing loss v3.14 EPHA10 Achchuthan Shanmugasundram changed review comment from: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies.

PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation.

Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected upregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model. Particularly, Eph overexpressed flies had a poorer performance compared to controls in negative geotaxis assay. These functional evidence suggests that 'gain of function' may be responsible for the hearing loss phenotype.

This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype.
Sources: Literature; to: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies.

PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation.

Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected upregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model. Particularly, Eph overexpressed flies had a poorer performance compared to controls in negative geotaxis assay. These functional evidence suggests that 'gain of function' may be responsible for the hearing loss phenotype.

This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype.
Sources: Literature
Monogenic hearing loss v3.14 EPHA10 Achchuthan Shanmugasundram changed review comment from: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies.

PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation.

Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected upregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model. These functional evidence suggests that 'gain of function' may be responsible for the hearing loss phenotype.

This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype.
Sources: Literature; to: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies.

PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation.

Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected upregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model. Particularly, Eph overexpressed flies had a poorer performance compared to controls in negative geotaxis assay. These functional evidence suggests that 'gain of function' may be responsible for the hearing loss phenotype.

This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype.
Sources: Literature
Monogenic hearing loss v3.14 OXR1 Achchuthan Shanmugasundram changed review comment from: Comment on gene rating: This gene should be rated AMBER as there is one case and supportive functional data to associate OXR1 with hearing loss.

A four years old girl was identified with a novel homozygous missense variant (c.233A > G, p.Lys78Arg) in OXR1 gene and was reported with sensorineural hearing loss.

Functional studies in zebrafish model showed that the ortholog orx1b gene is expressed in the statoacoustic ganglion (SAG, a sensory ganglion of ear) and posterior lateral line ganglion (pLL). In addition, knockdown of oxr1b resulted in a significant developmental defect of SAG and pLL and this phenotype was rescued by co-injection of wild-type human OXR1 mRNAs, but not mutant OXR1 (c.233A > G) mRNAs.
Sources: Literature; to: Comment on gene rating: This gene should be rated AMBER as there is one case and supportive functional data to associate OXR1 with hearing loss.

A four years old girl was identified with a novel homozygous missense variant (c.233A > G, p.Lys78Arg) in OXR1 gene and was reported with sensorineural hearing loss.

Functional studies in zebrafish model showed that the ortholog orx1b gene is expressed in the statoacoustic ganglion (SAG, a sensory ganglion of ear) and posterior lateral line ganglion (pLL). In addition, knockdown of oxr1b resulted in a significant developmental defect of SAG and pLL and this phenotype was rescued by co-injection of wild-type human OXR1 mRNAs, but not mutant OXR1 (c.233A > G) mRNAs.

This gene has not yet been associated with hearing loss either in OMIM or in Gene2Phenotype.
Sources: Literature
Monogenic hearing loss v3.14 OXR1 Achchuthan Shanmugasundram changed review comment from: Comment on gene rating: This gene should be rated AMBER as there is one case and supportive functional data to associate OXR1 with hearing loss.

A four years old girl was identified with a novel homozygous missense variant (c.233A > G, p.Lys78Arg) in OXR1 gene and was reported with sensorineural hearing loss.

Functional studies in zebrafish model showed that the ortholog orx1b gene is expressed in the statoacoustic ganglion (SAG, a sensory ganglion of ear) and posterior lateral line ganglion (pLL). In addition, knockdown of oxr1b resulted in a significant developmental defect of SAG and pLL and this phenotype was rescued by co-injection of wild-type human OXR1 mRNAs, but not mutant OXR1 (c.233A > G) mRNAs.
Sources: Literature; to: Comment on gene rating: This gene should be rated AMBER as there is one case and supportive functional data to associate OXR1 with hearing loss.

A four years old girl was identified with a novel homozygous missense variant (c.233A > G, p.Lys78Arg) in OXR1 gene and was reported with sensorineural hearing loss.

Functional studies in zebrafish model showed that the ortholog orx1b gene is expressed in the statoacoustic ganglion (SAG, a sensory ganglion of ear) and posterior lateral line ganglion (pLL). In addition, knockdown of oxr1b resulted in a significant developmental defect of SAG and pLL and this phenotype was rescued by co-injection of wild-type human OXR1 mRNAs, but not mutant OXR1 (c.233A > G) mRNAs.
Sources: Literature
Monogenic hearing loss v3.14 OXR1 Achchuthan Shanmugasundram Classified gene: OXR1 as Amber List (moderate evidence)
Monogenic hearing loss v3.14 OXR1 Achchuthan Shanmugasundram Gene: oxr1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v3.13 OXR1 Achchuthan Shanmugasundram gene: OXR1 was added
gene: OXR1 was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: OXR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OXR1 were set to 36130215
Phenotypes for gene: OXR1 were set to sensorineural hearing loss disorder, MONDO:0020678
Review for gene: OXR1 was set to AMBER
Added comment: Comment on gene rating: This gene should be rated AMBER as there is one case and supportive functional data to associate OXR1 with hearing loss.

A four years old girl was identified with a novel homozygous missense variant (c.233A > G, p.Lys78Arg) in OXR1 gene and was reported with sensorineural hearing loss.

Functional studies in zebrafish model showed that the ortholog orx1b gene is expressed in the statoacoustic ganglion (SAG, a sensory ganglion of ear) and posterior lateral line ganglion (pLL). In addition, knockdown of oxr1b resulted in a significant developmental defect of SAG and pLL and this phenotype was rescued by co-injection of wild-type human OXR1 mRNAs, but not mutant OXR1 (c.233A > G) mRNAs.
Sources: Literature
Monogenic hearing loss v3.12 EPHA10 Achchuthan Shanmugasundram changed review comment from: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies.

PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation.

Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected upregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model.
Sources: Literature; to: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies.

PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation.

Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected upregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model. These functional evidence suggests that 'gain of function' may be responsible for the hearing loss phenotype.

This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype.
Sources: Literature
Monogenic hearing loss v3.12 EPHA10 Achchuthan Shanmugasundram edited their review of gene: EPHA10: 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
Monogenic hearing loss v3.12 EPHA10 Achchuthan Shanmugasundram changed review comment from: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies.

PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation.

Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected unregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model.
Sources: Literature; to: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies.

PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation.

Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected upregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model.
Sources: Literature
Monogenic hearing loss v3.12 EPHA10 Achchuthan Shanmugasundram gene: EPHA10 was added
gene: EPHA10 was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: EPHA10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EPHA10 were set to 36048850
Phenotypes for gene: EPHA10 were set to postlingual non-syndromic genetic hearing loss, MONDO:0016298
Review for gene: EPHA10 was set to RED
Added comment: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies.

PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation.

Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected unregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model.
Sources: Literature
Paediatric disorders - additional genes v2.9 PLXND1 Achchuthan Shanmugasundram Classified gene: PLXND1 as Amber List (moderate evidence)
Paediatric disorders - additional genes v2.9 PLXND1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) to be promoted to GREEN rating at the next GMS panel update.
Paediatric disorders - additional genes v2.9 PLXND1 Achchuthan Shanmugasundram Gene: plxnd1 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v2.8 PLXND1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: PLXND1.
Fetal anomalies v2.15 PLXND1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: PLXND1.
Paediatric disorders - additional genes v2.8 PLXND1 Achchuthan Shanmugasundram gene: PLXND1 was added
gene: PLXND1 was added to Paediatric disorders - additional genes. Sources: Literature
Mode of inheritance for gene: PLXND1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXND1 were set to 35396997
Phenotypes for gene: PLXND1 were set to Truncus arteriosus, HP:0001660
Review for gene: PLXND1 was set to GREEN
Added comment: 10 individuals including four foetal cases from five unrelated families were identified with biallelic variants in PLXND1 gene and they presented with cardiac defects. The most frequent defect is common arterial trunk (CAT), which is also known as truncus arteriosus, a conotruncal malformation characterized by a single vessel exiting both ventricles.

This gene has already been associated with PLXND1-related cardiac malformation syndrome with the confidence category of 'strong' in DD panel of Gene2Phenotype. However, no relevant phenotypes have been currently reported in OMIM.
Sources: Literature
Fetal anomalies v2.15 PLXND1 Achchuthan Shanmugasundram Classified gene: PLXND1 as Amber List (moderate evidence)
Fetal anomalies v2.15 PLXND1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) to be promoted to GREEN rating at the next GMS panel update.
Fetal anomalies v2.15 PLXND1 Achchuthan Shanmugasundram Gene: plxnd1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v2.14 PLXND1 Achchuthan Shanmugasundram gene: PLXND1 was added
gene: PLXND1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PLXND1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXND1 were set to 35396997
Phenotypes for gene: PLXND1 were set to Truncus arteriosus, HP:0001660
Review for gene: PLXND1 was set to GREEN
Added comment: 10 individuals including four foetal cases from five unrelated families were identified with biallelic variants in PLXND1 gene and they presented with cardiac defects. The most frequent defect is common arterial trunk (CAT), which is also known as truncus arteriosus, a conotruncal malformation characterized by a single vessel exiting both ventricles.

This gene has already been associated with PLXND1-related cardiac malformation syndrome with the confidence category of 'strong' in DD panel of Gene2Phenotype. However, no relevant phenotypes have been currently reported in OMIM.
Sources: Literature
Early onset or syndromic epilepsy v3.104 DEPDC5 Achchuthan Shanmugasundram commented on gene: DEPDC5: The MOI of this gene should be reviewed at the next NHS GMS review on whether it can be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'.
Malformations of cortical development v3.12 DEPDC5 Achchuthan Shanmugasundram commented on gene: DEPDC5: The MOI of this gene should be reviewed at the next NHS GMS review on whether it can be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'.
Malformations of cortical development v3.12 DEPDC5 Achchuthan Shanmugasundram Tag Q1_23_MOI tag was added to gene: DEPDC5.
Malformations of cortical development v3.12 DEPDC5 Achchuthan Shanmugasundram Publications for gene: DEPDC5 were set to 24585383; 25623524; 31444548; 32848577; 33949696; 34055363
Malformations of cortical development v3.11 DEPDC5 Achchuthan Shanmugasundram changed review comment from: The association of monoallelic variants in DEPDC5 gene to familial focal epilepsy (MIM #604364) have already been established with previous reviews and the existence of this phenotype in both OMIM and Gene2Phenotype.

PMID:32848577 reported a child with a homozygous missense variant (p.Pro1031His) who presented with cortical dysplasia and childhood onset epilepsy.

PMID:36067010 reported homozygous missense variants in five unrelated families (three Irish Traveller families with same variant - p.Thr337Arg; and one Tunisian and one Lebanese families with the same variant - p.Arg806Cys). All nine children from these five families presented with consistent phenotypic features including extensive bilateral polymicrogyria, congenital macrocephaly, early onset refractory epilepsy and severe psychomotor developmental delay. Polymicrogyria is one of the most common malformations of cortical development, characterized by abnormal cortical lamination and excessive folding of the cortical surface

Skin biopsy immunohistochemistry suggested hyperactivation of the mTOR pathway. The disease mechanism is suggested as 'loss of function' as DEPDC5 is a repressor/inhibitor within the mTOR pathway.

The phenotypes caused by biallelic variants are not yet reported in OMIM or in Gene2Phenotype.; to: The association of monoallelic variants in DEPDC5 gene to familial focal epilepsy (MIM #604364) have already been established with previous reviews and the existence of this phenotype in both OMIM and Gene2Phenotype.

PMID:32848577 reported a child with a homozygous missense variant (p.Pro1031His) who presented with cortical dysplasia and childhood onset epilepsy.

PMID:36067010 reported homozygous missense variants in five unrelated families (three Irish Traveller families with same variant - p.Thr337Arg; and one Tunisian and one Lebanese families with the same variant - p.Arg806Cys). All nine children from these five families presented with consistent phenotypic features including extensive bilateral polymicrogyria, congenital macrocephaly, early onset refractory epilepsy and severe psychomotor developmental delay. Polymicrogyria is one of the most common malformations of cortical development, characterized by abnormal cortical lamination and excessive folding of the cortical surface. Skin biopsy immunohistochemistry suggested hyperactivation of the mTOR pathway. The disease mechanism is suggested as 'loss of function' as DEPDC5 is a repressor/inhibitor within the mTOR pathway.

The phenotypes caused by biallelic variants are not yet reported in OMIM or in Gene2Phenotype.
Malformations of cortical development v3.11 DEPDC5 Achchuthan Shanmugasundram reviewed gene: DEPDC5: Rating: GREEN; Mode of pathogenicity: None; Publications: 32848577, 36067010; Phenotypes: Epilepsy, familial focal, with variable foci 1, OMIM:604364, epilepsy, MONDO:0005027, Macrocephaly, HP:0000256, polymicrogyria, MONDO:0000087, cerebral cortical dysplasia, MONDO:0017094, neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v3.104 DEPDC5 Achchuthan Shanmugasundram Tag Q1_23_MOI tag was added to gene: DEPDC5.
Early onset or syndromic epilepsy v3.104 DEPDC5 Achchuthan Shanmugasundram Publications for gene: DEPDC5 were set to 14510823; 15329069; 10825362; 10577924; 9851433; 23542701; 32848577; 36067010
Early onset or syndromic epilepsy v3.104 DEPDC5 Achchuthan Shanmugasundram Publications for gene: DEPDC5 were set to 14510823; 15329069; 10825362; 10577924; 9851433; 23542701; 32848577; 36067010
Early onset or syndromic epilepsy v3.104 DEPDC5 Achchuthan Shanmugasundram Publications for gene: DEPDC5 were set to 14510823; 15329069; 10825362; 10577924; 9851433; 23542701; 32848577; 36067010
Early onset or syndromic epilepsy v3.104 DEPDC5 Achchuthan Shanmugasundram Publications for gene: DEPDC5 were set to 14510823; 15329069; 10825362; 10577924; 9851433; 23542701; 32848577; 36067010
Early onset or syndromic epilepsy v3.104 DEPDC5 Achchuthan Shanmugasundram Publications for gene: DEPDC5 were set to 14510823; 15329069; 10825362; 10577924; 9851433; 23542701; 32848577; 36067010
Early onset or syndromic epilepsy v3.103 DEPDC5 Achchuthan Shanmugasundram Publications for gene: DEPDC5 were set to 14510823; 15329069; 10825362; 10577924; 9851433; 23542701; 32848577; 36067010
Early onset or syndromic epilepsy v3.103 DEPDC5 Achchuthan Shanmugasundram Publications for gene: DEPDC5 were set to 14510823; 15329069; 10825362; 10577924; 9851433; 23542701; 32848577; 36067010
Early onset or syndromic epilepsy v3.103 DEPDC5 Achchuthan Shanmugasundram Publications for gene: DEPDC5 were set to 14510823; 15329069; 10825362; 10577924; 9851433; 23542701; 32848577; 36067010
Early onset or syndromic epilepsy v3.103 DEPDC5 Achchuthan Shanmugasundram Publications for gene: DEPDC5 were set to 14510823; 15329069; 10825362; 10577924; 9851433; 23542701; 36067010
Early onset or syndromic epilepsy v3.102 DEPDC5 Achchuthan Shanmugasundram reviewed gene: DEPDC5: Rating: GREEN; Mode of pathogenicity: None; Publications: 32848577, 36067010; Phenotypes: Epilepsy, familial focal, with variable foci 1, OMIM:604364, epilepsy, MONDO:0005027, Macrocephaly, HP:0000256, polymicrogyria, MONDO:0000087, neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v3.102 DEPDC5 Achchuthan Shanmugasundram Publications for gene: DEPDC5 were set to 14510823; 15329069; 10825362; 10577924; 9851433; 23542701; 36067010
Early onset or syndromic epilepsy v3.102 DEPDC5 Achchuthan Shanmugasundram Publications for gene: DEPDC5 were set to 14510823; 15329069; 10825362; 10577924; 9851433; 23542701; 36067010
Early onset or syndromic epilepsy v3.102 DEPDC5 Achchuthan Shanmugasundram Publications for gene: DEPDC5 were set to 14510823; 15329069; 10825362; 10577924; 9851433; 23542701
Skeletal dysplasia v3.11 KIF5B Achchuthan Shanmugasundram commented on gene: KIF5B: PMID:36018820 reported three additional unrelated cases with autosomal dominant KIF5B variants (p.Asn255del, p.Leu498Pro and p.Leu537Pro) resulting in a clinically wide phenotypic spectrum, ranging from dilated cardiomyopathy with adult-onset ophthalmoplegia and progressive skeletal myopathy to a neurodevelopmental condition characterised by severe hypotonia with or without seizures.
Skeletal dysplasia v3.11 KIF5B Achchuthan Shanmugasundram Classified gene: KIF5B as Amber List (moderate evidence)
Skeletal dysplasia v3.11 KIF5B Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN for skeletal dysplasia as there are four unrelated cases associated with monoallelic variants in KIF5B gene.
Skeletal dysplasia v3.11 KIF5B Achchuthan Shanmugasundram Gene: kif5b has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v3.10 KIF5B Achchuthan Shanmugasundram gene: KIF5B was added
gene: KIF5B was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: KIF5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF5B were set to 35342932
Phenotypes for gene: KIF5B were set to kyphomelic dysplasia, MONDO:0008881
Review for gene: KIF5B was set to GREEN
Added comment: 4 individuals were reported with Kyphomelic dysplasia, which is characterised by severe bowing of the limbs, sharp angulation of the femora and humeri, short stature, narrow thorax, distinctive facial features, and neonatal respiratory distress. All these individuals harboured a de novo heterozygous missense variant in KIF5B gene ( two with c.272A>G (p.Lys91Arg), one with c.584C>A (p.Thr195Lys), and the other with c.701G>T(p.Gly234Val)). All three variants involved conserved amino acids in or close to the ATPase activity-related motifs in the catalytic motor domain of the KIF5B protein.
Sources: Literature
Intellectual disability v4.110 YWHAZ Achchuthan Shanmugasundram gene: YWHAZ was added
gene: YWHAZ was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: YWHAZ was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: YWHAZ were set to 36001342
Phenotypes for gene: YWHAZ were set to Intellectual disability, MONDO:0001071
Review for gene: YWHAZ was set to RED
Added comment: PMID:36001342 reported one large three-generation family with intellectual disability and global developmental delay, where all affected members were identified with a heterozygous missense variant (c.147A>T/ p.Lys49Asn) in YWHAZ gene. Although there were 10 other rare variants located in 10 genes (ARHGAP4, AGPS, APOL3, CES3, DACT2, ECH1, FAM71E2, KREMEN1, YWHAZ, ZFYVE26) that co-segregated with the ID/GDD phenotype were identified in the family, they were either not present in all affected members or present in unaffected members.

In addition, computational modeling and knockdown/ knockin studies with Drosophila also confirmed the role of this YWHAZ variant in intellectual disability.
Sources: Literature
Intellectual disability v4.109 DEAF1 Achchuthan Shanmugasundram Phenotypes for gene: DEAF1 were changed from ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828 to ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828
Intellectual disability v4.110 DEAF1 Achchuthan Shanmugasundram Phenotypes for gene: DEAF1 were changed from ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828 to ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828
Intellectual disability v4.110 DEAF1 Achchuthan Shanmugasundram Phenotypes for gene: DEAF1 were changed from ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828 to ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828
Intellectual disability v4.109 DEAF1 Achchuthan Shanmugasundram Phenotypes for gene: DEAF1 were changed from ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828 to ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828
Intellectual disability v4.109 DEAF1 Achchuthan Shanmugasundram Phenotypes for gene: DEAF1 were changed from ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828 to ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828
Intellectual disability v4.109 DEAF1 Achchuthan Shanmugasundram Phenotypes for gene: DEAF1 were changed from ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828 to ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828
Intellectual disability v4.108 DEAF1 Achchuthan Shanmugasundram Publications for gene: DEAF1 were set to 21076407; 35981081
Intellectual disability v4.109 DEAF1 Achchuthan Shanmugasundram Phenotypes for gene: DEAF1 were changed from MENTAL RETARDATION, AUTOSOMAL DOMINANT 24; ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828 to ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828
Intellectual disability v4.108 DEAF1 Achchuthan Shanmugasundram Publications for gene: DEAF1 were set to 21076407; 35981081
Intellectual disability v4.108 DEAF1 Achchuthan Shanmugasundram Publications for gene: DEAF1 were set to 21076407; 35981081
Intellectual disability v4.107 DEAF1 Achchuthan Shanmugasundram Publications for gene: DEAF1 were set to 21076407; 35981081
Intellectual disability v4.107 DEAF1 Achchuthan Shanmugasundram Publications for gene: DEAF1 were set to 21076407
Glycogen storage disease v1.11 G6PC Achchuthan Shanmugasundram Publications for gene: G6PC were set to 20301489
Retinal disorders v3.34 EFEMP1 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with phenotype in OMIM (MIM #126600) and in Gene2Phenotype.
Retinal disorders v3.34 EFEMP1 Achchuthan Shanmugasundram Phenotypes for gene: EFEMP1 were changed from Macular Dystrophy/Degeneration/Stargardt Disease; Inherited macular dystrophy (Doyne/dominant drusen) to Doyne honeycomb degeneration of retina, OMIM:126600
Paediatric pseudo-obstruction syndrome v0.218 FLNA Achchuthan Shanmugasundram Publications for gene: FLNA were set to 17357080; 20871226; 23873601; 26059841; 31848803; 33729000
Adult onset hereditary spastic paraplegia v2.16 ATL1 Achchuthan Shanmugasundram Publications for gene: ATL1 were set to 11685207; 15517445
Hereditary spastic paraplegia v1.303 ATL1 Achchuthan Shanmugasundram Publications for gene: ATL1 were set to PMID: 11685207
Childhood onset hereditary spastic paraplegia v3.19 ATL1 Achchuthan Shanmugasundram Publications for gene: ATL1 were set to 11685207; 15517445
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.13 SELENON Achchuthan Shanmugasundram changed review comment from: Several patients with SEPN1(SELENON)-related myopathy have been reported with limb girdle weakness/ dystrophy.; to: Sufficient cases with SEPN1(SELENON)-related myopathy have been reported with limb girdle weakness/ dystrophy.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.13 SELENON Achchuthan Shanmugasundram Publications for gene: SELENON were set to 15122708; 11528383
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.12 SELENON Achchuthan Shanmugasundram reviewed gene: SELENON: Rating: GREEN; Mode of pathogenicity: None; Publications: 15668457, 27863379, 28558865, 29850975, 30642275, 32796131; Phenotypes: Congenital myopathy 3 with rigid spine, OMIM:602771; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v2.13 SELENON Achchuthan Shanmugasundram Added comment: Comment on phenotypes: Comment on phenotypes: OMIM associates 'Myopathy, congenital, with fiber-type disproportion, OMIM:255310' with TPM3 and not with SELENON. Hence, it has been removed here.
Fetal anomalies v2.13 SELENON Achchuthan Shanmugasundram Phenotypes for gene: SELENON were changed from Myopathy, congenital, with fiber-type disproportion 255310; Muscular dystrophy, rigid spine 602771 to Muscular dystrophy, rigid spine, 1, OMIM:602771
Congenital myopathy v3.125 SELENON Achchuthan Shanmugasundram changed review comment from: Comment on phenotypes: OMIM associates 'Myopathy, congenital, with fiber-type disproportion, OMIM:255310' with TPM3. Hence, it has been removed here.; to: Comment on phenotypes: OMIM associates 'Myopathy, congenital, with fiber-type disproportion, OMIM:255310' with TPM3 and not with SELENON. Hence, it has been removed here.
Arthrogryposis v4.13 SELENON Achchuthan Shanmugasundram Publications for gene: SELENON were set to 20301467
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.12 SELENON Achchuthan Shanmugasundram Phenotypes for gene: SELENON were changed from Muscular dystrophy, rigid spine, 1, 602771; congenital myopathy; muscular dystophy; rigid spine syndrome to Muscular dystrophy, rigid spine, 1, OMIM:602771
Congenital myopathy v3.125 SELENON Achchuthan Shanmugasundram Added comment: Comment on phenotypes: OMIM associates 'Myopathy, congenital, with fiber-type disproportion, OMIM:255310' with TPM3. Hence, it has been removed here.
Congenital myopathy v3.125 SELENON Achchuthan Shanmugasundram Phenotypes for gene: SELENON were changed from Muscular dystrophy, rigid spine, 1, OMIM:602771; Myopathy, congenital, with fiber-type disproportion, OMIM:255310 to Muscular dystrophy, rigid spine, 1, OMIM:602771
Arthrogryposis v4.12 SELENON Achchuthan Shanmugasundram Phenotypes for gene: SELENON were changed from Muscular dystrophy, rigid spine, 1, 602771; Myopathy, congenital, with fiber-type disproportion 255310 to Congenital myopathy 3 with rigid spine, OMIM:602771
Arthrogryposis v4.11 SELENON Achchuthan Shanmugasundram Tag Q1_23_MOI tag was added to gene: SELENON.
Arthrogryposis v4.11 SELENON Achchuthan Shanmugasundram reviewed gene: SELENON: Rating: GREEN; Mode of pathogenicity: None; Publications: 30642275, 32796131; Phenotypes: Congenital myopathy 3 with rigid spine, OMIM:602771; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v3.101 SARS Arina Puzriakova Publications for gene: SARS were set to 28236339; 34570399; 35790048
Early onset or syndromic epilepsy v3.100 SARS Arina Puzriakova edited their review of gene: SARS: Changed publications to: 35790048, 36041817
Early onset or syndromic epilepsy v3.100 SARS Arina Puzriakova changed review comment from: Comment on mode of inheritance: As only a single dominant case has been reported (details below), leaving MOI as biallelic for now with a watchlist_moi tag. Consider adding to other relevant panels if further cases are identified.

Single patient identified with de novo heterozygous splice site deletion (c.969_969+2delGGT) in the SARS1 gene. Phenotypes included complex spastic paraplegia with ataxia, intellectual disability, developmental delay and seizures, but without microcephaly. Functional studies in both yeast strains and patient fibroblasts demonstrated a LoF, dominant negative effect.; to: Comment on mode of inheritance: As only a single dominant case has been reported (details below), leaving MOI as biallelic for now with a watchlist_moi tag. Consider adding to other relevant panels if further cases are identified.

PMID: 36041817 - Single patient identified with de novo heterozygous splice site deletion (c.969_969+2delGGT) in the SARS1 gene. Phenotypes included complex spastic paraplegia with ataxia, intellectual disability, developmental delay and seizures, but without microcephaly. Functional studies in both yeast strains and patient fibroblasts demonstrated a LoF, dominant negative effect.
Early onset or syndromic epilepsy v3.100 SARS Arina Puzriakova changed review comment from: Comment on mode of inheritance: As only a single dominant case has been reported (details below), leaving MOI as biallelic for now with a watchlist_moi tag. Consider adding to other relevant panels if further cases are identified.

Single patient identified with de novo heterozygous splice site deletion (.969_969+2delGGT) in the SARS1 gene. Phenotypes included complex spastic paraplegia with ataxia, intellectual disability, developmental delay and seizures, but without microcephaly. Functional studies in both yeast strains and patient fibroblasts demonstrated a LoF, dominant negative effect.; to: Comment on mode of inheritance: As only a single dominant case has been reported (details below), leaving MOI as biallelic for now with a watchlist_moi tag. Consider adding to other relevant panels if further cases are identified.

Single patient identified with de novo heterozygous splice site deletion (c.969_969+2delGGT) in the SARS1 gene. Phenotypes included complex spastic paraplegia with ataxia, intellectual disability, developmental delay and seizures, but without microcephaly. Functional studies in both yeast strains and patient fibroblasts demonstrated a LoF, dominant negative effect.
Early onset or syndromic epilepsy v3.100 SARS Arina Puzriakova Added comment: Comment on mode of inheritance: As only a single dominant case has been reported (details below), leaving MOI as biallelic for now with a watchlist_moi tag. Consider adding to other relevant panels if further cases are identified.

Single patient identified with de novo heterozygous splice site deletion (.969_969+2delGGT) in the SARS1 gene. Phenotypes included complex spastic paraplegia with ataxia, intellectual disability, developmental delay and seizures, but without microcephaly. Functional studies in both yeast strains and patient fibroblasts demonstrated a LoF, dominant negative effect.
Early onset or syndromic epilepsy v3.100 SARS Arina Puzriakova Mode of inheritance for gene: SARS was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v3.99 SARS Arina Puzriakova Tag watchlist_moi tag was added to gene: SARS.
Early onset or syndromic epilepsy v3.99 SARS Arina Puzriakova Phenotypes for gene: SARS were changed from ?Neurodevelopmental disorder with microcephaly, ataxia, and seizures, OMIM:617709 to Neurodevelopmental disorder with microcephaly, ataxia, and seizures, OMIM:617709
Early onset or syndromic epilepsy v3.98 SARS Arina Puzriakova Publications for gene: SARS were set to 28236339; 34570399
Severe microcephaly v3.11 SARS Arina Puzriakova Phenotypes for gene: SARS were changed from ?Neurodevelopmental disorder with microcephaly, ataxia, and seizures, OMIM:617709 to Neurodevelopmental disorder with microcephaly, ataxia, and seizures, OMIM:617709
Severe microcephaly v3.10 SARS Arina Puzriakova Publications for gene: SARS were set to 28236339; 34570399
Severe microcephaly v3.9 SARS Arina Puzriakova Classified gene: SARS as Amber List (moderate evidence)
Severe microcephaly v3.9 SARS Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. At least three unrelated cases with biallelic variants in this gene - microcephaly detected in all families. Although severity only reaches threshold for this panel in two families, given the extent in these cases and the consistent presentation this feature, this gene should be included on R88.
Severe microcephaly v3.9 SARS Arina Puzriakova Gene: sars has been classified as Amber List (Moderate Evidence).
Severe microcephaly v3.8 SARS Arina Puzriakova Tag watchlist was removed from gene: SARS.
Tag Q1_23_promote_green tag was added to gene: SARS.
Early onset or syndromic epilepsy v3.97 SARS Arina Puzriakova Classified gene: SARS as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.97 SARS Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. At least three unrelated cases with biallelic variants in this gene - seizures detected in all families.
Early onset or syndromic epilepsy v3.97 SARS Arina Puzriakova Gene: sars has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v3.96 SARS Arina Puzriakova Tag watchlist was removed from gene: SARS.
Tag Q1_23_promote_green tag was added to gene: SARS.
Intellectual disability v4.106 SARS Arina Puzriakova Classified gene: SARS as Amber List (moderate evidence)
Intellectual disability v4.106 SARS Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. At least three unrelated cases with biallelic variants in this gene - DD/ID detected in all families.
Intellectual disability v4.106 SARS Arina Puzriakova Gene: sars has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v3.96 SARS Arina Puzriakova reviewed gene: SARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 35790048; Phenotypes: Neurodevelopmental disorder with microcephaly, ataxia, and seizures, OMIM:617709; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v3.8 SARS Arina Puzriakova reviewed gene: SARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 35790048; Phenotypes: Neurodevelopmental disorder with microcephaly, ataxia, and seizures, OMIM:617709; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.105 SARS Arina Puzriakova Phenotypes for gene: SARS were changed from ?Neurodevelopmental disorder with microcephaly, ataxia, and seizures, OMIM:617709 to Neurodevelopmental disorder with microcephaly, ataxia, and seizures, OMIM:617709
Intellectual disability v4.104 SARS Arina Puzriakova Publications for gene: SARS were set to 28236339; 34570399
Intellectual disability v4.103 SARS Arina Puzriakova Tag watchlist was removed from gene: SARS.
Tag Q1_23_promote_green tag was added to gene: SARS.
Intellectual disability v4.103 SARS Arina Puzriakova reviewed gene: SARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 35790048; Phenotypes: Neurodevelopmental disorder with microcephaly, ataxia, and seizures, OMIM:617709; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Extreme early-onset hypertension v1.21 CYP11B2 Achchuthan Shanmugasundram changed review comment from: Autosomal recessive variants in CYP11B2 causes Hypoaldosteronism, congenital, due to CMO I deficiency (MIM #203400) and due to CMO II deficiency (MIM #610600). Patients with these disorders present with salt loss and failure to thrive in early childhood and they do not present with hypertension.

Glucocorticoid-remediable aldosteronism (GRA, MIM #103900) is an autosomal-dominant disorder caused by chimeric duplication of CYP11B1 and CYP11B2 genes. These patients present with early-onset hypertension. Hence, the MOI in this should be 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' rather than 'BIALLELIC, autosomal or pseudoautosomal' as in 'Congenital adrenal hypoplasia' panel.; to: Autosomal recessive variants in CYP11B2 causes Hypoaldosteronism, congenital, due to CMO I deficiency (MIM #203400) and due to CMO II deficiency (MIM #610600). Patients with these disorders present with salt loss and failure to thrive in early childhood and they do not present with hypertension.

Glucocorticoid-remediable aldosteronism (GRA, MIM #103900) is an autosomal-dominant disorder caused by chimeric duplication of CYP11B1 and CYP11B2 genes. These patients present with early-onset hypertension. Hence, the MOI in this panel should be 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' rather than 'BIALLELIC, autosomal or pseudoautosomal' as in 'Congenital adrenal hypoplasia' panel.
Extreme early-onset hypertension v1.21 CYP11B2 Achchuthan Shanmugasundram changed review comment from: Autosomal recessive variants in CYP11B2 causes Hypoaldosteronism, congenital, due to CMO I deficiency (MIM #203400) and due to CMO II deficiency (MIM #610600). Patients with these disorders present with salt loss and failure to thrive in early childhood and they do no present hypertension.

Glucocorticoid-remediable aldosteronism (GRA, MIM #103900) is an autosomal-dominant disorder caused by chimeric duplication of CYP11B1 and CYP11B2 genes. These patients present with early-onset hypertension. Hence, the MOI in this should be 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' rather than 'BIALLELIC, autosomal or pseudoautosomal' as in 'Congenital adrenal hypoplasia' panel.; to: Autosomal recessive variants in CYP11B2 causes Hypoaldosteronism, congenital, due to CMO I deficiency (MIM #203400) and due to CMO II deficiency (MIM #610600). Patients with these disorders present with salt loss and failure to thrive in early childhood and they do not present with hypertension.

Glucocorticoid-remediable aldosteronism (GRA, MIM #103900) is an autosomal-dominant disorder caused by chimeric duplication of CYP11B1 and CYP11B2 genes. These patients present with early-onset hypertension. Hence, the MOI in this should be 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' rather than 'BIALLELIC, autosomal or pseudoautosomal' as in 'Congenital adrenal hypoplasia' panel.
Extreme early-onset hypertension v1.21 CYP11B2 Achchuthan Shanmugasundram Phenotypes for gene: CYP11B2 were changed from Aldosterone to renin ratio raised, Glucucorticoid-remediable hyperaldosteronsim to Aldosteronism, glucocorticoid-remediable, OMIM:103900; {Low renin hypertension, susceptibility to}; Aldosterone to renin ratio raised
Extreme early-onset hypertension v1.20 CYP11B2 Achchuthan Shanmugasundram changed review comment from: Autosomal recessive variants in CYP11B2 causes Hypoaldosteronism, congenital, due to CMO I deficiency (MIM #203400) and due to CMO II deficiency (MIM #610600). Patients with these disorders present with salt loss and failure to thrive in early childhood and they do no present hypertension.

Glucocorticoid-remediable aldosteronism (GRA, MIM #103900) is an autosomal-dominant disorder caused by chimeric duplication of CYP11B1 and CYP11B2 genes. These patients present with early-onset hypertension.; to: Autosomal recessive variants in CYP11B2 causes Hypoaldosteronism, congenital, due to CMO I deficiency (MIM #203400) and due to CMO II deficiency (MIM #610600). Patients with these disorders present with salt loss and failure to thrive in early childhood and they do no present hypertension.

Glucocorticoid-remediable aldosteronism (GRA, MIM #103900) is an autosomal-dominant disorder caused by chimeric duplication of CYP11B1 and CYP11B2 genes. These patients present with early-onset hypertension. Hence, the MOI in this should be 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' rather than 'BIALLELIC, autosomal or pseudoautosomal' as in 'Congenital adrenal hypoplasia' panel.
Extreme early-onset hypertension v1.20 CYP11B2 Achchuthan Shanmugasundram reviewed gene: CYP11B2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aldosteronism, glucocorticoid-remediable, OMIM:103900, {Low renin hypertension, susceptibility to}, Aldosterone to renin ratio raised; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Distal myopathies v2.4 MYOT Achchuthan Shanmugasundram Phenotypes for gene: MYOT were changed from Myopathy, myofibrillar, 3, OMIM:609200; Myopathy, spheroid body, OMIM:182920 to Myopathy, myofibrillar, 3, OMIM:609200; Myopathy, spheroid body, OMIM:182920
Distal myopathies v2.4 MYOT Achchuthan Shanmugasundram Phenotypes for gene: MYOT were changed from Myopathy, myofibrillar, 3, OMIM:609200; Myopathy, spheroid body, OMIM:182920 to Myopathy, myofibrillar, 3, OMIM:609200; Myopathy, spheroid body, OMIM:182920
Distal myopathies v2.4 MYOT Achchuthan Shanmugasundram Phenotypes for gene: MYOT were changed from Myopathy, myofibrillar 3, 609200 to Myopathy, myofibrillar, 3, OMIM:609200; Myopathy, spheroid body, OMIM:182920
Arthrogryposis v4.11 MYOT Achchuthan Shanmugasundram Phenotypes for gene: MYOT were changed from Spheroid Body Myopathy; Muscular dystrophy, limb-girdle, type 1A, 159000 to Myopathy, myofibrillar, 3, OMIM:609200; Myopathy, spheroid body, OMIM:182920
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.11 MYOT Achchuthan Shanmugasundram Phenotypes for gene: MYOT were changed from Myopathy, myofibrillar, 3, OMIM:609200; Myopathy, spheroid body, OMIM:182920 to Myopathy, myofibrillar, 3, OMIM:609200; Myopathy, spheroid body, OMIM:182920
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.11 MYOT Achchuthan Shanmugasundram Phenotypes for gene: MYOT were changed from Myopathy, myofibrillar, 3, OMIM:609200; Myopathy, spheroid body, OMIM:182920 to Myopathy, myofibrillar, 3, OMIM:609200; Myopathy, spheroid body, OMIM:182920
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.11 MYOT Achchuthan Shanmugasundram Phenotypes for gene: MYOT were changed from Myopathy, myofibrillar, 3, OMIM:609200 to Myopathy, myofibrillar, 3, OMIM:609200; Myopathy, spheroid body, OMIM:182920
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.10 MYOT Achchuthan Shanmugasundram edited their review of gene: MYOT: Changed phenotypes to: Myopathy, myofibrillar, 3, OMIM:609200, Myopathy, spheroid body, OMIM:182920
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.10 MYOT Achchuthan Shanmugasundram Phenotypes for gene: MYOT were changed from Limb-Girdle Muscular Dystrophy, Dominant; Muscular dystrophy, limb-girdle, type 1A, 159000; Limb-girdle muscular dystrophy to Myopathy, myofibrillar, 3, OMIM:609200
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.9 MYOT Achchuthan Shanmugasundram reviewed gene: MYOT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy, myofibrillar, 3, OMIM:609200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v2.25 SCO2 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: SCO2.
Hereditary neuropathy or pain disorder v2.25 SCO2 Achchuthan Shanmugasundram Classified gene: SCO2 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v2.25 SCO2 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are four unrelated cases identified with CMT type 4 (axonal polyneuropathy).
Hereditary neuropathy or pain disorder v2.25 SCO2 Achchuthan Shanmugasundram Gene: sco2 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v2.24 SCO2 Achchuthan Shanmugasundram Publications for gene: SCO2 were set to 29351582
Hereditary neuropathy or pain disorder v2.23 SCO2 Achchuthan Shanmugasundram Phenotypes for gene: SCO2 were changed from axonal Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease type 4, MONDO:0018995; Mitochondrial complex IV deficiency, nuclear type 2, OMIM:604377
Hereditary neuropathy or pain disorder v2.22 SCO2 Achchuthan Shanmugasundram Deleted their comment
Hereditary neuropathy or pain disorder v2.22 SCO2 Achchuthan Shanmugasundram edited their review of gene: SCO2: Changed rating: GREEN; Changed phenotypes to: Charcot-Marie-Tooth disease type 4, MONDO:0018995, Mitochondrial complex IV deficiency, nuclear type 2, OMIM:604377; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v2.22 SCO2 Achchuthan Shanmugasundram commented on gene: SCO2: As reviewed by Zornitza Stark, PMID:29351582 reported two unrelated cases with compound heterozygous variants in SCO2 gene (p.Glu140Lys/ p.Pro169Thr and p.Asp135Gly/ p.Arg171Gln). These two patients presented with axonal polyneuropathy (Charcot-Marie-Tooth disease type 4). They developed predominantly motor neuropathy, survived infancy, and have not yet developed the cardiomyopathy that causes death in early infancy in previously reported patients associated with Mitochondrial complex IV deficiency, nuclear type 2 (MIM #604377).

PMID:31844624 reported two siblings with homozygous missense variant in SCO2 gene (p.Arg255Trp) who presented with cerebellar ataxia, progressive peripheral axonal neuropathy and long survival. Similarly, homozygous variant p.Gly121Arg was identified in two brothers in PMID:35112411 and they were reported with axonal motor neuropathy like the other cases.

Autosomal recessive variants in this gene have been associated with Mitochondrial complex IV deficiency, nuclear type 2 (MIM #604377) in OMIM and Gene2Phenotype, which primarily has a cardiac phenotype. The axonal neuropathy phenotype without cardiac presentation has not yet been recorded in these resources.
Hereditary neuropathy or pain disorder v2.22 SCO2 Achchuthan Shanmugasundram reviewed gene: SCO2: Rating: ; Mode of pathogenicity: None; Publications: 29351582, 31844624, 35112411; Phenotypes: Charcot-Marie-Tooth disease type 4, MONDO:0018995, Mitochondrial complex IV deficiency, nuclear type 2 (MIM #604377).; Mode of inheritance: None
Hypertrophic cardiomyopathy v3.4 SCO2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: Hypertrophic cardiomyopathy is part of the overall OMIM phenotype of Mitochondrial complex IV deficiency, nuclear type 2 (MIM #604377), which is an autosomal recessive disorder. As autosomal dominant variants cause Myopia 6 (MIM #608908), the MOI should be changed to 'BIALLELIC, autosomal or pseudoautosomal'.
Hypertrophic cardiomyopathy v3.4 SCO2 Achchuthan Shanmugasundram Mode of inheritance for gene: SCO2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Classified gene: CTR9 as Amber List (moderate evidence)
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are sufficient unrelated cases (at least 10) reported with varying degrees (mild to severe) intellectual disability.
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Gene: ctr9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Classified gene: CTR9 as Amber List (moderate evidence)
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are sufficient unrelated cases (at least 10) reported with varying degrees (mild to severe) intellectual disability.
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Gene: ctr9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Classified gene: CTR9 as Amber List (moderate evidence)
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are sufficient unrelated cases (at least 10) reported with varying degrees (mild to severe) intellectual disability.
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Gene: ctr9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: CTR9.
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Classified gene: CTR9 as Amber List (moderate evidence)
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are sufficient unrelated cases (at least 10) reported with varying degrees (mild to severe) intellectual disability.
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Gene: ctr9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Classified gene: CTR9 as Amber List (moderate evidence)
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are sufficient unrelated cases (at least 10) reported with varying degrees (mild to severe) intellectual disability.
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Gene: ctr9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Classified gene: CTR9 as Amber List (moderate evidence)
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are sufficient unrelated cases (at least 10) reported with varying degrees (mild to severe) intellectual disability.
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Gene: ctr9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Classified gene: CTR9 as Amber List (moderate evidence)
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are sufficient unrelated cases (at least 10) reported with varying degrees (mild to severe) intellectual disability.
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Gene: ctr9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.101 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.100 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.101 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Phenotypes for gene: CTR9 were changed from Macrocephaly, HP:0000256; Motor delay, HP:0001270; intellectual disability, MONDO:0001071; Delayed speech and language development; Behavioral abnormality; Autistic behavior; Failure to thrive; Feeding difficulties; Abnormality of the cardiovascular system to Macrocephaly, HP:0000256; Motor delay, HP:0001270; intellectual disability, MONDO:0001071; Delayed speech and language development; Behavioral abnormality; Autistic behavior; Failure to thrive; Feeding difficulties; Abnormality of the cardiovascular system
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Phenotypes for gene: CTR9 were changed from Macrocephaly, HP:0000256; Motor delay, HP:0001270; intellectual disability, MONDO:0001071; Delayed speech and language development; Behavioral abnormality; Autistic behavior; Failure to thrive; Feeding difficulties; Abnormality of the cardiovascular system to Macrocephaly, HP:0000256; Motor delay, HP:0001270; intellectual disability, MONDO:0001071; Delayed speech and language development; Behavioral abnormality; Autistic behavior; Failure to thrive; Feeding difficulties; Abnormality of the cardiovascular system
Intellectual disability v4.100 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.101 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.101 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Phenotypes for gene: CTR9 were changed from Macrocephaly, HP:0000256; Motor delay, HP:0001270; intellectual disability, MONDO:0001071; Delayed speech and language development; Behavioral abnormality; Autistic behavior; Failure to thrive; Feeding difficulties; Abnormality of the cardiovascular system to Macrocephaly, HP:0000256; Motor delay, HP:0001270; intellectual disability, MONDO:0001071; Delayed speech and language development; Behavioral abnormality; Autistic behavior; Failure to thrive; Feeding difficulties; Abnormality of the cardiovascular system
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Phenotypes for gene: CTR9 were changed from Delayed speech and language development; Motor delay; Intellectual disability; Behavioral abnormality; Autistic behavior; Failure to thrive; Feeding difficulties; Abnormality of the cardiovascular system to Macrocephaly, HP:0000256; Motor delay, HP:0001270; intellectual disability, MONDO:0001071; Delayed speech and language development; Behavioral abnormality; Autistic behavior; Failure to thrive; Feeding difficulties; Abnormality of the cardiovascular system
Intellectual disability v4.99 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.100 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.99 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.101 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.100 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.100 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 2815719; 25363760; 27479843; 25099282; 29292210
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.99 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.99 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.99 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.97 CTR9 Achchuthan Shanmugasundram Mode of inheritance for gene: CTR9 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None
Intellectual disability v4.97 CTR9 Achchuthan Shanmugasundram Mode of inheritance for gene: CTR9 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.97 CTR9 Achchuthan Shanmugasundram Mode of inheritance for gene: CTR9 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.97 CTR9 Achchuthan Shanmugasundram Mode of inheritance for gene: CTR9 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.96 CTR9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.96 CTR9 Achchuthan Shanmugasundram edited their review of gene: CTR9: Added comment: As noted by the reviewer, PMID: 35499524 reported 13 unrelated cases identified with heterozygous variants in CTR9 gene (11 different variants) and they presented with overlapping neurodegenerative phenotypes including intellectual disability, hypotonia, joint hyperlaxity, speech delay, coordination problems, tremor, and autism spectrum disorder. Mild dysmorphism and cardiac anomalies were less frequent. The intellect levels were determined only for 11 patients (the rest are too young) and 8 out of these 11 patients were reported with variable degree of intellectual disability, while other three had impairments in other domains or learning difficulties.

PMID:35717577 reported two additional unrelated cases with non-synonymous heterozygous CTR9 variants (p.Glu15Asp and p.Pro25Arg) and they presented with macrocephaly, motor delay, and intellectual disability. In addition, functional studies in zebrafish also showed that knockout/ over-expression of CTR9 variants caused motor defects and enlargement of telencephalon (homologous to the mammalian cerebrum).

This gene has not yet been associated with relevant phenotypes in OMIM. It has been associated with Wilms tumour in Gene2Phenotype (phenotype not relevant to this panel).; Changed rating: GREEN; Changed publications to: 35499524, 35717577
Intellectual disability v4.96 CTR9 Achchuthan Shanmugasundram edited their review of gene: CTR9: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.96 CTR9 Achchuthan Shanmugasundram edited their review of gene: CTR9: Changed phenotypes to: Macrocephaly, HP:0000256, Motor delay, HP:0001270, intellectual disability, MONDO:0001071
Intellectual disability v4.96 RBSN Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene should be rated GREEN as bi-allelic variants in RBSN has been associated with a phenotype encompassing developmental delay and intellectual disability from four unrelated families.

This gene has not been associated with any phenotypes either in OMIM or in Gene2Phenotype.; to: Comment on list classification: This gene should be rated GREEN as bi-allelic variants in RBSN has been associated with a phenotype encompassing developmental delay and intellectual disability from four unrelated families.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Intellectual disability v4.96 RBSN Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.96 RBSN Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: RBSN.
Intellectual disability v4.96 RBSN Achchuthan Shanmugasundram Classified gene: RBSN as Amber List (moderate evidence)
Intellectual disability v4.96 RBSN Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as bi-allelic variants in RBSN has been associated with a phenotype encompassing developmental delay and intellectual disability from four unrelated families.

This gene has not been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Intellectual disability v4.96 RBSN Achchuthan Shanmugasundram Gene: rbsn has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.96 RBSN Achchuthan Shanmugasundram Classified gene: RBSN as Amber List (moderate evidence)
Intellectual disability v4.96 RBSN Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as bi-allelic variants in RBSN has been associated with a phenotype encompassing developmental delay and intellectual disability from four unrelated families.

This gene has not been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Intellectual disability v4.96 RBSN Achchuthan Shanmugasundram Gene: rbsn has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.95 RBSN Achchuthan Shanmugasundram gene: RBSN was added
gene: RBSN was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: RBSN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBSN were set to 25233840; 29784638; 35652444
Phenotypes for gene: RBSN were set to intellectual disability, MONDO:0001071
Review for gene: RBSN was set to GREEN
Added comment: PMID:25233840 reported a 6.5 year old female patient with a homozygous missense variant c.1273G > A (p.Gly425Arg) and her clinical presentation included intractable seizures, developmental delay, microcephaly, dysostosis, osteopenia, craniofacial dysmorphism, macrocytosis and megaloblastoid erythropoiesis.

PMID:29784638 reported three siblings with homozygous variant c.289G>C (p.Gly97Arg) in RBSN. The proband presented global developmental delay, had complete 46,XY male-to-female sex reversal and died at age 20 months after multiple infections. The other 2 affected siblings underwent unrelated-donor bone marrow or stem cell transplantation at 8 and 6.5 months of age, respectively. Both have severe intellectual disability and are nonambulatory and nonverbal.

PMID:35652444 reported two unrelated families (three siblings from a family of Iranian descent identified with homozygous variant c.547G>A (p.Gly183Arg) and four members from a family of indigenous Cree descent identified with homozygous variant c.538C>G (p.Arg180Gly)) with overlapping phenotypes including developmental delay, intellectual disability, distal motor axonal neuropathy and facial dysmorphism.
Sources: Literature
Intellectual disability v4.94 CTR9 Achchuthan Shanmugasundram changed review comment from: PMID:35717577 reported two additional unrelated cases with non-synonymous heterozygous CTR9 variants (p.Glu15Asp and p.Pro25Arg) and they presented with macrocephaly, motor delay, and intellectual disability. In addition, functional studies in also showed that knockout/ over-expression of CTR9 variants caused motor defects and enlargement of telencephalon (homologous to the mammalian cerebrum).

This gene has not yet been associated with relevant phenotypes in OMIM. It has been associated with Wilms tumour in Gene2Phenotype (phenotype not relevant to this panel).; to: PMID:35717577 reported two additional unrelated cases with non-synonymous heterozygous CTR9 variants (p.Glu15Asp and p.Pro25Arg) and they presented with macrocephaly, motor delay, and intellectual disability. In addition, functional studies in zebrafish also showed that knockout/ over-expression of CTR9 variants caused motor defects and enlargement of telencephalon (homologous to the mammalian cerebrum).

This gene has not yet been associated with relevant phenotypes in OMIM. It has been associated with Wilms tumour in Gene2Phenotype (phenotype not relevant to this panel).
Intellectual disability v4.94 DPYSL2 Achchuthan Shanmugasundram Classified gene: DPYSL2 as Amber List (moderate evidence)
Intellectual disability v4.94 DPYSL2 Achchuthan Shanmugasundram Gene: dpysl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.94 DPYSL2 Achchuthan Shanmugasundram Classified gene: DPYSL2 as Amber List (moderate evidence)
Intellectual disability v4.94 DPYSL2 Achchuthan Shanmugasundram Gene: dpysl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.93 DPYSL2 Achchuthan Shanmugasundram changed review comment from: This gene should be rated AMBER, as it has been associated with intellectual disability (ID) from two unrelated cases displaying monoallelic variants in DPYSL2/ CRMP2, and supported by functional studies. However, the evidence is not sufficient for green rating as there are variants reported in other (but different) genes in the two patients.

PMID:35861646 reported two cases identified with heterozygous variants (patient1: c.1693C>T (p.Arg565Cys); patient 2: c.42C>A (p.Ser14Arg). These patients had overlapping phenotypes including dysmorphic features, severe global developmental delay and hypoplasia of the corpus callosum. In addition, patient 2 was bed-ridden and could not roll out and had a history of myoclonic seizures and status epilepticus.

It should be noted that patient 1 is compound heterozygous for 2 missense variants in the EFCAB5 gene and was hemizygous for a maternally inherited missense variant in the GPKOW gene and patient 2 had 1 de novo missense variant in the COBLL1 gene and was compound heterozygous for 2 missense variants in the POTEF gene. The severity of the phenotypes between the two cases differs significantly and the additional variants may have possibly contributed to this phenotype.

Brain-specific Crmp2 knockout mice display neuronal development deficits and behavioural impairments associated with hypoplasia of the corpus callosum. In addition, functional studies performed in zebrafish and cell lines that the CRMP2 variants lead to the loss-of-function of CRMP2 protein and can cause intellectual disability.
Sources: Literature; to: This gene should be rated AMBER, as it has been associated with intellectual disability (ID) from two unrelated cases displaying monoallelic variants in DPYSL2/ CRMP2, and supported by functional studies. However, the evidence is not sufficient for green rating as there are variants reported in other (but different) genes in the two patients.

PMID:35861646 reported two cases identified with heterozygous variants (patient1: c.1693C>T (p.Arg565Cys); patient 2: c.42C>A (p.Ser14Arg). These patients had overlapping phenotypes including dysmorphic features, severe global developmental delay and hypoplasia of the corpus callosum. In addition, patient 2 was bed-ridden and could not roll out and had a history of myoclonic seizures and status epilepticus.

It should be noted that patient 1 is compound heterozygous for 2 missense variants in the EFCAB5 gene and was hemizygous for a maternally inherited missense variant in the GPKOW gene and patient 2 had 1 de novo missense variant in the COBLL1 gene and was compound heterozygous for 2 missense variants in the POTEF gene. The severity of the phenotypes between the two cases differs significantly and the additional variants may have possibly contributed to this phenotype.

Brain-specific Crmp2 knockout mice display neuronal development deficits and behavioural impairments associated with hypoplasia of the corpus callosum. In addition, functional studies performed in zebrafish and cell lines that the CRMP2 variants lead to the loss-of-function of CRMP2 protein and can cause intellectual disability.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v4.93 DPYSL2 Achchuthan Shanmugasundram gene: DPYSL2 was added
gene: DPYSL2 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: DPYSL2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DPYSL2 were set to 27249678; 35861646
Phenotypes for gene: DPYSL2 were set to intellectual disability, MONDO:0001071; Aplasia/Hypoplasia of the corpus callosum, HP:0007370
Review for gene: DPYSL2 was set to AMBER
Added comment: This gene should be rated AMBER, as it has been associated with intellectual disability (ID) from two unrelated cases displaying monoallelic variants in DPYSL2/ CRMP2, and supported by functional studies. However, the evidence is not sufficient for green rating as there are variants reported in other (but different) genes in the two patients.

PMID:35861646 reported two cases identified with heterozygous variants (patient1: c.1693C>T (p.Arg565Cys); patient 2: c.42C>A (p.Ser14Arg). These patients had overlapping phenotypes including dysmorphic features, severe global developmental delay and hypoplasia of the corpus callosum. In addition, patient 2 was bed-ridden and could not roll out and had a history of myoclonic seizures and status epilepticus.

It should be noted that patient 1 is compound heterozygous for 2 missense variants in the EFCAB5 gene and was hemizygous for a maternally inherited missense variant in the GPKOW gene and patient 2 had 1 de novo missense variant in the COBLL1 gene and was compound heterozygous for 2 missense variants in the POTEF gene. The severity of the phenotypes between the two cases differs significantly and the additional variants may have possibly contributed to this phenotype.

Brain-specific Crmp2 knockout mice display neuronal development deficits and behavioural impairments associated with hypoplasia of the corpus callosum. In addition, functional studies performed in zebrafish and cell lines that the CRMP2 variants lead to the loss-of-function of CRMP2 protein and can cause intellectual disability.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v3.6 TLN1 Achchuthan Shanmugasundram changed review comment from: PMID:35861643 reported a 20-year old man of Mexican ancestry with a complex phenotype including thrombocytopenia, T lymphopenia, and low IgG levels. The patient had an absolute lymphocyte counts <1000/mcL and low absolute T-cells. Recent B-cell subset analysis revealed 96% naïve and 4% switched memory B-cells and initial serum immunoglobulin levels at six years of age included: IgG 273, IgA 130, IgM 36. Because of poor antibody responses to pneumococcal vaccine, he was started on immunoglobulin replacement therapy, which he has continued to the present.

He continued to experienced intermittent sinusitis, otitis media and bronchitis since 10 years of age, which cleared with oral antibiotics. At 18 years of age, he had abdominal pain at times that was diagnosed as small intestinal bacterial overgrowth, headaches often treated as migraines, and joint pain with limited signs of active arthritis.

He was identified with a de novo heterozygous variant c.685C > T (p.Pro 229 Ser) that was not present in his parents.
Sources: Literature; to: PMID:35861643 reported a 20-year old man of Mexican ancestry with a complex phenotype including thrombocytopenia, T lymphopenia, and low IgG levels. The patient had an absolute lymphocyte count of <1000/mcL and low absolute T-cells. Recent B-cell subset analysis revealed 96% naïve and 4% switched memory B-cells and initial serum immunoglobulin levels at six years of age included: IgG 273, IgA 130, IgM 36. Because of poor antibody responses to pneumococcal vaccine, he was started on immunoglobulin replacement therapy, which he has continued to the present.

He continued to experienced intermittent sinusitis, otitis media and bronchitis since 10 years of age, which cleared with oral antibiotics. At 18 years of age, he had abdominal pain at times that was diagnosed as small intestinal bacterial overgrowth, headaches often treated as migraines, and joint pain with limited signs of active arthritis.

He was identified with a de novo heterozygous variant c.685C > T (p.Pro 229 Ser) that was not present in his parents.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v3.6 TLN1 Achchuthan Shanmugasundram gene: TLN1 was added
gene: TLN1 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: TLN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TLN1 were set to 35861643
Phenotypes for gene: TLN1 were set to lymphopenia, MONDO:0003783
Review for gene: TLN1 was set to RED
Added comment: PMID:35861643 reported a 20-year old man of Mexican ancestry with a complex phenotype including thrombocytopenia, T lymphopenia, and low IgG levels. The patient had an absolute lymphocyte counts <1000/mcL and low absolute T-cells. Recent B-cell subset analysis revealed 96% naïve and 4% switched memory B-cells and initial serum immunoglobulin levels at six years of age included: IgG 273, IgA 130, IgM 36. Because of poor antibody responses to pneumococcal vaccine, he was started on immunoglobulin replacement therapy, which he has continued to the present.

He continued to experienced intermittent sinusitis, otitis media and bronchitis since 10 years of age, which cleared with oral antibiotics. At 18 years of age, he had abdominal pain at times that was diagnosed as small intestinal bacterial overgrowth, headaches often treated as migraines, and joint pain with limited signs of active arthritis.

He was identified with a de novo heterozygous variant c.685C > T (p.Pro 229 Ser) that was not present in his parents.
Sources: Literature
Bleeding and platelet disorders v2.4 TLN1 Achchuthan Shanmugasundram gene: TLN1 was added
gene: TLN1 was added to Bleeding and platelet disorders. Sources: Literature
Mode of inheritance for gene: TLN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TLN1 were set to 35861643
Phenotypes for gene: TLN1 were set to thrombocytopenia, MONDO:0002049
Review for gene: TLN1 was set to RED
Added comment: PMID:35861643 reported a 20-year old man of Mexican ancestry with a complex phenotype including thrombocytopenia, T lymphopenia, and low IgG levels. The patient generally had a platelet count of <20 000/mcL, but without significant bleeding. He was identified with a de novo heterozygous variant c.685C > T (p.Pro 229 Ser) that was not present in his parents.
Sources: Literature
Likely inborn error of metabolism v3.13 SLC31A1 Achchuthan Shanmugasundram Classified gene: SLC31A1 as Amber List (moderate evidence)
Likely inborn error of metabolism v3.13 SLC31A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency.

This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM.
Likely inborn error of metabolism v3.13 SLC31A1 Achchuthan Shanmugasundram Gene: slc31a1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.13 SLC31A1 Achchuthan Shanmugasundram Classified gene: SLC31A1 as Amber List (moderate evidence)
Likely inborn error of metabolism v3.13 SLC31A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency.

This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM.
Likely inborn error of metabolism v3.13 SLC31A1 Achchuthan Shanmugasundram Gene: slc31a1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.13 SLC31A1 Achchuthan Shanmugasundram Classified gene: SLC31A1 as Amber List (moderate evidence)
Likely inborn error of metabolism v3.13 SLC31A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency.

This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM.
Likely inborn error of metabolism v3.13 SLC31A1 Achchuthan Shanmugasundram Gene: slc31a1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.12 SLC31A1 Achchuthan Shanmugasundram Classified gene: SLC31A1 as Amber List (moderate evidence)
Likely inborn error of metabolism v3.12 SLC31A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency.

This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM.
Likely inborn error of metabolism v3.12 SLC31A1 Achchuthan Shanmugasundram Gene: slc31a1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.12 SLC31A1 Achchuthan Shanmugasundram Classified gene: SLC31A1 as Amber List (moderate evidence)
Likely inborn error of metabolism v3.12 SLC31A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency.

This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM.
Likely inborn error of metabolism v3.12 SLC31A1 Achchuthan Shanmugasundram Gene: slc31a1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.12 SLC31A1 Achchuthan Shanmugasundram Classified gene: SLC31A1 as Amber List (moderate evidence)
Likely inborn error of metabolism v3.12 SLC31A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency.

This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM.
Likely inborn error of metabolism v3.12 SLC31A1 Achchuthan Shanmugasundram Gene: slc31a1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.11 SLC31A1 Achchuthan Shanmugasundram gene: SLC31A1 was added
gene: SLC31A1 was added to Inborn errors of metabolism. Sources: Literature
Mode of inheritance for gene: SLC31A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC31A1 were set to 35913762; 36562171
Phenotypes for gene: SLC31A1 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: SLC31A1 was set to AMBER
Added comment: PMID:35913762 reported an identical twin male infants identified with homozygous novel missense variant p.Arg95His in CTR1. The twins had hypotonia, global developmental delay, seizures, and rapid brain atrophy, consistent with profound central nervous system copper deficiency. In addition, the CSF copper levels were lower and functional studies including structural modelling of the variant showed impaired copper transport. Treatment with copper Histidinate in the patients' cultured cells and in the patients normalized CCO activity and enhanced mitochondrial respiration in vitro, and was associated with modest clinical improvements.

PMID:36562171 reported a newborn infant of consanguineous parents with a homozygous pathogenic variant p.Leu79Pro in CTR1. This infant was born with pulmonary hypoplasia. At two weeks of age, multifocal brain hemorrhages were diagnosed and the infant developed seizures. Laboratory investigations revealed very low serum concentrations of copper and ceruloplasmin. The infant died at one month of age.
Sources: Literature
Early onset or syndromic epilepsy v3.96 SLC31A1 Achchuthan Shanmugasundram Classified gene: SLC31A1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.96 SLC31A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as it has been associated with neurodegeneration involving seizures in two unrelated cases.

This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM.
Early onset or syndromic epilepsy v3.96 SLC31A1 Achchuthan Shanmugasundram Gene: slc31a1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v3.95 SLC31A1 Achchuthan Shanmugasundram Publications for gene: SLC31A1 were set to 35913762
Early onset or syndromic epilepsy v3.94 SLC31A1 Achchuthan Shanmugasundram edited their review of gene: SLC31A1: Added comment: PMID:36562171 reported a newborn infant of consanguineous parents with a homozygous pathogenic variant p.Leu79Pro in CTR1. This infant was born with pulmonary hypoplasia. At two weeks of age, multifocal brain hemorrhages were diagnosed and the infant developed seizures. The infant died at one month of age.; Changed rating: AMBER; Changed publications to: 35913762, 36562171
Early onset or syndromic epilepsy v3.94 SLC31A1 Achchuthan Shanmugasundram gene: SLC31A1 was added
gene: SLC31A1 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: SLC31A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC31A1 were set to 35913762
Phenotypes for gene: SLC31A1 were set to Neurodevelopmental disorder, MONDO:0700092; Epilepsy, MONDO:0005027
Review for gene: SLC31A1 was set to RED
Added comment: This gene has been associated with seizures in an identical twin male infants identified with homozygous novel missense variant p.Arg95His in CTR1. The twins had hypotonia, global developmental delay, seizures, and rapid brain atrophy, consistent with profound central nervous system copper deficiency.
Sources: Literature
Adult onset neurodegenerative disorder v3.58 CHCHD2 Achchuthan Shanmugasundram Publications for gene: CHCHD2 were set to 25662902; 26067114; 26705026; 26067110
Amyotrophic lateral sclerosis/motor neuron disease v1.62 NEK1 Andrey Gagunashvili gene: NEK1 was added
gene: NEK1 was added to Amyotrophic lateral sclerosis/motor neuron disease. Sources: Literature,Research,ClinGen
Mode of inheritance for gene: NEK1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NEK1 were set to 26945885; 27455347
Phenotypes for gene: NEK1 were set to Amyotrophic lateral sclerosis, susceptibility to, 24
Penetrance for gene: NEK1 were set to unknown
Added comment: Definitive ALS gene according to both ALSoD (https://alsod.ac.uk) and ClinGen.
Sources: Literature, Research, ClinGen
Adult onset neurodegenerative disorder v3.57 NEK1 Sarah Leigh edited their review of gene: NEK1: Added comment: Associated with Amyotrophic lateral sclerosis, susceptibility to, 24 (OMIM:617892), but not associated with a relevant phenotype in Gen2Phen. At least 12 NEK1 variants have been reported in amyotrophic lateral sclerosis cases (PMID: 30093141; 31768050; 26945885; 27455347), together with supportive functional studies (PMID: 2992911).; Changed rating: GREEN
Amyotrophic lateral sclerosis/motor neuron disease v1.62 SPAST Andrey Gagunashvili gene: SPAST was added
gene: SPAST was added to Amyotrophic lateral sclerosis/motor neuron disease. Sources: Literature,Research
Mode of inheritance for gene: SPAST was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SPAST were set to 16832076; 18401025; 33589474
Phenotypes for gene: SPAST were set to Spastic paraplegia 4, autosomal dominant
Penetrance for gene: SPAST were set to unknown
Review for gene: SPAST was set to AMBER
Added comment: Shall be added to "Amyotrophic lateral sclerosis/motor neuron disease" gene panel due to the phenotypic overlap of ALS/MND and spastic paraplegia.

This gene is included in Sheffield's group ALS/MND gene panel (Sheffield Institute for Translational Neuroscience, The University of Sheffield).
Sources: Literature, Research
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 SPRY1 Rebecca Tooze gene: SPRY1 was added
gene: SPRY1 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: SPRY1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPRY1 were set to PMID: 36543535
Review for gene: SPRY1 was set to AMBER
Added comment: • Single report of a homozygous loss of function variant (c.80T>A; p.(Leu27*)) in a patient with sagittal craniosynostosis, alongside hearing and kidney anomalies. Functional studies show complete absence of the protein and support variant pathogenicity (Tooze et al., 2022a). This is the first human description but there are available animal models showing the role of SPRY1 in craniofacial development.
• An individual was described with a heterozygous variant in SPRY1: p.(Gln6fs) (Timberlake et al., 2017), but evidence suggests that heterozygous loss-of-function variants are not pathogenic (see above reference).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 OGT Rebecca Tooze gene: OGT was added
gene: OGT was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: OGT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for gene: OGT was set to AMBER
Added comment: • A de novo variant in OGT was identified within the 100kGP cohort: c.539A>G; p.(Tyr180Cys) (Hyder et al., 2021).
• An analysis of a cohort of patients with trigonocephaly identified a splicing variant in OGT: c.1947+5A>C. The patient displayed a delay in speech acquisition, hyperkinesia, sleep disorders and trigonocephaly (Suzuki et al., 2020).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 MAN2B1 Rebecca Tooze gene: MAN2B1 was added
gene: MAN2B1 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: MAN2B1 was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: MAN2B1 was set to GREEN
Added comment: • A Norwegian study of patients with craniosynostosis identified a homozygous missense variant in MAN2B1: c.1055 T>C; p.(Leu352Pro) (Tønne et al., 2021).
• Compound heterozygous variant were identified through screening 114 families with craniosynostosis within the UK 100kGP: c.1830+1G>C; p.(?) and c.2248C>T; p.(Arg750Trp) (Hyder et al., 2021).
• One patient out of 12 with recessive variants in MAN2B1 was described with craniosynostosis: c.2245C>T; p.(Arg749Trp), and c.2355G>A; p.(Thr785*) (Lipiński et al., 2022).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 IL6ST Rebecca Tooze gene: IL6ST was added
gene: IL6ST was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: IL6ST was set to BIALLELIC, autosomal or pseudoautosomal
Added comment: • A homozygous non-synonymous variant in IL6ST (p.(Arg281Gln)) was described in a patient with craniosynostosis and retained deciduous teeth. Findings were supported using a mouse model with the missense variant which resulted in lower litter sizes, facial synostosis, and teeth abnormalities. The model phenocopies aspects of IL11RA deficiency in humans and mice (Schwerd et al., 2020).
• A patient with a homozygous variant in IL6ST presented with recurrent infections, eczema, bronchiectasis, high IgE, eosinophilia, defective B cell memory, and an impaired acute-phase response, as well as skeletal abnormalities including craniosynostosis. They were shown to harbour a p.(Asn404Tyr) missense substitution (Schwerd et al., 2017).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 FBXO11 Rebecca Tooze gene: FBXO11 was added
gene: FBXO11 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: FBXO11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for gene: FBXO11 was set to GREEN
Added comment: • A de novo insertion was identified within the 100kGP cohort of patients with craniosynostosis: c.2731_2732insGACA; p.(Thr911Argfs*5) (Hyder et al., 2021).
• Two patients were described with craniosynostosis and variants in FBXO11: c.2518T>C, p.(Ser840Pro) in an individual with sagittal synostosis, and hg19: chr2: g.48060020C>G, c.1042- 1G>C; p.(?) (Gregor et al., 2018).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 DPH1 Rebecca Tooze gene: DPH1 was added
gene: DPH1 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: DPH1 was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: DPH1 was set to AMBER
Added comment: • A patient was described with short stature, sagittal craniosynostosis and dysmorphic features including scaphocephaly, sparse hair, multiple dental anomalies, epicanthal folds and hypoplastic toenails to harbour a homozygous missense variant in DPH1: c.17T>A; p.(Met6Lys) (born to consanguineous parents).
• A family with two affected siblings were described and one was confirmed to have metopic synostosis. They harboured a recessive c.335A>G; p.(Tyr112Cys) variant (Urreizti et al., 2020).
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 DPF2 Rebecca Tooze gene: DPF2 was added
gene: DPF2 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: DPF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for gene: DPF2 was set to AMBER
Added comment: • Variants in DPF2 are associated with Coffin Siris syndrome. Two patients with sagittal synostosis were found to harbour a de novo c.1037A>G; p.(Asp346Gly) variant. A third patient with suspected metopic synostosis, owing to trigonocephaly, was identified with a c.1099+1G>A; p.(Asp340Glufs*12) frameshifting variant. All patients displayed phenotypic features of Coffin Siris syndrome (Vasileiou et al., 2018).
Sources: Literature
Adult onset neurodegenerative disorder v3.57 NEK1 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: NEK1.
Adult onset neurodegenerative disorder v3.57 NEK1 Sarah Leigh Classified gene: NEK1 as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v3.57 NEK1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Adult onset neurodegenerative disorder v3.57 NEK1 Sarah Leigh Gene: nek1 has been classified as Amber List (Moderate Evidence).
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 CDK13 Rebecca Tooze gene: CDK13 was added
gene: CDK13 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: CDK13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for gene: CDK13 was set to GREEN
Added comment: • A de novo missense variant was identified within the UK 100kGP cohort of patients with craniosynostosis: c.2563G>C; p.(Asp855His) (Hyder et al., 2021).
• A further de novo variant was identified in an individual within the Norwegian cohort: c.2524A>G; p.(Asn842Asp) (Tønne et al., 2021).
• Two patients were described with craniosynostosis in a cohort of patients with congenital heart defects, dysmorphic facial features, and intellectual disability (Bostwick et al., 2017)

Four independent cases identified.
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 BCL11B Rebecca Tooze reviewed gene: BCL11B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 ASXL3 Rebecca Tooze gene: ASXL3 was added
gene: ASXL3 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: ASXL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for gene: ASXL3 was set to AMBER
Added comment: • A de novo c.3033dup; p.(Leu1012Serfs*23) was identified in a patient with metopic synostosis within the Norwegian cohort (Tønne et al., 2021).
• A six-year-old with microcephaly, autism, global developmental delay, and metopic craniosynostosis was found on exome sequencing to harbour a heterozygous two base pair de novo deletion, c.1897_1898delCA; p.(Gln633Valfs*13) in ASXL3 (Dinwiddie et al., 2013).
• A heterozygous de novo single nucleotide variant (c.3039+1G>A; p.(?)) in the invariant “GT” splice donor site of exon 11 was identified in an individual with a prominent forehead, thick eyebrows, long lashes, exotropia, depressed nasal ridge, thin upper lip vermillion, hirsutism, microcephaly, bilateral camptodactyly of third, fourth and fifth fingers, deep palmar creases, and small hands and feet. Craniosynostosis is not confirmed (Hori et al., 2016).

Two cases of loss-of-function variants in ASXL3; only one has radiologically confirmed craniosynostosis.
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 ARID1B Rebecca Tooze gene: ARID1B was added
gene: ARID1B was added to Craniosynostosis. Sources: Literature,Research
Mode of inheritance for gene: ARID1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for gene: ARID1B was set to GREEN
Added comment: • Analysis of the UK 100kGP identified a frameshift variant in ARID1B in a patient with intellectual disability and sagittal synostosis: c.3594delinsCCCCCA; p.(Gly1199Profs*14) (Hyder et al., 2021).
• A further frameshifting variant was described in an individual within the Chinese cohort with sagittal craniosynostosis c.2346_2352del; p.(Ser784Cysfs*59) (Chen et al., 2022).
• An additional patient was described with trigonocephaly and motor developmental delay with a variant in ARID1B: c.2277delC; p.(Pro760fs) (Suzuki et al., 2020).
• A de novo variant affecting ARID1B (c.1468_1472delTGGGC; p.(Trp490Glyfs*43)) was identified in an individual with craniosynostosis out of a cohort of neurodevelopmental disorder patients (Mignot et al., 2016).
Sources: Literature, Research
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 SH3PXD2B Rebecca Tooze changed review comment from: • Two heterozygous variants were identified in the Clarke cohort: c.1265T>C; p.(Ile433Thr) and c.2276C>G; p.(Pro759Arg) (Clarke et al., 2018) - see review: doi.org/10.3390/genes14030615; to: • Two heterozygous variants were identified in the Clarke cohort: c.1265T>C; p.(Ile433Thr) and c.2276C>G; p.(Pro759Arg) (Clarke et al., 2018). Other documented cases are homozygous so likely incidental. - see review: doi.org/10.3390/genes14030615
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 SH3PXD2B Rebecca Tooze reviewed gene: SH3PXD2B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 RSPRY1 Rebecca Tooze reviewed gene: RSPRY1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 NFIX Rebecca Tooze reviewed gene: NFIX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 KAT6B Rebecca Tooze reviewed gene: KAT6B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 IRX5 Rebecca Tooze reviewed gene: IRX5: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 IFT43 Rebecca Tooze reviewed gene: IFT43: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 IFT140 Rebecca Tooze reviewed gene: IFT140: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 GPC3 Rebecca Tooze reviewed gene: GPC3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 FREM1 Rebecca Tooze reviewed gene: FREM1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 FGF9 Rebecca Tooze reviewed gene: FGF9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 FBN1 Rebecca Tooze reviewed gene: FBN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 AXIN2 Rebecca Tooze reviewed gene: AXIN2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 AHDC1 Rebecca Tooze reviewed gene: AHDC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 ADAMTSL4 Rebecca Tooze reviewed gene: ADAMTSL4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 ADAMTSL4 Rebecca Tooze Deleted their review
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 ADAMTSL4 Rebecca Tooze reviewed gene: ADAMTSL4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v3.16 PRDX3 Achchuthan Shanmugasundram Phenotypes for gene: PRDX3 were changed from Cerebellar ataxia (early onset, mild to moderate, progressive) to Spinocerebellar ataxia, autosomal recessive 32, OMIM:619862
Ataxia and cerebellar anomalies - narrow panel v3.41 PRDX3 Achchuthan Shanmugasundram changed review comment from: Comment on publications: PMID:35766882 reports a case of infantile-onset cerebellar ataxia that started ate 19 months old and presented with severe cerebellar atrophy and peripheral neuropathy early in the course of disease. This patient was identified with a homozygous variant in PRDX3 gene (p.Asp163Glu).; to: Comment on publications: PMID:35766882 reports a case of infantile-onset cerebellar ataxia that started ate 19 months old and presented with severe cerebellar atrophy and peripheral neuropathy early in the course of disease. This patient was identified with the homozygous variant p.Asp163Glu in PRDX3 gene.
Ataxia and cerebellar anomalies - narrow panel v3.41 PRDX3 Achchuthan Shanmugasundram Phenotypes for gene: PRDX3 were changed from Cerebellar ataxia (early onset, mild to moderate, progressive) to Spinocerebellar ataxia, autosomal recessive 32, OMIM:619862
Ataxia and cerebellar anomalies - narrow panel v3.40 PRDX3 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:35766882 reports a case of infantile-onset cerebellar ataxia that started ate 19 months old and presented with severe cerebellar atrophy and peripheral neuropathy early in the course of disease. This patient was identified with a homozygous variant in PRDX3 gene (p.Asp163Glu).
Ataxia and cerebellar anomalies - narrow panel v3.40 PRDX3 Achchuthan Shanmugasundram Publications for gene: PRDX3 were set to 33889951
Adult onset neurodegenerative disorder v3.56 NEK1 Sarah Leigh Phenotypes for gene: NEK1 were changed from {Amyotrophic lateral sclerosis, susceptibility to, 24}, OMIM:617892 to {Amyotrophic lateral sclerosis, susceptibility to, 24}, OMIM:617892; amyotrophic lateral sclerosis, susceptibility to, 24, MONDO:0054750
Adult onset neurodegenerative disorder v3.55 NEK1 Sarah Leigh Publications for gene: NEK1 were set to 29650794; 26945885; 30093141
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 SOX6 Rebecca Tooze reviewed gene: SOX6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 SMAD3 Rebecca Tooze reviewed gene: SMAD3: Rating: ; Mode of pathogenicity: None; Publications: https://doi.org/10.3390/genes14030615; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 PRRX1 Rebecca Tooze reviewed gene: PRRX1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://doi.org/10.3390/genes14030615; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset dystonia, chorea or related movement disorder v2.8 VPS35 Achchuthan Shanmugasundram Publications for gene: VPS35 were set to 23408866; 21763483; 21763482; 26547032; 22991136; 27777137; 22517097; 24854799; 35766879
Adult onset dystonia, chorea or related movement disorder v2.8 VPS35 Achchuthan Shanmugasundram Publications for gene: VPS35 were set to 23408866; 21763483; 21763482; 26547032; 22991136; 27777137; 22517097; 24854799
Adult onset neurodegenerative disorder v3.54 VPS35 Achchuthan Shanmugasundram Publications for gene: VPS35 were set to 27777137; 22517097; 23408866; 26547032; 21763482; 22991136; 21763483; 24854799
Intellectual disability v4.92 CTR9 Achchuthan Shanmugasundram changed review comment from: PMID:35717577 reported two additional unrelated cases with non-synonymous heterozygous CTR9 variants (p.Glu15Asp and p.Pro25Arg) and they presented with macrocephaly, motor delay, and intellectual disability. In addition, functional studies in also showed that knockout/ over-expression of CTR9 variants caused motor defects and enlargement of telencephalon (homologous to the mammalian cerebrum).; to: PMID:35717577 reported two additional unrelated cases with non-synonymous heterozygous CTR9 variants (p.Glu15Asp and p.Pro25Arg) and they presented with macrocephaly, motor delay, and intellectual disability. In addition, functional studies in also showed that knockout/ over-expression of CTR9 variants caused motor defects and enlargement of telencephalon (homologous to the mammalian cerebrum).

This gene has not yet been associated with relevant phenotypes in OMIM. It has been associated with Wilms tumour in Gene2Phenotype (phenotype not relevant to this panel).
Intellectual disability v4.92 CTR9 Achchuthan Shanmugasundram edited their review of gene: CTR9: Added comment: PMID:35717577 reported two additional unrelated cases with non-synonymous heterozygous CTR9 variants (p.Glu15Asp and p.Pro25Arg) and they presented with macrocephaly, motor delay, and intellectual disability. In addition, functional studies in also showed that knockout/ over-expression of CTR9 variants caused motor defects and enlargement of telencephalon (homologous to the mammalian cerebrum).; Changed phenotypes to: Macrocephaly, HP:0000256, Motor delay, HP:0001270, intellectual disability, MONDO_0001071
Intellectual disability v4.92 CTR9 Achchuthan Shanmugasundram reviewed gene: CTR9: Rating: AMBER; Mode of pathogenicity: None; Publications: 35717577; Phenotypes: Macrocephaly, HP:0000256, Motor delay, HP:0001270, intellectual disability, MONDO_000107; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v4.92 NUP214 Eleanor Williams changed review comment from: Associated with {Encephalopathy, acute, infection-induced, susceptibility to, 9} 618426 in OMIM and Gene2Phenotype (probable).

PMID: 31178128 - Fichtman et al 2019 - report on two families one of Palestinian decent, the other Northern European (not Finnish descent). Each had two affected siblings in which neurological decline was seen after febrile events. The older son in family A, exhibited minor developmental delay from infancy. A homozygous missense variant was identified in NUP214 (p.Arg38Cys) in family A and segregated with the disease in available family members. In family B affected sisters were compound heterozygous for a frameshift and a missense variant in NUP214 (p.Pro387Ser and p.Pro525Leufs∗6). Functional studies with fibroblasts from one patient in family A showed a decrease in NUP214 and NUP88 levels compared to controls,

PMID: 30758658 - Shamseldin et al 2019 - describe a multiplex consanguineous family in which four affected members presented with severe neonatal hypotonia, profound global developmental delay, progressive microcephaly and early death (<2 year old). Whole exome sequencing revealed the presence of a novel homozygous missense variant in NUP214, p.D154G.

PMID: 29483668 - Egloff et al 2018 - report a 4-year-old girl presenting with developmental delay, growth retardation and facial dysmorphism. She was found to have a 9q deletion inherited from her healthy mother and a hemizygous one-base pair deletion in the NUP214 gene inherited from her father. From patient leukocytes it was found that the expression level of the NUP214 transcript was significantly decreased and close to zero in the patient compared to the controls. ; to: Associated with {Encephalopathy, acute, infection-induced, susceptibility to, 9} 618426 in OMIM and Gene2Phenotype (probable).

PMID: 31178128 - Fichtman et al 2019 - report on two families one of Palestinian decent, the other Northern European (not Finnish descent). Each had two affected family members in which neurological decline was seen after febrile events. The older son in family A, exhibited minor developmental delay from infancy. A homozygous missense variant was identified in NUP214 (p.Arg38Cys) in family A and segregated with the disease in available family members. In family B affected sisters were compound heterozygous for a frameshift and a missense variant in NUP214 (p.Pro387Ser and p.Pro525Leufs∗6). Functional studies with fibroblasts from one patient in family A showed a decrease in NUP214 and NUP88 levels compared to controls,

PMID: 30758658 - Shamseldin et al 2019 - describe a multiplex consanguineous family in which four affected members presented with severe neonatal hypotonia, profound global developmental delay, progressive microcephaly and early death (<2 year old). Whole exome sequencing revealed the presence of a novel homozygous missense variant in NUP214, p.D154G.

PMID: 29483668 - Egloff et al 2018 - report a 4-year-old girl presenting with developmental delay, growth retardation and facial dysmorphism. She was found to have a 9q deletion inherited from her healthy mother and a hemizygous one-base pair deletion in the NUP214 gene inherited from her father. From patient leukocytes it was found that the expression level of the NUP214 transcript was significantly decreased and close to zero in the patient compared to the controls.
Intellectual disability v4.92 NUP214 Eleanor Williams edited their review of gene: NUP214: Changed publications to: 31178128, 30758658, 29483668
Likely inborn error of metabolism v3.10 CRLS1 Achchuthan Shanmugasundram Classified gene: CRLS1 as Amber List (moderate evidence)
Likely inborn error of metabolism v3.10 CRLS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are three unrelated cases and supporting functional evidence to link this gene with a mitochondrial metabolic disorder. This gene has already been associated with this phenotype in OMIM (MIM #620167).
Likely inborn error of metabolism v3.10 CRLS1 Achchuthan Shanmugasundram Gene: crls1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.10 CRLS1 Achchuthan Shanmugasundram Classified gene: CRLS1 as Amber List (moderate evidence)
Likely inborn error of metabolism v3.10 CRLS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are three unrelated cases and supporting functional evidence to link this gene with a mitochondrial metabolic disorder. This gene has already been associated with this phenotype in OMIM (MIM #620167).
Likely inborn error of metabolism v3.10 CRLS1 Achchuthan Shanmugasundram Gene: crls1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.9 CRLS1 Achchuthan Shanmugasundram Classified gene: CRLS1 as Amber List (moderate evidence)
Likely inborn error of metabolism v3.9 CRLS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are three unrelated cases and supporting functional evidence to link this gene with a mitochondrial metabolic disorder. This gene has already been associated with this phenotype in OMIM (MIM #620167).
Likely inborn error of metabolism v3.9 CRLS1 Achchuthan Shanmugasundram Gene: crls1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.9 CRLS1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: CRLS1.
Likely inborn error of metabolism v3.9 CRLS1 Achchuthan Shanmugasundram Classified gene: CRLS1 as Amber List (moderate evidence)
Likely inborn error of metabolism v3.9 CRLS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are three unrelated cases and supporting functional evidence to link this gene with a mitochondrial metabolic disorder. This gene has already been associated with this phenotype in OMIM (MIM #620167).
Likely inborn error of metabolism v3.9 CRLS1 Achchuthan Shanmugasundram Gene: crls1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v3.8 CRLS1 Achchuthan Shanmugasundram gene: CRLS1 was added
gene: CRLS1 was added to Inborn errors of metabolism. Sources: Literature
Mode of inheritance for gene: CRLS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRLS1 were set to 35147173
Phenotypes for gene: CRLS1 were set to Combined oxidative phosphorylation deficiency 57, OMIM:620167
Review for gene: CRLS1 was set to GREEN
Added comment: Three individuals from two unrelated families were identified with the same homozygous variant in CRLS1 (p.Ile109Asn). They presented with a mitochondrial disorder characterized by an evolving pattern of cardiomyopathy, encephalopathy, bilateral auditory neuropathy spectrum disorder, bull’s eye maculopathy, diabetes insipidus, autonomic instability and low complex IV activity in skeletal muscle.

A fourth individual was identified with a compound heterozygous CRLS1 variant (p.Ala172Asp/ p.Leu217Phe) that presented with developmental regression beginning in late infancy, with acquired microcephaly, sensorineural hearing loss and impaired vision.

Lipidomics in fibroblasts from 2 patients demonstrated that cardiolipin was reduced, cardiolipin acyl side chains had an abnormal distribution, and substrates of CRLS1 were abnormally elevated, including an elevation of phosphatidylglycerol.
Sources: Literature
Hereditary ataxia with onset in adulthood v3.15 FGF14_GAA Eleanor Williams Phenotypes for STR: FGF14_GAA were changed from Late-onset cerebellar ataxia; Episodic features; Nystagmus to Late-onset cerebellar ataxia; Episodic features; Nystagmus; Spinocerebellar ataxia 27B, late-onset, OMIM:620174
Hereditary ataxia with onset in adulthood v3.14 FGF14_GAA Eleanor Williams Publications for STR: FGF14_GAA were set to PMID: 36516086
Hereditary ataxia with onset in adulthood v3.13 FGF14_GAA Eleanor Williams Classified STR: FGF14_GAA as Amber List (moderate evidence)
Hereditary ataxia with onset in adulthood v3.13 FGF14_GAA Eleanor Williams Added comment: Comment on list classification: Promoting to amber but there is sufficient evidence to promote to green following GMS review, and configuration in the Rare Disease analysis pipeline.
Hereditary ataxia with onset in adulthood v3.13 FGF14_GAA Eleanor Williams Str: fgf14_gaa has been classified as Amber List (Moderate Evidence).
Hereditary ataxia with onset in adulthood v3.12 FGF14_GAA Eleanor Williams Tag Q1_23_promote_green tag was added to STR: FGF14_GAA.
Tag Q1_23_expert_review tag was added to STR: FGF14_GAA.
Tag Q1_23_NHS_review tag was added to STR: FGF14_GAA.
Hereditary ataxia with onset in adulthood v3.12 FGF14_GAA Eleanor Williams reviewed STR: FGF14_GAA: Rating: ; Mode of pathogenicity: None; Publications: 36516086, 36493768; Phenotypes: Spinocerebellar ataxia 27B, late-onset, OMIM:620174; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Renal tubulopathies v3.6 WDR72 Eleanor Williams Publications for gene: WDR72 were set to 30028003
Renal tubulopathies v3.5 WDR72 Eleanor Williams Phenotypes for gene: WDR72 were changed from distal RTA; hereditary distal renal tubular acidosis to distal RTA; hereditary distal renal tubular acidosis; distal renal tubular acidosis, MONDO:0015827; Amelogenesis imperfecta, type IIA3, OMIM:613211; amelogenesis imperfecta hypomaturation type 2A3, MONDO:0013181
Renal tubulopathies v3.4 WDR72 Eleanor Williams Tag Q1_23_promote_green tag was added to gene: WDR72.
Renal tubulopathies v3.4 WDR72 Eleanor Williams commented on gene: WDR72: Additional families reported with distal renal tubular acidosis, along with amelogenesis imperfecta.

PMID: 30779877 (Zhang et al 2019) - 6 families (1 African, 5 Turkish) identified using WES with biallelic WDR72 variants. The affected members showed generalized hypomaturation Amelogenesis imperfecta. 2 families, although unrelated, shared the same variant. 3 out of the 8 tested patients showed decreased serum pH, consistent with a diagnosis of renal tubular acidosis.

PMID: 31959358 - (Jobst-Schwan et al 2020) - 2 families (Indian, Turkish) with different homozygous variants in WDR72 identified by WES. All 3 affected individuals had Distal renal tubular acidosis. 1 individual is reported to have nephrocalcinosis.

PMID: 33033857 - Khandelwal et al 2021 - 4 patients, from three unrelated consanguineous families, with RTA and amelogenesis imperfecta. Genome analysis of 3 of the patients identified 3 different homozygous nonsense variants in WDR72. Ultrasound showed bilateral grade I medullary nephrocalcinosis in the 3 patients.
Nephrocalcinosis or nephrolithiasis v3.7 WDR72 Eleanor Williams Tag Q1_23_promote_green tag was added to gene: WDR72.
Tag Q1_23_NHS_review tag was added to gene: WDR72.
Nephrocalcinosis or nephrolithiasis v3.7 WDR72 Eleanor Williams Phenotypes for gene: WDR72 were changed from distal renal tubular acidosis; amelogenesis imperfecta to distal renal tubular acidosis, MONDO:0015827; Amelogenesis imperfecta, type IIA3, OMIM:613211; amelogenesis imperfecta hypomaturation type 2A3, MONDO:0013181
Mitochondrial disorders v3.12 CRLS1 Achchuthan Shanmugasundram changed review comment from: Three individuals from two unrelated families were identified with the same homozygous variant in CRLS1 (p.Ile109Asn). They presented with a mitochondrial disorder characterized by an evolving pattern of cardiomyopathy, encephalopathy, bilateral auditory neuropathy spectrum disorder, bull’s eye maculopathy, diabetes insipidus, autonomic instability and low complex IV activity in skeletal muscle.

A fourth individual was identified with a compound heterozygous CRLS1 variant (p.Ala172Asp/ p.Leu217Phe) that presented with developmental regression beginning in late infancy, with acquired microcephaly, sensorineural hearing loss and impaired vision.

Functional studies using patient-derived fibroblasts provide evidence that CRLS1 variants cause mitochondrial disease.
Sources: Literature; to: Three individuals from two unrelated families were identified with the same homozygous variant in CRLS1 (p.Ile109Asn). They presented with a mitochondrial disorder characterized by an evolving pattern of cardiomyopathy, encephalopathy, bilateral auditory neuropathy spectrum disorder, bull’s eye maculopathy, diabetes insipidus, autonomic instability and low complex IV activity in skeletal muscle.

A fourth individual was identified with a compound heterozygous CRLS1 variant (p.Ala172Asp/ p.Leu217Phe) that presented with developmental regression beginning in late infancy, with acquired microcephaly, sensorineural hearing loss and impaired vision.

Functional studies using patient-derived fibroblasts provide evidence that CRLS1 variants cause mitochondrial disease.
Sources: Literature
Monogenic hearing loss v3.11 CRLS1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene should be rated GREEN as it has been associated with auditory neuropathy in two unrelated cases with homozygous variant and with sensorineural hearing loss in an additional case with compound heterozygous variant.; to: Comment on list classification: This gene should be rated GREEN as it has been associated with auditory neuropathy in two unrelated cases with homozygous variant and with sensorineural hearing loss in an additional case with compound heterozygous variant. This is also supported by functional studies.
Monogenic hearing loss v3.11 CRLS1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: CRLS1.
Monogenic hearing loss v3.11 CRLS1 Achchuthan Shanmugasundram Classified gene: CRLS1 as Amber List (moderate evidence)
Monogenic hearing loss v3.11 CRLS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as it has been associated with auditory neuropathy in two unrelated cases with homozygous variant and with sensorineural hearing loss in an additional case with compound heterozygous variant.
Monogenic hearing loss v3.11 CRLS1 Achchuthan Shanmugasundram Gene: crls1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v3.10 CRLS1 Achchuthan Shanmugasundram Publications for gene: CRLS1 were set to 5147173
Monogenic hearing loss v3.9 CRLS1 Achchuthan Shanmugasundram edited their review of gene: CRLS1: Changed publications to: 35147173
Monogenic hearing loss v3.9 CRLS1 Achchuthan Shanmugasundram gene: CRLS1 was added
gene: CRLS1 was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: CRLS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRLS1 were set to 5147173
Phenotypes for gene: CRLS1 were set to Combined oxidative phosphorylation deficiency 57, OMIM:620167
Review for gene: CRLS1 was set to GREEN
Added comment: Three individuals from two unrelated families were identified with the same homozygous variant in CRLS1 (p.Ile109Asn). They presented with a mitochondrial disorder characterized by an evolving pattern of cardiomyopathy, encephalopathy, bilateral auditory neuropathy spectrum disorder, bull’s eye maculopathy, diabetes insipidus, autonomic instability and low complex IV activity in skeletal muscle.

A fourth individual was identified with a compound heterozygous CRLS1 variant (p.Ala172Asp/ p.Leu217Phe) that presented with developmental regression beginning in late infancy, with acquired microcephaly, sensorineural hearing loss and impaired vision.

Functional studies using patient-derived fibroblasts provide evidence that CRLS1 variants cause mitochondrial disease.
Sources: Literature
Nephrocalcinosis or nephrolithiasis v3.6 WDR72 Eleanor Williams Publications for gene: WDR72 were set to PMID: 30028003; 30779877; 31959358; 33033857
Nephrocalcinosis or nephrolithiasis v3.5 WDR72 Eleanor Williams Classified gene: WDR72 as Amber List (moderate evidence)
Nephrocalcinosis or nephrolithiasis v3.5 WDR72 Eleanor Williams Added comment: Comment on list classification: Promoting this gene to amber with a recommendation of green rating following GMS review. There are 5 cases with nephrocalcinosis reported and biallelic variants in this gene.
Nephrocalcinosis or nephrolithiasis v3.5 WDR72 Eleanor Williams Gene: wdr72 has been classified as Amber List (Moderate Evidence).
Nephrocalcinosis or nephrolithiasis v3.4 WDR72 Eleanor Williams commented on gene: WDR72
Paediatric or syndromic cardiomyopathy v2.8 CRLS1 Achchuthan Shanmugasundram Classified gene: CRLS1 as Amber List (moderate evidence)
Paediatric or syndromic cardiomyopathy v2.8 CRLS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two cases with cardiac defects and they harbour the same homozygous variant. In addition, functional studies from patient fibroblasts showed that these variants impair mitochondrial function.
Paediatric or syndromic cardiomyopathy v2.8 CRLS1 Achchuthan Shanmugasundram Gene: crls1 has been classified as Amber List (Moderate Evidence).
Paediatric or syndromic cardiomyopathy v2.7 CRLS1 Achchuthan Shanmugasundram gene: CRLS1 was added
gene: CRLS1 was added to Cardiomyopathies - including childhood onset. Sources: Literature
Mode of inheritance for gene: CRLS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRLS1 were set to 35147173
Phenotypes for gene: CRLS1 were set to Combined oxidative phosphorylation deficiency 57, OMIM:620167
Review for gene: CRLS1 was set to AMBER
Added comment: Three individuals from two unrelated families were identified with the same homozygous variant in CRLS1 (p.Ile109Asn). They presented with a mitochondrial disorder characterized by an evolving pattern of cardiomyopathy, encephalopathy, bilateral auditory neuropathy spectrum disorder, bull’s eye maculopathy, diabetes insipidus, autonomic instability and low complex IV activity in skeletal muscle.

Of these, patient from family 1 had left ventricular noncompaction and biventricular systolic dysfunction, as diagnosed by echocardiogram at 2 days of life, which evolved to hypertrophic cardiomyopathy by 7 weeks of age. The ECG of second patient from family 2 (patient II:3) demonstrated evere biventricular dysfunction, which subsequently improved, while the other patient from the same family with the variant did not exhibit any cardiac phenotype./

A fourth individual was identified with a compound heterozygous CRLS1 variant (p.Ala172Asp/ p.Leu217Phe) that presented with developmental regression beginning in late infancy, with acquired microcephaly, sensorineural hearing loss and impaired vision. This patient did not show any cardiac phenotype.

Functional studies using patient-derived fibroblasts provide evidence that CRLS1 variants cause mitochondrial disease.
Sources: Literature
Renal tubulopathies v3.4 WDR72 Eleanor Williams changed review comment from: No association with a renal phenotype in OMIM (only with Amelogenesis imperfecta) or Gene2Phenotype.

PMID: 30028003 (Rungroj et al 2018) report 2 families, of Thai and Indian ethnicities, with compound heterozygous and homozygous nonsense WDR72 variations respectively. Both were affected by hereditary distal renal tubular acidosis (dRTA). 3 different variants were found in WDR72; c.1777A>G:p.R593G and c.2522T>A:p.L841Q (predicted as disease causing or damaging, found as compound heterzygotes in family 1) and c.2686C>T:p.R896X. (protein truncating, homozygous in family 2). The truncating variant has been previously reported in a Pakistani family affected by hypomaturation AI, however no other clinical phenotypes in the patients were reported (PMID: 21196691).

Patients in family 1 presented with proximal muscle weakness and/or growth retardation at ages under 7 years. One member of family 1 also had nephrolithiasis and localized enamel hypoplasia. Family 2 has consanguineous parents with one affected child which presented with hypoplastic amelogenesis imperfect in addition to dRTA.; to: No association with a renal phenotype in OMIM (only with Amelogenesis imperfecta) or Gene2Phenotype.

PMID: 30028003 (Rungroj et al 2018) report 2 families, of Thai and Indian ethnicities, with compound heterozygous and homozygous nonsense WDR72 variations respectively. Both were affected by hereditary distal renal tubular acidosis (dRTA). 3 different variants were found in WDR72; c.1777A>G:p.R593G and c.2522T>A:p.L841Q (predicted as disease causing or damaging, found as compound heterzygotes in family 1) and c.2686C>T:p.R896X. (protein truncating, homozygous in family 2). The truncating variant has been previously reported in a Pakistani family affected by hypomaturation AI, however no other clinical phenotypes in the patients were reported (PMID: 21196691).

Patients in family 1 presented with proximal muscle weakness and/or growth retardation at ages under 7 years. One member of family 1 also had nephrolithiasis and localized enamel hypoplasia. Family 2 has consanguineous parents with one affected child which presented with hypoplastic amelogenesis imperfect in addition to dRTA. She also showed nephrocalcinosis.
Possible mitochondrial disorder - nuclear genes v2.7 CRLS1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: CRLS1.
Possible mitochondrial disorder - nuclear genes v2.7 CRLS1 Achchuthan Shanmugasundram Classified gene: CRLS1 as Amber List (moderate evidence)
Possible mitochondrial disorder - nuclear genes v2.7 CRLS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as it has been associated with mitochondrial disorders, as identified from three unrelated cases, and supported by functional evidence.
Possible mitochondrial disorder - nuclear genes v2.7 CRLS1 Achchuthan Shanmugasundram Gene: crls1 has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder - nuclear genes v2.6 CRLS1 Achchuthan Shanmugasundram edited their review of gene: CRLS1: Changed rating: GREEN
Mitochondrial disorders v3.12 CRLS1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: CRLS1.
Mitochondrial disorders v3.12 CRLS1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene should be rated GREEN as it has been associated with mitochondrial disorders, as identified from three unrelated cases, and supported by functional evidence.; to: Comment on list classification: This gene should be rated GREEN as it has been associated with mitochondrial disorders, as identified from three unrelated cases, and supported by functional evidence.
Mitochondrial disorders v3.12 CRLS1 Achchuthan Shanmugasundram Classified gene: CRLS1 as Amber List (moderate evidence)
Mitochondrial disorders v3.12 CRLS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as it has been associated with mitochondrial disorders, as identified from three unrelated cases, and supported by functional evidence.
Mitochondrial disorders v3.12 CRLS1 Achchuthan Shanmugasundram Gene: crls1 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v3.11 CRLS1 Achchuthan Shanmugasundram edited their review of gene: CRLS1: Changed rating: GREEN
Possible mitochondrial disorder - nuclear genes v2.6 CRLS1 Achchuthan Shanmugasundram gene: CRLS1 was added
gene: CRLS1 was added to Possible mitochondrial disorder - nuclear genes. Sources: Literature
Mode of inheritance for gene: CRLS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRLS1 were set to 35147173
Phenotypes for gene: CRLS1 were set to Combined oxidative phosphorylation deficiency 57, OMIM:620167
Review for gene: CRLS1 was set to AMBER
Added comment: Three individuals from two unrelated families were identified with the same homozygous variant in CRLS1 (p.Ile109Asn). They presented with a mitochondrial disorder characterized by an evolving pattern of cardiomyopathy, encephalopathy, bilateral auditory neuropathy spectrum disorder, bull’s eye maculopathy, diabetes insipidus, autonomic instability and low complex IV activity in skeletal muscle.

A fourth individual was identified with a compound heterozygous CRLS1 variant (p.Ala172Asp/ p.Leu217Phe) that presented with developmental regression beginning in late infancy, with acquired microcephaly, sensorineural hearing loss and impaired vision.

Functional studies using patient-derived fibroblasts provide evidence that CRLS1 variants cause mitochondrial disease.
Sources: Literature
Mitochondrial disorders v3.11 CRLS1 Achchuthan Shanmugasundram gene: CRLS1 was added
gene: CRLS1 was added to Mitochondrial disorders. Sources: Literature
Mode of inheritance for gene: CRLS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRLS1 were set to 35147173
Phenotypes for gene: CRLS1 were set to Combined oxidative phosphorylation deficiency 57, OMIM:620167
Review for gene: CRLS1 was set to AMBER
Added comment: Three individuals from two unrelated families were identified with the same homozygous variant in CRLS1 (p.Ile109Asn). They presented with a mitochondrial disorder characterized by an evolving pattern of cardiomyopathy, encephalopathy, bilateral auditory neuropathy spectrum disorder, bull’s eye maculopathy, diabetes insipidus, autonomic instability and low complex IV activity in skeletal muscle.

A fourth individual was identified with a compound heterozygous CRLS1 variant (p.Ala172Asp/ p.Leu217Phe) that presented with developmental regression beginning in late infancy, with acquired microcephaly, sensorineural hearing loss and impaired vision.

Functional studies using patient-derived fibroblasts provide evidence that CRLS1 variants cause mitochondrial disease.
Sources: Literature
Dilated and arrhythmogenic cardiomyopathy v2.7 RYR2 Arina Puzriakova Publications for gene: RYR2 were set to 20301310; 19926015; 17875969
Idiopathic ventricular fibrillation v1.2 RYR2 Arina Puzriakova Phenotypes for gene: RYR2 were changed from CPVT to Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, OMIM:115000; Ventricular tachycardia, catecholaminergic polymorphic, 1, OMIM:604772
Dilated Cardiomyopathy and conduction defects v1.82 RYR2 Arina Puzriakova Publications for gene: RYR2 were set to
Optic neuropathy v3.12 OPA1 Achchuthan Shanmugasundram Publications for gene: OPA1 were set to 15531309; 16158427; 17306754; 18065439; 18158317; 19029523; 20417570; 20157015; 21636302; 25012220; 25146916
Early onset or syndromic epilepsy v3.93 SEMA6B Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:35604360 reported new unrelated cases identified with heterozygous variants in SEMA6B. Out of 16 patients referred for ID clinic, 10 of them had epilepsy or myoclonus.

Functional studies of selected variants and shRNA knock down studies showed mislocalisation and abnormal protein function.
Early onset or syndromic epilepsy v3.93 SEMA6B Achchuthan Shanmugasundram Publications for gene: SEMA6B were set to 32169168; 35604360
Early onset or syndromic epilepsy v3.92 SEMA6B Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:35604360 reported new unrelated cases identified with heterozygous variants in SEMA6B. Out of 16 patients referred for ID clinic, 10 of them had epilepsy or myoclonus.

Functional studies of selected variants and shRNA knock down studies showed mislocalisation and abnormal protein function.
Early onset or syndromic epilepsy v3.92 SEMA6B Achchuthan Shanmugasundram Publications for gene: SEMA6B were set to 32169168; 35604360
Early onset or syndromic epilepsy v3.92 SEMA6B Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:35604360 reported new unrelated cases identified with heterozygous variants in SEMA6B. Out of 16 patients referred for ID clinic, 10 of them had epilepsy or myoclonus.

Functional studies of selected variants and shRNA knock down studies showed mislocalisation and abnormal protein function.
Early onset or syndromic epilepsy v3.92 SEMA6B Achchuthan Shanmugasundram Publications for gene: SEMA6B were set to 32169168
Intellectual disability v4.92 SEMA6B Achchuthan Shanmugasundram Classified gene: SEMA6B as Amber List (moderate evidence)
Intellectual disability v4.92 SEMA6B Achchuthan Shanmugasundram Gene: sema6b has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.92 SEMA6B Achchuthan Shanmugasundram Classified gene: SEMA6B as Amber List (moderate evidence)
Intellectual disability v4.92 SEMA6B Achchuthan Shanmugasundram Gene: sema6b has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.92 SEMA6B Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: SEMA6B.
Intellectual disability v4.92 SEMA6B Achchuthan Shanmugasundram Classified gene: SEMA6B as Amber List (moderate evidence)
Intellectual disability v4.92 SEMA6B Achchuthan Shanmugasundram Gene: sema6b has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.91 SEMA6B Achchuthan Shanmugasundram gene: SEMA6B was added
gene: SEMA6B was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: SEMA6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEMA6B were set to 35604360
Phenotypes for gene: SEMA6B were set to Intellectual disability, MONDO:0001071
Review for gene: SEMA6B was set to GREEN
Added comment: Comment on gene classification: This gene should be rated GREEN in this panel as monoallelic variants in this gene has been associated with a final diagnosis of intellectual disability (ID) in 11 unrelated cases.

PMID:35604360 reports 14 heterozygous variants (11 novel and 3 previously reported variants) observed in 16 unrelated individuals referred for ID. Out of these, 11 of them had a final diagnosis of ID. Heterozygous variants in SEMA6B has previously been reported in patients with progressive myoclonic epilepsy (MIM #618876) and there were no cases of ID reported before. This study indicated that the clinical spectrum is wider and included ID without epilepsy or myoclonus.

Functional studies of selected variants and shRNA knock down studies showed mislocalisation and abnormal protein function.
Sources: Literature
Intellectual disability v4.90 EMC1 Achchuthan Shanmugasundram Phenotypes for gene: EMC1 were changed from Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875 to Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875
Intellectual disability v4.90 EMC1 Achchuthan Shanmugasundram Phenotypes for gene: EMC1 were changed from Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875 to Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875
Intellectual disability v4.90 EMC1 Achchuthan Shanmugasundram Phenotypes for gene: EMC1 were changed from Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875 to Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875
Intellectual disability v4.90 EMC1 Achchuthan Shanmugasundram Phenotypes for gene: EMC1 were changed from Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875 to Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875
Intellectual disability v4.89 EMC1 Achchuthan Shanmugasundram Phenotypes for gene: EMC1 were changed from Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875 to Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875
Intellectual disability v4.89 EMC1 Achchuthan Shanmugasundram Phenotypes for gene: EMC1 were changed from Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875 to Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875
Intellectual disability v4.89 EMC1 Achchuthan Shanmugasundram Phenotypes for gene: EMC1 were changed from Cerebellar atrophy, visual impairment, and psychomotor retardation, MIM 616875; Cerebellar atrophy, visual impairment, and psychomotor retardation, 616875 to Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875
Likely inborn error of metabolism v3.7 GABRG2 Achchuthan Shanmugasundram Publications for gene: GABRG2 were set to 23708187; 16510738; 15342642; 34957497
Likely inborn error of metabolism v3.7 GABRG2 Achchuthan Shanmugasundram Publications for gene: GABRG2 were set to 23708187; 16510738; 15342642; 34957497
Likely inborn error of metabolism v3.7 GABRG2 Achchuthan Shanmugasundram Publications for gene: GABRG2 were set to 23708187; 16510738; 15342642; 34957497
Likely inborn error of metabolism v3.7 GABRG2 Achchuthan Shanmugasundram Publications for gene: GABRG2 were set to 23708187; 16510738; 15342642; 34957497
Likely inborn error of metabolism v3.7 GABRG2 Achchuthan Shanmugasundram Publications for gene: GABRG2 were set to 23708187; 16510738; 15342642; 34957497
Likely inborn error of metabolism v3.7 GABRG2 Achchuthan Shanmugasundram Publications for gene: GABRG2 were set to 23708187; 16510738; 15342642; 34957497
Likely inborn error of metabolism v3.7 GABRG2 Achchuthan Shanmugasundram Publications for gene: GABRG2 were set to 23708187; 16510738; 15342642
Undiagnosed metabolic disorders v1.572 GABRG2 Achchuthan Shanmugasundram Publications for gene: GABRG2 were set to 16510738; 15342642; 23708187
Early onset or syndromic epilepsy v3.91 GABRG2 Achchuthan Shanmugasundram Publications for gene: GABRG2 were set to 27066572; 11326275; 11326274; 34957497
Early onset or syndromic epilepsy v3.91 GABRG2 Achchuthan Shanmugasundram Publications for gene: GABRG2 were set to 27066572; 11326275; 11326274
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.9 POGLUT1 Sarah Leigh commented on gene: POGLUT1: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 21 POGLUT1 variants have been reported in at least 20 unrelated cases (PMID: 27807076; 31897643; 33861953). Supportive in vitro and in vivo functional studies were presented in PMID: 31897643.
Congenital muscular dystrophy v3.97 POGLUT1 Sarah Leigh Phenotypes for gene: POGLUT1 were changed from Muscular dystrophy, limb-girdle, autosomal recessive 21, OMIM:617232 to Muscular dystrophy, limb-girdle, autosomal recessive 21, OMIM:617232; autosomal recessive limb-girdle muscular dystrophy type 2R1, MONDO:0014977
Congenital muscular dystrophy v3.96 POGLUT1 Sarah Leigh Publications for gene: POGLUT1 were set to 27807076; 31897643
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.9 POGLUT1 Sarah Leigh Publications for gene: POGLUT1 were set to 27807076; 29034878
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.8 POGLUT1 Sarah Leigh Phenotypes for gene: POGLUT1 were changed from Muscular dystrophy, limb-girdle, autosomal recessive 21, 617232 to Muscular dystrophy, limb-girdle, autosomal recessive 21, OMIM:617232; autosomal recessive limb-girdle muscular dystrophy type 2R1, MONDO:0014977
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.7 POGLUT1 Sarah Leigh Classified gene: POGLUT1 as Amber List (moderate evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.7 POGLUT1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.7 POGLUT1 Sarah Leigh Gene: poglut1 has been classified as Amber List (Moderate Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.6 POGLUT1 Sarah Leigh reviewed gene: POGLUT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31897643; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 21, OMIM:617232, autosomal recessive limb-girdle muscular dystrophy type 2R1, MONDO:0014977; Mode of inheritance: None
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.6 POGLUT1 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: POGLUT1.
Intellectual disability v4.88 CPLX1 Sarah Leigh Entity copied from Genetic epilepsy syndromes v3.90
Intellectual disability v4.88 CPLX1 Sarah Leigh gene: CPLX1 was added
gene: CPLX1 was added to Intellectual disability. Sources: Expert list,Expert Review Amber
Q1_23_promote_green tags were added to gene: CPLX1.
Mode of inheritance for gene: CPLX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPLX1 were set to 26539891; 28422131
Phenotypes for gene: CPLX1 were set to Developmental and epileptic encephalopathy 63, OMIM:617976; developmental and epileptic encephalopathy, 63, MONDO:0033372
Early onset or syndromic epilepsy v3.90 CPLX1 Sarah Leigh edited their review of gene: CPLX1: Added comment: Associated with Developmental and epileptic encephalopathy 63 (OMIM:617976), but not associated with a phenotype in Gen2Phen. Three CPLX1 variants have been reported in three unrelated cases, who all have intellectual disability and seizures (PMID:26539891; 28422131).; Changed rating: GREEN
Early onset or syndromic epilepsy v3.90 CPLX1 Sarah Leigh Classified gene: CPLX1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.90 CPLX1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v3.90 CPLX1 Sarah Leigh Gene: cplx1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v3.89 CPLX1 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: CPLX1.
Early onset or syndromic epilepsy v3.89 CPLX1 Sarah Leigh Phenotypes for gene: CPLX1 were changed from Epileptic encephalopathy, early infantile, 63, MIM# 617976 to Developmental and epileptic encephalopathy 63, OMIM:617976; developmental and epileptic encephalopathy, 63, MONDO:0033372
Early onset or syndromic epilepsy v3.88 CPLX1 Sarah Leigh Classified gene: CPLX1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.88 CPLX1 Sarah Leigh Gene: cplx1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.87 STXBP1 Sarah Leigh Tag Q1_23_MOI tag was added to gene: STXBP1.
Intellectual disability v4.87 STXBP1 Sarah Leigh Added comment: Comment on mode of inheritance: Due to the report of biallelic STXBP1 variants in a family with encephalopathy, developmental delay, intellectual disability and epilepsy (PMID: 31855252), the mode of inheritance for this gene should be changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Intellectual disability v4.87 STXBP1 Sarah Leigh Mode of inheritance for gene: STXBP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.86 STXBP1 Sarah Leigh Phenotypes for gene: STXBP1 were changed from Epileptic encephalopathy, early infantile, 4, 612164 (2); ANGELMAN/PITT HOPKINS SYNDROME-LIKE DISORDER to Developmental and epileptic encephalopathy 4, OMIM:612164; developmental and epileptic encephalopathy, 4, MONDO:0012812
Intellectual disability v4.85 STXBP1 Sarah Leigh Publications for gene: STXBP1 were set to 31855252; 18469812; 19557857
Early onset or syndromic epilepsy v3.87 STXBP1 Sarah Leigh Publications for gene: STXBP1 were set to 31855252; 18469812; 19557857
Intellectual disability v4.84 STXBP1 Sarah Leigh Publications for gene: STXBP1 were set to
Intellectual disability v4.83 STXBP1 Sarah Leigh reviewed gene: STXBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v3.86 STXBP1 Sarah Leigh Added comment: Comment on mode of inheritance: Due to the report of biallelic STXBP1 variants in a family with encephalopathy, developmental delay, intellectual disability and epilepsy (PMID: 31855252), the mode of inheritance for this gene should be changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Early onset or syndromic epilepsy v3.86 STXBP1 Sarah Leigh Mode of inheritance for gene: STXBP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v3.85 STXBP1 Sarah Leigh reviewed gene: STXBP1: Rating: ; Mode of pathogenicity: None; Publications: 31855252, 35190816; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Dilated Cardiomyopathy and conduction defects v1.81 PSEN1 Dmitrijs Rots reviewed gene: PSEN1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy; Mode of inheritance: None
Early onset or syndromic epilepsy v3.85 STXBP1 Sarah Leigh Tag Q1_23_MOI tag was added to gene: STXBP1.
Arthrogryposis v4.10 SMN1 Achchuthan Shanmugasundram Phenotypes for gene: SMN1 were changed from arthrogryposis; SMA 0; Spinal muscular atrophy-1, 253300; Spinal muscular atrophy-2, 253550; Spinal muscular atrophy-3, 253400; Spinal muscular atrophy-4, 271150 to arthrogryposis; Spinal muscular atrophy-1, 253300; Spinal muscular atrophy-2, 253550; Spinal muscular atrophy-3, 253400; Spinal muscular atrophy-4, 271150
Hereditary neuropathy v1.461 SMN1 Achchuthan Shanmugasundram Phenotypes for gene: SMN1 were changed from Spinal muscular atrophy to Spinal muscular atrophy-3, OMIM:253400; Spinal muscular atrophy-4, OMIM:271150; Spinal muscular atrophy-2, OMIM:253550; Spinal muscular atrophy-1, OMIM:253300
Hereditary neuropathy or pain disorder v2.22 SMN1 Achchuthan Shanmugasundram Phenotypes for gene: SMN1 were changed from Spinal muscular atrophy to Spinal muscular atrophy-3, OMIM:253400; Spinal muscular atrophy-4, OMIM:271150; Spinal muscular atrophy-2, OMIM:253550; Spinal muscular atrophy-1, OMIM:253300
Intellectual disability v4.83 TASP1 Achchuthan Shanmugasundram Publications for gene: TASP1 were set to 29633245; 31209944; 31350873; 35512351
Intellectual disability v4.83 TASP1 Achchuthan Shanmugasundram Publications for gene: TASP1 were set to 29633245; 31209944; 31350873; 35512351
Intellectual disability v4.83 TASP1 Achchuthan Shanmugasundram Publications for gene: TASP1 were set to 29633245; 31209944; 31350873; 35512351
Intellectual disability v4.83 TASP1 Achchuthan Shanmugasundram Publications for gene: TASP1 were set to 29633245; 31209944; 31350873; 35512351
Intellectual disability v4.83 TASP1 Achchuthan Shanmugasundram Publications for gene: TASP1 were set to 29633245; 31209944; 31350873; 35512351
Intellectual disability v4.83 TASP1 Achchuthan Shanmugasundram Publications for gene: TASP1 were set to 31209944; 31350873
Intellectual disability v4.82 TASP1 Achchuthan Shanmugasundram Phenotypes for gene: TASP1 were changed from Suleiman-El-Hattab syndrome, OMIM:618950 to Suleiman-El-Hattab syndrome, OMIM:618950
Intellectual disability v4.82 TASP1 Achchuthan Shanmugasundram Phenotypes for gene: TASP1 were changed from Suleiman-El-Hattab syndrome, OMIM:618950 to Suleiman-El-Hattab syndrome, OMIM:618950
Intellectual disability v4.82 TASP1 Achchuthan Shanmugasundram Phenotypes for gene: TASP1 were changed from Suleiman-El-Hattab syndrome, OMIM:618950 to Suleiman-El-Hattab syndrome, OMIM:618950
Intellectual disability v4.82 TASP1 Achchuthan Shanmugasundram Phenotypes for gene: TASP1 were changed from Suleiman-El-Hattab syndrome, OMIM:618950 to Suleiman-El-Hattab syndrome, OMIM:618950
Intellectual disability v4.81 TASP1 Achchuthan Shanmugasundram Phenotypes for gene: TASP1 were changed from Suleiman-El-Hattab syndrome, OMIM:618950 to Suleiman-El-Hattab syndrome, OMIM:618950
Intellectual disability v4.81 TASP1 Achchuthan Shanmugasundram Phenotypes for gene: TASP1 were changed from Suleiman-El-Hattab syndrome, OMIM:618950 to Suleiman-El-Hattab syndrome, OMIM:618950
Intellectual disability v4.81 TASP1 Achchuthan Shanmugasundram Phenotypes for gene: TASP1 were changed from Suleiman-El-Hattab syndrome, OMIM:618950 to Suleiman-El-Hattab syndrome, OMIM:618950
Intellectual disability v4.81 TASP1 Achchuthan Shanmugasundram Phenotypes for gene: TASP1 were changed from Developmental delay; microcephaly; dysmorphic features; congenital abnormalities to Suleiman-El-Hattab syndrome, OMIM:618950
Early onset or syndromic epilepsy v3.85 STXBP1 Sarah Leigh Phenotypes for gene: STXBP1 were changed from Epileptic encephalopathy, early infantile, 4 to Developmental and epileptic encephalopathy 4, OMIM:612164; developmental and epileptic encephalopathy, 4, MONDO:0012812
Early onset or syndromic epilepsy v3.84 STXBP1 Sarah Leigh Publications for gene: STXBP1 were set to Saitsu et al (2008) Nature Genet 40 (6): 782-788
Early onset or syndromic epilepsy v3.83 EXT2 Sarah Leigh edited their review of gene: EXT2: Added comment: Associated Seizures, scoliosis, and macrocephaly syndrome in OMIM, but not associated with an equivalent phenotype in Gen2Phen. Six EXT2 variants have been reported four unrelated cases (PMID:26246518; 30288735; 30997052; 30075207).; Changed rating: GREEN
Early onset or syndromic epilepsy v3.83 EXT2 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: EXT2.
Early onset or syndromic epilepsy v3.83 EXT2 Sarah Leigh Classified gene: EXT2 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.83 EXT2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v3.83 EXT2 Sarah Leigh Gene: ext2 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v3.82 EXT2 Sarah Leigh Phenotypes for gene: EXT2 were changed from Seizures, scoliosis, and macrocephaly syndrome, 616682 to Seizures, scoliosis, and macrocephaly syndrome, OMIM:616682; seizures-scoliosis-macrocephaly syndrome, MONDO:0014731
Early onset or syndromic epilepsy v3.81 EXT2 Sarah Leigh Publications for gene: EXT2 were set to 26246518; 30997052; 30288735; 30075207; 30806661
Early onset or syndromic epilepsy v3.80 EXT2 Sarah Leigh Publications for gene: EXT2 were set to 26246518; 30997052; 30288735; 30075207
Congenital adrenal hypoplasia v3.6 CYP11B2 Achchuthan Shanmugasundram commented on gene: CYP11B2: 'Treatable' tag has been added as children with ASD achieved catchup growth when treated with fludrocortisone.
Congenital adrenal hypoplasia v3.6 CYP11B2 Achchuthan Shanmugasundram Tag treatable tag was added to gene: CYP11B2.
Adult onset neurodegenerative disorder v3.53 MAG Arina Puzriakova Tag watchlist was removed from gene: MAG.
Hereditary neuropathy or pain disorder v2.21 MAG Arina Puzriakova Entity copied from Hereditary spastic paraplegia - childhood onset v3.18
Hereditary neuropathy or pain disorder v2.21 MAG Arina Puzriakova gene: MAG was added
gene: MAG was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,Expert Review Amber,Literature,Yorkshire and North East GLH,London North GLH
Q1_23_promote_green tags were added to gene: MAG.
Mode of inheritance for gene: MAG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAG were set to 24482476; 26179919; 31402626; 32629324; 32340215
Phenotypes for gene: MAG were set to Spastic paraplegia 75, autosomal recessive, OMIM:616680
Optic neuropathy v3.11 MAG Arina Puzriakova Entity copied from Hereditary spastic paraplegia - childhood onset v3.18
Optic neuropathy v3.11 MAG Arina Puzriakova gene: MAG was added
gene: MAG was added to Optic neuropathy. Sources: Yorkshire and North East GLH,London North GLH,Literature,Expert Review Amber,NHS GMS
Q1_23_promote_green tags were added to gene: MAG.
Mode of inheritance for gene: MAG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAG were set to 24482476; 26179919; 31402626; 32629324; 32340215
Phenotypes for gene: MAG were set to Spastic paraplegia 75, autosomal recessive, OMIM:616680
Ataxia and cerebellar anomalies - narrow panel v3.39 MAG Arina Puzriakova Entity copied from Hereditary spastic paraplegia - childhood onset v3.18
Ataxia and cerebellar anomalies - narrow panel v3.39 MAG Arina Puzriakova gene: MAG was added
gene: MAG was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Yorkshire and North East GLH,London North GLH,Literature,Expert Review Amber,NHS GMS
Q1_23_promote_green tags were added to gene: MAG.
Mode of inheritance for gene: MAG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAG were set to 24482476; 26179919; 31402626; 32629324; 32340215
Phenotypes for gene: MAG were set to Spastic paraplegia 75, autosomal recessive, OMIM:616680
Childhood onset hereditary spastic paraplegia v3.18 MAG Arina Puzriakova Tag Q1_23_promote_green tag was added to gene: MAG.
Hereditary spastic paraplegia v1.302 MAG Arina Puzriakova Classified gene: MAG as Green List (high evidence)
Hereditary spastic paraplegia v1.302 MAG Arina Puzriakova Gene: mag has been classified as Green List (High Evidence).
Adult onset neurodegenerative disorder v3.53 MAG Arina Puzriakova Publications for gene: MAG were set to 24482476; 26179919
Adult onset hereditary spastic paraplegia v2.15 MAG Arina Puzriakova Publications for gene: MAG were set to 26179919; 24482476
Hereditary spastic paraplegia v1.301 MAG Arina Puzriakova Publications for gene: MAG were set to 24482476; 26179919
Adult onset hereditary spastic paraplegia v2.14 MAG Arina Puzriakova Classified gene: MAG as Red List (low evidence)
Adult onset hereditary spastic paraplegia v2.14 MAG Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as onset is in early childhood
Adult onset hereditary spastic paraplegia v2.14 MAG Arina Puzriakova Gene: mag has been classified as Red List (Low Evidence).
Hereditary spastic paraplegia v1.300 MAG Arina Puzriakova Classified gene: MAG as Amber List (moderate evidence)
Hereditary spastic paraplegia v1.300 MAG Arina Puzriakova Added comment: Comment on list classification: Promoted from Amber to Green and removed watchlist tag as there are now at least 12 individuals from 8 families with biallelic variants in this gene. Clinical features are characterised by spasticity (9/13), neuropathy (8/13), optic atrophy (7/13), variable cognitive deficits (7/13), and cerebellar signs (10/13) including ataxia in some (8/13) although 3/10 showed normal brain MRI results.
Hereditary spastic paraplegia v1.300 MAG Arina Puzriakova Gene: mag has been classified as Amber List (Moderate Evidence).
Hereditary spastic paraplegia v1.299 MAG Arina Puzriakova Tag watchlist was removed from gene: MAG.
Childhood onset hereditary spastic paraplegia v3.18 MAG Arina Puzriakova Publications for gene: MAG were set to 26179919; 24482476
Childhood onset hereditary spastic paraplegia v3.17 MAG Arina Puzriakova Classified gene: MAG as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v3.17 MAG Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.

At least 12 individuals from 8 families have been identified with biallelic variants in this gene. Clinical features are characterised by spasticity (9/13), neuropathy (8/13), optic atrophy (7/13), variable cognitive deficits (7/13), and cerebellar signs (10/13) including ataxia in some (8/13) although 3/10 showed normal brain MRI results.
Childhood onset hereditary spastic paraplegia v3.17 MAG Arina Puzriakova Gene: mag has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v3.52 MAG Arina Puzriakova Phenotypes for gene: MAG were changed from Spastic paraplegia 75, autosomal recessive, 616680 to Spastic paraplegia 75, autosomal recessive, OMIM:616680
Adult onset hereditary spastic paraplegia v2.13 MAG Arina Puzriakova Phenotypes for gene: MAG were changed from Spastic paraplegia 75, autosomal recessive, 616680 to Spastic paraplegia 75, autosomal recessive, OMIM:616680
Hereditary spastic paraplegia v1.299 MAG Arina Puzriakova Phenotypes for gene: MAG were changed from Spastic paraplegia 75, autosomal recessive, 616680 to Spastic paraplegia 75, autosomal recessive, OMIM:616680
Childhood onset hereditary spastic paraplegia v3.16 MAG Arina Puzriakova Phenotypes for gene: MAG were changed from Spastic paraplegia 75, autosomal recessive, 616680 to Spastic paraplegia 75, autosomal recessive, OMIM:616680
Childhood onset hereditary spastic paraplegia v3.15 KLC2 Arina Puzriakova Classified gene: KLC2 as Red List (low evidence)
Childhood onset hereditary spastic paraplegia v3.15 KLC2 Arina Puzriakova Added comment: Comment on list classification: Rating Red as this would not currently be picked up by the pipeline but will make a note in our internal log of additional entities to investigate methods of incorporating this variants in the future.
Childhood onset hereditary spastic paraplegia v3.15 KLC2 Arina Puzriakova Gene: klc2 has been classified as Red List (Low Evidence).
Childhood onset hereditary spastic paraplegia v3.14 KLC2 Arina Puzriakova Phenotypes for gene: KLC2 were changed from Spastic paraplegia, optic atrophy, and neuropathy, MIM#609541 to Spastic paraplegia, optic atrophy, and neuropathy, OMIM:609541
Childhood onset hereditary spastic paraplegia v3.13 KLC2 Arina Puzriakova Publications for gene: KLC2 were set to
Childhood onset hereditary spastic paraplegia v3.12 KLC2 Arina Puzriakova Tag currently-ngs-unreportable tag was added to gene: KLC2.
Intellectual disability v4.80 FOXP4 Achchuthan Shanmugasundram Publications for gene: FOXP4 were set to 33110267; 36301021; 36646976
Intellectual disability v4.81 FOXP4 Achchuthan Shanmugasundram Publications for gene: FOXP4 were set to 33110267; 36301021; 36646976
Intellectual disability v4.81 FOXP4 Achchuthan Shanmugasundram Publications for gene: FOXP4 were set to 33110267; 36301021; 36646976
Intellectual disability v4.81 FOXP4 Achchuthan Shanmugasundram Publications for gene: FOXP4 were set to 33110267; 36301021; 36646976
Intellectual disability v4.81 FOXP4 Achchuthan Shanmugasundram Publications for gene: FOXP4 were set to 33110267; 36301021; 36646976
Intellectual disability v4.80 FOXP4 Achchuthan Shanmugasundram Publications for gene: FOXP4 were set to 33110267; 36301021; 36646976
Intellectual disability v4.80 FOXP4 Achchuthan Shanmugasundram Publications for gene: FOXP4 were set to 33110267; 36301021; 36646976
Intellectual disability v4.80 FOXP4 Achchuthan Shanmugasundram Publications for gene: FOXP4 were set to 33110267; 36301021; 36646976
Intellectual disability v4.80 FOXP4 Achchuthan Shanmugasundram Publications for gene: FOXP4 were set to 33110267
Intellectual disability v4.79 FOXP4 Achchuthan Shanmugasundram reviewed gene: FOXP4: Rating: AMBER; Mode of pathogenicity: None; Publications: 33110267, 36301021, 36646976; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.79 FOXP4 Achchuthan Shanmugasundram Deleted their review
Intellectual disability v4.79 FOXP4 Achchuthan Shanmugasundram edited their review of gene: FOXP4: Changed publications to: 33110267, 36301021, 36646976
Intellectual disability v4.79 FOXP4 Achchuthan Shanmugasundram reviewed gene: FOXP4: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: 33110267, 36301021, 36646976; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.79 PRRT2 Arina Puzriakova commented on gene: PRRT2
Intellectual disability v4.79 PRRT2 Arina Puzriakova Publications for gene: PRRT2 were set to 21937992; 23352743; 25595153; 23398397; 23126439
Congenital adrenal hypoplasia v3.6 CYP11B2 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: CYP11B2.
Congenital adrenal hypoplasia v3.6 CYP11B2 Achchuthan Shanmugasundram edited their review of gene: CYP11B2: Changed phenotypes to: Hypoaldosteronism, congenital, due to CMO I deficiency, OMIM:203400, Hypoaldosteronism, congenital, due to CMO II deficiency, OMIM:610600, Aldosterone to renin ratio raised
Congenital adrenal hypoplasia v3.6 CYP11B2 Achchuthan Shanmugasundram Phenotypes for gene: CYP11B2 were changed from Hypoaldosteronism, congenital, due to CMO I deficiency, OMIM:203400; Hypoaldosteronism, congenital, due to CMO II deficiency, OMIM:610600 to Hypoaldosteronism, congenital, due to CMO I deficiency, OMIM:203400; Hypoaldosteronism, congenital, due to CMO II deficiency, OMIM:610600; Aldosterone to renin ratio raised
Congenital adrenal hypoplasia v3.5 CYP11B2 Achchuthan Shanmugasundram Phenotypes for gene: CYP11B2 were changed from Hypoaldosteronism; Hyponatremia; Hyperkalemia; Increased serum renin; Dehydration; Failure to thrive to Hypoaldosteronism, congenital, due to CMO I deficiency, OMIM:203400; Hypoaldosteronism, congenital, due to CMO II deficiency, OMIM:610600
Congenital adrenal hypoplasia v3.4 CYP11B2 Achchuthan Shanmugasundram Publications for gene: CYP11B2 were set to 1594605; 8439335; 9360501; 12788848
Congenital adrenal hypoplasia v3.3 CYP11B2 Achchuthan Shanmugasundram Classified gene: CYP11B2 as Amber List (moderate evidence)
Congenital adrenal hypoplasia v3.3 CYP11B2 Achchuthan Shanmugasundram Gene: cyp11b2 has been classified as Amber List (Moderate Evidence).
Congenital adrenal hypoplasia v3.2 CYP11B2 Achchuthan Shanmugasundram reviewed gene: CYP11B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 1594605, 8439335, 9360501, 12788848, 31302112, 33098647, 33438832, 34415991, 35848593; Phenotypes: Hypoaldosteronism, congenital, due to CMO I deficiency, OMIM:203400, Hypoaldosteronism, congenital, due to CMO II deficiency, OMIM:610600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v3.5 TBX1 Arina Puzriakova Tag Q1_23_NHS_review tag was added to gene: TBX1.
Skeletal dysplasia v3.9 DDRGK1 Achchuthan Shanmugasundram Classified gene: DDRGK1 as Amber List (moderate evidence)
Skeletal dysplasia v3.9 DDRGK1 Achchuthan Shanmugasundram Gene: ddrgk1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v3.9 DDRGK1 Achchuthan Shanmugasundram Classified gene: DDRGK1 as Amber List (moderate evidence)
Skeletal dysplasia v3.9 DDRGK1 Achchuthan Shanmugasundram Gene: ddrgk1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v3.8 DDRGK1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: DDRGK1.
Skeletal dysplasia v3.8 DDRGK1 Achchuthan Shanmugasundram gene: DDRGK1 was added
gene: DDRGK1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: DDRGK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDRGK1 were set to 28263186; 35377455; 35670300; 36243336
Phenotypes for gene: DDRGK1 were set to Spondyloepimetaphyseal dysplasia, Shohat type, OMIM:602557
Review for gene: DDRGK1 was set to GREEN
Added comment: Comment on gene classification: This gene should be rated GREEN as it has been associated with Spondyloepimetaphyseal dysplasia, Shohat type from seven unrelated cases from multiple ethnicities and supported by functional studies.

PMID:28263186 reported six individuals from three different families of Iraqi Jewish descent (three patients from family 1 and one individual each from families 2-4) identified with homozygous c.408+1G>A donor splice site loss-of-function mutation in DDRGK1 and presented with Shohat-type spondyloepimetaphyseal dysplasia (SEMD). It is a skeletal dysplasia that affects cartilage development.

PMID: 35670300 reported two unrelated cases of Moroccan descent identified with homozygous missense variant c.406G>A and presented with SEMD. PMID:36243336 reported an Omani female patient identified with the same homozygous variant as the Iraqi cases and was reported with SEMD.

In addition, studies on both zebrafish and mouse models confirms the physiological role of DDRGK1 in the development and maintenance of the growth plate cartilage and deficiency of DDRGK1 recapitulate the clinical phenotype of short stature and joint abnormalities observed in patients with Shohat type SEMD (PMID:28263186; PMID:35377455).

This gene has been associated with relevant phenotype in OMIM (MIM #602557), but not in Gene2Phenotype.
Sources: Literature
Early onset or syndromic epilepsy v3.79 FOXRED1 Sarah Leigh Classified gene: FOXRED1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.79 FOXRED1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v3.79 FOXRED1 Sarah Leigh Gene: foxred1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v3.78 FOXRED1 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: FOXRED1.
Early onset or syndromic epilepsy v3.78 FOXRED1 Sarah Leigh edited their review of gene: FOXRED1: Added comment: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. At least eleven variants have been reported in seven unrelated cases of Mitochondrial complex I deficiency, nuclear type 19, OMIM:618241 (20858599;20818383;27215383;31434271;30723688;33613441). Seizures were evident in six of these cases.; Changed rating: GREEN
Early onset or syndromic epilepsy v3.78 FOXRED1 Sarah Leigh Publications for gene: FOXRED1 were set to 20858599; 20818383; 27215383; 31434271; 30723688
Early onset or syndromic epilepsy v3.77 FOXRED1 Sarah Leigh Publications for gene: FOXRED1 were set to 20858599; 20818383; 27215383; 31434271
Early onset or syndromic epilepsy v3.76 FOXRED1 Sarah Leigh Mode of inheritance for gene: FOXRED1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v3.75 FOXRED1 Sarah Leigh Publications for gene: FOXRED1 were set to 20858599, 20818383; 27215383; 31434271
Intellectual disability v4.78 FOXRED1 Sarah Leigh Phenotypes for gene: FOXRED1 were changed from MITOCHONDRIAL COMPLEX I DEFICIENCY to Mitochondrial complex I deficiency, nuclear type 19, OMIM:618241; mitochondrial complex 1 deficiency, nuclear type 19, MONDO:0032624
Early onset or syndromic epilepsy v3.74 FOXRED1 Sarah Leigh Phenotypes for gene: FOXRED1 were changed from to Mitochondrial complex I deficiency, nuclear type 19, OMIM:618241; mitochondrial complex 1 deficiency, nuclear type 19, MONDO:0032624
Early onset or syndromic epilepsy v3.73 FOXRED1 Sarah Leigh Publications for gene: FOXRED1 were set to
Early onset or syndromic epilepsy v3.72 GRIA2 Sarah Leigh Classified gene: GRIA2 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.72 GRIA2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v3.72 GRIA2 Sarah Leigh Gene: gria2 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v3.71 GRIA2 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: GRIA2.
Early onset or syndromic epilepsy v3.71 GRIA2 Sarah Leigh reviewed gene: GRIA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v4.77 GRIA2 Sarah Leigh Publications for gene: GRIA2 were set to 28725178; 26350204; 24896178; 22669415; 28630856; 31300657
Intellectual disability v4.76 GRIA2 Sarah Leigh Phenotypes for gene: GRIA2 were changed from Epileptic encephalopathy intellectual disability stereotypic hand movements; Neurodevelopmental disorder with language impairment and behavioral abnormalities MIM#618917 to Neurodevelopmental disorder with language impairment and behavioral abnormalities, OMIM:618917; neurodevelopmental disorder with language impairment and behavioral abnormalities, MONDO:0030060
Early onset or syndromic epilepsy v3.71 GRIA2 Sarah Leigh Phenotypes for gene: GRIA2 were changed from Intellectual disability; Seizures; myoclonic seizures; status epilepticus; tonic-clonic seizures; focal seizures to Neurodevelopmental disorder with language impairment and behavioral abnormalities, OMIM:618917; neurodevelopmental disorder with language impairment and behavioral abnormalities, MONDO:0030060
Early onset or syndromic epilepsy v3.70 MAGI2 Sarah Leigh changed review comment from: Comment on list classification: There is not enough evidence for this gene to be rated GREEN at the next major review.; to: Comment on list classification: There is not enough evidence for this gene to be rated GREEN on this panel.
Early onset or syndromic epilepsy v3.70 MAGI2 Sarah Leigh Classified gene: MAGI2 as Green List (high evidence)
Early onset or syndromic epilepsy v3.70 MAGI2 Sarah Leigh Added comment: Comment on list classification: There is not enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v3.70 MAGI2 Sarah Leigh Gene: magi2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v3.69 MAGI2 Sarah Leigh Tag Q1_23_demote_red tag was added to gene: MAGI2.
Early onset or syndromic epilepsy v3.69 MAGI2 Sarah Leigh edited their review of gene: MAGI2: Added comment: The association of MAGI2 deletions with epilepsy is disputed according to the ClinGen Epilepsy Gene Curation Expert Panel report (https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_7d622b88-9c77-47f8-93b1-808517da0cff-2018-06-19T160000.000Z?page=1&size=25&search= ). This expert panel outlines that although some of the deletions seen in epilepsy patients encompases MAGI2, other do not, suggesting the presence of another locus responsible for the epilepsy. Furthermore, no single-gene deletions or single nucleotide variants have been reported in MAGI2 in individuals with epilepsy.; Changed rating: RED
Early onset or syndromic epilepsy v3.69 MAGI2 Sarah Leigh Publications for gene: MAGI2 were set to 18565486; 27932480; 21694734
Early onset or syndromic epilepsy v3.68 MAGI2 Sarah Leigh Publications for gene: MAGI2 were set to 18565486; 27932480
Severe microcephaly v3.8 NUP214 Sarah Leigh Entity copied from Genetic epilepsy syndromes v3.67
Severe microcephaly v3.8 NUP214 Sarah Leigh gene: NUP214 was added
gene: NUP214 was added to Severe microcephaly. Sources: Expert list,Expert Review Amber
Q1_23_promote_green tags were added to gene: NUP214.
Mode of inheritance for gene: NUP214 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP214 were set to 31178128; 30758658
Phenotypes for gene: NUP214 were set to Encephalopathy, acute, infection-induced, susceptibility to, 9, OMIM:618426; encephalopathy, acute, infection-induced, susceptibility to, 9, MONDO:0032742
Early onset or syndromic epilepsy v3.67 NUP214 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: NUP214.
Early onset or syndromic epilepsy v3.67 NUP214 Sarah Leigh edited their review of gene: NUP214: Added comment: Associated with Encephalopathy, acute, infection-induced, susceptibility to, 9, (OMIM:618426) and as strong Gen2Phen gene for Acute Febrile Encephalopathy. Four NUP214 variants have been reported in three unrelated families (PMID: 31178128; 30758658). Patient fibroblasts homozygous for rs1564175808 showed dysmorphic nuclei with an abnormal surface morphology and dramatic disruption of NUP214 localization from the nuclear rim similar to that observed in cells with knockdown of the NUP214 gene (PMID: 30758658). Developmental delay, epilespy and progressive severe microcephaly were reported in the three families reported above.; Changed rating: GREEN
Early onset or syndromic epilepsy v3.67 NUP214 Sarah Leigh Phenotypes for gene: NUP214 were changed from Encephalopathy, acute, infection-induced, susceptibility to, 9, MIM# 618426; epileptic encephalopathy; developmental regression; microcephaly to Encephalopathy, acute, infection-induced, susceptibility to, 9, OMIM:618426; encephalopathy, acute, infection-induced, susceptibility to, 9, MONDO:0032742
Early onset or syndromic epilepsy v3.66 NUP214 Sarah Leigh Classified gene: NUP214 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.66 NUP214 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v3.66 NUP214 Sarah Leigh Gene: nup214 has been classified as Amber List (Moderate Evidence).
Dilated and arrhythmogenic cardiomyopathy v2.6 LMNA Achchuthan Shanmugasundram Publications for gene: LMNA were set to 20186049; 27532257
Arrhythmogenic right ventricular cardiomyopathy v3.3 LMNA Achchuthan Shanmugasundram Publications for gene: LMNA were set to
Dilated and arrhythmogenic cardiomyopathy v2.5 DSP Achchuthan Shanmugasundram Publications for gene: DSP were set to 23500315; 27532257
Arrhythmogenic right ventricular cardiomyopathy v3.2 DSP Achchuthan Shanmugasundram Publications for gene: DSP were set to 27532257; 23500315
Albinism or congenital nystagmus v2.4 ROBO1 Achchuthan Shanmugasundram gene: ROBO1 was added
gene: ROBO1 was added to Albinism or congenital nystagmus. Sources: Literature
Mode of inheritance for gene: ROBO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ROBO1 were set to 35348658
Phenotypes for gene: ROBO1 were set to nystagmus, congenital, autosomal recessive, MONDO:0009762
Review for gene: ROBO1 was set to RED
Added comment: Comment on classification of gene: This gene should be rated RED as this gene has been associated with nystagmus from only one family.

PMID:35348658 reported three male siblings from the same family with nystagmus and they were identified with a homozygous missense variant p.Ser1522Leu.

This gene has not yet been associated with any phenotypes either in OMIM or Gene2Phenotype.
Sources: Literature
Intellectual disability v4.75 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.75 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: ROBO1.
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram changed review comment from: Comment on gene classification: This gene should be rated green as this gene has been associated with intellectual disability from six unrelated cases. However, the MOI should be set as "BIALLELIC, autosomal or pseudoautosomal" as five of these cases were reported with biallelic variants and only one case was reported with monoallelic variant.

PMID:28286008 reported a boy with compound heterozygous variants that was presented with developmental delay in 13 months and had severe intellectual disability and hyperactivity at nine years of age. He was nonverbal and wheelchair dependent because of spastic diplegia and ataxia.

PMID:30692597 reported a five year old boy identified with a homozygous ROBO1 variant who had combined pituitary hormone deficiency, psychomotor developmental delay, severe intellectual disability, sensorineural hearing loss, strabismus and characteristic facial features.

PMID:35227688 reported eight patients including the boy reported in PMID:30692597. Of the other seven patients, three were presented with intellectual disability. Of these three patients, two harboured compound heterozygous and one harboured homozygous variants.

PMID:35348658 reported a patient identified with monoallelic de novo variant (p.D422G) who presented with early-onset epileptic encephalopathy and had severe developmental delay.

This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype.; to: Comment on gene classification: This gene should be rated green as this gene has been associated with intellectual disability from six unrelated cases. However, the MOI should be set as "BIALLELIC, autosomal or pseudoautosomal" as five of these cases were reported with biallelic variants and only one case was reported with monoallelic variant.

PMID:28286008 reported a boy with compound heterozygous variants that was presented with developmental delay in 13 months and had severe intellectual disability and hyperactivity at nine years of age. He was nonverbal and wheelchair dependent because of spastic diplegia and ataxia.

PMID:30692597 reported a five year old boy identified with a homozygous ROBO1 variant who had combined pituitary hormone deficiency, psychomotor developmental delay, severe intellectual disability, sensorineural hearing loss, strabismus and characteristic facial features.

PMID:35227688 reported eight patients including the boy reported in PMID:30692597. Of the other seven patients, three were presented with intellectual disability. Of these three patients, two harboured compound heterozygous and one harboured homozygous variants.

PMID:35348658 reported a patient identified with monoallelic de novo variant (p.D422G) who presented with early-onset epileptic encephalopathy and had severe developmental delay.

This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype.
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.76 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.75 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.75 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.75 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.74 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.75 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.74 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.74 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.73 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.73 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Classified gene: ROBO1 as Amber List (moderate evidence)
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Gene: robo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Classified gene: ROBO1 as Amber List (moderate evidence)
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Gene: robo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Classified gene: ROBO1 as Amber List (moderate evidence)
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Gene: robo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Classified gene: ROBO1 as Amber List (moderate evidence)
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Gene: robo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.70 ROBO1 Achchuthan Shanmugasundram Classified gene: ROBO1 as Amber List (moderate evidence)
Intellectual disability v4.70 ROBO1 Achchuthan Shanmugasundram Gene: robo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.70 ROBO1 Achchuthan Shanmugasundram Classified gene: ROBO1 as Amber List (moderate evidence)
Intellectual disability v4.70 ROBO1 Achchuthan Shanmugasundram Gene: robo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.69 ROBO1 Achchuthan Shanmugasundram reviewed gene: ROBO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28286008, 30692597, 35227688, 35348658; Phenotypes: intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inherited renal cancer v1.23 ELOC Achchuthan Shanmugasundram changed review comment from: Comment on gene classification: This gene should be rated red as there is only one case with germline variant found so far.

A female patient was identified with a germline de novo missense variant in ELOC gene (c.236A>G/ p.Tyr79Cys) and satisfied the clinical diagnostic criteria for von Hippel-Lindau (VHL) disease. The patient had left retinal haemangioblastomas, renal cell carcinomas, cyst of the right kidney, spinal haemangioblastoma, a haemangioblastoma at the cervicomedullary junction and Henoch-Schonlein purpura (PMID:35323939).

This is the only germline variant detected in ELOC gene and was associated with VHL so far. However, ~20 somatic ELOC variants have been reported to be associated with renal cell carcinomas so far.

This gene has not yet been associated with relevant phenotypes in OMIM or Gene2Phenotype.
Sources: Literature; to: Comment on gene classification: This gene should be rated red as there is only one case with germline variant found so far.

A female patient was identified with a germline de novo missense variant in ELOC gene (c.236A>G/ p.Tyr79Cys) and satisfied the clinical diagnostic criteria for von Hippel-Lindau (VHL) disease. The patient had left retinal haemangioblastomas, renal cell carcinomas, cyst of the right kidney, spinal haemangioblastoma, a haemangioblastoma at the cervicomedullary junction and Henoch-Schonlein purpura (PMID:35323939).

This is the only germline variant detected in ELOC gene and was associated with VHL so far. However, ~20 somatic ELOC variants have been reported to be associated with renal cell carcinomas so far.

This gene has not yet been associated with relevant phenotypes in OMIM or Gene2Phenotype.
Sources: Literature
Inherited renal cancer v1.23 ELOC Achchuthan Shanmugasundram gene: ELOC was added
gene: ELOC was added to Inherited renal cancer. Sources: Literature
Mode of inheritance for gene: ELOC was set to Unknown
Publications for gene: ELOC were set to 35323939
Phenotypes for gene: ELOC were set to von Hippel-Lindau disease, MONDO:0008667; renal cell carcinoma, MONDO:0005086; retinal hemangioblastoma, MONDO:0003343
Review for gene: ELOC was set to RED
Added comment: Comment on gene classification: This gene should be rated red as there is only one case with germline variant found so far.

A female patient was identified with a germline de novo missense variant in ELOC gene (c.236A>G/ p.Tyr79Cys) and satisfied the clinical diagnostic criteria for von Hippel-Lindau (VHL) disease. The patient had left retinal haemangioblastomas, renal cell carcinomas, cyst of the right kidney, spinal haemangioblastoma, a haemangioblastoma at the cervicomedullary junction and Henoch-Schonlein purpura (PMID:35323939).

This is the only germline variant detected in ELOC gene and was associated with VHL so far. However, ~20 somatic ELOC variants have been reported to be associated with renal cell carcinomas so far.

This gene has not yet been associated with relevant phenotypes in OMIM or Gene2Phenotype.
Sources: Literature
Intellectual disability v4.69 CHAMP1 Achchuthan Shanmugasundram Publications for gene: CHAMP1 were set to 35271727
Intellectual disability v4.69 CHAMP1 Achchuthan Shanmugasundram Publications for gene: CHAMP1 were set to 35271727
Intellectual disability v4.69 CHAMP1 Achchuthan Shanmugasundram Publications for gene: CHAMP1 were set to 35271727
Intellectual disability v4.69 CHAMP1 Achchuthan Shanmugasundram Publications for gene: CHAMP1 were set to 35271727
Intellectual disability v4.69 CHAMP1 Achchuthan Shanmugasundram Publications for gene: CHAMP1 were set to 0
Intellectual disability v4.68 CHAMP1 Achchuthan Shanmugasundram Phenotypes for gene: CHAMP1 were changed from Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579 to Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579
Fetal anomalies v2.12 CHAMP1 Achchuthan Shanmugasundram Phenotypes for gene: CHAMP1 were changed from INTELLECTUAL DISABILITY to Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579
Intellectual disability v4.68 CHAMP1 Achchuthan Shanmugasundram Phenotypes for gene: CHAMP1 were changed from Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579 to Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579
Intellectual disability v4.68 CHAMP1 Achchuthan Shanmugasundram Phenotypes for gene: CHAMP1 were changed from Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579 to Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579
Intellectual disability v4.68 CHAMP1 Achchuthan Shanmugasundram Phenotypes for gene: CHAMP1 were changed from Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579 to Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579
Intellectual disability v4.67 CHAMP1 Achchuthan Shanmugasundram Phenotypes for gene: CHAMP1 were changed from Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579 to Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579
Intellectual disability v4.67 CHAMP1 Achchuthan Shanmugasundram Phenotypes for gene: CHAMP1 were changed from Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579 to Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579
Intellectual disability v4.67 CHAMP1 Achchuthan Shanmugasundram Phenotypes for gene: CHAMP1 were changed from INTELLECTUAL DISABILITY to Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579
Early onset or syndromic epilepsy v3.65 CAMLG Achchuthan Shanmugasundram gene: CAMLG was added
gene: CAMLG was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: CAMLG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAMLG were set to 35262690
Phenotypes for gene: CAMLG were set to Congenital disorder of glycosylation, type IIz, OMIM:620201
Review for gene: CAMLG was set to RED
Added comment: Comment on classification of gene: This gene should be rated red as there is only one patient reported so far.

PMID:35262690 reported one patient with homozygous c.633 + 4A>G splice variant in CAMLG presented with a predominantly neurological phenotype with psychomotor disability, hypotonia, epilepsy and structural brain abnormalities.

This gene has already been associated with phenotype in OMIM (MIM #620201), but not in Gene2Phenotype.
Sources: Literature
Congenital disorders of glycosylation v3.5 CAMLG Achchuthan Shanmugasundram changed review comment from: Comment on classification of gene: This gene should be rated red as there is only one patient reported so far.

PMID:35262690 reported one patient with homozygous c.633 + 4A>G splice variant in CAMLG presented with a predominantly neurological phenotype with psychomotor disability, hypotonia, epilepsy and structural brain abnormalities. Biochemically, a combined O-linked and type II N-linked glycosylation defect was found.

This gene has already been associated with phenotype in OMIM (MIM #620201), but not in Gene2Phenotype.
Sources: Literature; to: Comment on classification of gene: This gene should be rated red as there is only one patient reported so far.

PMID:35262690 reported one patient with homozygous c.633 + 4A>G splice variant in CAMLG presented with a predominantly neurological phenotype with psychomotor disability, hypotonia, epilepsy and structural brain abnormalities. Biochemically, a combined O-linked and type II N-linked glycosylation defect was found.

This gene has already been associated with phenotype in OMIM (MIM #620201), but not in Gene2Phenotype.
Sources: Literature
Early onset or syndromic epilepsy v3.64 SLC39A8 Sarah Leigh edited their review of gene: SLC39A8: Added comment: Associated with Congenital disorder of glycosylation, type IIn (OMIM:616721) in OMIM and as definitive Gen2Phen gene for Intellectual Disability with Cerebellar Atrophy. At least five SLC39A8 variants have been reported in four unrelated cases of OMIM:616721 where seizures, infantile spasms or epilepsy have been reported (PMID: 26637978; 26637979). Haplotype analysis of the cases reported by PMID: 26637978, confirm that although the cases both were homozygous for the same variant (rs778210210), they were unrelated.; Changed rating: GREEN
Arthrogryposis v4.9 CAMLG Achchuthan Shanmugasundram gene: CAMLG was added
gene: CAMLG was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: CAMLG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAMLG were set to 35262690
Phenotypes for gene: CAMLG were set to Congenital disorder of glycosylation, type IIz, OMIM:620201
Review for gene: CAMLG was set to RED
Added comment: Comment on classification of gene: This gene should be rated red as there is only one patient reported so far.

PMID:35262690 reported one patient with homozygous c.633 + 4A>G splice variant in CAMLG presented with a predominantly neurological phenotype with psychomotor disability, contractures, epilepsy, hypotonia and brain malformations.

This gene has already been associated with phenotype in OMIM (MIM #620201), but not in Gene2Phenotype.
Sources: Literature
Congenital disorders of glycosylation v3.5 CAMLG Achchuthan Shanmugasundram changed review comment from: Comment on classification of gene: This gene should be rated red as there is only one patient reported so far.

PMID:35262690 reported one patient with homozygous c.633 + 4A>G splice variant in CAMLG presented with a predominantly neurological phenotype with psychomotor disability, hypotonia, epilepsy and structural brain abnormalities. Biochemically, a combined O-linked and type II N-linked glycosylation defect was found.

This gene has already been associated with phenotype in OMIM (MIM #620201), but not in Gene2Phenotype.
Sources: Literature; to: Comment on classification of gene: This gene should be rated red as there is only one patient reported so far.

PMID:35262690 reported one patient with homozygous c.633 + 4A>G splice variant in CAMLG presented with a predominantly neurological phenotype with psychomotor disability, hypotonia, epilepsy and structural brain abnormalities. Biochemically, a combined O-linked and type II N-linked glycosylation defect was found.

This gene has already been associated with phenotype in OMIM (MIM #620201), but not in Gene2Phenotype.
Sources: Literature
Early onset or syndromic epilepsy v3.64 SLC39A8 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: SLC39A8.
Early onset or syndromic epilepsy v3.64 SLC39A8 Sarah Leigh Classified gene: SLC39A8 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.64 SLC39A8 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v3.64 SLC39A8 Sarah Leigh Gene: slc39a8 has been classified as Amber List (Moderate Evidence).
Congenital disorders of glycosylation v3.5 CAMLG Achchuthan Shanmugasundram gene: CAMLG was added
gene: CAMLG was added to Congenital disorders of glycosylation. Sources: Literature
Mode of inheritance for gene: CAMLG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAMLG were set to 35262690
Phenotypes for gene: CAMLG were set to Congenital disorder of glycosylation, type IIz, OMIM:620201
Review for gene: CAMLG was set to RED
Added comment: Comment on classification of gene: This gene should be rated red as there is only one patient reported so far.

PMID:35262690 reported one patient with homozygous c.633 + 4A>G splice variant in CAMLG presented with a predominantly neurological phenotype with psychomotor disability, hypotonia, epilepsy and structural brain abnormalities. Biochemically, a combined O-linked and type II N-linked glycosylation defect was found.

This gene has already been associated with phenotype in OMIM (MIM #620201), but not in Gene2Phenotype.
Sources: Literature
Ectodermal dysplasia v2.8 RIPK4 Achchuthan Shanmugasundram changed review comment from: Comment on classification of gene: RIPK4 should be rated green as biallelic variants in this gene has been implicated in ectodermal dysplasias (ED) of varying severity in multiple (>3) unrelated patients and supported by functional studies.

This gene has already been associated with relevant phenotypes in both OMIM and Gene2Phenotype.

The clinically distinct ED syndromes reported with RIPK4 variants include early lethal BPS (MIM #263650) and milder forms such as PPS and CHAND syndrome (MIM #214350). BPS1 is characterized by multiple popliteal pterygia, ankyloblepharon, filiform bands between the jaws, cleft lip and palate, and syndactyly and CHAND is characterized by ankyloblepharon, sparse, curly, and woolly hair, nail dysplasia, and oral frenula.

PMID:35220430 reported two siblings with novel biallelic (compound heterozygous) variants presented with cutaneous syndactyly associated to hair defects, alopecia, nail dysplasia and hyperkeratosis. This phenotype expands the clinical spectrum of the disorder further and is intermediary between BPS and CHAND syndrome.
Sources: Literature; to: Comment on classification of gene: RIPK4 should be rated green as biallelic variants in this gene has been implicated in ectodermal dysplasias (ED) of varying severity in multiple (>3) unrelated patients and supported by functional studies.

This gene has already been associated with relevant phenotypes in both OMIM and Gene2Phenotype.

The clinically distinct ED syndromes reported with RIPK4 variants include early lethal BPS (MIM #263650) and milder forms such as PPS and CHAND syndrome (MIM #214350). BPS1 is characterized by multiple popliteal pterygia, ankyloblepharon, filiform bands between the jaws, cleft lip and palate, and syndactyly and CHAND is characterized by ankyloblepharon, sparse, curly, and woolly hair, nail dysplasia, and oral frenula.

PMID:35220430 reported two siblings with novel biallelic (compound heterozygous) variants presented with cutaneous syndactyly associated to hair defects, alopecia, nail dysplasia and hyperkeratosis. This phenotype expands the clinical spectrum of the disorder further and is intermediary between BPS and CHAND syndrome.
Sources: Literature
Ectodermal dysplasia v2.8 RIPK4 Achchuthan Shanmugasundram Tag Q1_22_rating tag was added to gene: RIPK4.
Ectodermal dysplasia v2.8 RIPK4 Achchuthan Shanmugasundram Classified gene: RIPK4 as Amber List (moderate evidence)
Ectodermal dysplasia v2.8 RIPK4 Achchuthan Shanmugasundram Gene: ripk4 has been classified as Amber List (Moderate Evidence).
Ectodermal dysplasia v2.7 RIPK4 Achchuthan Shanmugasundram gene: RIPK4 was added
gene: RIPK4 was added to Ectodermal dysplasia. Sources: Literature
Mode of inheritance for gene: RIPK4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIPK4 were set to 26129644; 28940926; 33713555; 35220430
Phenotypes for gene: RIPK4 were set to CHAND syndrome, OMIM:214350; Popliteal pterygium syndrome, Bartsocas-Papas type 1, OMIM:263650; ectodermal dysplasia syndrome, MONDO:0019287
Review for gene: RIPK4 was set to GREEN
Added comment: Comment on classification of gene: RIPK4 should be rated green as biallelic variants in this gene has been implicated in ectodermal dysplasias (ED) of varying severity in multiple (>3) unrelated patients and supported by functional studies.

This gene has already been associated with relevant phenotypes in both OMIM and Gene2Phenotype.

The clinically distinct ED syndromes reported with RIPK4 variants include early lethal BPS (MIM #263650) and milder forms such as PPS and CHAND syndrome (MIM #214350). BPS1 is characterized by multiple popliteal pterygia, ankyloblepharon, filiform bands between the jaws, cleft lip and palate, and syndactyly and CHAND is characterized by ankyloblepharon, sparse, curly, and woolly hair, nail dysplasia, and oral frenula.

PMID:35220430 reported two siblings with novel biallelic (compound heterozygous) variants presented with cutaneous syndactyly associated to hair defects, alopecia, nail dysplasia and hyperkeratosis. This phenotype expands the clinical spectrum of the disorder further and is intermediary between BPS and CHAND syndrome.
Sources: Literature
Mitochondrial disorders v3.10 SLC39A8 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 variants reported in 3 unrelated cases; to: Associated with Congenital disorder of glycosylation, type IIn, OMIM:616721 and as definitive gene in Gen2Phen for Intellectual Disability with Cerebellar Atrophy. However, as stated by Zornitza Stark (Australian Genomics) there is insufficient evidence for mitochondrial phenotype associated with this gene.
Mitochondrial disorders v3.10 SLC39A8 Sarah Leigh Publications for gene: SLC39A8 were set to 29903433
Mitochondrial disorders v3.9 SLC39A8 Sarah Leigh Phenotypes for gene: SLC39A8 were changed from Congenital disorder of glycosylation, type IIn 616721 to Congenital disorder of glycosylation, type IIn, OMIM:616721; SLC39A8-CDG, MONDO:0014746
Early onset or syndromic epilepsy v3.63 SLC39A8 Sarah Leigh Phenotypes for gene: SLC39A8 were changed from Congenital disorder of glycosylation, type IIn , MIM#16721 to Congenital disorder of glycosylation, type IIn, OMIM:616721; SLC39A8-CDG, MONDO:0014746
Mitochondrial disorders v3.8 SLC39A8 Sarah Leigh Mode of inheritance for gene: SLC39A8 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v3.62 ST3GAL3 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: ST3GAL3.
Early onset or syndromic epilepsy v3.62 ST3GAL3 Sarah Leigh edited their review of gene: ST3GAL3: Added comment: Associated with Developmental and epileptic encephalopathy 15, OMIM:615006, but not associated with the same phenotype in Gen2Phen. At least two variants have been reported in two unrelated families (PMIDs: 23252400 & 31584066). Supportive functional studies are presented in PMID: 30089820.; Changed rating: GREEN; Changed publications to: 23252400, 30089820, 31584066
Early onset or syndromic epilepsy v3.62 ST3GAL3 Sarah Leigh Classified gene: ST3GAL3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.62 ST3GAL3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v3.62 ST3GAL3 Sarah Leigh Gene: st3gal3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v3.61 ST3GAL3 Sarah Leigh Publications for gene: ST3GAL3 were set to 27604308; 21907012; 23252400; 31584066; 17120046; 25529582
Early onset or syndromic epilepsy v3.60 ST3GAL3 Sarah Leigh Mode of inheritance for gene: ST3GAL3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v3.59 ST3GAL3 Sarah Leigh Added comment: Comment on phenotypes: ST3GAL3 are also associated with: Intellectual developmental disorder, autosomal recessive 12, OMIM:611090; intellectual disability, autosomal recessive 12, MONDO:0012612, however, this phenotype does not include seizures.
Early onset or syndromic epilepsy v3.59 ST3GAL3 Sarah Leigh Phenotypes for gene: ST3GAL3 were changed from Developmental and epileptic encephalopathy 15, OMIM:615006; developmental and epileptic encephalopathy, 15, MONDO:0014003; Intellectual developmental disorder, autosomal recessive 12, OMIM:611090; intellectual disability, autosomal recessive 12, MONDO:0012612 to Developmental and epileptic encephalopathy 15, OMIM:615006; developmental and epileptic encephalopathy, 15, MONDO:0014003
Early onset or syndromic epilepsy v3.58 DOLK Sarah Leigh Tag Q1_23_promote_green tag was added to gene: DOLK.
Early onset or syndromic epilepsy v3.58 DOLK Sarah Leigh edited their review of gene: DOLK: Added comment: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. At least five DOLK variants have been reported in four unrelated cases of Congenital disorder of glycosylation, type Im, OMIM:610768, where seizures were reported in the patients (PMID: 28816422 table 1)(PMID 24144945;23890587;17273964).; Changed rating: GREEN
Early onset or syndromic epilepsy v3.58 DOLK Sarah Leigh Phenotypes for gene: DOLK were changed from Congenital disorder of glycosylation, type Im, 610768 to Congenital disorder of glycosylation, type Im, OMIM:610768; DK1-congenital disorder of glycosylation, MONDO:0012556
Early onset or syndromic epilepsy v3.57 DOLK Sarah Leigh Classified gene: DOLK as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.57 DOLK Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v3.57 DOLK Sarah Leigh Gene: dolk has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v3.51 GBA Achchuthan Shanmugasundram Publications for gene: GBA were set to 29400127; 27779773; 15525722; 17620502; 27648471; 27632223; 27717005
Ophthalmological ciliopathies v2.7 TMEM218 Achchuthan Shanmugasundram Publications for gene: TMEM218 were set to 25161209; 33791682; 35137054
Ophthalmological ciliopathies v2.7 TMEM218 Achchuthan Shanmugasundram Publications for gene: TMEM218 were set to 25161209; 33791682
Neurological ciliopathies v2.7 TMEM218 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:35137054 reports three additional cases from two unrelated families and functional evidence including results from zebrafish model.
Neurological ciliopathies v2.7 TMEM218 Achchuthan Shanmugasundram Publications for gene: TMEM218 were set to 25161209; 33791682; 35137054
Neurological ciliopathies v2.7 TMEM218 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:35137054 reports three additional cases from two unrelated families and functional evidence including results from zebrafish model.
Neurological ciliopathies v2.7 TMEM218 Achchuthan Shanmugasundram Publications for gene: TMEM218 were set to 25161209; 33791682
Early onset or syndromic epilepsy v3.56 DOLK Sarah Leigh Publications for gene: DOLK were set to 23890587; 17273964; 24144945; 28816422
Early onset or syndromic epilepsy v3.55 FGFR3 Sarah Leigh edited their review of gene: FGFR3: Added comment: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene for hypochondroplasia. The variant NM_000142.5(FGFR3):c.1620C>A (p.Asn540Lys) has been reported in at least six unrelated cases of hypochondroplasia (OMIM:146000), in which the patients also display epileptic seizures (PMIDs:12794698; 16222682;17621485 ;2463028; 23165795; 27485793). Biallelic FGFR3 variants have been also been reported in a novel phenotype of achondroplasia, which also includes seizures (PMID: 30160829). Migrating neonatal seizures were also reported in a case of Muenke syndrome (OMIM:602849), carrying the variant: NM_000142.5(FGFR3):c.749C>G (p.Pro250Arg)(PMID: 28551036).; Changed rating: GREEN
Early onset or syndromic epilepsy v3.55 FGFR3 Sarah Leigh Classified gene: FGFR3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.55 FGFR3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v3.55 FGFR3 Sarah Leigh Gene: fgfr3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v3.54 FGFR3 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: FGFR3.
Early onset or syndromic epilepsy v3.54 FGFR3 Sarah Leigh Publications for gene: FGFR3 were set to 30160829; 28551036; 27485793; 23649205; 24630288; 17621485; 16222682; 12794698; 23044018; 12794698; 18000976; http://doi.org/10.15844/pedneurbriefs-26-12-6; http://www.ashg.org/genetics/ashg07s/f20570.htm; https://jicna.org/index.php/journal/article/view/100
Early onset or syndromic epilepsy v3.53 FGFR3 Sarah Leigh Added comment: Comment on phenotypes: Isolated seizures have also been reported in cases with: Muenke syndrome, OMIM:602849;Muenke syndrome, MONDO:0011274;SADDAN, OMIM:616482;severe achondroplasia-developmental delay-acanthosis nigricans syndrome, MONDO:0014658
Early onset or syndromic epilepsy v3.53 FGFR3 Sarah Leigh Phenotypes for gene: FGFR3 were changed from Hypochondroplasia, OMIM:146000; hypochondroplasia, MONDO:0007793; Muenke syndrome, OMIM:602849; Muenke syndrome, MONDO:0011274; SADDAN, OMIM:616482; severe achondroplasia-developmental delay-acanthosis nigricans syndrome, MONDO:0014658 to Hypochondroplasia, OMIM:146000; hypochondroplasia, MONDO:0007793
Renal tubulopathies v3.4 CTNS Achchuthan Shanmugasundram Publications for gene: CTNS were set to 27604308; 9537412; 19863563
Lysosomal storage disorder v2.4 CTNS Achchuthan Shanmugasundram Publications for gene: CTNS were set to
Retinal disorders v3.33 PDE6B Achchuthan Shanmugasundram Publications for gene: PDE6B were set to
Rare genetic inflammatory skin disorders v2.5 LTV1 Achchuthan Shanmugasundram changed review comment from: Comment on classification of gene: This gene should be rated amber as it has been implicated in inflammatory poikiloderma with hair abnormalities and acral keratoses as identified from two unrelated families harbouring the same biallelic variant and supported by functional studies.

PMID:34999892 reported four UK women of South Asian origin (three Pakistani sisters and an unrelated Indian woman) identified with homozygous variant c.503A>G, (p.Asn168Ser) and presented with poikiloderma, hair abnormalities, and acral keratoses, which the authors named as inflammatory poikiloderma with hair abnormalities and acral keratoses (IPHAK).

Both in silico modelling and splicing assays from a patient sample showed that this variant is responsible for splicing defects and defects in LTV1 alter the export of nascent ribosomal subunits to the cytoplasm in yeast.

This gene has already been associated with relevant phenotype (MIM #620199) in OMIM, but not in Gene2Phenotype.
Sources: Literature; to: Comment on classification of gene: This gene should be rated amber as it has been implicated in inflammatory poikiloderma with hair abnormalities and acral keratoses as identified from two unrelated families harbouring the same biallelic variant and supported by functional studies.

PMID:34999892 reported four UK women of South Asian origin (three Pakistani sisters and an unrelated Indian woman) identified with homozygous variant c.503A>G, (p.Asn168Ser) and presented with poikiloderma, hair abnormalities, and acral keratoses, which the authors named as inflammatory poikiloderma with hair abnormalities and acral keratoses (IPHAK).

Both in silico modelling and splicing assays from a patient sample showed that this variant is responsible for splicing defects and defects in LTV1 alter the export of nascent ribosomal subunits to the cytoplasm in yeast.

This gene has already been associated with relevant phenotype (MIM #620199) in OMIM, but not in Gene2Phenotype.
Sources: Literature
Rare genetic inflammatory skin disorders v2.5 LTV1 Achchuthan Shanmugasundram Classified gene: LTV1 as Amber List (moderate evidence)
Rare genetic inflammatory skin disorders v2.5 LTV1 Achchuthan Shanmugasundram Gene: ltv1 has been classified as Amber List (Moderate Evidence).
Pigmentary skin disorders v2.5 LTV1 Achchuthan Shanmugasundram Classified gene: LTV1 as Amber List (moderate evidence)
Pigmentary skin disorders v2.5 LTV1 Achchuthan Shanmugasundram Gene: ltv1 has been classified as Amber List (Moderate Evidence).
Rare genetic inflammatory skin disorders v2.4 LTV1 Achchuthan Shanmugasundram gene: LTV1 was added
gene: LTV1 was added to Rare genetic inflammatory skin disorders. Sources: Literature
Mode of inheritance for gene: LTV1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LTV1 were set to 34999892
Phenotypes for gene: LTV1 were set to Inflammatory poikiloderma with hair abnormalities and acral keratoses, OMIM:620199
Review for gene: LTV1 was set to AMBER
Added comment: Comment on classification of gene: This gene should be rated amber as it has been implicated in inflammatory poikiloderma with hair abnormalities and acral keratoses as identified from two unrelated families harbouring the same biallelic variant and supported by functional studies.

PMID:34999892 reported four UK women of South Asian origin (three Pakistani sisters and an unrelated Indian woman) identified with homozygous variant c.503A>G, (p.Asn168Ser) and presented with poikiloderma, hair abnormalities, and acral keratoses, which the authors named as inflammatory poikiloderma with hair abnormalities and acral keratoses (IPHAK).

Both in silico modelling and splicing assays from a patient sample showed that this variant is responsible for splicing defects and defects in LTV1 alter the export of nascent ribosomal subunits to the cytoplasm in yeast.

This gene has already been associated with relevant phenotype (MIM #620199) in OMIM, but not in Gene2Phenotype.
Sources: Literature
Pigmentary skin disorders v2.4 LTV1 Achchuthan Shanmugasundram gene: LTV1 was added
gene: LTV1 was added to Pigmentary skin disorders. Sources: Literature
Mode of inheritance for gene: LTV1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LTV1 were set to 34999892
Phenotypes for gene: LTV1 were set to Inflammatory poikiloderma with hair abnormalities and acral keratoses, OMIM:620199
Review for gene: LTV1 was set to AMBER
Added comment: Comment on classification of gene: This gene should be rated amber as it has been implicated in inflammatory poikiloderma with hair abnormalities and acral keratoses as identified from two unrelated families harbouring the same biallelic variant and supported by functional studies.

PMID:34999892 reported four UK women of South Asian origin (three Pakistani sisters and an unrelated Indian woman) identified with homozygous variant c.503A>G, (p.Asn168Ser) and presented with poikiloderma, hair abnormalities, and acral keratoses, which the authors named as inflammatory poikiloderma with hair abnormalities and acral keratoses (IPHAK).

Both in silico modelling and splicing assays from a patient sample showed that this variant is responsible for splicing defects and defects in LTV1 alter the export of nascent ribosomal subunits to the cytoplasm in yeast.

This gene has already been associated with relevant phenotype (MIM #620199) in OMIM, but not in Gene2Phenotype.
Sources: Literature
Early onset or syndromic epilepsy v3.52 FGFR3 Sarah Leigh Publications for gene: FGFR3 were set to 28551036; 27485793; 23649205; 24630288; 17621485; 16222682; 12794698; 23044018; 12794698; 18000976; http://doi.org/10.15844/pedneurbriefs-26-12-6; http://www.ashg.org/genetics/ashg07s/f20570.htm; https://jicna.org/index.php/journal/article/view/100
Early onset or syndromic epilepsy v3.51 FGFR3 Sarah Leigh Phenotypes for gene: FGFR3 were changed from Hypochondroplasia, 146000; Focal Epilepsy; Muenke syndrome, 602849; Epilepsy to Hypochondroplasia, OMIM:146000; hypochondroplasia, MONDO:0007793; Muenke syndrome, OMIM:602849; Muenke syndrome, MONDO:0011274; SADDAN, OMIM:616482; severe achondroplasia-developmental delay-acanthosis nigricans syndrome, MONDO:0014658
Early onset or syndromic epilepsy v3.50 GABRB1 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: GABRB1.
Early onset or syndromic epilepsy v3.50 GABRB1 Sarah Leigh edited their review of gene: GABRB1: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least three variants have been reported in unrelated cases with epilepsy (PMID: 26950270, 27273810, 31618474).; Changed rating: GREEN
Early onset or syndromic epilepsy v3.50 GABRB1 Sarah Leigh Classified gene: GABRB1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.50 GABRB1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v3.50 GABRB1 Sarah Leigh Gene: gabrb1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v3.49 GABRB1 Sarah Leigh Phenotypes for gene: GABRB1 were changed from Epileptic encephalopathy, early infantile, 45, 617153 to Epileptic encephalopathy, early infantile, 45, OMIM:617153; developmental and epileptic encephalopathy, 45, MONDO:0014942
Early onset or syndromic epilepsy v3.48 GABRB1 Sarah Leigh Publications for gene: GABRB1 were set to 26950270; 27273810
Early onset or syndromic epilepsy v3.47 NEDD4L Sarah Leigh Tag Q1_23_promote_green tag was added to gene: NEDD4L.
Early onset or syndromic epilepsy v3.47 NEDD4L Sarah Leigh edited their review of gene: NEDD4L: Added comment: Associated with relevant phenotype in OMIM and as strong Gen2Phen gene. At least five variants have been reported in cases where seizures are reported (PMIDs:28515470, 27694961, 32117442).; Changed rating: GREEN; Changed publications to: 32117442
Early onset or syndromic epilepsy v3.47 NEDD4L Sarah Leigh Classified gene: NEDD4L as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.47 NEDD4L Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v3.47 NEDD4L Sarah Leigh Gene: nedd4l has been classified as Amber List (Moderate Evidence).
Congenital hyperinsulinism v2.33 CACNA1C Eleanor Williams Phenotypes for gene: CACNA1C were changed from non-syndromic congeital hyperinsulinism; Timothy syndrome, OMIM:601005; Timothy syndrome, MONDO:0010979 to non-syndromic congeital hyperinsulinism; Timothy syndrome, OMIM:601005; Timothy syndrome, MONDO:0010979; CACNA1C-related disorder
Early onset or syndromic epilepsy v3.46 CACNA1C Eleanor Williams Added comment: Comment on phenotypes: Adding back the phenotype of 'CACNA1C-related disorder' as this was specifically asked to be added by NHSE.
Early onset or syndromic epilepsy v3.46 CACNA1C Eleanor Williams Phenotypes for gene: CACNA1C were changed from Timothy syndrome OMIM:601005 to Timothy syndrome OMIM:601005; CACNA1C-related disorder
Cytopenias and congenital anaemias v1.111 RAD51 Øystein Holla gene: RAD51 was added
gene: RAD51 was added to Cytopenias and congenital anaemias. Sources: Literature
Mode of inheritance for gene: RAD51 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RAD51 were set to 26681308; 30907510; 26253028
Phenotypes for gene: RAD51 were set to Fanconi anemia, atypical
Penetrance for gene: RAD51 were set to unknown
Review for gene: RAD51 was set to GREEN
Added comment: Three cases published, all with de novo variants and atypical Fanconi phenotype. Dominant negative effect. RAD51 haploinsufficiency cause mirror movements.
Sources: Literature
Cytopenias and congenital anaemias v1.111 RFWD3 Øystein Holla changed review comment from: Only one compund heterozygote published, c.205_206dupCC; p.L69Pfs*12) and c.1916T>A; p.I639K. (PMID:28691929).
Sources: Literature; to: Only one compound heterozygote published, c.205_206dupCC; p.L69Pfs*12) and c.1916T>A; p.I639K. (PMID:28691929).
Sources: Literature
Cytopenias and congenital anaemias v1.111 RFWD3 Øystein Holla changed review comment from: Only one compund heterozygote published, c.205_206dupCC; p.L69Pfs*12) and c.1916T>A; p.I639K. (PMID:28691929)
Sources: Literature; to: Only one compund heterozygote published, c.205_206dupCC; p.L69Pfs*12) and c.1916T>A; p.I639K. (PMID:28691929).
Sources: Literature
Hereditary ataxia with onset in adulthood v3.12 FGF14_GAA Philip Twiss STR: FGF14_GAA was added
STR: FGF14_GAA was added to Hereditary ataxia - adult onset. Sources: Literature
Mode of inheritance for STR: FGF14_GAA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: FGF14_GAA were set to PMID: 36516086
Phenotypes for STR: FGF14_GAA were set to Late-onset cerebellar ataxia; Episodic features; Nystagmus
Penetrance for STR: FGF14_GAA were set to Complete
Review for STR: FGF14_GAA was set to AMBER
Added comment: New STR disease loci reported to account for significant number of dominant late onset ataxia cases. Not current standard of care therefore no diagnostic accredited PCR assays available currently in UK.
Sources: Literature
Cytopenias and congenital anaemias v1.111 RFWD3 Øystein Holla gene: RFWD3 was added
gene: RFWD3 was added to Cytopenias and congenital anaemias. Sources: Literature
Mode of inheritance for gene: RFWD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RFWD3 were set to 28691929
Phenotypes for gene: RFWD3 were set to Fanconi anemia
Penetrance for gene: RFWD3 were set to unknown
Review for gene: RFWD3 was set to RED
Added comment: Only one compund heterozygote published, c.205_206dupCC; p.L69Pfs*12) and c.1916T>A; p.I639K. (PMID:28691929)
Sources: Literature
Adult onset hereditary spastic paraplegia v2.12 SPAST Achchuthan Shanmugasundram Publications for gene: SPAST were set to 16240363; 15248095
Early onset or syndromic epilepsy v3.45 ARX Achchuthan Shanmugasundram Publications for gene: ARX were set to Tsurusaki et al (2002) Nature 30: 441-445; Kato et al (2004) Hum Mut 23: 147-159; Bienvenu et al (2002) Hum Mol Genet 11(8): 981-991; Partington et al (1998) Am J Med Genet 30: 251-262; 35094084
Early onset or syndromic epilepsy v3.44 ARX Achchuthan Shanmugasundram Publications for gene: ARX were set to Tsurusaki et al (2002) Nature 30: 441-445; Kato et al (2004) Hum Mut 23: 147-159; Bienvenu et al (2002) Hum Mol Genet 11(8): 981-991; Partington et al (1998) Am J Med Genet 30: 251-262
Hereditary spastic paraplegia v1.298 SPAST Achchuthan Shanmugasundram Publications for gene: SPAST were set to Hazan et al (1999)
Osteogenesis imperfecta v3.7 WNT11 Achchuthan Shanmugasundram changed review comment from: Comment on gene classification: The rating of this gene can be added as green as this gene has been implicated in early-onset osteoporosis from three unrelated cases and was supported by evidence from functional studies. All three patients harboured heterozygous variants in WNT11 gene.

Three unrelated cases are reported in PMID: 34875064. A four year-old boy harbouring de novo heterozygous loss-of-function variant c.677_678dupGG (p.Leu227Glyfs*22) was reported with low BMD, osteopenia and several fractures.

A 51 year-old woman and her 69 year-old mother were identified with a heterozygous missense variant c.217G>A (p.Ala73Thr). The woman was reported with bone fragility, several fractures, osteoarthritis and osteoporosis, while her mother also had several osteoporotic fractures.

A 61 year-old woman that was reported with lumbar spine osteoarthritis had several fractures since 55 years of age was identified with a heterozygous missense variant c.865G>A (p.Val289Met).

This was also supported by results from functional studies, where cell lines with the loss-of-function variant generated by CRISPR-Cas9 showed reduced cell proliferation and osteoblast differentiation in comparison to wild-type. The expression of genes in the Wnt canonical and non-canonical pathways was inhibited in these mutant cells.
Sources: Literature; to: Comment on gene classification: The rating of this gene can be added as green as this gene has been implicated in early-onset osteoporosis from three unrelated cases and was supported by evidence from functional studies. All three patients harboured heterozygous variants in WNT11 gene.

Three unrelated cases are reported in PMID: 34875064. A four year-old boy harbouring de novo heterozygous loss-of-function variant c.677_678dupGG (p.Leu227Glyfs*22) was reported with low BMD, osteopenia and several fractures.

A 51 year-old woman and her 69 year-old mother were identified with a heterozygous missense variant c.217G>A (p.Ala73Thr). The woman was reported with bone fragility, several fractures, osteoarthritis and osteoporosis, while her mother also had several osteoporotic fractures.

A 61 year-old woman that was reported with lumbar spine osteoarthritis had several fractures since 55 years of age was identified with a heterozygous missense variant c.865G>A (p.Val289Met).

This was also supported by results from functional studies, where cell lines with the loss-of-function variant generated by CRISPR-Cas9 showed reduced cell proliferation and osteoblast differentiation in comparison to wild-type. The expression of genes in the Wnt canonical and non-canonical pathways was inhibited in these mutant cells.

This gene has not yet been reported with any phenotypes either in OMIM or in G2P.
Sources: Literature
Osteogenesis imperfecta v3.7 WNT11 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: WNT11.
Osteogenesis imperfecta v3.7 WNT11 Achchuthan Shanmugasundram Classified gene: WNT11 as Amber List (moderate evidence)
Osteogenesis imperfecta v3.7 WNT11 Achchuthan Shanmugasundram Gene: wnt11 has been classified as Amber List (Moderate Evidence).
Osteogenesis imperfecta v3.6 WNT11 Achchuthan Shanmugasundram gene: WNT11 was added
gene: WNT11 was added to Osteogenesis imperfecta. Sources: Literature
Mode of inheritance for gene: WNT11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WNT11 were set to 34875064
Phenotypes for gene: WNT11 were set to osteoporosis, MONDO:0005298; osteoarthritis, MONDO:0005178; recurrent fractures
Review for gene: WNT11 was set to GREEN
Added comment: Comment on gene classification: The rating of this gene can be added as green as this gene has been implicated in early-onset osteoporosis from three unrelated cases and was supported by evidence from functional studies. All three patients harboured heterozygous variants in WNT11 gene.

Three unrelated cases are reported in PMID: 34875064. A four year-old boy harbouring de novo heterozygous loss-of-function variant c.677_678dupGG (p.Leu227Glyfs*22) was reported with low BMD, osteopenia and several fractures.

A 51 year-old woman and her 69 year-old mother were identified with a heterozygous missense variant c.217G>A (p.Ala73Thr). The woman was reported with bone fragility, several fractures, osteoarthritis and osteoporosis, while her mother also had several osteoporotic fractures.

A 61 year-old woman that was reported with lumbar spine osteoarthritis had several fractures since 55 years of age was identified with a heterozygous missense variant c.865G>A (p.Val289Met).

This was also supported by results from functional studies, where cell lines with the loss-of-function variant generated by CRISPR-Cas9 showed reduced cell proliferation and osteoblast differentiation in comparison to wild-type. The expression of genes in the Wnt canonical and non-canonical pathways was inhibited in these mutant cells.
Sources: Literature
Early onset or syndromic epilepsy v3.43 NEDD4L Sarah Leigh Phenotypes for gene: NEDD4L were changed from Periventricular nodular heterotopia 7, 617201 to Periventricular nodular heterotopia 7, OMIM:617201; periventricular nodular heterotopia 7, MONDO:0014966
Early onset or syndromic epilepsy v3.42 NEDD4L Sarah Leigh Publications for gene: NEDD4L were set to 28515470; 23934111; 28212375; 27694961
Early onset or syndromic epilepsy v3.41 NEDD4L Sarah Leigh Publications for gene: NEDD4L were set to 27694961; 23934111
Skeletal dysplasia v3.7 WNT1 Achchuthan Shanmugasundram Publications for gene: WNT1 were set to 23499309; 23499310; 23434763; 23656646
Skeletal dysplasia v3.7 WNT1 Achchuthan Shanmugasundram Publications for gene: WNT1 were set to 34875064
Skeletal dysplasia v3.6 WNT1 Achchuthan Shanmugasundram Publications for gene: WNT1 were set to 34875064
Skeletal dysplasia v3.6 WNT1 Achchuthan Shanmugasundram Publications for gene: WNT1 were set to
Neurological segmental overgrowth v2.5 Catherine Snow Panel signed off version 2.2 has been removed
Neurological segmental overgrowth v2.3 Catherine Snow Panel version 2.2 has been signed off on 2023-02-13
Severe early-onset obesity v3.4 ADCY3 Dmitrijs Rots gene: ADCY3 was added
gene: ADCY3 was added to Severe early-onset obesity. Sources: Literature
Mode of inheritance for gene: ADCY3 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ADCY3 were set to 29311637; 35026759
Phenotypes for gene: ADCY3 were set to Monogenic severe obesity
Penetrance for gene: ADCY3 were set to unknown
Review for gene: ADCY3 was set to GREEN
Added comment: Multiple idependet cases reported with early onset severe obesity and LoF variants ir ADCY3.
Sources: Literature
Congenital myopathy v3.124 ZC4H2 Anna Sarkozy reviewed gene: ZC4H2: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Congenital myopathy v3.124 TRDN Anna Sarkozy reviewed gene: TRDN: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:25922419, 28202702, 30649896; Phenotypes: skeletal myopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v3.40 NPRL2 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:34965576 describes conditional knockout mouse model of NPRL2-related epilepsy.
Early onset or syndromic epilepsy v3.40 NPRL2 Achchuthan Shanmugasundram Publications for gene: NPRL2 were set to 26505888; 27173016; 30093711
Early onset or syndromic epilepsy v3.39 NPRL3 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:34965576 describes conditional knockout mouse model of NPRL3-related epilepsy.
Early onset or syndromic epilepsy v3.39 NPRL3 Achchuthan Shanmugasundram Publications for gene: NPRL3 were set to 26505888; 26285051; 27173016; 34965576
Early onset or syndromic epilepsy v3.38 NPRL3 Achchuthan Shanmugasundram Publications for gene: NPRL3 were set to 26505888; 26285051; 27173016
Intellectual disability v4.66 HIST1H1E Achchuthan Shanmugasundram Publications for gene: HIST1H1E were set to 28475857
Intellectual disability v4.65 RAB39B Achchuthan Shanmugasundram Added comment: Comment on publications: Additional cases diagnosed with intellectual disability, autism, macrocephaly and poor motor coordination reported in PMIDs 29152164, 32873259 & 34761259. There are also ample functional evidence including studies from animal models described in these and other publications.
Intellectual disability v4.65 RAB39B Achchuthan Shanmugasundram Publications for gene: RAB39B were set to 20159109; 25434005; 11050621; 29152164; 32873259; 34761259
Intellectual disability v4.64 RAB39B Achchuthan Shanmugasundram Publications for gene: RAB39B were set to
Intellectual disability v4.63 RAB39B Achchuthan Shanmugasundram Phenotypes for gene: RAB39B were changed from Mental retardation, X-linked 72, 300271; Mental Retardation, X-linked; MENTAL RETARDATION X-LINKED TYPE 72 (MRX72) +/- PARKINSONS to Intellectual developmental disorder, X-linked 72, OMIM:300271; Waisman syndrome, OMIM:311510
Fetal anomalies v2.11 RAB39B Achchuthan Shanmugasundram Phenotypes for gene: RAB39B were changed from MENTAL RETARDATION X-LINKED TYPE 72 (MRX72) +/- PARKINSONS to Intellectual developmental disorder, X-linked 72, OMIM:300271; Waisman syndrome, OMIM:311510
Adult onset neurodegenerative disorder v3.50 RAB39B Achchuthan Shanmugasundram Phenotypes for gene: RAB39B were changed from early-onset parkinsonism and intellectual disability; ?Waisman syndrome to early-onset parkinsonism and intellectual disability; Waisman syndrome, OMIM:311510
Parkinson Disease and Complex Parkinsonism v1.111 RAB39B Achchuthan Shanmugasundram Phenotypes for gene: RAB39B were changed from ?Waisman syndrome; early-onset parkinsonism and intellectual disability to Waisman syndrome, OMIM:311510; early-onset parkinsonism and intellectual disability
Renal ciliopathies v2.9 ANKS6 Achchuthan Shanmugasundram Phenotypes for gene: ANKS6 were changed from Polycystic Kidney Disease, Nephronophthisis And Related Disorders 22 Gene Panel; Nephronophthisis 16, OMIM:615382 to Polycystic Kidney Disease, Nephronophthisis And Related Disorders 22 Gene Panel; Nephronophthisis 16, OMIM:615382
Renal ciliopathies v2.9 ANKS6 Achchuthan Shanmugasundram Phenotypes for gene: ANKS6 were changed from Polycystic Kidney Disease, Nephronophthisis And Related Disorders 22 Gene Panel; Nephronophthisis 16, OMIM:615382 to Polycystic Kidney Disease, Nephronophthisis And Related Disorders 22 Gene Panel; Nephronophthisis 16, OMIM:615382
Renal ciliopathies v2.8 ANKS6 Achchuthan Shanmugasundram Phenotypes for gene: ANKS6 were changed from Polycystic Kidney Disease, Nephronophthisis And Related Disorders 22 Gene Panel; Nephronophthisis 16, OMIM:615382 to Polycystic Kidney Disease, Nephronophthisis And Related Disorders 22 Gene Panel; Nephronophthisis 16, OMIM:615382
Renal ciliopathies v2.8 ANKS6 Achchuthan Shanmugasundram Phenotypes for gene: ANKS6 were changed from Polycystic Kidney Disease, Nephronophthisis And Related Disorders 22 Gene Panel; Nephronophthisis 16, 615382; Nephronophthisis to Polycystic Kidney Disease, Nephronophthisis And Related Disorders 22 Gene Panel; Nephronophthisis 16, OMIM:615382
Renal ciliopathies v2.7 ANKS6 Achchuthan Shanmugasundram Publications for gene: ANKS6 were set to 34740236
Renal ciliopathies v2.6 ANKS6 Achchuthan Shanmugasundram Added comment: Comment on publications: Additional cases (two affected siblings identified with biallelic ANKS6 variants and reported with late-onset chronic kidney disease) and functional studies in PMID:34740236.
Renal ciliopathies v2.6 ANKS6 Achchuthan Shanmugasundram Publications for gene: ANKS6 were set to 34740236
Renal ciliopathies v2.5 ANKS6 Achchuthan Shanmugasundram Added comment: Comment on publications: Additional cases (two affected siblings identified with biallelic ANKS6 variants and reported with late-onset chronic kidney disease) and functional studies in PMID:34740236.
Renal ciliopathies v2.5 ANKS6 Achchuthan Shanmugasundram Publications for gene: ANKS6 were set to
Cystic kidney disease v3.7 ANKS6 Achchuthan Shanmugasundram Added comment: Comment on publications: Additional cases (two affected siblings identified with biallelic ANKS6 variants and reported with late-onset chronic kidney disease) and functional studies in PMID:34740236.
Cystic kidney disease v3.7 ANKS6 Achchuthan Shanmugasundram Publications for gene: ANKS6 were set to
Cystic kidney disease v3.6 ANKS6 Achchuthan Shanmugasundram Phenotypes for gene: ANKS6 were changed from Ciliopathy genes associated with cystic kidney disease; Nephronophthisis 16, OMIM:615382 to Ciliopathy genes associated with cystic kidney disease; Nephronophthisis 16, OMIM:615382
Cystic kidney disease v3.5 ANKS6 Achchuthan Shanmugasundram Phenotypes for gene: ANKS6 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Nephronophthisis 16, OMIM:615382
Ehlers Danlos syndrome with a likely monogenic cause v2.69 COL5A1 Achchuthan Shanmugasundram Publications for gene: COL5A1 were set to 28306229; 28192633; 22696272; 15264295; 9042913
Hereditary neuropathy or pain disorder v2.20 IGHMBP2 Achchuthan Shanmugasundram Publications for gene: IGHMBP2 were set to 26392352
Hereditary neuropathy v1.460 IGHMBP2 Achchuthan Shanmugasundram Publications for gene: IGHMBP2 were set to 26392352
Paediatric motor neuronopathies v2.11 IGHMBP2 Achchuthan Shanmugasundram Publications for gene: IGHMBP2 were set to 34726235
Paediatric motor neuronopathies v2.10 IGHMBP2 Achchuthan Shanmugasundram Publications for gene: IGHMBP2 were set to
Retinal disorders v3.32 CWC27 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:34726245 reports functional studies from mouse model in support of the association of this gene to retinal abnormalities.
Retinal disorders v3.32 CWC27 Achchuthan Shanmugasundram Publications for gene: CWC27 were set to 28285769
Retinal disorders v3.31 RDH5 Achchuthan Shanmugasundram changed review comment from: Comment on publications: A domestic cat model with a loss-of-function missense mutation in RDH5 (c.542G > T; p.Gly181Val) has been described in PMID:34726233 and the affected cats have a marked delay in recovery of dark adaptation and develop a degeneration of the area centralis (human equivalent is macula).; to: Comment on publications: A domestic cat model with a loss-of-function missense mutation in RDH5 (c.542G > T; p.Gly181Val) has been described in PMID:34726233 and the affected cats have a marked delay in recovery of dark adaptation and develop a degeneration of the area centralis (human equivalent is macula).

In addition, a review of the database of patients with inherited retinal disease at Moorfields Eye Hospital London and The Hospital for Sick Children Toronto identified 17 patients with confirmed biallelic mutations in RDH5. Of these, seven patients (from six families) had macular atrophy evident on SD-OCT and/or fundus autofluorescence imaging.
Retinal disorders v3.31 RDH5 Achchuthan Shanmugasundram Added comment: Comment on publications: A domestic cat model with a loss-of-function missense mutation in RDH5 (c.542G > T; p.Gly181Val) has been described in PMID:34726233 and the affected cats have a marked delay in recovery of dark adaptation and develop a degeneration of the area centralis (human equivalent is macula).
Retinal disorders v3.31 RDH5 Achchuthan Shanmugasundram Publications for gene: RDH5 were set to 21529959
Palmoplantar keratodermas v2.7 KDSR Achchuthan Shanmugasundram Added comment: Comment on publications: Additional case reported in PMID:34686882.
Palmoplantar keratodermas v2.7 KDSR Achchuthan Shanmugasundram Publications for gene: KDSR were set to
Ichthyosis and erythrokeratoderma v2.13 KDSR Achchuthan Shanmugasundram Added comment: Comment on publications: Additional case reported in PMID:34686882.
Ichthyosis and erythrokeratoderma v2.13 KDSR Achchuthan Shanmugasundram Publications for gene: KDSR were set to 28575652
Palmoplantar keratoderma and erythrokeratodermas v1.28 KDSR Achchuthan Shanmugasundram Added comment: Comment on publications: Additional case reported in PMID:34686882.
Palmoplantar keratoderma and erythrokeratodermas v1.28 KDSR Achchuthan Shanmugasundram Publications for gene: KDSR were set to 28575652; 34686882
Palmoplantar keratoderma and erythrokeratodermas v1.27 KDSR Achchuthan Shanmugasundram Deleted their comment
Palmoplantar keratoderma and erythrokeratodermas v1.27 KDSR Achchuthan Shanmugasundram Added comment: Comment on publications: Additional patient reported in PMID:34686882.
Palmoplantar keratoderma and erythrokeratodermas v1.27 KDSR Achchuthan Shanmugasundram Publications for gene: KDSR were set to 28575652
Retinal disorders v3.30 KCNV2 Achchuthan Shanmugasundram reviewed gene: KCNV2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23221069, 31960170, 34535971, 34652420; Phenotypes: Retinal cone dystrophy 3B, OMIM:610356; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.62 TRPM3 Eleanor Williams Phenotypes for gene: TRPM3 were changed from Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures, OMIM:620224
Intellectual disability v4.61 TRPM3 Eleanor Williams Tag gene-checked was removed from gene: TRPM3.
Early onset or syndromic epilepsy v3.37 TRPM3 Eleanor Williams Tag gene-checked was removed from gene: TRPM3.
Early onset or syndromic epilepsy v3.37 TRPM3 Eleanor Williams Phenotypes for gene: TRPM3 were changed from Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures, OMIM:620224
Unexplained death in infancy and sudden unexplained death in childhood v3.45 Eleanor Williams Panel name changed from Unexplained death in infancy and childhood to Unexplained death in infancy and sudden unexplained death in childhood
Cerebral vascular malformations v2.68 COL3A1 Eleanor Williams Tag Q3_22_MOI was removed from gene: COL3A1.
Tag Q3_22_expert_review was removed from gene: COL3A1.
Cerebral vascular malformations v2.68 COL3A1 Eleanor Williams commented on gene: COL3A1: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed and remains as 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'.
Early onset or syndromic epilepsy v3.36 FAR1 Eleanor Williams Tag Q2_21_expert_review was removed from gene: FAR1.
Tag Q2_21_MOI was removed from gene: FAR1.
Tag Q3_22_NHS_review was removed from gene: FAR1.
Early onset or syndromic epilepsy v3.36 FAR1 Eleanor Williams commented on gene: FAR1
Early onset or syndromic epilepsy v3.36 FAR1 Eleanor Williams Classified gene: FAR1 as Green List (high evidence)
Early onset or syndromic epilepsy v3.36 FAR1 Eleanor Williams Gene: far1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v3.35 MED12 Eleanor Williams Tag Q3_21_MOI was removed from gene: MED12.
Tag Q3_21_expert_review was removed from gene: MED12.
Clefting v3.6 MED12 Eleanor Williams commented on gene: MED12: The mode of inheritance has been left as 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' with agreement from the Genomics Unit at NHSE.
Hypophosphataemia or rickets v3.1 SLC9A3R1 Eleanor Williams commented on gene: SLC9A3R1
Hypophosphataemia or rickets v3.1 SLC9A3R1 Eleanor Williams Tag new-gene-name tag was added to gene: SLC9A3R1.
Renal tubulopathies v3.3 SLC9A3R1 Eleanor Williams Tag new-gene-name tag was added to gene: SLC9A3R1.
Renal tubulopathies v3.3 SLC9A3R1 Eleanor Williams commented on gene: SLC9A3R1: Added new-gene-name tag, new approved HGNC gene symbol for SLC9A3R1 (HGNC:11075) is NHERF1.
Nephrocalcinosis or nephrolithiasis v3.4 SLC9A3R1 Eleanor Williams Tag new-gene-name tag was added to gene: SLC9A3R1.
Nephrocalcinosis or nephrolithiasis v3.4 SLC9A3R1 Eleanor Williams commented on gene: SLC9A3R1: Added new-gene-name tag, new approved HGNC gene symbol for SLC9A3R1 (HGNC:11075) is NHERF1.
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 RNU12 Eleanor Williams Tag gene-checked tag was added to gene: RNU12.
Rare genetic inflammatory skin disorders v2.3 RNU12 Eleanor Williams Tag gene-checked tag was added to gene: RNU12.
Neonatal diabetes v3.3 ZNF808 Eleanor Williams Tag gene-checked tag was added to gene: ZNF808.
Intellectual disability v4.61 TMEM63C Eleanor Williams Tag gene-checked tag was added to gene: TMEM63C.
Childhood onset hereditary spastic paraplegia v3.12 TMEM63C Eleanor Williams Tag gene-checked tag was added to gene: TMEM63C.
White matter disorders and cerebral calcification - narrow panel v2.9 TMEM63A Eleanor Williams Tag gene-checked tag was added to gene: TMEM63A.
Childhood onset dystonia, chorea or related movement disorder v2.11 SPATA5L1 Eleanor Williams Tag gene-checked tag was added to gene: SPATA5L1.
Intellectual disability v4.61 SPATA5L1 Eleanor Williams Tag gene-checked tag was added to gene: SPATA5L1.
Early onset or syndromic epilepsy v3.35 SPATA5L1 Eleanor Williams Tag gene-checked tag was added to gene: SPATA5L1.
Monogenic hearing loss v3.8 SPATA5L1 Eleanor Williams Tag gene-checked tag was added to gene: SPATA5L1.
Childhood onset hereditary spastic paraplegia v3.12 SPATA5L1 Eleanor Williams Tag gene-checked tag was added to gene: SPATA5L1.
Severe microcephaly v3.7 SPATA5L1 Eleanor Williams Tag gene-checked tag was added to gene: SPATA5L1.
Pituitary hormone deficiency v2.106 RNPC3 Eleanor Williams Tag gene-checked tag was added to gene: RNPC3.
Optic neuropathy v3.10 DNAJC30 Eleanor Williams Phenotypes for gene: DNAJC30 were changed from to Leber hereditary optic neuropathy, MONDO:0010788
Optic neuropathy v3.9 DNAJC30 Eleanor Williams Publications for gene: DNAJC30 were set to
Optic neuropathy v3.8 DNAJC30 Eleanor Williams Tag gene-checked tag was added to gene: DNAJC30.
Intellectual disability v4.61 CCDC32 Eleanor Williams Tag gene-checked tag was added to gene: CCDC32.
Mitochondrial disorders v3.7 NAXD Eleanor Williams Added comment: Comment on mode of inheritance: Setting the mode of inheritance to Biallelic as per OMIM and the expert reviewer.
Mitochondrial disorders v3.7 NAXD Eleanor Williams Mode of inheritance for gene: NAXD was changed from to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v4.8 KIF21A Achchuthan Shanmugasundram edited their review of gene: KIF21A: Changed phenotypes to: arthrogryposis, MONDO:0008779, fetal akinesia
Arthrogryposis v4.8 KIF21A Achchuthan Shanmugasundram Phenotypes for gene: KIF21A were changed from Arthrogryposis; fetal akinesia to arthrogryposis, MONDO:0008779; fetal akinesia
Arthrogryposis v4.7 KIF21A Achchuthan Shanmugasundram Publications for gene: KIF21A were set to 34740919
Arthrogryposis v4.6 KIF21A Achchuthan Shanmugasundram Classified gene: KIF21A as Amber List (moderate evidence)
Arthrogryposis v4.6 KIF21A Achchuthan Shanmugasundram Gene: kif21a has been classified as Amber List (Moderate Evidence).
Arthrogryposis v4.5 KIF21A Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: KIF21A.
Arthrogryposis v4.5 KIF21A Achchuthan Shanmugasundram reviewed gene: KIF21A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32686171, 34740919; Phenotypes: arthrogryposis, MONDO:0008779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v2.10 WNT7B Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: WNT7B.
Intellectual disability v4.61 WNK3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: WNK3.
Malformations of cortical development v3.11 WNK3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: WNK3.
Early onset or syndromic epilepsy v3.35 WNK3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: WNK3.
Ehlers Danlos syndrome with a likely monogenic cause v2.68 TPSAB1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TPSAB1.
Skeletal ciliopathies v2.5 TBC1D32 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TBC1D32.
Neurological ciliopathies v2.6 TBC1D32 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TBC1D32.
Structural eye disease v2.3 TBC1D32 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TBC1D32.
Thoracic dystrophies v1.18 TBC1D32 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TBC1D32.
Pituitary hormone deficiency v2.106 TBC1D32 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TBC1D32.
Intellectual disability v4.61 SRRM2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: SRRM2.
Pituitary hormone deficiency v2.106 SLC20A1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: SLC20A1.
Fetal anomalies v2.10 SLC20A1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: SLC20A1.
Paediatric disorders - additional genes v2.7 SIX2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: SIX2.
Paediatric pseudo-obstruction syndrome v0.217 SEMA3F Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: SEMA3F.
Hypogonadotropic hypogonadism (GMS) v2.5 SEMA3F Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: SEMA3F.
Intellectual disability v4.61 SCAMP5 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: SCAMP5.
Early onset or syndromic epilepsy v3.35 SCAMP5 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: SCAMP5.
Intellectual disability v4.61 SCAF4 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: SCAF4.
Early onset or syndromic epilepsy v3.35 RAB11A Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: RAB11A.
DDG2P v3.1 RAB11A Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: RAB11A.
Fetal anomalies v2.10 RAB11A Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: RAB11A.
Intellectual disability v4.61 RAB11A Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: RAB11A.
Paediatric pseudo-obstruction syndrome v0.217 PROKR1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: PROKR1.
Paediatric pseudo-obstruction syndrome v0.217 PROK1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: PROK1.
Hypogonadotropic hypogonadism (GMS) v2.5 PLXNA3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: PLXNA3.
Ataxia and cerebellar anomalies - narrow panel v3.38 MTCL1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: MTCL1.
Hypogonadotropic hypogonadism (GMS) v2.5 KLB Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: KLB.
Intellectual disability v4.61 HMGB1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: HMGB1.
Limb disorders v3.6 HMGB1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: HMGB1.
Severe microcephaly v3.7 HMGB1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: HMGB1.
Severe microcephaly v3.7 GINS3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: GINS3.
Intellectual disability v4.61 FOXP4 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: FOXP4.
Fetal anomalies v2.10 FOXP4 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: FOXP4.
Paediatric disorders - additional genes v2.7 FOXP4 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: FOXP4.
Monogenic hearing loss v3.8 DVL2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DVL2.
Limb disorders v3.6 DVL2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DVL2.
Skeletal dysplasia v3.5 DVL2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DVL2.
Intellectual disability v4.61 DROSHA Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DROSHA.
Early onset or syndromic epilepsy v3.35 DROSHA Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DROSHA.
Skeletal dysplasia v3.5 DROSHA Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DROSHA.
Severe microcephaly v3.7 DROSHA Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DROSHA.
DDG2P v3.1 CRIM1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: CRIM1.
Structural eye disease v2.3 CRIM1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: CRIM1.
Intellectual disability v4.61 CDK9 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: CDK9.
Bilateral congenital or childhood onset cataracts v3.3 CDK9 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: CDK9.
Intellectual disability v4.61 BLOC1S1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: BLOC1S1.
Early onset or syndromic epilepsy v3.35 BLOC1S1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: BLOC1S1.
Childhood onset hereditary spastic paraplegia v3.12 BLOC1S1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: BLOC1S1.
Optic neuropathy v3.8 BLOC1S1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: BLOC1S1.
White matter disorders and cerebral calcification - narrow panel v2.9 BLOC1S1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: BLOC1S1.
Rare anaemia v2.5 RPS27 Achchuthan Shanmugasundram reviewed gene: RPS27: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Rare anaemia v2.5 RPS27 Achchuthan Shanmugasundram Deleted their review
Rare anaemia v2.5 RPS27 Achchuthan Shanmugasundram Classified gene: RPS27 as Amber List (moderate evidence)
Rare anaemia v2.5 RPS27 Achchuthan Shanmugasundram Gene: rps27 has been classified as Amber List (Moderate Evidence).
Rare anaemia v2.4 RPS27 Achchuthan Shanmugasundram Deleted their comment
Rare anaemia v2.4 RPL27 Achchuthan Shanmugasundram reviewed gene: RPL27: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Rare anaemia v2.4 RPL27 Achchuthan Shanmugasundram Deleted their review
Rare anaemia v2.4 RPL27 Achchuthan Shanmugasundram Classified gene: RPL27 as Amber List (moderate evidence)
Rare anaemia v2.4 RPL27 Achchuthan Shanmugasundram Gene: rpl27 has been classified as Amber List (Moderate Evidence).
Rare anaemia v2.3 RPL27 Achchuthan Shanmugasundram Deleted their comment
Cytopenia - NOT Fanconi anaemia v2.4 RPL27 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated to Amber following NHS Genomic Medicine Service approval. The GMS reviewers note that this gene should be demoted to amber as there is only one case, but supported by functional studies and mutation of multiple other ribosomal genes results in the same phenotype.; to: The rating of this gene has been updated to Amber following NHS Genomic Medicine Service approval. The GMS reviewers note that this gene should be demoted to amber as there is only one case, but supported by functional studies and mutation of multiple other ribosomal genes results in the same phenotype.
Cytopenia - NOT Fanconi anaemia v2.4 RPL27 Achchuthan Shanmugasundram reviewed gene: RPL27: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cytopenia - NOT Fanconi anaemia v2.4 RPL27 Achchuthan Shanmugasundram Deleted their review
Cytopenia - NOT Fanconi anaemia v2.4 RPL27 Achchuthan Shanmugasundram Deleted their comment
Cytopenia - NOT Fanconi anaemia v2.4 RPL27 Achchuthan Shanmugasundram Classified gene: RPL27 as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v2.4 RPL27 Achchuthan Shanmugasundram Gene: rpl27 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.61 ASCC3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ASCC3.
DDG2P v3.1 ASCC3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ASCC3.
Congenital myopathy v3.124 ASCC3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ASCC3.
Cerebral vascular malformations v2.68 ANGPTL6 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ANGPTL6.
Arthrogryposis v4.5 ADAMTS15 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ADAMTS15.
Intellectual disability v4.61 PGM2L1 Achchuthan Shanmugasundram Phenotypes for gene: PGM2L1 were changed from Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191 to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191
Intellectual disability v4.60 PGM2L1 Achchuthan Shanmugasundram Phenotypes for gene: PGM2L1 were changed from Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191 to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191
Intellectual disability v4.61 PGM2L1 Achchuthan Shanmugasundram Phenotypes for gene: PGM2L1 were changed from Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191 to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191
Intellectual disability v4.60 PGM2L1 Achchuthan Shanmugasundram Phenotypes for gene: PGM2L1 were changed from Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191 to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191
Early onset or syndromic epilepsy v3.35 PGM2L1 Achchuthan Shanmugasundram Phenotypes for gene: PGM2L1 were changed from Neurodevelopmental disorder to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191
Intellectual disability v4.60 PGM2L1 Achchuthan Shanmugasundram Phenotypes for gene: PGM2L1 were changed from Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191 to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191
Early onset or syndromic epilepsy v3.34 PGM2L1 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: PGM2L1.
Intellectual disability v4.60 PGM2L1 Achchuthan Shanmugasundram Phenotypes for gene: PGM2L1 were changed from Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191 to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191
Intellectual disability v4.60 PGM2L1 Achchuthan Shanmugasundram Phenotypes for gene: PGM2L1 were changed from Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191 to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191
Intellectual disability v4.60 PGM2L1 Achchuthan Shanmugasundram Phenotypes for gene: PGM2L1 were changed from Neurodevelopmental disorder to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191
Intellectual disability v4.59 PGM2L1 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: PGM2L1.
Severe early-onset obesity v3.4 PGM2L1 Achchuthan Shanmugasundram Phenotypes for gene: PGM2L1 were changed from Neurodevelopmental disorder to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191
COVID-19 research v1.136 DCLRE1B Achchuthan Shanmugasundram Tag gene-checked was removed from gene: DCLRE1B.
COVID-19 research v1.136 DCLRE1B Achchuthan Shanmugasundram Phenotypes for gene: DCLRE1B were changed from Intrauterine growth retardation, microcephaly, nail dystrophy, sparse scalp hair and eyelashes, hyperpigmentation of skin, palmar hyperkeratosis, premalignant oral leukoplakia, pancytopenia, myelodysplasia, +/- recurrent infections. A severe phenotype with developmental delay and cerebellar hypoplasia known as Hoyeraal-Hreidarsson Syndrome (HHS) may occur in some DKC patients; Combined immunodeficiencies with associated or syndromic features; Hoyeraal-Hreidarsson syndrome to Dyskeratosis congenita, autosomal recessive 8, OMIM:620133
Primary immunodeficiency or monogenic inflammatory bowel disease v3.5 DCLRE1B Achchuthan Shanmugasundram Tag gene-checked was removed from gene: DCLRE1B.
Intellectual disability v4.59 THUMPD1 Eleanor Williams Added comment: Comment on mode of inheritance: Adding the mode of inheritance of biallelic as this was missing. Autosomal recessive MOI in OMIM for a relevant phenotype.
Intellectual disability v4.59 THUMPD1 Eleanor Williams Mode of inheritance for gene: THUMPD1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.58 THUMPD1 Eleanor Williams Phenotypes for gene: THUMPD1 were changed from THUMPD1 neurodevelopment disorder to Neurodevelopmental disorder with speech delay and variable ocular anomalies, OMIM:619989
Primary immunodeficiency or monogenic inflammatory bowel disease v3.5 DCLRE1B Achchuthan Shanmugasundram Phenotypes for gene: DCLRE1B were changed from Hoyeraal-Hreidarsson syndrome; Intrauterine growth retardation, microcephaly, nail dystrophy, sparse scalp hair and eyelashes, hyperpigmentation of skin, palmar hyperkeratosis, premalignant oral leukoplakia, pancytopenia, myelodysplasia, +/- recurrent infections. A severe phenotype with developmental delay and cerebellar hypoplasia known as Hoyeraal-Hreidarsson Syndrome (HHS) may occur in some DKC patients; Combined immunodeficiencies with associated or syndromic features to Dyskeratosis congenita, autosomal recessive 8, OMIM:620133
Non-syndromic hypotrichosis v1.12 C3orf52 Achchuthan Shanmugasundram Phenotypes for gene: C3orf52 were changed from Localized hypotrichosis to Hypotrichosis 15, OMIM:620177
Ectodermal dysplasia v2.6 C3orf52 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: C3orf52.
Ectodermal dysplasia v2.6 C3orf52 Achchuthan Shanmugasundram Phenotypes for gene: C3orf52 were changed from Localized hypotrichosis to Hypotrichosis 15, OMIM:620177
Iron metabolism disorders - NOT common HFE mutations v1.40 BMP6 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: BMP6.
Iron metabolism disorders - NOT common HFE mutations v1.40 BMP6 Achchuthan Shanmugasundram Phenotypes for gene: BMP6 were changed from {Iron overload, susceptibility to}, OMIM:620121; Hemochromatosis type 5 ORPHA:447792 to {Iron overload, susceptibility to}, OMIM:620121
Iron metabolism disorders - NOT common HFE mutations v1.39 BMP6 Achchuthan Shanmugasundram Phenotypes for gene: BMP6 were changed from Hemochromatosis type 5 ORPHA:447792 to {Iron overload, susceptibility to}, OMIM:620121; Hemochromatosis type 5 ORPHA:447792
Early onset or syndromic epilepsy v3.34 CAPRIN1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: CAPRIN1.
Early onset or syndromic epilepsy v3.34 CAPRIN1 Achchuthan Shanmugasundram Publications for gene: CAPRIN1 were set to 35979925; 35977029; 28135719; 31398340; https://doi.org/10.1101/2021.12.20.21267194
Early onset or syndromic epilepsy v3.33 CAPRIN1 Achchuthan Shanmugasundram Classified gene: CAPRIN1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.33 CAPRIN1 Achchuthan Shanmugasundram Gene: caprin1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v3.32 CAPRIN1 Achchuthan Shanmugasundram reviewed gene: CAPRIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35979925; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, Epilepsy, MONDO:0005027; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.57 ISCA-37429-Loss Arina Puzriakova Phenotypes for Region: ISCA-37429-Loss were changed from Wolf-Hirschhorn syndrome, OMIM:194190 to Wolf-Hirschhorn syndrome, OMIM:194190
Intellectual disability v4.57 ISCA-37429-Loss Arina Puzriakova Phenotypes for Region: ISCA-37429-Loss were changed from 194190; Wolf-Hirschhorn syndrome to Wolf-Hirschhorn syndrome, OMIM:194190
Early onset or syndromic epilepsy v3.32 ISCA-37429-Loss Arina Puzriakova Phenotypes for Region: ISCA-37429-Loss were changed from 194190; Wolf-Hirschhorn syndrome to Wolf-Hirschhorn syndrome, OMIM:194190
Paediatric motor neuronopathies v2.9 ISCA-37429-Loss Arina Puzriakova Phenotypes for Region: ISCA-37429-Loss were changed from 194190; Wolf-Hirschhorn syndrome to Wolf-Hirschhorn syndrome, OMIM:194190
IUGR and IGF abnormalities v1.58 ISCA-37429-Loss Arina Puzriakova Phenotypes for Region: ISCA-37429-Loss were changed from 194190; Wolf-Hirschhorn syndrome to Wolf-Hirschhorn syndrome, OMIM:194190
Congenital myopathy v3.124 ISCA-37429-Loss Arina Puzriakova Phenotypes for Region: ISCA-37429-Loss were changed from 194190; Wolf-Hirschhorn syndrome to Wolf-Hirschhorn syndrome, OMIM:194190
Paediatric motor neuronopathies v2.8 ISCA-37420-Loss Arina Puzriakova Phenotypes for Region: ISCA-37420-Loss were changed from PMID: 18628315 developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behaviour, other clinically important features include epilepsy, heart defects and kidney/urologic anomalies; 610443; PMID: 25217958; Koolen-De Vries syndrome 610443 to Koolen-De Vries syndrome, OMIM:610443; Developmental delay/intellectual disability, hypotonia, distinctive facial features, congenital malformations, and behavioural feature
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 ISCA-37420-Loss Arina Puzriakova Phenotypes for Region: ISCA-37420-Loss were changed from Koolen-de Vries/KANSL haploinsufficiency syndrome. to Koolen-De Vries syndrome, OMIM:610443; Developmental delay/intellectual disability, hypotonia, distinctive facial features, congenital malformations, and behavioural feature
Intellectual disability v4.56 ISCA-37420-Loss Arina Puzriakova Phenotypes for Region: ISCA-37420-Loss were changed from PMID: 18628315 developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behaviour, other clinically important features include epilepsy, heart defects and kidney/urologic anomalies; 610443; PMID: 25217958; Koolen-De Vries syndrome 610443 to Koolen-De Vries syndrome, OMIM:610443; Developmental delay/intellectual disability, hypotonia, distinctive facial features, congenital malformations, and behavioural feature
IUGR and IGF abnormalities v1.57 ISCA-37420-Loss Arina Puzriakova Phenotypes for Region: ISCA-37420-Loss were changed from PMID: 18628315 developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behaviour, other clinically important features include epilepsy, heart defects and kidney/urologic anomalies; 610443; PMID: 25217958; Koolen-De Vries syndrome 610443 to Koolen-De Vries syndrome, OMIM:610443; Developmental delay/intellectual disability, hypotonia, distinctive facial features, congenital malformations, and behavioural feature
Intellectual disability v4.55 ISCA-37420-Loss Arina Puzriakova commented on Region: ISCA-37420-Loss: Previously in phenotypes field:

PMID: 18628315 developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behaviour, other clinically important features include epilepsy, heart defects and kidney/urologic anomalies; 610443; PMID: 25217958; Koolen-De Vries syndrome 610443
Paediatric motor neuronopathies v2.7 ISCA-37420-Loss Arina Puzriakova commented on Region: ISCA-37420-Loss: Previously in phenotypes field:

PMID: 18628315 developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behaviour, other clinically important features include epilepsy, heart defects and kidney/urologic anomalies; 610443; PMID: 25217958; Koolen-De Vries syndrome 610443
Congenital myopathy v3.123 ISCA-37420-Loss Arina Puzriakova commented on Region: ISCA-37420-Loss: Previously in phenotypes field:

PMID: 18628315 developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behaviour, other clinically important features include epilepsy, heart defects and kidney/urologic anomalies; 610443; PMID: 25217958; Koolen-De Vries syndrome 610443
IUGR and IGF abnormalities v1.56 ISCA-37420-Loss Arina Puzriakova commented on Region: ISCA-37420-Loss: Previously in phenotypes field:

PMID: 18628315 developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behaviour, other clinically important features include epilepsy, heart defects and kidney/urologic anomalies; 610443; PMID: 25217958; Koolen-De Vries syndrome 610443
Congenital myopathy v3.123 ISCA-37420-Loss Arina Puzriakova Phenotypes for Region: ISCA-37420-Loss were changed from PMID: 18628315 developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behaviour, other clinically important features include epilepsy, heart defects and kidney/urologic anomalies; 610443; PMID: 25217958; Koolen-De Vries syndrome 610443 to Koolen-De Vries syndrome, OMIM:610443; Developmental delay/intellectual disability, hypotonia, distinctive facial features, congenital malformations, and behavioural features
Intellectual disability v4.55 ISCA-37408-Loss Arina Puzriakova commented on Region: ISCA-37408-Loss
Paediatric motor neuronopathies v2.7 ISCA-37408-Loss Arina Puzriakova commented on Region: ISCA-37408-Loss
Severe microcephaly v3.7 ISCA-37408-Loss Arina Puzriakova commented on Region: ISCA-37408-Loss
Intellectual disability v4.55 ISCA-37408-Loss Arina Puzriakova Phenotypes for Region: ISCA-37408-Loss were changed from PMID: 16963482 idiopathic intellectual disability including moderate to severe intellectual disability, autism/autistic features, microcephaly, structural brain anomalies including cortical dysplasia/pachygyria, renal anomalies (multicystic kidney, hydronephrosis), digital camptodactyly, visual impairment, strabismus, neuromotor deficits, communication and attention impairments, and a distinctive pattern of craniofacial features. Dysmorphic craniofacial features include progressive microcephaly, flat occiput, widened inner canthal distance, small palpebral fissures, ptosis, long and straight eyelashes, broad and high nasal root extending to a widened, prominent nasal tip with elongated, smooth philtrum, rounding of the upper vermillion border and everted lower lips. PMID: 18245392 A 32-year-old, mentally retarded male was referred to our centre for further clinical genetic analysis. He was born to non-consanguineous parents after 42 weeks gestation with a birth weight of 3500 g. He had a healthy older brother. In the neonatal period he was hypotonic and at 8 weeks of age he underwent surgery because of an inguinal hernia with removal of an atrophic right testis. His motor development was severely delayed with sitting at 3.5 years and walking at 5 years of age. Speech was poorly developed, characterised by the usage of only a few words. During infancy an optic nerve hypoplasia was diagnosed, and during childhood he frequently suffered from luxations of the patellae, which required surgery. At the age of 32 years his height is 163 cm (_3 SDS) and head circumference 52.5 cm (_2.5 SDS). He has a narrow receding forehead, widened inner canthal distance of 3.5 cm (90th centile), normal outer canthal distance of 8.5 cm (25th centile), telecanthus, short and down slanting palpebral fissures, epicanthal folds, ptosis, long, straight eyelashes, high nasal bridge, low set large ears, flat philtrum, small mouth with high, narrow palate and retrognathia. The thorax is broad with increased internipple distance and slight gynaecomastia. A recent renal ultrasound revealed multiple cysts in the left, dystrophic kidney and two uncomplicated cysts in the enlarged, right kidney. The patient has a normally sized phallus with absent right testis and small left testis. His hands show a simian crease right and tapering fingers with broad proximal interphalangeal joints. He shows sandal gaps on both flat feet with clinodactyly of the fourth and fifth toes (and more); 612513; PMID: 22579565 severe developmental delay, congenital microcephaly, intractable epilepsy, and renal anomalies, as well as a congenital choledochal cyst which has not been previously reported in other patients with this cytogenetic defect to Dysmorphic features, moderate to severe intellectual disability, microcephaly and renal anomalies
Paediatric motor neuronopathies v2.7 ISCA-37408-Loss Arina Puzriakova Phenotypes for Region: ISCA-37408-Loss were changed from PMID: 16963482 idiopathic intellectual disability including moderate to severe intellectual disability, autism/autistic features, microcephaly, structural brain anomalies including cortical dysplasia/pachygyria, renal anomalies (multicystic kidney, hydronephrosis), digital camptodactyly, visual impairment, strabismus, neuromotor deficits, communication and attention impairments, and a distinctive pattern of craniofacial features. Dysmorphic craniofacial features include progressive microcephaly, flat occiput, widened inner canthal distance, small palpebral fissures, ptosis, long and straight eyelashes, broad and high nasal root extending to a widened, prominent nasal tip with elongated, smooth philtrum, rounding of the upper vermillion border and everted lower lips. PMID: 18245392 A 32-year-old, mentally retarded male was referred to our centre for further clinical genetic analysis. He was born to non-consanguineous parents after 42 weeks gestation with a birth weight of 3500 g. He had a healthy older brother. In the neonatal period he was hypotonic and at 8 weeks of age he underwent surgery because of an inguinal hernia with removal of an atrophic right testis. His motor development was severely delayed with sitting at 3.5 years and walking at 5 years of age. Speech was poorly developed, characterised by the usage of only a few words. During infancy an optic nerve hypoplasia was diagnosed, and during childhood he frequently suffered from luxations of the patellae, which required surgery. At the age of 32 years his height is 163 cm (_3 SDS) and head circumference 52.5 cm (_2.5 SDS). He has a narrow receding forehead, widened inner canthal distance of 3.5 cm (90th centile), normal outer canthal distance of 8.5 cm (25th centile), telecanthus, short and down slanting palpebral fissures, epicanthal folds, ptosis, long, straight eyelashes, high nasal bridge, low set large ears, flat philtrum, small mouth with high, narrow palate and retrognathia. The thorax is broad with increased internipple distance and slight gynaecomastia. A recent renal ultrasound revealed multiple cysts in the left, dystrophic kidney and two uncomplicated cysts in the enlarged, right kidney. The patient has a normally sized phallus with absent right testis and small left testis. His hands show a simian crease right and tapering fingers with broad proximal interphalangeal joints. He shows sandal gaps on both flat feet with clinodactyly of the fourth and fifth toes (and more); 612513; PMID: 22579565 severe developmental delay, congenital microcephaly, intractable epilepsy, and renal anomalies, as well as a congenital choledochal cyst which has not been previously reported in other patients with this cytogenetic defect to Dysmorphic features, moderate to severe intellectual disability, microcephaly and renal anomalies
Severe microcephaly v3.7 ISCA-37408-Loss Arina Puzriakova Phenotypes for Region: ISCA-37408-Loss were changed from PMID: 16963482 idiopathic intellectual disability including moderate to severe intellectual disability, autism/autistic features, microcephaly, structural brain anomalies including cortical dysplasia/pachygyria, renal anomalies (multicystic kidney, hydronephrosis), digital camptodactyly, visual impairment, strabismus, neuromotor deficits, communication and attention impairments, and a distinctive pattern of craniofacial features. Dysmorphic craniofacial features include progressive microcephaly, flat occiput, widened inner canthal distance, small palpebral fissures, ptosis, long and straight eyelashes, broad and high nasal root extending to a widened, prominent nasal tip with elongated, smooth philtrum, rounding of the upper vermillion border and everted lower lips. PMID: 18245392 A 32-year-old, mentally retarded male was referred to our centre for further clinical genetic analysis. He was born to non-consanguineous parents after 42 weeks gestation with a birth weight of 3500 g. He had a healthy older brother. In the neonatal period he was hypotonic and at 8 weeks of age he underwent surgery because of an inguinal hernia with removal of an atrophic right testis. His motor development was severely delayed with sitting at 3.5 years and walking at 5 years of age. Speech was poorly developed, characterised by the usage of only a few words. During infancy an optic nerve hypoplasia was diagnosed, and during childhood he frequently suffered from luxations of the patellae, which required surgery. At the age of 32 years his height is 163 cm (_3 SDS) and head circumference 52.5 cm (_2.5 SDS). He has a narrow receding forehead, widened inner canthal distance of 3.5 cm (90th centile), normal outer canthal distance of 8.5 cm (25th centile), telecanthus, short and down slanting palpebral fissures, epicanthal folds, ptosis, long, straight eyelashes, high nasal bridge, low set large ears, flat philtrum, small mouth with high, narrow palate and retrognathia. The thorax is broad with increased internipple distance and slight gynaecomastia. A recent renal ultrasound revealed multiple cysts in the left, dystrophic kidney and two uncomplicated cysts in the enlarged, right kidney. The patient has a normally sized phallus with absent right testis and small left testis. His hands show a simian crease right and tapering fingers with broad proximal interphalangeal joints. He shows sandal gaps on both flat feet with clinodactyly of the fourth and fifth toes (and more); 612513; PMID: 22579565 severe developmental delay, congenital microcephaly, intractable epilepsy, and renal anomalies, as well as a congenital choledochal cyst which has not been previously reported in other patients with this cytogenetic defect to Dysmorphic features, moderate to severe intellectual disability, microcephaly and renal anomalies
Congenital myopathy v3.122 ISCA-37408-Loss Arina Puzriakova Phenotypes for Region: ISCA-37408-Loss were changed from PMID: 16963482 idiopathic intellectual disability including moderate to severe intellectual disability, autism/autistic features, microcephaly, structural brain anomalies including cortical dysplasia/pachygyria, renal anomalies (multicystic kidney, hydronephrosis), digital camptodactyly, visual impairment, strabismus, neuromotor deficits, communication and attention impairments, and a distinctive pattern of craniofacial features. Dysmorphic craniofacial features include progressive microcephaly, flat occiput, widened inner canthal distance, small palpebral fissures, ptosis, long and straight eyelashes, broad and high nasal root extending to a widened, prominent nasal tip with elongated, smooth philtrum, rounding of the upper vermillion border and everted lower lips. PMID: 18245392 A 32-year-old, mentally retarded male was referred to our centre for further clinical genetic analysis. He was born to non-consanguineous parents after 42 weeks gestation with a birth weight of 3500 g. He had a healthy older brother. In the neonatal period he was hypotonic and at 8 weeks of age he underwent surgery because of an inguinal hernia with removal of an atrophic right testis. His motor development was severely delayed with sitting at 3.5 years and walking at 5 years of age. Speech was poorly developed, characterised by the usage of only a few words. During infancy an optic nerve hypoplasia was diagnosed, and during childhood he frequently suffered from luxations of the patellae, which required surgery. At the age of 32 years his height is 163 cm (_3 SDS) and head circumference 52.5 cm (_2.5 SDS). He has a narrow receding forehead, widened inner canthal distance of 3.5 cm (90th centile), normal outer canthal distance of 8.5 cm (25th centile), telecanthus, short and down slanting palpebral fissures, epicanthal folds, ptosis, long, straight eyelashes, high nasal bridge, low set large ears, flat philtrum, small mouth with high, narrow palate and retrognathia. The thorax is broad with increased internipple distance and slight gynaecomastia. A recent renal ultrasound revealed multiple cysts in the left, dystrophic kidney and two uncomplicated cysts in the enlarged, right kidney. The patient has a normally sized phallus with absent right testis and small left testis. His hands show a simian crease right and tapering fingers with broad proximal interphalangeal joints. He shows sandal gaps on both flat feet with clinodactyly of the fourth and fifth toes (and more); 612513; PMID: 22579565 severe developmental delay, congenital microcephaly, intractable epilepsy, and renal anomalies, as well as a congenital choledochal cyst which has not been previously reported in other patients with this cytogenetic defect to Dysmorphic features, moderate to severe intellectual disability, microcephaly and renal anomalies
Congenital myopathy v3.121 ISCA-37408-Loss Arina Puzriakova commented on Region: ISCA-37408-Loss
Adult onset hereditary spastic paraplegia v2.11 SPTAN1 Achchuthan Shanmugasundram Mode of inheritance for gene: SPTAN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset hereditary spastic paraplegia v2.10 SPTAN1 Achchuthan Shanmugasundram Publications for gene: SPTAN1 were set to 18065176; 20493457; 22656320; 35150594; 36331550
Adult onset hereditary spastic paraplegia v2.9 SPTAN1 Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be rated Green as there are several unrelated cases (many more than three cases identified with different variants) from multiple ethnicities reported with spastic paraplegia and supported by functional studies.

OMIM reports Developmental and epileptic encephalopathy 5 (OMIM #613477) as a phenotype for SPTAN1 variants. Spastic quadriplegia is one of the clinical manifestations that has been reported as part of this phenotype.

Two of three patients identified with SPTAN1 variants in PMID:20493457 were reported with spastic quadriplegia, while it has also been reported in one year old male from PMID:22656320 and two patients from PMID:18065176. Out of 22 patients from 14 families identified with SPTAN1 variants in PMID:35150594, fifteen patients from seven families displaying p.Arg19Trp variant were reported with hereditary spastic paraplegia with age of onset ranging from congenital to adolescence, while three other patients displaying other variants (p.Arg1624Cys, p.Arg1098Cys & p.Gln2205Pro) displayed different extremes of spastic ataxia spectrum.

In PMID:36331550, authors carried out SPTAN1 gene enrichment analysis in the rare disease component of the 100,000 Genomes Project and screened 100,000 Genomes Project, DECIPHER database, and GeneMatcher to identify individuals with SPTAN1 variants. Statistically significant enrichment of rare probably damaging SPTAN1 variants were identified in families with hereditary ataxia (HA) or spastic paraplegia (HSP). Out of 31 individuals identified with SPTAN1 variants, five (three families) were presented with complex HA/HSP, two were presented with complex HSP and one with pure HSP.
Sources: Literature; to: Comment on classification: This gene should be rated Green as there are several unrelated cases (many more than three cases identified with different variants) reported with spastic paraplegia and supported by functional studies. Both autosomal dominant and autosomal recessive variants of this gene are implicated in spastic paraplegia and at least three cases are reported for both disorders.

Autosomal dominant disorder:

OMIM reports Developmental and epileptic encephalopathy 5 (OMIM #613477) as a phenotype for SPTAN1 variants. Spastic quadriplegia is one of the clinical manifestations that has been reported as part of this phenotype.

Two of three patients identified with SPTAN1 variants in PMID:20493457 were reported with spastic quadriplegia, while it has also been reported in one year old male from PMID:22656320 and two patients from PMID:18065176. Out of 22 patients from 14 families identified with SPTAN1 variants in PMID:35150594, fifteen patients from seven families displaying p.Arg19Trp variant were reported with hereditary spastic paraplegia with age of onset ranging from congenital to adolescence, while three other patients displaying other variants (p.Arg1624Cys, p.Arg1098Cys & p.Gln2205Pro) displayed different extremes of spastic ataxia spectrum.

In PMID:36331550, authors carried out SPTAN1 gene enrichment analysis in the rare disease component of the 100,000 Genomes Project and screened 100,000 Genomes Project, DECIPHER database, and GeneMatcher to identify individuals with SPTAN1 variants. Statistically significant enrichment of rare probably damaging SPTAN1 variants were identified in families with hereditary ataxia (HA) or spastic paraplegia (HSP). Out of 31 individuals identified with SPTAN1 variants, five (three families) were presented with complex HA/HSP, two were presented with complex HSP and one with pure HSP.

Autosomal recessive disorder:

PMID:31515523 reported two cases of juvenile/ adult-onset spastic paraplegia caused by compound heterozygous variants (p.Ala858Ser/ p.Ala1428Gly & p.Ala858Ser/ Met2330Ile). PMID:34526651 reported a female patient with juvenile/ adult-onset spastic paraplegia and was identified with homozygous missense variant p.Ile1388Val.
Sources: Literature
Adult onset hereditary spastic paraplegia v2.9 SPTAN1 Achchuthan Shanmugasundram edited their review of gene: SPTAN1: Changed publications to: 18065176, 20493457, 22656320, 31515523, 34526651, 35150594, 36331550; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.38 NPTX1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: NPTX1.
Ataxia and cerebellar anomalies - narrow panel v3.38 NPTX1 Achchuthan Shanmugasundram Phenotypes for gene: NPTX1 were changed from Ataxia to Spinocerebellar ataxia 50, OMIM:620158
Ataxia and cerebellar anomalies - narrow panel v3.37 NPTX1 Achchuthan Shanmugasundram Publications for gene: NPTX1 were set to 34788392; 35285082; 35560436
Ataxia and cerebellar anomalies - narrow panel v3.36 NPTX1 Achchuthan Shanmugasundram Classified gene: NPTX1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v3.36 NPTX1 Achchuthan Shanmugasundram Gene: nptx1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v3.35 NPTX1 Achchuthan Shanmugasundram reviewed gene: NPTX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34788392, 35285082, 35288776, 35560436; Phenotypes: Spinocerebellar ataxia 50, OMIM:620158; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v3.12 SPTAN1 Achchuthan Shanmugasundram Classified gene: SPTAN1 as Amber List (moderate evidence)
Hereditary ataxia with onset in adulthood v3.12 SPTAN1 Achchuthan Shanmugasundram Gene: sptan1 has been classified as Amber List (Moderate Evidence).
Hereditary ataxia with onset in adulthood v3.11 SPTAN1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: SPTAN1.
Hereditary ataxia with onset in adulthood v3.11 SPTAN1 Achchuthan Shanmugasundram gene: SPTAN1 was added
gene: SPTAN1 was added to Hereditary ataxia - adult onset. Sources: Literature
Mode of inheritance for gene: SPTAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPTAN1 were set to 33790315; 35150594; 36331550; 36408834
Phenotypes for gene: SPTAN1 were set to Developmental and epileptic encephalopathy 5, OMIM:613477; Cerebellar ataxia, MONDO:0000437; Hereditary spastic paraplegia, MONDO:0019064
Review for gene: SPTAN1 was set to GREEN
Added comment: Comment on classification: This gene should be rated Green as there are several unrelated cases (many more than three cases identified with different variants) from multiple ethnicities reported with adult-onset ataxia and was also supported by functional studies including results from mouse model.

Out of 22 patients from 14 families identified with SPTAN1 variants in PMID:35150594, four unrelated patients displaying p.Lys2083del variant were reported with cerebellar ataxia, of these two had early-onset, one had juvenile-onset and one had adult-onset.

In PMID:36331550, authors carried out SPTAN1 gene enrichment analysis in the rare disease component of the 100,000 Genomes Project and screened 100,000 Genomes Project, DECIPHER database, and GeneMatcher to identify individuals with SPTAN1 variants. Statistically significant enrichment of rare probably damaging SPTAN1 variants were identified in families with hereditary ataxia (HA) or spastic paraplegia (HSP). Out of 31 individuals identified with SPTAN1 variants, five (from three families) were presented with complex HA/HSP and two were presented with pure HA. The two patients presented with pure ataxia had adult-onset.

A 33-year old Korean woman identified with SPTAN1 variant (p.Lys2083del) was reported with cerebellar ataxia in PMID:36408834, being the first reported case of SPTAN1-related cerebellar ataxia.

In addition, a strain of C57BL/6J mice harbouring a single point mutation in Sptan1 (c.3293G > A/ p.Arg1098Gln) with reduced CaM affinity and intrinsically enhanced sensitivity to calpain proteolysis was reported in PMID:33790315. Homozygotes are embryonically lethal and heterozygotes develop a progressive ataxia.
Sources: Literature
Childhood onset hereditary spastic paraplegia v3.12 SPTAN1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: SPTAN1.
Childhood onset hereditary spastic paraplegia v3.12 SPTAN1 Achchuthan Shanmugasundram Classified gene: SPTAN1 as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v3.12 SPTAN1 Achchuthan Shanmugasundram Gene: sptan1 has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v3.11 SPTAN1 Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be rated Green as there are several unrelated cases (>3 cases identified with different variants) reported with childhood/ early-onset spastic paraplegia.

Two of three patients identified with SPTAN1 variants in PMID:20493457 were reported with spastic quadriplegia whose age of onset were three years and seven years, while it has also been reported in one year old male from PMID:22656320. Out of 22 patients from 14 families identified with SPTAN1 variants in PMID:35150594, fifteen patients from seven families displaying p.Arg19Trp variant were reported with hereditary spastic paraplegia with age of onset ranging from congenital to adolescence.
Sources: Literature; to: Comment on classification: This gene should be rated Green as there are several unrelated cases (>3 cases identified with different variants) reported with childhood/ early-onset spastic paraplegia.

Two of three patients identified with SPTAN1 variants in PMID:20493457 were reported with spastic quadriplegia whose age of onset were three years and seven years, while it has also been reported in one year old male from PMID:22656320. Out of 22 patients from 14 families identified with SPTAN1 variants in PMID:35150594, fifteen patients from seven families displaying p.Arg19Trp variant were reported with hereditary spastic paraplegia with age of onset ranging from congenital to adolescence (2 cases with congenital, 11 with childhood and 2 with adolescence-onset).
Sources: Literature
Childhood onset hereditary spastic paraplegia v3.11 SPTAN1 Achchuthan Shanmugasundram gene: SPTAN1 was added
gene: SPTAN1 was added to Hereditary spastic paraplegia - childhood onset. Sources: Literature
Mode of inheritance for gene: SPTAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPTAN1 were set to 20493457; 22656320; 35150594
Phenotypes for gene: SPTAN1 were set to Developmental and epileptic encephalopathy 5, OMIM:613477; Cerebellar ataxia, MONDO:0000437; Hereditary spastic paraplegia, MONDO:0019064
Review for gene: SPTAN1 was set to GREEN
Added comment: Comment on classification: This gene should be rated Green as there are several unrelated cases (>3 cases identified with different variants) reported with childhood/ early-onset spastic paraplegia.

Two of three patients identified with SPTAN1 variants in PMID:20493457 were reported with spastic quadriplegia whose age of onset were three years and seven years, while it has also been reported in one year old male from PMID:22656320. Out of 22 patients from 14 families identified with SPTAN1 variants in PMID:35150594, fifteen patients from seven families displaying p.Arg19Trp variant were reported with hereditary spastic paraplegia with age of onset ranging from congenital to adolescence.
Sources: Literature
Congenital muscular dystrophy v3.95 SYNE2 Arina Puzriakova Source was removed from SYNE2.
Congenital muscular dystrophy v3.94 DAG1 Arina Puzriakova Source was removed from DAG1.
Congenital myopathy v3.121 ZC4H2 Arina Puzriakova Phenotypes for gene: ZC4H2 were changed from Wieacker-Wolff syndrome, 314580 to Wieacker-Wolff syndrome, OMIM:314580; Wieacker-Wolff syndrome, female-restricted, OMIM:301041
Congenital myopathy v3.120 YARS2 Arina Puzriakova Phenotypes for gene: YARS2 were changed from Hereditary Sideroblastic Anemia with Myopathy and LacticAcidosis; Myopathy, lactic acidosis, and sideroblastic anemia 2, 613561 to Myopathy, lactic acidosis, and sideroblastic anemia 2, OMIM:613561
Congenital myopathy v3.119 VPS33B Arina Puzriakova Phenotypes for gene: VPS33B were changed from vacuolar myopathy; Arthrogryposis renal dysfunction, and cholestasis 1, 208085 to Arthrogryposis, renal dysfunction, and cholestasis 1, OMIM:208085
Congenital myopathy v3.118 VMA21 Arina Puzriakova Phenotypes for gene: VMA21 were changed from vacuolar myopathy? to Myopathy, X-linked, with excessive autophagy, OMIM:310440
Congenital myopathy v3.117 VCP Arina Puzriakova Phenotypes for gene: VCP were changed from Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia 613954; Charcot-Marie-Tooth disease, type 2Y 616687; Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia 1 167320 to Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia 1, OMIM:167320
Adult onset hereditary spastic paraplegia v2.9 SPTAN1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: SPTAN1.
Adult onset hereditary spastic paraplegia v2.9 SPTAN1 Achchuthan Shanmugasundram Classified gene: SPTAN1 as Amber List (moderate evidence)
Adult onset hereditary spastic paraplegia v2.9 SPTAN1 Achchuthan Shanmugasundram Gene: sptan1 has been classified as Amber List (Moderate Evidence).
Adult onset hereditary spastic paraplegia v2.8 SPTAN1 Achchuthan Shanmugasundram gene: SPTAN1 was added
gene: SPTAN1 was added to Hereditary spastic paraplegia - adult onset. Sources: Literature
Mode of inheritance for gene: SPTAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPTAN1 were set to 18065176; 20493457; 22656320; 35150594; 36331550
Phenotypes for gene: SPTAN1 were set to Developmental and epileptic encephalopathy 5, OMIM:613477; Cerebellar ataxia, MONDO:0000437; Hereditary spastic paraplegia, MONDO:0019064
Review for gene: SPTAN1 was set to GREEN
Added comment: Comment on classification: This gene should be rated Green as there are several unrelated cases (many more than three cases identified with different variants) from multiple ethnicities reported with spastic paraplegia and supported by functional studies.

OMIM reports Developmental and epileptic encephalopathy 5 (OMIM #613477) as a phenotype for SPTAN1 variants. Spastic quadriplegia is one of the clinical manifestations that has been reported as part of this phenotype.

Two of three patients identified with SPTAN1 variants in PMID:20493457 were reported with spastic quadriplegia, while it has also been reported in one year old male from PMID:22656320 and two patients from PMID:18065176. Out of 22 patients from 14 families identified with SPTAN1 variants in PMID:35150594, fifteen patients from seven families displaying p.Arg19Trp variant were reported with hereditary spastic paraplegia with age of onset ranging from congenital to adolescence, while three other patients displaying other variants (p.Arg1624Cys, p.Arg1098Cys & p.Gln2205Pro) displayed different extremes of spastic ataxia spectrum.

In PMID:36331550, authors carried out SPTAN1 gene enrichment analysis in the rare disease component of the 100,000 Genomes Project and screened 100,000 Genomes Project, DECIPHER database, and GeneMatcher to identify individuals with SPTAN1 variants. Statistically significant enrichment of rare probably damaging SPTAN1 variants were identified in families with hereditary ataxia (HA) or spastic paraplegia (HSP). Out of 31 individuals identified with SPTAN1 variants, five (three families) were presented with complex HA/HSP, two were presented with complex HSP and one with pure HSP.
Sources: Literature
Congenital myopathy v3.116 UNC45B Arina Puzriakova Phenotypes for gene: UNC45B were changed from Myofibrillar myopathy 11, OMIM:619178; myofibrillar myopathy 11, MONDO:0030927 to Myofibrillar myopathy 11, OMIM:619178
Ataxia and cerebellar anomalies - narrow panel v3.35 SPTAN1 Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be rated Green as there are several unrelated cases (many more than three cases identified with different variants) from multiple ethnicities reported with ataxia and was also supported by functional studies including results from mouse model.

One patient each was identified with SPTAN1 variants and was reported with ataxia from PMID:29050398 and PMID:30548380. Out of three patients identified with SPTAN1 variants and reported with Developmental and epileptic encephalopathy 5 in PMID:34590414, one patient had ataxia and another had mild ataxia. Out of 22 patients from 14 families identified with SPTAN1 variants in PMID:35150594, four unrelated patients displaying p.Lys2083del variant were reported with cerebellar ataxia, while three other patients displaying other variants (p.Arg1624Cys, p.Arg1098Cys & p.Gln2205Pro) displayed different extremes of spastic ataxia spectrum.

In PMID:36331550, authors carried out SPTAN1 gene enrichment analysis in the rare disease component of the 100,000 Genomes Project and screened 100,000 Genomes Project, DECIPHER database, and GeneMatcher to identify individuals with SPTAN1 variants. Statistically significant enrichment of rare probably damaging SPTAN1 variants were identified in families with hereditary ataxia (HA) or spastic paraplegia (HSP). Out of 31 individuals identified with SPTAN1 variants, 3 were presented with complex HA/HSP and two were presented with pure HA.

A 33-year old Korean woman identified with SPTAN1 variant was reported with cerebellar ataxia in PMID:36408834, being the first reported case of SPTAN1-related cerebellar ataxia.

In addition, a strain of C57BL/6J mice harbouring a single point mutation in Sptan1 (c.3293G > A/ p.Arg1098Gln) with reduced CaM affinity and intrinsically enhanced sensitivity to calpain proteolysis was reported in PMID:33790315. Homozygotes are embryonically lethal and heterozygotes develop a progressive ataxia.; to: Comment on classification: This gene should be rated Green as there are several unrelated cases (many more than three cases identified with different variants) from multiple ethnicities reported with ataxia and was also supported by functional studies including results from mouse model.

One patient each was identified with SPTAN1 variants and was reported with ataxia from PMID:29050398 and PMID:30548380. Out of three patients identified with SPTAN1 variants and reported with Developmental and epileptic encephalopathy 5 in PMID:34590414, one patient had ataxia and another had mild ataxia. Out of 22 patients from 14 families identified with SPTAN1 variants in PMID:35150594, four unrelated patients displaying p.Lys2083del variant were reported with cerebellar ataxia, while three other patients displaying other variants (p.Arg1624Cys, p.Arg1098Cys & p.Gln2205Pro) displayed different extremes of spastic ataxia spectrum.

In PMID:36331550, authors carried out SPTAN1 gene enrichment analysis in the rare disease component of the 100,000 Genomes Project and screened 100,000 Genomes Project, DECIPHER database, and GeneMatcher to identify individuals with SPTAN1 variants. Statistically significant enrichment of rare probably damaging SPTAN1 variants were identified in families with hereditary ataxia (HA) or spastic paraplegia (HSP). Out of 31 individuals identified with SPTAN1 variants, five (from three families) were presented with complex HA/HSP and two were presented with pure HA.

A 33-year old Korean woman identified with SPTAN1 variant was reported with cerebellar ataxia in PMID:36408834, being the first reported case of SPTAN1-related cerebellar ataxia.

In addition, a strain of C57BL/6J mice harbouring a single point mutation in Sptan1 (c.3293G > A/ p.Arg1098Gln) with reduced CaM affinity and intrinsically enhanced sensitivity to calpain proteolysis was reported in PMID:33790315. Homozygotes are embryonically lethal and heterozygotes develop a progressive ataxia.
Congenital myopathy v3.115 TTN Arina Puzriakova Phenotypes for gene: TTN were changed from Myopathy, early-onset, with fatal cardiomyopathy, 611705 to Salih myopathy, OMIM:611705
Congenital myopathy v3.114 TRIP4 Arina Puzriakova Phenotypes for gene: TRIP4 were changed from Spinal muscular atrophy with congenital bone fractures 1, OMIM:616866; Prenatal-onset spinal muscular atrophy with congenital bone fractures, MONDO:0000209; Spinal muscular atrophy with congenital bone fractures 1, MONDO:0014806; ?Muscular dystrophy, congenital, Davignon-Chauveau type, OMIM:617066; Congenital muscular dystrophy-respiratory failure-skin abnormalities-joint hyperlaxity syndrome, MONDO:0014896 to Muscular dystrophy, congenital, Davignon-Chauveau type, OMIM:617066; Spinal muscular atrophy with congenital bone fractures 1, OMIM:616866
Congenital myopathy v3.113 TRDN Arina Puzriakova Phenotypes for gene: TRDN were changed from Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness, 615441 to Cardiac arrhythmia syndrome, with or without skeletal muscle weakness, OMIM:615441
Congenital muscular dystrophy v3.93 TRAPPC11 Arina Puzriakova Phenotypes for gene: TRAPPC11 were changed from congenital muscular dystrophy (CMD), progressive fatty liver and infantile-onset cataract; infantile-onset muscle weakness; Muscular dystrophy, limb-girdle, autosomal recessive 18, 615356 to Muscular dystrophy, limb-girdle, autosomal recessive 18, OMIM:615356
Congenital myopathy v3.112 TPM3 Arina Puzriakova Phenotypes for gene: TPM3 were changed from CAP myopathy 1 609284; Myopathy, congenital, with fiber-type disproportion 255310; Nemaline myopathy 1, autosomal dominant or recessive 609284 to CAP myopathy 1, OMIM:609284; Myopathy, congenital, with fiber-type disproportion, OMIM:255310; Nemaline myopathy 1, autosomal dominant or recessive, OMIM:609284
Congenital myopathy v3.111 TPM2 Arina Puzriakova Phenotypes for gene: TPM2 were changed from CAP myopathy 2, OMIM:609285; Nemaline myopathy 4, autosomal dominant, OMIM:609285; Congenital myopathy, MONDO:0019952; Multiple pterygium syndrome, MONDO:0017415 to CAP myopathy 2, OMIM:609285; Nemaline myopathy 4, autosomal dominant, OMIM:609285
Congenital myopathy v3.110 TPM2 Arina Puzriakova Tag watchlist_moi tag was added to gene: TPM2.
Congenital myopathy v3.110 TNNT3 Arina Puzriakova Phenotypes for gene: TNNT3 were changed from Arthrogryposis, distal, type 2B2, OMIM:618435; Arthrogryposis, distal, type 2B2, MONDO:0032750 to Arthrogryposis, distal, type 2B2, OMIM:618435
Congenital myopathy v3.109 TNNT1 Arina Puzriakova Publications for gene: TNNT1 were set to 26296490; 25430424
Congenital myopathy v3.108 TNNT1 Arina Puzriakova Phenotypes for gene: TNNT1 were changed from nemaline myopathy; Nemaline Myopathy, Recessive; Nemaline myopathy 5, Amish type, 605355 to Nemaline myopathy 5, Amish type, OMIM:605355
Congenital myopathy v3.107 TNNI2 Arina Puzriakova Phenotypes for gene: TNNI2 were changed from Arthrogryposis multiplex congenita, distal, type 2B, 601680 to Arthrogryposis, distal, type 2B1, OMIM:601680
Congenital myopathy v3.106 TNNC2 Arina Puzriakova Phenotypes for gene: TNNC2 were changed from congenital myopathy, MONDO:0019952 to Myopathy, congenital, with neonatal respiratory insufficiency, OMIM:620161
Congenital muscular dystrophy v3.92 TMEM5 Arina Puzriakova Source was removed from TMEM5.
Congenital muscular dystrophy v3.91 TMEM43 Arina Puzriakova Source was removed from TMEM43.
Congenital muscular dystrophy v3.91 TMEM5 Arina Puzriakova Phenotypes for gene: TMEM5 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10, OMIM:615041
Congenital muscular dystrophy v3.90 TMEM43 Arina Puzriakova Phenotypes for gene: TMEM43 were changed from Emery-Dreifuss muscular dystrophy 7, AD 614302 to Emery-Dreifuss muscular dystrophy 7, AD, OMIM:614302
Unexplained death in infancy and sudden unexplained death in childhood v3.38 Eleanor Williams Panel status changed from internal to public
Congenital myopathy v3.105 TIA1 Arina Puzriakova Phenotypes for gene: TIA1 were changed from Welander distal myopathy, 604454 to Welander distal myopathy, OMIM:604454
Congenital muscular dystrophy v3.89 TCAP Arina Puzriakova Source was removed from TCAP.
Congenital muscular dystrophy v3.88 TCAP Arina Puzriakova Phenotypes for gene: TCAP were changed from Congenital muscular dystrophies to Muscular dystrophy, limb-girdle, autosomal recessive 7, OMIM:601954
Congenital muscular dystrophy v3.87 SYNE2 Arina Puzriakova Phenotypes for gene: SYNE2 were changed from Emery-Dreifuss Muscular Dystrophy; Emery-Dreifuss muscular dystrophy 5, autosomal dominant, 612999 to Emery-Dreifuss muscular dystrophy 5, autosomal dominant, OMIM:612999
Ataxia and cerebellar anomalies - narrow panel v3.35 SPTAN1 Achchuthan Shanmugasundram Phenotypes for gene: SPTAN1 were changed from Ataxia; hereditary spastic paraplegia to Developmental and epileptic encephalopathy 5, OMIM:613477; Cerebellar ataxia, MONDO:0000437; Hereditary spastic paraplegia, MONDO:0019064
Ataxia and cerebellar anomalies - narrow panel v3.34 SPTAN1 Achchuthan Shanmugasundram Publications for gene: SPTAN1 were set to 36331550; 35150594
Ataxia and cerebellar anomalies - narrow panel v3.33 SPTAN1 Achchuthan Shanmugasundram edited their review of gene: SPTAN1: Changed phenotypes to: Developmental and epileptic encephalopathy 5, OMIM:613477, Cerebellar ataxia, MONDO:0000437, Hereditary spastic paraplegia, MONDO:0019064
Ataxia and cerebellar anomalies - narrow panel v3.33 SPTAN1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: SPTAN1.
Ataxia and cerebellar anomalies - narrow panel v3.33 SPTAN1 Achchuthan Shanmugasundram Classified gene: SPTAN1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v3.33 SPTAN1 Achchuthan Shanmugasundram Gene: sptan1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v3.32 SPTAN1 Achchuthan Shanmugasundram reviewed gene: SPTAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29050398, 30548380, 33790315, 34590414, 35150594, 36331550, 36408834; Phenotypes: Developmental and epileptic encephalopathy 5, OMIM:613477, Cerebellar ataxia, MONDO:0000437; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital muscular dystrophy v3.86 SYNE1 Arina Puzriakova Phenotypes for gene: SYNE1 were changed from Emery-Dreifuss muscular dystrophy 4, autosomal dominant 612998; complex phenotypic spectrum ranging from Emery-Dreifuss muscular dystrophy to ataxia (SCA8) to Emery-Dreifuss muscular dystrophy 4, autosomal dominant, OMIM:612998; Arthrogryposis multiplex congenita 3, myogenic type, OMIM:618484
Congenital myopathy v3.104 SVIL Arina Puzriakova Phenotypes for gene: SVIL were changed from Myopathy to Myofibrillar myopathy 10, OMIM:619040
Congenital myopathy v3.103 STIM2 Arina Puzriakova Mode of inheritance for gene: STIM2 was changed from to Unknown
Congenital myopathy v3.102 STIM1 Arina Puzriakova Phenotypes for gene: STIM1 were changed from Myopathy, tubular aggregate, 160565 to Myopathy, tubular aggregate, 1, OMIM:160565
Congenital myopathy v3.101 STAC3 Arina Puzriakova Phenotypes for gene: STAC3 were changed from Myopathy, congenital, Baily-Bloch, 255995 to Myopathy, congenital, Baily-Bloch, OMIM:255995
Congenital myopathy v3.100 SRPK3 Arina Puzriakova Phenotypes for gene: SRPK3 were changed from Nemaline myopathy to Nemaline myopathy, MONDO:0018958
Congenital myopathy v3.99 SPTBN4 Arina Puzriakova Tag Q1_23_promote_green tag was added to gene: SPTBN4.
Congenital myopathy v3.99 SPTBN4 Arina Puzriakova Publications for gene: SPTBN4 were set to 28540413; 29861105; 33772159
Congenital myopathy v3.98 SPTBN4 Arina Puzriakova Classified gene: SPTBN4 as Amber List (moderate evidence)
Congenital myopathy v3.98 SPTBN4 Arina Puzriakova Added comment: Comment on list classification: Overall there is evidence to support inclusion of this gene with a green rating on this panel. Given the phenotype features severe muscular hypotonia and weakness with relevant age of onset, it is plausible that patients may be tested under the congenital myopathy clinical indication.
Congenital myopathy v3.98 SPTBN4 Arina Puzriakova Gene: sptbn4 has been classified as Amber List (Moderate Evidence).
Congenital myopathy v3.97 SPTBN4 Arina Puzriakova reviewed gene: SPTBN4: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v3.97 SPTBN4 Arina Puzriakova Publications for gene: SPTBN4 were set to 28540413
Congenital myopathy v3.96 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from ?Myopathy, congenital, with neuropathy and deafness, 617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
Congenital myopathy v3.95 SPEG Arina Puzriakova Publications for gene: SPEG were set to PMID 25087613
Congenital myopathy v3.94 SPEG Arina Puzriakova Phenotypes for gene: SPEG were changed from Centronuclear myopathy 5 615959 to Centronuclear myopathy 5, OMIM:615959
Congenital muscular dystrophy v3.85 SMCHD1 Arina Puzriakova Source was removed from SMCHD1.
Mode of inheritance for gene SMCHD1 was changed from to Other
Congenital muscular dystrophy v3.84 SMCHD1 Arina Puzriakova Phenotypes for gene: SMCHD1 were changed from Fascioscapulohumeral muscular dystrophy 2, digenic, 158901 to Fascioscapulohumeral muscular dystrophy 2, digenic, OMIM:158901
Congenital myopathy v3.93 SLC25A4 Arina Puzriakova Publications for gene: SLC25A4 were set to PMID:25732997; 27693233
Congenital myopathy v3.92 SLC25A4 Arina Puzriakova Phenotypes for gene: SLC25A4 were changed from itochondrial myopathy; Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD 617184; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2 60928 to Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, OMIM:617184
Congenital muscular dystrophy v3.83 SIL1 Arina Puzriakova Phenotypes for gene: SIL1 were changed from Marinesco-Sjogren syndrome, 248800 to Marinesco-Sjogren syndrome, OMIM:248800
Congenital myopathy v3.91 SELENON Arina Puzriakova Phenotypes for gene: SELENON were changed from Muscular dystrophy, rigid spine, 1 602771; Myopathy, congenital, with fiber-type disproportion 255310 to Muscular dystrophy, rigid spine, 1, OMIM:602771; Myopathy, congenital, with fiber-type disproportion, OMIM:255310
Congenital myopathy v3.90 SELENON Arina Puzriakova Publications for gene: SELENON were set to 26780752; 16365872
Congenital myopathy v3.89 SCN4A Arina Puzriakova Phenotypes for gene: SCN4A were changed from congenital myopathy to Congenital myopathy, MONDO:0019952
Congenital myopathy v3.88 RYR3 Arina Puzriakova Phenotypes for gene: RYR3 were changed from childhood-onset nemaline myopathy to Nemaline myopathy, MONDO:0018958
Congenital myopathy v3.87 RYR1 Arina Puzriakova Phenotypes for gene: RYR1 were changed from Central core disease 117000; Minicore myopathy with external ophthalmoplegia 255320; Neuromuscular disease, congenital, with uniform type 1 fiber 117000; Malignant hyperthermia susceptibility 1 145600 to Central core disease, OMIM:117000; Neuromuscular disease, congenital, with uniform type 1 fiber, OMIM:117000; Minicore myopathy with external ophthalmoplegia, OMIM:255320; King-Denborough syndrome, OMIM:619542
Congenital myopathy v3.86 PYROXD1 Arina Puzriakova Phenotypes for gene: PYROXD1 were changed from Myopathy, myofibrillar, 8, 617258; myopathy; early-onset myopathy with internalized nuclei and myofibrillar disorganization to Myopathy, myofibrillar, 8, OMIM:617258
Congenital myopathy v3.85 PUS1 Arina Puzriakova Phenotypes for gene: PUS1 were changed from Mitochondrial myopathy and sideroblastic anemia 1, 600462; Myopathy, Lactic Acidosis, and Sideroblastic Anemia to Myopathy, lactic acidosis, and sideroblastic anemia 1, OMIM:600462
Congenital myopathy v3.84 PPA2 Arina Puzriakova Phenotypes for gene: PPA2 were changed from Sudden cardiac failure, infantile, 617222 to Sudden cardiac failure, infantile, OMIM:617222
Congenital muscular dystrophy v3.82 POMT2 Arina Puzriakova Source was removed from POMT2.
Congenital muscular dystrophy v3.81 POMT2 Arina Puzriakova Phenotypes for gene: POMT2 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2 613156; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 613158 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2, OMIM:613150; Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 2, OMIM:613156
Congenital muscular dystrophy v3.80 POMT1 Arina Puzriakova Source was removed from POMT1.
Congenital muscular dystrophy v3.79 POMT1 Arina Puzriakova Phenotypes for gene: POMT1 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1, OMIM:236670; Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 1, OMIM:613155; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1, OMIM:609308
Congenital muscular dystrophy v3.78 POMK Arina Puzriakova Source was removed from POMK.
Congenital muscular dystrophy v3.77 POMK Arina Puzriakova Phenotypes for gene: POMK were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12, OMIM:615249
Congenital muscular dystrophy v3.76 POMGNT2 Arina Puzriakova Source was removed from POMGNT2.
Congenital muscular dystrophy v3.75 POMGNT2 Arina Puzriakova Phenotypes for gene: POMGNT2 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies type; Walker-Warburg syndrome to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8, OMIM:614830
Congenital muscular dystrophy v3.74 POMGNT1 Arina Puzriakova Source was removed from POMGNT1.
Congenital muscular dystrophy v3.73 POMGNT1 Arina Puzriakova Phenotypes for gene: POMGNT1 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 253280; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 3 613151; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3 613157 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3, OMIM:253280; Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 3, OMIM:613151
Congenital muscular dystrophy v3.72 POGLUT1 Arina Puzriakova Phenotypes for gene: POGLUT1 were changed from Muscular dystrophy, limb-girdle, autosomal recessive 21, OMIM:617232; autosomal recessive limb-girdle muscular dystrophy type 2R1, MONDO:0014977 to Muscular dystrophy, limb-girdle, autosomal recessive 21, OMIM:617232
Congenital myopathy v3.83 PNPLA2 Arina Puzriakova Phenotypes for gene: PNPLA2 were changed from Neutral Lipid Storage Disease with Myopathy; Neutral lipid storage disease with myopathy, 610717 to Neutral lipid storage disease with myopathy, OMIM:610717
Congenital muscular dystrophy v3.71 PLEC Arina Puzriakova Source was removed from PLEC.
Congenital myopathy v3.82 PIEZO2 Arina Puzriakova Phenotypes for gene: PIEZO2 were changed from Arthrogryposis, distal, type 3, 114300: Arthrogryposis, distal, type 5, 108145: Arthrogryposis, distal, with proprioception and touch, 617146 to Arthrogryposis, distal, type 3, OMIM:114300: Arthrogryposis, distal, type 5, OMIM:108145: Arthrogryposis, distal, with proprioception and touch, OMIM:617146
Congenital myopathy v3.81 PAX7 Arina Puzriakova Phenotypes for gene: PAX7 were changed from Hypotonia; Axial hypotonia; Ptosis; Scoliosis; Delayed motor milestones; Myopathy, congenital, progressive, with scoliosis, 618578 to Myopathy, congenital, progressive, with scoliosis, OMIM:618578
Congenital muscular dystrophy v3.70 PABPN1 Arina Puzriakova Source was removed from PABPN1.
Congenital muscular dystrophy v3.69 PABPN1 Arina Puzriakova Phenotypes for gene: PABPN1 were changed from Oculopharyngeal muscular dystrophy, 164300; Oculopharyngeal muscular dystrophy to Oculopharyngeal muscular dystrophy, OMIM:164300
Ataxia and cerebellar anomalies - narrow panel v3.32 CAPRIN1 Achchuthan Shanmugasundram Phenotypes for gene: CAPRIN1 were changed from Infantile-onset ataxia to Cerebellar ataxia, MONDO:0000437; Early-onset ataxia
Ataxia and cerebellar anomalies - narrow panel v3.31 CAPRIN1 Achchuthan Shanmugasundram Classified gene: CAPRIN1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v3.31 CAPRIN1 Achchuthan Shanmugasundram Gene: caprin1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v3.30 CAPRIN1 Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence.

PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor > sensory axonal neuropathy) as the other two patients.

In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics.

These functional evidences also suggest a gain-of-function mechanism for P512L variant.; to: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. The 'watchlist' tag has been added to look out for new evidence in order to promote this gene to green.

PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor > sensory axonal neuropathy) as the other two patients.

In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics.

These functional evidences also suggest a gain-of-function mechanism for P512L variant.
Ataxia and cerebellar anomalies - narrow panel v3.30 CAPRIN1 Achchuthan Shanmugasundram Tag watchlist tag was added to gene: CAPRIN1.
Ataxia and cerebellar anomalies - narrow panel v3.30 CAPRIN1 Achchuthan Shanmugasundram reviewed gene: CAPRIN1: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 36136249; Phenotypes: Cerebellar ataxia, MONDO:0000437, Early-onset ataxia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v3.30 COL9A3 Achchuthan Shanmugasundram commented on gene: COL9A3: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Retinal disorders v3.30 COL9A3 Achchuthan Shanmugasundram Deleted their comment
Retinal disorders v3.30 COL11A1 Achchuthan Shanmugasundram Classified gene: COL11A1 as Green List (high evidence)
Retinal disorders v3.30 COL11A1 Achchuthan Shanmugasundram Gene: col11a1 has been classified as Green List (High Evidence).
Retinal disorders v3.29 COL11A1 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: COL11A1.
Tag Q1_23_promote_green was removed from gene: COL11A1.
Tag Q1_23_expert_review was removed from gene: COL11A1.
Retinal disorders v3.29 COL11A1 Achchuthan Shanmugasundram edited their review of gene: COL11A1: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Retinal disorders v3.29 COL11A1 Achchuthan Shanmugasundram Deleted their comment
Retinal disorders v3.29 COL9A3 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: COL9A3.
Tag Q1_23_promote_green was removed from gene: COL9A3.
Tag Q1_23_expert_review was removed from gene: COL9A3.
Retinal disorders v3.29 COL9A3 Achchuthan Shanmugasundram Classified gene: COL9A3 as Green List (high evidence)
Retinal disorders v3.29 COL9A3 Achchuthan Shanmugasundram Gene: col9a3 has been classified as Green List (High Evidence).
Retinal disorders v3.28 COL9A3 Achchuthan Shanmugasundram Deleted their comment
Retinal disorders v3.28 COL9A3 Achchuthan Shanmugasundram edited their review of gene: COL9A3: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Retinal disorders v3.28 COL9A2 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: COL9A2.
Tag Q1_23_promote_green was removed from gene: COL9A2.
Tag Q1_23_expert_review was removed from gene: COL9A2.
Retinal disorders v3.28 COL9A2 Achchuthan Shanmugasundram Classified gene: COL9A2 as Green List (high evidence)
Retinal disorders v3.28 COL9A2 Achchuthan Shanmugasundram Gene: col9a2 has been classified as Green List (High Evidence).
Retinal disorders v3.27 COL9A2 Achchuthan Shanmugasundram Deleted their comment
Retinal disorders v3.27 COL9A2 Achchuthan Shanmugasundram edited their review of gene: COL9A2: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Retinal disorders v3.27 COL9A1 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: COL9A1.
Tag Q1_23_promote_green was removed from gene: COL9A1.
Tag Q1_23_expert_review was removed from gene: COL9A1.
Retinal disorders v3.27 COL9A1 Achchuthan Shanmugasundram edited their review of gene: COL9A1: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Retinal disorders v3.27 COL9A1 Achchuthan Shanmugasundram Classified gene: COL9A1 as Green List (high evidence)
Retinal disorders v3.27 COL9A1 Achchuthan Shanmugasundram Gene: col9a1 has been classified as Green List (High Evidence).
Retinal disorders v3.26 COL9A1 Achchuthan Shanmugasundram Deleted their comment
Retinal disorders v3.26 COL2A1 Achchuthan Shanmugasundram Deleted their comment
Unexplained death in infancy and sudden unexplained death in childhood v3.37 Eleanor Williams Panel types changed to GMS Rare Disease Virtual; Super Panel
Childhood onset dystonia, chorea or related movement disorder v2.11 CACNB4 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene was proposed to be changed to Both mono and biallelic in 2022 but since there is no new evidence since it was last considered by the GMS, it has been decided to keep it as just monoallelic.
Childhood onset dystonia, chorea or related movement disorder v2.11 CACNB4 Eleanor Williams Mode of inheritance for gene: CACNB4 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v3.30 TGM6 Eleanor Williams Tag Q2_21_rating was removed from gene: TGM6.
Tag Q2_21_expert_review was removed from gene: TGM6.
Ataxia and cerebellar anomalies - narrow panel v3.30 SPG7 Eleanor Williams Tag Q3_22_rating was removed from gene: SPG7.
Tag Q3_22_expert_review was removed from gene: SPG7.
Ataxia and cerebellar anomalies - narrow panel v3.30 XRCC1 Eleanor Williams Tag Q2_21_rating was removed from gene: XRCC1.
Ataxia and cerebellar anomalies - narrow panel v3.30 UCHL1 Eleanor Williams Tag Q2_21_rating was removed from gene: UCHL1.
Ataxia and cerebellar anomalies - narrow panel v3.30 UBTF Eleanor Williams Tag Q2_21_rating was removed from gene: UBTF.
Ataxia and cerebellar anomalies - narrow panel v3.30 TDP2 Eleanor Williams Tag Q2_21_rating was removed from gene: TDP2.
Ataxia and cerebellar anomalies - narrow panel v3.30 TBC1D23 Eleanor Williams Tag Q2_21_rating was removed from gene: TBC1D23.
Ataxia and cerebellar anomalies - narrow panel v3.30 SQSTM1 Eleanor Williams Tag Q2_21_rating was removed from gene: SQSTM1.
Ataxia and cerebellar anomalies - narrow panel v3.30 SPR Eleanor Williams Tag Q2_21_rating was removed from gene: SPR.
Ataxia and cerebellar anomalies - narrow panel v3.30 SNX14 Eleanor Williams Tag Q3_21_MOI was removed from gene: SNX14.
Ataxia and cerebellar anomalies - narrow panel v3.30 SNAP25 Eleanor Williams Tag Q2_21_rating was removed from gene: SNAP25.
Ataxia and cerebellar anomalies - narrow panel v3.30 SLC9A1 Eleanor Williams Tag Q2_21_rating was removed from gene: SLC9A1.
Ataxia and cerebellar anomalies - narrow panel v3.30 SLC44A1 Eleanor Williams Tag Q2_21_rating was removed from gene: SLC44A1.
Ataxia and cerebellar anomalies - narrow panel v3.30 SLC17A5 Eleanor Williams Tag Q2_21_rating was removed from gene: SLC17A5.
Ataxia and cerebellar anomalies - narrow panel v3.30 SCYL1 Eleanor Williams Tag Q2_21_rating was removed from gene: SCYL1.
Ataxia and cerebellar anomalies - narrow panel v3.30 SCN8A Eleanor Williams Tag Q2_21_rating was removed from gene: SCN8A.
Ataxia and cerebellar anomalies - narrow panel v3.30 SCN1A Eleanor Williams Tag Q2_21_rating was removed from gene: SCN1A.
Ataxia and cerebellar anomalies - narrow panel v3.30 SAR1B Eleanor Williams Tag Q2_21_rating was removed from gene: SAR1B.
Ataxia and cerebellar anomalies - narrow panel v3.30 RORA Eleanor Williams Tag Q2_21_rating was removed from gene: RORA.
Ataxia and cerebellar anomalies - narrow panel v3.30 RNF220 Eleanor Williams Tag Q4_21_rating was removed from gene: RNF220.
Ataxia and cerebellar anomalies - narrow panel v3.30 PRDX3 Eleanor Williams Tag Q1_22_rating was removed from gene: PRDX3.
Ataxia and cerebellar anomalies - narrow panel v3.30 POU4F1 Eleanor Williams Tag Q2_21_rating was removed from gene: POU4F1.
Ataxia and cerebellar anomalies - narrow panel v3.30 POLR3B Eleanor Williams Tag Q2_21_rating was removed from gene: POLR3B.
Ataxia and cerebellar anomalies - narrow panel v3.30 PMPCB Eleanor Williams Tag Q2_21_rating was removed from gene: PMPCB.
Ataxia and cerebellar anomalies - narrow panel v3.30 PITRM1 Eleanor Williams Tag Q2_21_rating was removed from gene: PITRM1.
Ataxia and cerebellar anomalies - narrow panel v3.30 PI4KA Eleanor Williams Tag Q3_21_rating was removed from gene: PI4KA.
Ataxia and cerebellar anomalies - narrow panel v3.30 PEX6 Eleanor Williams Tag Q2_22_rating was removed from gene: PEX6.
Ataxia and cerebellar anomalies - narrow panel v3.30 OPA1 Eleanor Williams Tag Q2_21_rating was removed from gene: OPA1.
Ataxia and cerebellar anomalies - narrow panel v3.30 NKX2-1 Eleanor Williams Tag Q2_21_rating was removed from gene: NKX2-1.
Ataxia and cerebellar anomalies - narrow panel v3.30 NAXE Eleanor Williams Tag Q2_21_rating was removed from gene: NAXE.
Ataxia and cerebellar anomalies - narrow panel v3.30 MVK Eleanor Williams Tag Q2_21_rating was removed from gene: MVK.
Ataxia and cerebellar anomalies - narrow panel v3.30 MTFMT Eleanor Williams Tag Q2_21_rating was removed from gene: MTFMT.
Ataxia and cerebellar anomalies - narrow panel v3.30 MTCL1 Eleanor Williams Tag Q2_21_rating was removed from gene: MTCL1.
Ataxia and cerebellar anomalies - narrow panel v3.30 MSTO1 Eleanor Williams Tag Q2_21_rating was removed from gene: MSTO1.
Ataxia and cerebellar anomalies - narrow panel v3.30 MINPP1 Eleanor Williams Tag Q2_21_rating was removed from gene: MINPP1.
Ataxia and cerebellar anomalies - narrow panel v3.30 MAPK8IP3 Eleanor Williams Tag Q4_21_rating was removed from gene: MAPK8IP3.
Ataxia and cerebellar anomalies - narrow panel v3.30 LAMA1 Eleanor Williams Tag Q2_21_rating was removed from gene: LAMA1.
Ataxia and cerebellar anomalies - narrow panel v3.30 KIF1A Eleanor Williams Tag Q3_21_rating was removed from gene: KIF1A.
Ataxia and cerebellar anomalies - narrow panel v3.30 KCNN2 Eleanor Williams Tag Q2_21_rating was removed from gene: KCNN2.
Ataxia and cerebellar anomalies - narrow panel v3.30 KCNA2 Eleanor Williams Tag Q2_21_rating was removed from gene: KCNA2.
Ataxia and cerebellar anomalies - narrow panel v3.30 IRF2BPL Eleanor Williams Tag Q2_21_rating was removed from gene: IRF2BPL.
Ataxia and cerebellar anomalies - narrow panel v3.30 GEMIN5 Eleanor Williams Tag Q2_21_rating was removed from gene: GEMIN5.
Ataxia and cerebellar anomalies - narrow panel v3.30 FBXL4 Eleanor Williams Tag Q2_21_rating was removed from gene: FBXL4.
Ataxia and cerebellar anomalies - narrow panel v3.30 FA2H Eleanor Williams Tag Q2_21_rating was removed from gene: FA2H.
Ataxia and cerebellar anomalies - narrow panel v3.30 EBF3 Eleanor Williams Tag Q2_21_rating was removed from gene: EBF3.
Ataxia and cerebellar anomalies - narrow panel v3.30 DPYSL5 Eleanor Williams Tag Q3_21_rating was removed from gene: DPYSL5.
Ataxia and cerebellar anomalies - narrow panel v3.30 DOCK3 Eleanor Williams Tag Q2_21_rating was removed from gene: DOCK3.
Ataxia and cerebellar anomalies - narrow panel v3.30 DHDDS Eleanor Williams Tag Q4_21_rating was removed from gene: DHDDS.
Ataxia and cerebellar anomalies - narrow panel v3.30 CSTB Eleanor Williams Tag Q2_21_rating was removed from gene: CSTB.
Ataxia and cerebellar anomalies - narrow panel v3.30 COA7 Eleanor Williams Tag Q2_21_rating was removed from gene: COA7.
Ataxia and cerebellar anomalies - narrow panel v3.30 CLP1 Eleanor Williams Tag Q2_21_rating was removed from gene: CLP1.
Ataxia and cerebellar anomalies - narrow panel v3.30 CLN5 Eleanor Williams Tag Q2_21_rating was removed from gene: CLN5.
Ataxia and cerebellar anomalies - narrow panel v3.30 CLCN2 Eleanor Williams Tag Q4_21_MOI was removed from gene: CLCN2.
Ataxia and cerebellar anomalies - narrow panel v3.30 CAD Eleanor Williams Tag Q2_21_rating was removed from gene: CAD.
Ataxia and cerebellar anomalies - narrow panel v3.30 BBS1 Eleanor Williams Tag Q2_21_rating was removed from gene: BBS1.
Ataxia and cerebellar anomalies - narrow panel v3.30 B4GAT1 Eleanor Williams Tag Q3_21_rating was removed from gene: B4GAT1.
Ataxia and cerebellar anomalies - narrow panel v3.30 ATP8A2 Eleanor Williams Tag Q2_21_rating was removed from gene: ATP8A2.
Ataxia and cerebellar anomalies - narrow panel v3.30 ATAD3A Eleanor Williams Tag Q2_21_rating was removed from gene: ATAD3A.
Ataxia and cerebellar anomalies - narrow panel v3.30 ALDH5A1 Eleanor Williams Tag Q3_21_rating was removed from gene: ALDH5A1.
Ataxia and cerebellar anomalies - narrow panel v3.30 ADPRHL2 Eleanor Williams Tag Q2_21_rating was removed from gene: ADPRHL2.
Ataxia and cerebellar anomalies - narrow panel v3.30 ACO2 Eleanor Williams Tag Q2_21_rating was removed from gene: ACO2.
Tag Q2_22_MOI was removed from gene: ACO2.
Ataxia and cerebellar anomalies - narrow panel v3.30 ABCB7 Eleanor Williams Tag Q3_21_MOI was removed from gene: ABCB7.
Ataxia and cerebellar anomalies - narrow panel v3.30 STUB1 Eleanor Williams Tag Q3_22_MOI was removed from gene: STUB1.
Ataxia and cerebellar anomalies - narrow panel v3.30 PRDM13 Eleanor Williams Tag Q3_22_rating was removed from gene: PRDM13.
Ataxia and cerebellar anomalies - narrow panel v3.30 OGDHL Eleanor Williams Tag Q3_22_rating was removed from gene: OGDHL.
Ataxia and cerebellar anomalies - narrow panel v3.30 CYP2U1 Eleanor Williams Tag Q3_22_rating was removed from gene: CYP2U1.
Tag Q3_22_expert_review was removed from gene: CYP2U1.
Ataxia and cerebellar anomalies - narrow panel v3.30 CACNA1A Eleanor Williams Tag Q3_22_MOI was removed from gene: CACNA1A.
Tag Q3_22_NHS_review was removed from gene: CACNA1A.
Ataxia and cerebellar anomalies - narrow panel v3.30 ATP6V0A1 Eleanor Williams Tag Q3_22_rating was removed from gene: ATP6V0A1.
Ataxia and cerebellar anomalies - narrow panel v3.30 ATG7 Eleanor Williams Tag Q3_22_rating was removed from gene: ATG7.
Ataxia and cerebellar anomalies - narrow panel v3.30 TGM6 Eleanor Williams reviewed gene: TGM6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SPG7 Eleanor Williams edited their review of gene: SPG7: Added comment: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains green. The reviewers note that the age of onset includes under 16. Gene should be included in a diagnostic test for ataxia. At least 2 patients with age of onset of 15 years in 30588500; further 2 patients with onset 11 and 14 in 14985266.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v3.30 SAR1B Eleanor Williams commented on gene: SAR1B: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.
Ataxia and cerebellar anomalies - narrow panel v3.30 CYP2U1 Eleanor Williams edited their review of gene: CYP2U1: Added comment: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.; Changed rating: RED
Ataxia and cerebellar anomalies - narrow panel v3.30 XRCC1 Eleanor Williams reviewed gene: XRCC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 UCHL1 Eleanor Williams reviewed gene: UCHL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 UBTF Eleanor Williams reviewed gene: UBTF: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 TDP2 Eleanor Williams reviewed gene: TDP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 TBC1D23 Eleanor Williams reviewed gene: TBC1D23: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SQSTM1 Eleanor Williams reviewed gene: SQSTM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SPR Eleanor Williams reviewed gene: SPR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SNAP25 Eleanor Williams reviewed gene: SNAP25: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SLC9A1 Eleanor Williams reviewed gene: SLC9A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SLC44A1 Eleanor Williams reviewed gene: SLC44A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SLC17A5 Eleanor Williams reviewed gene: SLC17A5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SCYL1 Eleanor Williams reviewed gene: SCYL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SCN8A Eleanor Williams reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SCN1A Eleanor Williams reviewed gene: SCN1A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 RORA Eleanor Williams reviewed gene: RORA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 RNF220 Eleanor Williams reviewed gene: RNF220: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 PRDX3 Eleanor Williams reviewed gene: PRDX3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 POU4F1 Eleanor Williams reviewed gene: POU4F1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 POLR3B Eleanor Williams reviewed gene: POLR3B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 PMPCB Eleanor Williams reviewed gene: PMPCB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 PITRM1 Eleanor Williams reviewed gene: PITRM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 PI4KA Eleanor Williams reviewed gene: PI4KA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 OPA1 Eleanor Williams reviewed gene: OPA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 NKX2-1 Eleanor Williams reviewed gene: NKX2-1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 NAXE Eleanor Williams reviewed gene: NAXE: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 MVK Eleanor Williams reviewed gene: MVK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 MTFMT Eleanor Williams reviewed gene: MTFMT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 MTCL1 Eleanor Williams reviewed gene: MTCL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 MSTO1 Eleanor Williams reviewed gene: MSTO1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 MINPP1 Eleanor Williams reviewed gene: MINPP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 MAPK8IP3 Eleanor Williams edited their review of gene: MAPK8IP3: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v3.30 LAMA1 Eleanor Williams reviewed gene: LAMA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 KIF1A Eleanor Williams reviewed gene: KIF1A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 KCNN2 Eleanor Williams reviewed gene: KCNN2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 KCNA2 Eleanor Williams reviewed gene: KCNA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 IRF2BPL Eleanor Williams reviewed gene: IRF2BPL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 GEMIN5 Eleanor Williams reviewed gene: GEMIN5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 FBXL4 Eleanor Williams reviewed gene: FBXL4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 FA2H Eleanor Williams reviewed gene: FA2H: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 EBF3 Eleanor Williams reviewed gene: EBF3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 DPYSL5 Eleanor Williams reviewed gene: DPYSL5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 DOCK3 Eleanor Williams reviewed gene: DOCK3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 DHDDS Eleanor Williams reviewed gene: DHDDS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 CSTB Eleanor Williams reviewed gene: CSTB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 COA7 Eleanor Williams reviewed gene: COA7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 CLP1 Eleanor Williams reviewed gene: CLP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 CLN5 Eleanor Williams reviewed gene: CLN5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 CAD Eleanor Williams reviewed gene: CAD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 BBS1 Eleanor Williams reviewed gene: BBS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 B4GAT1 Eleanor Williams reviewed gene: B4GAT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 ATP8A2 Eleanor Williams reviewed gene: ATP8A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 ATAD3A Eleanor Williams reviewed gene: ATAD3A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 ALDH5A1 Eleanor Williams reviewed gene: ALDH5A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 ADPRHL2 Eleanor Williams reviewed gene: ADPRHL2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 ATP6V0A1 Eleanor Williams reviewed gene: ATP6V0A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 PEX6 Eleanor Williams reviewed gene: PEX6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 ACO2 Eleanor Williams reviewed gene: ACO2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 PRDM13 Eleanor Williams reviewed gene: PRDM13: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 OGDHL Eleanor Williams reviewed gene: OGDHL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 ATG7 Eleanor Williams reviewed gene: ATG7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 ABCB7 Eleanor Williams commented on gene: ABCB7
Ataxia and cerebellar anomalies - narrow panel v3.30 STUB1 Eleanor Williams commented on gene: STUB1
Ataxia and cerebellar anomalies - narrow panel v3.30 CACNA1A Eleanor Williams commented on gene: CACNA1A
Ataxia and cerebellar anomalies - narrow panel v3.30 SNX14 Eleanor Williams commented on gene: SNX14
Ataxia and cerebellar anomalies - narrow panel v3.30 CLCN2 Eleanor Williams commented on gene: CLCN2
Ataxia and cerebellar anomalies - narrow panel v3.29 TGM6 Eleanor Williams Source NHS GMS was added to TGM6.
Source Expert Review Amber was added to TGM6.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 XRCC1 Eleanor Williams Source Expert Review Green was added to XRCC1.
Source NHS GMS was added to XRCC1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 UCHL1 Eleanor Williams Source Expert Review Green was added to UCHL1.
Source NHS GMS was added to UCHL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 UBTF Eleanor Williams Source Expert Review Green was added to UBTF.
Source NHS GMS was added to UBTF.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 TDP2 Eleanor Williams Source Expert Review Green was added to TDP2.
Source NHS GMS was added to TDP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 TBC1D23 Eleanor Williams Source Expert Review Green was added to TBC1D23.
Source NHS GMS was added to TBC1D23.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 STUB1 Eleanor Williams Source NHS GMS was added to STUB1.
Mode of inheritance for gene STUB1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.29 SQSTM1 Eleanor Williams Source Expert Review Green was added to SQSTM1.
Source NHS GMS was added to SQSTM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 SPR Eleanor Williams Source Expert Review Green was added to SPR.
Source NHS GMS was added to SPR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 SNX14 Eleanor Williams Source NHS GMS was added to SNX14.
Mode of inheritance for gene SNX14 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.29 SNAP25 Eleanor Williams Source Expert Review Green was added to SNAP25.
Source NHS GMS was added to SNAP25.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 SLC9A1 Eleanor Williams Source Expert Review Green was added to SLC9A1.
Source NHS GMS was added to SLC9A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 SLC44A1 Eleanor Williams Source Expert Review Green was added to SLC44A1.
Source NHS GMS was added to SLC44A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 SLC17A5 Eleanor Williams Source Expert Review Green was added to SLC17A5.
Source NHS GMS was added to SLC17A5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 SCYL1 Eleanor Williams Source Expert Review Green was added to SCYL1.
Source NHS GMS was added to SCYL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 SCN8A Eleanor Williams Source Expert Review Green was added to SCN8A.
Source NHS GMS was added to SCN8A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 SCN1A Eleanor Williams Source Expert Review Green was added to SCN1A.
Source NHS GMS was added to SCN1A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 SAR1B Eleanor Williams Source Expert Review Red was added to SAR1B.
Source NHS GMS was added to SAR1B.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 RORA Eleanor Williams Source Expert Review Green was added to RORA.
Source NHS GMS was added to RORA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 RNF220 Eleanor Williams Source Expert Review Green was added to RNF220.
Source NHS GMS was added to RNF220.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 PRDX3 Eleanor Williams Source Expert Review Green was added to PRDX3.
Source NHS GMS was added to PRDX3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 PRDM13 Eleanor Williams Source Expert Review Green was added to PRDM13.
Source NHS GMS was added to PRDM13.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 POU4F1 Eleanor Williams Source Expert Review Green was added to POU4F1.
Source NHS GMS was added to POU4F1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 POLR3B Eleanor Williams Source Expert Review Green was added to POLR3B.
Source NHS GMS was added to POLR3B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 PMPCB Eleanor Williams Source Expert Review Green was added to PMPCB.
Source NHS GMS was added to PMPCB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 PITRM1 Eleanor Williams Source Expert Review Green was added to PITRM1.
Source NHS GMS was added to PITRM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 PI4KA Eleanor Williams Source Expert Review Green was added to PI4KA.
Source NHS GMS was added to PI4KA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 PEX6 Eleanor Williams Source Expert Review Green was added to PEX6.
Source NHS GMS was added to PEX6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 OPA1 Eleanor Williams Source Expert Review Green was added to OPA1.
Source NHS GMS was added to OPA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 OGDHL Eleanor Williams Source Expert Review Green was added to OGDHL.
Source NHS GMS was added to OGDHL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 NKX2-1 Eleanor Williams Source Expert Review Green was added to NKX2-1.
Source NHS GMS was added to NKX2-1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 NAXE Eleanor Williams Source Expert Review Green was added to NAXE.
Source NHS GMS was added to NAXE.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 MVK Eleanor Williams Source Expert Review Green was added to MVK.
Source NHS GMS was added to MVK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 MTFMT Eleanor Williams Source Expert Review Green was added to MTFMT.
Source NHS GMS was added to MTFMT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 MTCL1 Eleanor Williams Source Expert Review Green was added to MTCL1.
Source NHS GMS was added to MTCL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 MSTO1 Eleanor Williams Source Expert Review Green was added to MSTO1.
Source NHS GMS was added to MSTO1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 MINPP1 Eleanor Williams Source Expert Review Green was added to MINPP1.
Source NHS GMS was added to MINPP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 MAPK8IP3 Eleanor Williams Source Expert Review Green was added to MAPK8IP3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 LAMA1 Eleanor Williams Source Expert Review Green was added to LAMA1.
Source NHS GMS was added to LAMA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 KIF1A Eleanor Williams Source Expert Review Green was added to KIF1A.
Source NHS GMS was added to KIF1A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 KCNN2 Eleanor Williams Source Expert Review Green was added to KCNN2.
Source NHS GMS was added to KCNN2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 KCNA2 Eleanor Williams Source Expert Review Green was added to KCNA2.
Source NHS GMS was added to KCNA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 IRF2BPL Eleanor Williams Source Expert Review Green was added to IRF2BPL.
Source NHS GMS was added to IRF2BPL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 GEMIN5 Eleanor Williams Source Expert Review Green was added to GEMIN5.
Source NHS GMS was added to GEMIN5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 FBXL4 Eleanor Williams Source Expert Review Green was added to FBXL4.
Source NHS GMS was added to FBXL4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 FA2H Eleanor Williams Source Expert Review Green was added to FA2H.
Source NHS GMS was added to FA2H.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 EBF3 Eleanor Williams Source Expert Review Green was added to EBF3.
Source NHS GMS was added to EBF3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 DPYSL5 Eleanor Williams Source Expert Review Green was added to DPYSL5.
Source NHS GMS was added to DPYSL5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 DOCK3 Eleanor Williams Source Expert Review Green was added to DOCK3.
Source NHS GMS was added to DOCK3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 DHDDS Eleanor Williams Source Expert Review Green was added to DHDDS.
Source NHS GMS was added to DHDDS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 CYP2U1 Eleanor Williams Source Expert Review Red was added to CYP2U1.
Source NHS GMS was added to CYP2U1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 CSTB Eleanor Williams Source Expert Review Green was added to CSTB.
Source NHS GMS was added to CSTB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 COA7 Eleanor Williams Source Expert Review Green was added to COA7.
Source NHS GMS was added to COA7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 CLP1 Eleanor Williams Source Expert Review Green was added to CLP1.
Source NHS GMS was added to CLP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 CLN5 Eleanor Williams Source Expert Review Green was added to CLN5.
Source NHS GMS was added to CLN5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 CLCN2 Eleanor Williams Source NHS GMS was added to CLCN2.
Mode of inheritance for gene CLCN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.29 CAD Eleanor Williams Source Expert Review Green was added to CAD.
Source NHS GMS was added to CAD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 CACNA1A Eleanor Williams Source NHS GMS was added to CACNA1A.
Mode of inheritance for gene CACNA1A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.29 BBS1 Eleanor Williams Source Expert Review Green was added to BBS1.
Source NHS GMS was added to BBS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 B4GAT1 Eleanor Williams Source Expert Review Green was added to B4GAT1.
Source NHS GMS was added to B4GAT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 ATP8A2 Eleanor Williams Source Expert Review Green was added to ATP8A2.
Source NHS GMS was added to ATP8A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 ATP6V0A1 Eleanor Williams Source Expert Review Green was added to ATP6V0A1.
Source NHS GMS was added to ATP6V0A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 ATG7 Eleanor Williams Source Expert Review Green was added to ATG7.
Source NHS GMS was added to ATG7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 ATAD3A Eleanor Williams Source Expert Review Green was added to ATAD3A.
Source NHS GMS was added to ATAD3A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 ALDH5A1 Eleanor Williams Source Expert Review Green was added to ALDH5A1.
Source NHS GMS was added to ALDH5A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 ADPRHL2 Eleanor Williams Source Expert Review Green was added to ADPRHL2.
Source NHS GMS was added to ADPRHL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 ACO2 Eleanor Williams Source Expert Review Green was added to ACO2.
Source NHS GMS was added to ACO2.
Mode of inheritance for gene ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 ABCB7 Eleanor Williams Source NHS GMS was added to ABCB7.
Mode of inheritance for gene ABCB7 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Congenital myopathy v3.80 ORAI1 Arina Puzriakova Phenotypes for gene: ORAI1 were changed from Myopathy, tubular aggregate, 2 615883 to Myopathy, tubular aggregate, 2, OMIM:615883
Congenital myopathy v3.79 NEFL Arina Puzriakova Mode of inheritance for gene: NEFL was changed from MONOALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital myopathy v3.78 NEB Arina Puzriakova Phenotypes for gene: NEB were changed from nemaline myopathy; Nemaline Myopathy, Recessive; Nemaline myopathy 2, autosomal recessive, 256030 to Nemaline myopathy 2, autosomal recessive, OMIM:256030
Congenital myopathy v3.77 MYPN Arina Puzriakova Phenotypes for gene: MYPN were changed from Congenital cap myopathy; Nemaline myopathy, 617336 to Nemaline myopathy 11, autosomal recessive, OMIM:617336
Congenital myopathy v3.76 MYOT Arina Puzriakova Phenotypes for gene: MYOT were changed from Muscular dystrophy, limb-girdle, type 1A 159000; Myopathy, myofibrillar, 3 609200; Myopathy, spheroid body 182920 to Myopathy, myofibrillar, 3, OMIM:609200; Myopathy, spheroid body, OMIM:182920
Congenital myopathy v3.75 MYO18B Arina Puzriakova Phenotypes for gene: MYO18B were changed from Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism, OMIM:616549; Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome, MONDO:0014689 to Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism, OMIM:616549
Congenital myopathy v3.74 MYMK Arina Puzriakova Phenotypes for gene: MYMK were changed from Carey-Fineman-Ziter syndrome, OMIM:254940; Carey-Fineman-Ziter syndrome, MONDO:0009700 to Carey-Fineman-Ziter syndrome, OMIM:254940
Congenital myopathy v3.73 MYL2 Arina Puzriakova Phenotypes for gene: MYL2 were changed from infantile muscle type I hypotrophy with myofibrillar disorganization and dilated cardiomyopathy; Cardiomyopathy, hypertrophic, 10, OMIM:608758 to Myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy, OMIM:619424
Congenital myopathy v3.72 MYL1 Arina Puzriakova Phenotypes for gene: MYL1 were changed from Myopathy, congenital, with fast-twitch (type II) fiber atrophy, OMIM:618414; Congenital myopathy with reduced type 2 muscle fibers, MONDO:0034109 to Myopathy, congenital, with fast-twitch (type II) fiber atrophy, OMIM:618414
Congenital myopathy v3.71 MYH3 Arina Puzriakova Phenotypes for gene: MYH3 were changed from Arthrogryposis, distal, type 2A 193700; Arthrogryposis, distal, type 2B 601680; Arthrogryposis, distal, type 8 178110 to Arthrogryposis, distal, type 2A (Freeman-Sheldon), OMIM:193700; Arthrogryposis, distal, type 2B3 (Sheldon-Hall), OMIM:618436
Congenital myopathy v3.70 MYH2 Arina Puzriakova Phenotypes for gene: MYH2 were changed from Proximal myopathy and ophthalmoplegia, OMIM:605637; Myopathy, proximal, and ophthalmoplegia, MONDO:0011577 to Proximal myopathy and ophthalmoplegia, OMIM:605637
Congenital myopathy v3.69 MYH14 Arina Puzriakova Phenotypes for gene: MYH14 were changed from ?Peripheral neuropathy, myopathy, hoarseness, and hearing loss 614369; Deafness, autosomal dominant 4A 600652 to ?Peripheral neuropathy, myopathy, hoarseness, and hearing loss, OMIM:614369
Congenital myopathy v3.68 MYF6 Arina Puzriakova Phenotypes for gene: MYF6 were changed from Centronuclear Myopathy, Dominant; Myopathy, centronuclear, 3, 614408 to Centronuclear Myopathy, Dominant
Congenital myopathy v3.67 MYBPC3 Arina Puzriakova Phenotypes for gene: MYBPC3 were changed from myopathy and cardiomyopathy; Cardiomyopathy, hypertrophic, 4, 115197 to Cardiomyopathy, dilated, 1MM, OMIM:615396; Cardiomyopathy, hypertrophic, 4, OMIM:115197
Congenital myopathy v3.66 MYBPC1 Arina Puzriakova Phenotypes for gene: MYBPC1 were changed from Arthrogryposis, distal, type 1B, 614335; Lethal congenital contracture syndrome 4, 614915 to Arthrogryposis, distal, type 1B, OMIM:614335; Lethal congenital contracture syndrome 4, OMIM:614915; Myopathy, congenital, with tremor, OMIM:618524
Congenital myopathy v3.65 MTMR14 Arina Puzriakova Phenotypes for gene: MTMR14 were changed from centronuclear myopathy; Centronuclear myopathy, autosomal, modifier of, 160150 to {Centronuclear myopathy, autosomal, modifier of}, OMIM:160150
Congenital myopathy v3.64 MT-TL1 Arina Puzriakova Phenotypes for gene: MT-TL1 were changed from MITOCHONDRIAL MYOPATHY, ENCEPHALOPATHY, LACTIC ACIDOSIS, AND STROKE-LIKE EPISODES; MELAS 540000 to MELAS syndrome, MONDO:0010789
Congenital muscular dystrophy v3.68 MSTO1 Arina Puzriakova Phenotypes for gene: MSTO1 were changed from Myopathy, mitochondrial, and ataxia OMIM:617675; mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome MONDO:0044714 to Myopathy, mitochondrial, and ataxia, OMIM:617675
Congenital myopathy v3.63 MLIP Arina Puzriakova Phenotypes for gene: MLIP were changed from Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis, MIM# 620138 to Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis, OMIM:620138
Congenital myopathy v3.62 MICU1 Arina Puzriakova Phenotypes for gene: MICU1 were changed from Myopathy with extrapyramidal signs, 615673 to Myopathy with extrapyramidal signs, OMIM:615673
Congenital myopathy v3.61 MEGF10 Arina Puzriakova Phenotypes for gene: MEGF10 were changed from Myopathy, Early-Onset, Areflexia, Respiratory Distress, andDysphagia; Myopathy, areflexia, respiratory distress, and dysphagia, early-onset, 614399 to Myopathy, areflexia, respiratory distress, and dysphagia, early-onset, OMIM:614399; Myopathy, areflexia, respiratory distress, and dysphagia, early-onset, mild variant, OMIM:614399
Congenital myopathy v3.60 MATR3 Arina Puzriakova Phenotypes for gene: MATR3 were changed from Amyotrophic lateral sclerosis 21 606070 to Amyotrophic lateral sclerosis 21, OMIM:606070
Congenital myopathy v3.59 MAP3K20 Arina Puzriakova Phenotypes for gene: MAP3K20 were changed from Centronuclear myopathy 6 with fiber-type disproportion, OMIM:617760; Myopathy, centronuclear, 6, with fiber-type disproportion, MONDO:0054695 to Centronuclear myopathy 6 with fiber-type disproportion, OMIM:617760
Congenital myopathy v3.58 LMOD3 Arina Puzriakova Publications for gene: LMOD3 were updated from PMID 25250574 to PMID 25250574
Congenital myopathy v3.57 LMOD3 Arina Puzriakova Phenotypes for gene: LMOD3 were changed from Nemaline myopathy 10 616165 to Nemaline myopathy 10, OMIM:616165
Congenital myopathy v3.56 LGI4 Arina Puzriakova Phenotypes for gene: LGI4 were changed from Arthrogryposis Multiplex Congenita; Arthrogryposis multiplex congenita, neurogenic, with myelin defect, 617468; AMCNMY to Arthrogryposis multiplex congenita 1, neurogenic, with myelin defect, OMIM:617468
Congenital myopathy v3.55 LDB3 Arina Puzriakova Phenotypes for gene: LDB3 were changed from Myofibrillar Myopathy, Dominant; Myopathy, myofibrillar, 4, 609452 to Myopathy, myofibrillar, 4, OMIM:609452
Congenital muscular dystrophy v3.67 LARGE1 Arina Puzriakova Source was removed from LARGE1.
Congenital muscular dystrophy v3.66 LARGE1 Arina Puzriakova Phenotypes for gene: LARGE1 were changed from Congenital Muscular Dystrophy, alpha-dystroglycan related; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6 613154; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6 608840 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, OMIM:613154; Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 6, OMIM:608840
Congenital myopathy v3.54 LAMP2 Arina Puzriakova Phenotypes for gene: LAMP2 were changed from vacuolar myopathy?; Danon disease, 300257 to Danon disease, OMIM:300257
Congenital muscular dystrophy v3.65 LAMA2 Arina Puzriakova Source was removed from LAMA2.
Congenital muscular dystrophy v3.64 LAMA2 Arina Puzriakova Phenotypes for gene: LAMA2 were changed from Congenital Muscular Dystrophy, LAMA2-related; Muscular dystrophy, congenital merosin-deficient, 607855; Muscular dystrophy, congenital, due to partial LAMA2 deficiency 607855 to Muscular dystrophy, congenital, merosin deficient or partially deficient, OMIM:607855
Congenital myopathy v3.53 KY Arina Puzriakova Phenotypes for gene: KY were changed from Myopathy, myofibrillar 7 OMIM:617114 to Myopathy, myofibrillar, 7, OMIM:617114
Congenital myopathy v3.52 KLHL41 Arina Puzriakova Phenotypes for gene: KLHL41 were changed from Nemaline myopathy 9, 615731 to Nemaline myopathy 9, OMIM:615731
Congenital myopathy v3.51 KLHL40 Arina Puzriakova Phenotypes for gene: KLHL40 were changed from Nemaline myopathy 8, autosomal recessive, 615348 to Nemaline myopathy 8, autosomal recessive, OMIM:615348
Congenital myopathy v3.50 KBTBD13 Arina Puzriakova Phenotypes for gene: KBTBD13 were changed from Nemaline Myopathy, Dominant; Nemaline myopathy 6, autosomal dominant, 609273 to Nemaline myopathy 6, autosomal dominant, OMIM:609273
Congenital muscular dystrophy v3.63 JAG2 Arina Puzriakova Phenotypes for gene: JAG2 were changed from muscular dystrophy, MONDO:0020121 to Muscular dystrophy, limb-girdle, autosomal recessive 27, OMIM:619566
Congenital muscular dystrophy v3.62 ITGA7 Arina Puzriakova Source was removed from ITGA7.
Congenital muscular dystrophy v3.61 ITGA7 Arina Puzriakova Phenotypes for gene: ITGA7 were changed from Congenital Muscular Dystrophy, ITGA7-related; Muscular dystrophy, congenital, due to ITGA7 deficiency, 613204 to Muscular dystrophy, congenital, due to ITGA7 deficiency, OMIM:613204
Congenital muscular dystrophy v3.60 ISPD Arina Puzriakova Source was removed from ISPD.
Congenital muscular dystrophy v3.59 ISPD Arina Puzriakova Publications for gene: ISPD were set to 22522420, 22522421
Congenital muscular dystrophy v3.58 ISPD Arina Puzriakova Phenotypes for gene: ISPD were changed from Congenital Muscular Dystrophy, alpha-dystroglycan related; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type; Walker-Warburg syndrome (WWS); Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7; 614643; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7; 616052 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, OMIM:614643
Congenital myopathy v3.49 ISCU Arina Puzriakova Phenotypes for gene: ISCU were changed from Myopathy with lactic acidosis, hereditary, 255125 to Myopathy with lactic acidosis, hereditary, OMIM:255125
Congenital muscular dystrophy v3.57 INPP5K Arina Puzriakova Phenotypes for gene: INPP5K were changed from Congenital Muscular Dystrophy Overlapping Marinesco-Sjogren Syndrome and Dystroglycanopathy; Congenital Muscular Dystrophy with Cataracts and Mild Cognitive Impairment to Muscular dystrophy, congenital, with cataracts and intellectual disability, OMIM:617404
Congenital myopathy v3.48 HTRA2 Arina Puzriakova Phenotypes for gene: HTRA2 were changed from 3-methylglutaconic aciduria, type VIII 617248 to 3-methylglutaconic aciduria, type VIII, OMIM:617248
Congenital myopathy v3.47 HRAS Arina Puzriakova Phenotypes for gene: HRAS were changed from Costello syndrome 218040; Congenital myopathy with excess of muscle spindles 218040 to Costello syndrome, OMIM:218040; Congenital myopathy with excess of muscle spindles, OMIM:218040
Congenital myopathy v3.46 HNRNPA2B1 Arina Puzriakova Tag watchlist was removed from gene: HNRNPA2B1.
Congenital muscular dystrophy v3.56 HNRNPA2B1 Arina Puzriakova Phenotypes for gene: HNRNPA2B1 were changed from early-onset oculopharyngeal muscular dystrophy, muscular dystrophy, congenital myopathy to Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2, OMIM:615422
Congenital muscular dystrophy v3.55 HNRNPA2B1 Arina Puzriakova Tag watchlist was removed from gene: HNRNPA2B1.
Congenital myopathy v3.46 HNRNPA1 Arina Puzriakova Phenotypes for gene: HNRNPA1 were changed from ?Inclusion body myopathy wtih early-onset Paget disease without frontotemporal to ?Inclusion body myopathy with early-onset Paget disease without frontotemporal dementia 3, OMIM:615424
Congenital myopathy v3.45 HACD1 Arina Puzriakova Phenotypes for gene: HACD1 were changed from congenital myopathy, MONDO:0019952 to Myopathy, congenital, nonprogressive, OMIM:619967
Congenital muscular dystrophy v3.55 GOSR2 Arina Puzriakova Phenotypes for gene: GOSR2 were changed from Congenital muscular dystrophy with hypoglycosylation of alpha-dystroglycan to Muscular dystrophy, congenital, with or without seizures, OMIM:620166
Congenital myopathy v3.44 GNE Arina Puzriakova Phenotypes for gene: GNE were changed from Nonaka myopathy 605820 to Nonaka myopathy, OMIM:605820
Congenital muscular dystrophy v3.54 GMPPB Arina Puzriakova Source was removed from GMPPB.
Congenital muscular dystrophy v3.53 GMPPB Arina Puzriakova Phenotypes for gene: GMPPB were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 OMIM:615350; muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14 MONDO:0014140; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 OMIM:615351; muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14 MONDO:0014141; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 OMIM:615352; autosomal recessive limb-girdle muscular dystrophy type 2T MONDO:0014142 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14, OMIM:615350; Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14, OMIM:615351; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14, OMIM:615352
Congenital myopathy v3.43 GFER Arina Puzriakova Phenotypes for gene: GFER were changed from Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay,613076 to Myopathy, mitochondrial progressive, with congenital cataract and developmental delay, OMIM:613076
Congenital myopathy v3.42 FXR1 Arina Puzriakova Phenotypes for gene: FXR1 were changed from Congenital multi-minicore myopathy; ?Myopathy, congenital proximal, with minicore lesions #618823; ?Myopathy, congenital, with respiratory insufficiency and bone fractures #618822 to Myopathy, congenital proximal, with minicore lesions, OMIM:618823; Myopathy, congenital, with respiratory insufficiency and bone fractures, OMIM:618822
Congenital myopathy v3.41 FLNC Arina Puzriakova Phenotypes for gene: FLNC were changed from Myopathy, distal, 4, OMIM:614065; Distal myopathy with posterior leg and anterior hand involvement, MONDO:0013550; Myopathy, myofibrillar, 5, OMIM:609524; Myopathy, myofibrillar, 5, MONDO:0012289 to Myopathy, distal, 4, OMIM:614065; Myopathy, myofibrillar, 5, OMIM:609524
Congenital muscular dystrophy v3.52 FKTN Arina Puzriakova Source was removed from FKTN.
Congenital muscular dystrophy v3.51 FKTN Arina Puzriakova Phenotypes for gene: FKTN were changed from Fukuyama congenital muscular dystrophy; Fukuyama Congenital Muscular Dystrophy; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4, OMIM:253800; Muscular dystrophy-dystroglycanopathy (congenital without impaired intellectual development), type B, 4, OMIM:613152; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4, OMIM:611588
Congenital muscular dystrophy v3.50 FKRP Arina Puzriakova Source was removed from FKRP.
Congenital muscular dystrophy v3.49 FKRP Arina Puzriakova Phenotypes for gene: FKRP were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5; Muscular dystrophy-dystroglycanopathy (congenital with or without mental retardation), type B, 5 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5, OMIM:613153; Muscular dystrophy-dystroglycanopathy (congenital with or without impaired intellectual development), type B, 5, OMIM:606612
Congenital myopathy v3.40 FKBP14 Arina Puzriakova Phenotypes for gene: FKBP14 were changed from Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss 6, 14557 to Ehlers-Danlos syndrome, kyphoscoliotic type, 2, OMIM:614557
Congenital muscular dystrophy v3.48 FHL1 Arina Puzriakova Phenotypes for gene: FHL1 were changed from Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset, 300717; Reducing body myopathy, X-linked 1b, with late childhood or adult onset, 300718 to Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset, OMIM:300717
Congenital myopathy v3.39 FAM111B Arina Puzriakova Phenotypes for gene: FAM111B were changed from Poikiloderma, hereditary fibrosing, with tendon contractures, myopathy, and pulmonaryfibrosis, 615704 to Poikiloderma, hereditary fibrosing, with tendon contractures, myopathy, and pulmonary fibrosis, OMIM:615704
Congenital myopathy v3.38 EPG5 Arina Puzriakova Phenotypes for gene: EPG5 were changed from vacuolar myopathy? to Vici syndrome, OMIM:242840
Congenital muscular dystrophy v3.47 EMD Arina Puzriakova Source was removed from EMD.
Congenital muscular dystrophy v3.46 EMD Arina Puzriakova Phenotypes for gene: EMD were changed from Emery-Dreifuss muscular dystrophy 1, X-linked, 310300 to Emery-Dreifuss muscular dystrophy 1, X-linked, OMIM:310300
Congenital myopathy v3.37 ECEL1 Arina Puzriakova Phenotypes for gene: ECEL1 were changed from Arthrogryposis, distal, type 5D, 615065 to Arthrogryposis, distal, type 5D, OMIM:615065
Congenital muscular dystrophy v3.45 DYSF Arina Puzriakova Source was removed from DYSF.
Congenital muscular dystrophy v3.44 DYSF Arina Puzriakova Phenotypes for gene: DYSF were changed from Muscular dystrophy, limb-girdle, type 2B, 253601; Myopathy, distal, with anterior tibial onset, 606768; Miyoshi muscular dystrophy 1, 254130 to Miyoshi muscular dystrophy 1, OMIM:254130; Muscular dystrophy, limb-girdle, autosomal recessive 2, OMIM:253601; Myopathy, distal, with anterior tibial onset, OMIM:606768
Congenital muscular dystrophy v3.43 DUX4 Arina Puzriakova Source was removed from DUX4.
Congenital muscular dystrophy v3.42 DUX4 Arina Puzriakova Mode of inheritance for gene: DUX4 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital muscular dystrophy v3.41 DPM3 Arina Puzriakova Source was removed from DPM3.
Congenital muscular dystrophy v3.40 DPM3 Arina Puzriakova Phenotypes for gene: DPM3 were changed from Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15, OMIM:612937; DPM3-congenital disorder of glycosylation, MONDO:0013049; ?Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 15, OMIM:618992; muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type b, 15, MONDO:0033556 to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15, OMIM:612937; ?Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 15, OMIM:618992
Congenital muscular dystrophy v3.39 DPM2 Arina Puzriakova Source was removed from DPM2.
Congenital muscular dystrophy v3.38 DPM1 Arina Puzriakova Source was removed from DPM1.
Congenital muscular dystrophy v3.37 DOLK Arina Puzriakova Phenotypes for gene: DOLK were changed from Congenital disorder of glycosylation, type Im to Congenital disorder of glycosylation, type Im, OMIM:610768
Congenital myopathy v3.36 DOK7 Arina Puzriakova Phenotypes for gene: DOK7 were changed from Fetal akinesia deformation sequence, 208150; Myasthenic syndrome, congenital, 10, 254300 to Fetal akinesia deformation sequence 3, OMIM:618389; Myasthenic syndrome, congenital, 10, OMIM:254300
Congenital myopathy v3.35 DNM2 Arina Puzriakova Phenotypes for gene: DNM2 were changed from Myopathy, centronuclear, 160150; Charcot-Marie-Tooth disease, axonal, type 2M, 606482 to Centronuclear myopathy 1, OMIM:160150
Congenital myopathy v3.34 DNAJB6 Arina Puzriakova Phenotypes for gene: DNAJB6 were changed from Myofibrillar Myopathy, Dominant; Muscular dystrophy, limb-girdle, type 1E 603511 to Muscular dystrophy, limb-girdle, autosomal dominant 1, OMIM:603511
Congenital muscular dystrophy v3.36 DMD Arina Puzriakova Phenotypes for gene: DMD were changed from Duchenne muscular dystrophy, 310200; Becker muscular dystrophy, 300376 to Becker muscular dystrophy, OMIM:300376; Duchenne muscular dystrophy, OMIM:310200
Congenital myopathy v3.33 DHX16 Arina Puzriakova Phenotypes for gene: DHX16 were changed from Neuromuscular disease and ocular or auditory anomalies with or without seizures, MIM# 618733 to Neuromuscular disease and ocular or auditory anomalies with or without seizures, OMIM:618733
Congenital myopathy v3.32 DES Arina Puzriakova Phenotypes for gene: DES were changed from Myopathy, myofibrillar, 1, 601419; Scapuloperoneal syndrome, neurogenic, Kaeser type, 181400 to Myopathy, myofibrillar, 1, OMIM:601419; Scapuloperoneal syndrome, neurogenic, Kaeser type, OMIM:181400
Congenital muscular dystrophy v3.35 DAG1 Arina Puzriakova Phenotypes for gene: DAG1 were changed from congenital muscular dystrophies; congenital muscular dystrophies, MDDGA9 (WWS), also hyperckaemia and MDDG C9; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9 616538; Walker-Warburg syndrome to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9, OMIM:616538; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9, OMIM:613818
Congenital myopathy v3.31 COL6A2 Arina Puzriakova Phenotypes for gene: COL6A2 were changed from Bethlem myopathy, 158810; Ullrich congenital muscular dystrophy, 254090 to Bethlem myopathy, OMIM:158810; Ullrich congenital muscular dystrophy, OMIM:254090
Congenital muscular dystrophy v3.34 COL6A1 Arina Puzriakova Source was removed from COL6A1.
Congenital muscular dystrophy v3.33 COL4A2 Arina Puzriakova Mode of inheritance for gene: COL4A2 was changed from to Unknown
Congenital muscular dystrophy v3.32 COL4A1 Arina Puzriakova Phenotypes for gene: COL4A1 were changed from walker warburg syndrome, muscle eye brain disease; Brain small vessel disease with or without ocular anomalies, 175780 to Walker Warburg Syndrome
Congenital muscular dystrophy v3.31 CHKB Arina Puzriakova Source was removed from CHKB.
Congenital muscular dystrophy v3.30 CHKB Arina Puzriakova Publications for gene: CHKB were set to 16371353, 21665002
Congenital muscular dystrophy v3.29 CHKB Arina Puzriakova Phenotypes for gene: CHKB were changed from Congenital Muscular Dystrophy, CKHB-related; Muscular dystrophy, congenital, megaconial type, 602541 to Muscular dystrophy, congenital, megaconial type, OMIM:602541
Congenital myopathy v3.30 CHCHD10 Arina Puzriakova Phenotypes for gene: CHCHD10 were changed from ?Myopathy, isolated mitochondrial, autosomal dominant 616209; Frontotemporal dementia and/or amyotrophic lateral sclerosis 2 615911; Spinal muscular atrophy, Jokela type 615048 to Myopathy, isolated mitochondrial, autosomal dominant, OMIM:616209; Frontotemporal dementia and/or amyotrophic lateral sclerosis 2, OMIM:615911; Spinal muscular atrophy, Jokela type, OMIM:615048
Congenital myopathy v3.29 CFL2 Arina Puzriakova Publications for gene: CFL2 were set to 22560515; 17160903; 24610938
Congenital myopathy v3.28 CFL2 Arina Puzriakova Phenotypes for gene: CFL2 were changed from Nemaline myopathy 7, autosomal recessive, 610687; Nemaline Myopathy, Recessive to Nemaline myopathy 7, autosomal recessive, OMIM:610687
Congenital myopathy v3.27 CCDC78 Arina Puzriakova Phenotypes for gene: CCDC78 were changed from Myopathy, centronuclear, 4, 614807 to Myopathy, centronuclear, 4, OMIM:614807
Congenital myopathy v3.26 CAV3 Arina Puzriakova Phenotypes for gene: CAV3 were changed from Cardiomyopathy, familial hypertrophic 192600; Creatine phosphokinase, elevated serum 123320; Long QT syndrome 9 611818; Muscular dystrophy, limb-girdle, type IC 607801; Myopathy, distal, Tateyama type 614321; Rippling muscle disease 606072 to Myopathy, distal, Tateyama type, OMIM:614321
Congenital myopathy v3.25 CASQ1 Arina Puzriakova Mode of inheritance for gene: CASQ1 was changed from MONOALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital myopathy v3.24 CASQ1 Arina Puzriakova Publications for gene: CASQ1 were set to 25116801
Congenital myopathy v3.23 CASQ1 Arina Puzriakova Phenotypes for gene: CASQ1 were changed from Vacuolar myopathy with CASQ1 aggregates (VMCQA); Myopathy, vacuolar, with CASQ1 aggregates, 616231 to Myopathy, vacuolar, with CASQ1 aggregates, OMIM:616231
Congenital myopathy v3.22 CACNA1S Arina Puzriakova Phenotypes for gene: CACNA1S were changed from congenital myopathy to Congenital myopathy, MONDO:0019952
Congenital myopathy v3.21 BIN1 Arina Puzriakova Publications for gene: BIN1 were set to
Congenital myopathy v3.20 BIN1 Arina Puzriakova Phenotypes for gene: BIN1 were changed from Centronuclear Myopathy, Recessive; Myopathy, centronuclear, autosomal recessive, 255200 to Centronuclear myopathy 2, OMIM:255200
Congenital myopathy v3.19 BAG3 Arina Puzriakova Phenotypes for gene: BAG3 were changed from Myopathy, myofibrillar, 6, 612954 to Myopathy, myofibrillar, 6, OMIM:612954
Congenital muscular dystrophy v3.28 B4GAT1 Arina Puzriakova Source was removed from B4GAT1.
Congenital muscular dystrophy v3.27 B4GAT1 Arina Puzriakova Phenotypes for gene: B4GAT1 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), typeA, 13, 615287 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13, OMIM:615287
Congenital muscular dystrophy v3.26 B3GALNT2 Arina Puzriakova Source was removed from B3GALNT2.
Congenital muscular dystrophy v3.25 B3GALNT2 Arina Puzriakova Phenotypes for gene: B3GALNT2 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies typeA 11; congenital muscular dystrophies to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 11, OMIM:615181
Congenital myopathy v3.18 ATP2A1 Arina Puzriakova Phenotypes for gene: ATP2A1 were changed from Brody Myopathy; Brody myopathy, 601003 to Brody myopathy, OMIM:601003
Congenital myopathy v3.17 ASCC3 Arina Puzriakova Publications for gene: ASCC3 were set to 21937992; https://doi.org/10.1016/j.xhgg.2021.100024
Congenital muscular dystrophy v3.24 ANO5 Arina Puzriakova Source was removed from ANO5.
Congenital muscular dystrophy v3.23 ANO5 Arina Puzriakova Phenotypes for gene: ANO5 were changed from Gnathodiaphyseal dysplasia, 166260; Muscular dystrophy, limb-girdle, type 2L, 611307Miyoshi muscular dystrophy 3, 613319; Limb-Girdle Muscular Dystrophy, Recessive to Miyoshi muscular dystrophy 3, OMIM:613319; Muscular dystrophy, limb-girdle, autosomal recessive 12, OMIM:611307
Congenital myopathy v3.16 ADSSL1 Arina Puzriakova Phenotypes for gene: ADSSL1 were changed from Myopathy, distal, 5, 617030 to Myopathy, distal, 5, OMIM:617030
Hereditary neuropathy v1.459 SETX Achchuthan Shanmugasundram Tag Q2_22_MOI was removed from gene: SETX.
Hereditary neuropathy v1.459 SETX Achchuthan Shanmugasundram Mode of inheritance for gene: SETX was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital myopathy v3.15 ACTN2 Arina Puzriakova Phenotypes for gene: ACTN2 were changed from Multiple structured Core Disease; progressive early-onset muscle weakness to Myopathy, congenital with structured cores and Z-line abnormalities, OMIM:618654
Neurotransmitter disorders v1.9 ALDH5A1 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: ALDH5A1.
Fetal hydrops v1.58 PEX6 Achchuthan Shanmugasundram Tag Q1_22_MOI was removed from gene: PEX6.
Fetal hydrops v1.58 PEX6 Achchuthan Shanmugasundram Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Tubulointerstitial kidney disease v2.4 XPNPEP3 Achchuthan Shanmugasundram Tag Q1_22_rating was removed from gene: XPNPEP3.
Osteogenesis imperfecta v3.5 P4HB Eleanor Williams Tag Q2_22_MOI was removed from gene: P4HB.
Osteogenesis imperfecta v3.5 SGMS2 Eleanor Williams Tag Q3_21_rating was removed from gene: SGMS2.
Osteogenesis imperfecta v3.5 DSPP Eleanor Williams Tag Q3_22_rating was removed from gene: DSPP.
Tag Q3_22_expert_review was removed from gene: DSPP.
Osteogenesis imperfecta v3.5 COPB2 Eleanor Williams Tag Q3_21_rating was removed from gene: COPB2.
Osteogenesis imperfecta v3.5 P4HB Eleanor Williams commented on gene: P4HB: The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Osteogenesis imperfecta v3.5 SGMS2 Eleanor Williams edited their review of gene: SGMS2: Added comment: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. The reviewers note that the associated phenotype appears variable, and that R104 Skeletal Dysplasia panel looks a better fit for this gene.; Changed rating: AMBER
Osteogenesis imperfecta v3.5 DSPP Eleanor Williams edited their review of gene: DSPP: Added comment: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.; Changed rating: RED
Osteogenesis imperfecta v3.5 COPB2 Eleanor Williams commented on gene: COPB2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Osteogenesis imperfecta v3.4 P4HB Eleanor Williams Mode of inheritance for gene P4HB was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Osteogenesis imperfecta v3.4 DSPP Eleanor Williams Source Expert Review Red was added to DSPP.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Osteogenesis imperfecta v3.4 COPB2 Eleanor Williams Source Expert Review Green was added to COPB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v3.6 ISCA-46303-Loss Arina Puzriakova reviewed Region: ISCA-46303-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v4.54 ISCA-46553-Loss Arina Puzriakova reviewed Region: ISCA-46553-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v3.28 ISCA-46553-Loss Arina Puzriakova reviewed Region: ISCA-46553-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v4.54 ISCA-46742-Loss Arina Puzriakova reviewed Region: ISCA-46742-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Severe microcephaly v3.6 ISCA-46742-Loss Arina Puzriakova reviewed Region: ISCA-46742-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy or pain disorder v2.19 ISCA-37436-Loss Arina Puzriakova reviewed Region: ISCA-37436-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy v1.458 ISCA-37436-Loss Arina Puzriakova reviewed Region: ISCA-37436-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy v1.458 ISCA-37436-Gain Arina Puzriakova changed review comment from: New green region added based on ClinGen Region Curation Results (version on 05 Aug 2022) following NHS Genomic Medicine Service approval. Additional comments: About 80% of hereditary neuropathy with liability to pressure palsies (HNPP) cases associated with this recurrent region.; to: Genomic coordinates updated based on ClinGen Region Curation Results (version on 05 Aug 2022) following NHS Genomic Medicine Service approval. Additional comments: About 80% of hereditary neuropathy with liability to pressure palsies (HNPP) cases associated with this recurrent region.
Hereditary neuropathy or pain disorder v2.19 ISCA-37436-Gain Arina Puzriakova reviewed Region: ISCA-37436-Gain: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy v1.458 ISCA-37436-Gain Arina Puzriakova edited their review of Region: ISCA-37436-Gain: Added comment: New green region added based on ClinGen Region Curation Results (version on 05 Aug 2022) following NHS Genomic Medicine Service approval. Additional comments: About 80% of hereditary neuropathy with liability to pressure palsies (HNPP) cases associated with this recurrent region.; Changed rating: GREEN
Intellectual disability v4.54 ISCA-46297-Loss Arina Puzriakova reviewed Region: ISCA-46297-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v3.31 ISCA-46297-Loss Arina Puzriakova reviewed Region: ISCA-46297-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Monogenic hearing loss v3.8 ISCA-46297-Loss Arina Puzriakova edited their review of Region: ISCA-46297-Loss: Changed rating: GREEN
Monogenic hearing loss v3.8 ISCA-46297-Loss Arina Puzriakova commented on Region: ISCA-46297-Loss
Intellectual disability v4.54 ISCA-37495-Loss Arina Puzriakova reviewed Region: ISCA-37495-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v4.54 ISCA-46304-Gain Arina Puzriakova reviewed Region: ISCA-46304-Gain: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v3.31 ISCA-46304-Gain Arina Puzriakova edited their review of Region: ISCA-46304-Gain: Changed rating: GREEN
Early onset or syndromic epilepsy v3.31 ISCA-46304-Gain Arina Puzriakova commented on Region: ISCA-46304-Gain
Childhood onset hereditary spastic paraplegia v3.10 ISCA-46304-Gain Arina Puzriakova reviewed Region: ISCA-46304-Gain: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v4.54 ISCA-37423-Loss Arina Puzriakova edited their review of Region: ISCA-37423-Loss: Added comment: Following Genomics England clinical review and NHS Genomic Medicine Service approval, the genomic coordinates of this region were updated based on ClinGen Region Curation Results (version on 05 Aug 2022).; Changed rating: GREEN
Familial non syndromic congenital heart disease v1.80 ISCA-37423-Loss Arina Puzriakova edited their review of Region: ISCA-37423-Loss: Added comment: Following Genomics England clinical review and NHS Genomic Medicine Service approval, the genomic coordinates of this region were updated based on ClinGen Region Curation Results (version on 05 Aug 2022).; Changed rating: GREEN
Intellectual disability v4.54 ISCA-37423-Gain Arina Puzriakova edited their review of Region: ISCA-37423-Gain: Added comment: Following Genomics England clinical review and NHS Genomic Medicine Service approval, the genomic coordinates and triplosensitivity score (from 3 to 2) of this region were updated based on ClinGen Region Curation Results (version on 05 Aug 2022). Regardless of the change in triplosensitivity score, it was deemed appropriate for this regions to remain green as evidence to support pathogenicity remains.; Changed rating: GREEN
Early onset or syndromic epilepsy v3.31 ISCA-37423-Gain Arina Puzriakova edited their review of Region: ISCA-37423-Gain: Added comment: Following Genomics England clinical review and NHS Genomic Medicine Service approval, the genomic coordinates and triplosensitivity score (from 3 to 2) of this region were updated based on ClinGen Region Curation Results (version on 05 Aug 2022). Regardless of the change in triplosensitivity score, it was deemed appropriate for this regions to remain green as evidence to support pathogenicity remains.; Changed rating: GREEN
Clefting v3.6 ISCA-37423-Gain Arina Puzriakova edited their review of Region: ISCA-37423-Gain: Added comment: Following Genomics England clinical review and NHS Genomic Medicine Service approval, the genomic coordinates and triplosensitivity score (from 3 to 2) of this region were updated based on ClinGen Region Curation Results (version on 05 Aug 2022). Regardless of the change in triplosensitivity score, it was deemed appropriate for this regions to remain green as evidence to support pathogenicity remains.; Changed rating: GREEN
Familial non syndromic congenital heart disease v1.80 ISCA-37423-Gain Arina Puzriakova edited their review of Region: ISCA-37423-Gain: Added comment: Following Genomics England clinical review and NHS Genomic Medicine Service approval, the genomic coordinates and triplosensitivity score (from 3 to 2) of this region were updated based on ClinGen Region Curation Results (version on 05 Aug 2022). Regardless of the change in triplosensitivity score, it was deemed appropriate for this regions to remain green as evidence to support pathogenicity remains.; Changed rating: GREEN
Clefting v3.6 ISCA-46303-Loss Arina Puzriakova Region: ISCA-46303-Loss was added
Region: ISCA-46303-Loss was added to Clefting. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46303-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-46303-Loss were set to 24934569; 26663529; 19234473
Ataxia and cerebellar anomalies - narrow panel v3.28 ISCA-46553-Loss Arina Puzriakova Region: ISCA-46553-Loss was added
Region: ISCA-46553-Loss was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46553-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-46553-Loss were set to 21204220; 15338008; 22067867; 21471554; 28503614
Intellectual disability v4.54 ISCA-46553-Loss Arina Puzriakova Region: ISCA-46553-Loss was added
Region: ISCA-46553-Loss was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46553-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-46553-Loss were set to 21204220; 15338008; 22067867; 21471554; 28503614
Severe microcephaly v3.6 ISCA-46742-Loss Arina Puzriakova Region: ISCA-46742-Loss was added
Region: ISCA-46742-Loss was added to Severe microcephaly. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46742-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-46742-Loss were set to 27633570; 32562408; 29274487; 29220674
Intellectual disability v4.54 ISCA-46742-Loss Arina Puzriakova Region: ISCA-46742-Loss was added
Region: ISCA-46742-Loss was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46742-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-46742-Loss were set to 27633570; 32562408; 29274487; 29220674
Hereditary neuropathy v1.458 ISCA-37436-Loss Arina Puzriakova GRCh38 position for ISCA-37436-Loss was changed from 14194598-15567587 to 14194598-15519638.
Hereditary neuropathy v1.458 ISCA-37436-Gain Arina Puzriakova GRCh38 position for ISCA-37436-Gain was changed from 14194598-15567587 to 14194598-15519638.
Hereditary neuropathy or pain disorder v2.19 ISCA-37436-Loss Arina Puzriakova Region: ISCA-37436-Loss was added
Region: ISCA-37436-Loss was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-37436-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37436-Loss were set to 20301566
Hereditary neuropathy or pain disorder v2.19 ISCA-37436-Gain Arina Puzriakova Region: ISCA-37436-Gain was added
Region: ISCA-37436-Gain was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-37436-Gain was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37436-Gain were set to 20301384
Early onset or syndromic epilepsy v3.31 ISCA-46297-Loss Arina Puzriakova Region: ISCA-46297-Loss was added
Region: ISCA-46297-Loss was added to Genetic epilepsy syndromes. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46297-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-46297-Loss were set to 31204719; 19888295; 20301607; 25719193; 30836598
Intellectual disability v4.54 ISCA-46297-Loss Arina Puzriakova Region: ISCA-46297-Loss was added
Region: ISCA-46297-Loss was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46297-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-46297-Loss were set to 31204719; 19888295; 20301607; 25719193; 30836598
Monogenic hearing loss v3.8 ISCA-46297-Loss Arina Puzriakova Region: ISCA-46297-Loss was added
Region: ISCA-46297-Loss was added to Monogenic hearing loss. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46297-Loss was set to BIALLELIC, autosomal or pseudoautosomal
Publications for Region: ISCA-46297-Loss were set to 31204719; 19888295; 20301607; 25719193; 30836598
Intellectual disability v4.54 ISCA-37495-Loss Arina Puzriakova Region: ISCA-37495-Loss was added
Region: ISCA-37495-Loss was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-37495-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37495-Loss were set to 26227573
Childhood onset hereditary spastic paraplegia v3.10 ISCA-46304-Gain Arina Puzriakova Region: ISCA-46304-Gain was added
Region: ISCA-46304-Gain was added to Hereditary spastic paraplegia - childhood onset. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46304-Gain 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 Region: ISCA-46304-Gain were set to 22679399; 29141583; 29618507; 32043567
Early onset or syndromic epilepsy v3.31 ISCA-46304-Gain Arina Puzriakova Region: ISCA-46304-Gain was added
Region: ISCA-46304-Gain was added to Genetic epilepsy syndromes. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46304-Gain 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 Region: ISCA-46304-Gain were set to 22679399; 29141583; 29618507; 32043567
Intellectual disability v4.54 ISCA-46304-Gain Arina Puzriakova Region: ISCA-46304-Gain was added
Region: ISCA-46304-Gain was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46304-Gain 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 Region: ISCA-46304-Gain were set to 22679399; 29141583; 29618507; 32043567
Familial non syndromic congenital heart disease v1.80 ISCA-37423-Loss Arina Puzriakova GRCh38 position for ISCA-37423-Loss was changed from 8261773-11908210 to 8242542-11908820.
Intellectual disability v4.54 ISCA-37423-Loss Arina Puzriakova GRCh38 position for ISCA-37423-Loss was changed from 8261773-11908210 to 8242542-11908820.
Familial non syndromic congenital heart disease v1.80 ISCA-37423-Gain Arina Puzriakova GRCh38 position for ISCA-37423-Gain was changed from 8261773-11908210 to 8242542-11908820.
Triplosensitivity Score for ISCA-37423-Gain was changed from 3 to 2.
Intellectual disability v4.54 ISCA-37423-Gain Arina Puzriakova GRCh38 position for ISCA-37423-Gain was changed from 8261773-11908210 to 8242542-11908820.
Triplosensitivity Score for ISCA-37423-Gain was changed from 3 to 2.
Early onset or syndromic epilepsy v3.31 ISCA-37423-Gain Arina Puzriakova GRCh38 position for ISCA-37423-Gain was changed from 8261773-11908210 to 8242542-11908820.
Triplosensitivity Score for ISCA-37423-Gain was changed from 3 to 2.
Clefting v3.6 ISCA-37423-Gain Arina Puzriakova GRCh38 position for ISCA-37423-Gain was changed from 8261773-11908210 to 8242542-11908820.
Triplosensitivity Score for ISCA-37423-Gain was changed from 3 to 2.
Endocrine neoplasia v2.2 PTEN Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: PTEN.
Tag Q2_21_phenotype was removed from gene: PTEN.
Tag Q2_21_expert_review was removed from gene: PTEN.
Tag Q2_21_NHS_review was removed from gene: PTEN.
Endocrine neoplasia v2.2 PMS2 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: PMS2.
Tag Q2_21_phenotype was removed from gene: PMS2.
Tag Q2_21_expert_review was removed from gene: PMS2.
Tag Q2_21_NHS_review was removed from gene: PMS2.
Endocrine neoplasia v2.2 MSH6 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: MSH6.
Tag Q2_21_phenotype was removed from gene: MSH6.
Tag Q2_21_expert_review was removed from gene: MSH6.
Tag Q2_21_NHS_review was removed from gene: MSH6.
Endocrine neoplasia v2.2 MSH2 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: MSH2.
Tag Q2_21_phenotype was removed from gene: MSH2.
Tag Q2_21_expert_review was removed from gene: MSH2.
Tag Q2_21_NHS_review was removed from gene: MSH2.
Endocrine neoplasia v2.2 MLH1 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: MLH1.
Tag Q2_21_phenotype was removed from gene: MLH1.
Tag Q2_21_expert_review was removed from gene: MLH1.
Tag Q2_21_NHS_review was removed from gene: MLH1.
Endocrine neoplasia v2.2 PTEN Achchuthan Shanmugasundram reviewed gene: PTEN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Endocrine neoplasia v2.2 PMS2 Achchuthan Shanmugasundram reviewed gene: PMS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Endocrine neoplasia v2.2 MSH6 Achchuthan Shanmugasundram reviewed gene: MSH6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Endocrine neoplasia v2.2 MSH2 Achchuthan Shanmugasundram reviewed gene: MSH2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Endocrine neoplasia v2.2 MLH1 Achchuthan Shanmugasundram reviewed gene: MLH1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v3.26 COL2A1 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: COL2A1.
Tag Q3_22_NHS_review was removed from gene: COL2A1.
Tag Q3_22_expert_review was removed from gene: COL2A1.
Clefting v3.5 MED12 Achchuthan Shanmugasundram Tag Q3_21_MOI was removed from gene: MED12.
Primary immunodeficiency or monogenic inflammatory bowel disease v3.4 TLR8 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: TLR8.
Primary immunodeficiency or monogenic inflammatory bowel disease v3.4 IKBKB Achchuthan Shanmugasundram Tag Q3_22_MOI was removed from gene: IKBKB.
Primary immunodeficiency or monogenic inflammatory bowel disease v3.4 IFNAR2 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: IFNAR2.
Primary immunodeficiency or monogenic inflammatory bowel disease v3.4 FOXN1 Achchuthan Shanmugasundram Tag Q3_22_MOI was removed from gene: FOXN1.
Primary immunodeficiency or monogenic inflammatory bowel disease v3.4 PRIM1 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: PRIM1.
Primary immunodeficiency or monogenic inflammatory bowel disease v3.4 FASLG Achchuthan Shanmugasundram Tag Q2_22_MOI was removed from gene: FASLG.
Primary immunodeficiency or monogenic inflammatory bowel disease v3.4 AGR2 Achchuthan Shanmugasundram Tag Q1_22_rating was removed from gene: AGR2.
Primary immunodeficiency or monogenic inflammatory bowel disease v3.4 UBA1 Achchuthan Shanmugasundram Tag Q2_22_rating was removed from gene: UBA1.
Tag Q2_22_expert_review was removed from gene: UBA1.
Tag Q2_22_NHS_review was removed from gene: UBA1.
Primary immunodeficiency or monogenic inflammatory bowel disease v3.4 TLR8 Achchuthan Shanmugasundram reviewed gene: TLR8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v3.4 IKBKB Achchuthan Shanmugasundram commented on gene: IKBKB
Primary immunodeficiency or monogenic inflammatory bowel disease v3.4 IFNAR2 Achchuthan Shanmugasundram reviewed gene: IFNAR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v3.4 FOXN1 Achchuthan Shanmugasundram commented on gene: FOXN1
Primary immunodeficiency or monogenic inflammatory bowel disease v3.4 PRIM1 Achchuthan Shanmugasundram reviewed gene: PRIM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v3.4 FASLG Achchuthan Shanmugasundram commented on gene: FASLG
Primary immunodeficiency or monogenic inflammatory bowel disease v3.4 AGR2 Achchuthan Shanmugasundram reviewed gene: AGR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v3.4 UBA1 Achchuthan Shanmugasundram reviewed gene: UBA1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v3.3 TLR8 Achchuthan Shanmugasundram Source Expert Review Green was added to TLR8.
Source NHS GMS was added to TLR8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v3.3 PRIM1 Achchuthan Shanmugasundram Source Expert Review Green was added to PRIM1.
Source NHS GMS was added to PRIM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v3.3 IKBKB Achchuthan Shanmugasundram Mode of inheritance for gene IKBKB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v3.3 IFNAR2 Achchuthan Shanmugasundram Source Expert Review Green was added to IFNAR2.
Source NHS GMS was added to IFNAR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v3.3 FOXN1 Achchuthan Shanmugasundram Mode of inheritance for gene FOXN1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v3.3 FASLG Achchuthan Shanmugasundram Mode of inheritance for gene FASLG was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v3.3 AGR2 Achchuthan Shanmugasundram Source Expert Review Green was added to AGR2.
Source NHS GMS was added to AGR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare anaemia v2.3 RPS27 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: RPS27.
Tag Q3_22_expert_review was removed from gene: RPS27.
Rare anaemia v2.3 RPL27 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: RPL27.
Tag Q3_22_expert_review was removed from gene: RPL27.
Cytopenia - NOT Fanconi anaemia v2.3 RPL27 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: RPL27.
Tag Q3_22_expert_review was removed from gene: RPL27.
Hydrocephalus v3.5 AP1S2 Eleanor Williams Deleted their comment
Hydrocephalus v3.5 AP1S2 Eleanor Williams Deleted their comment
Optic neuropathy v3.8 SSBP1 Achchuthan Shanmugasundram Classified gene: SSBP1 as Green List (high evidence)
Optic neuropathy v3.8 SSBP1 Achchuthan Shanmugasundram Gene: ssbp1 has been classified as Green List (High Evidence).
Clefting v3.5 SF3B2 Achchuthan Shanmugasundram Tag Q4_21_rating was removed from gene: SF3B2.
Clefting v3.5 PLCB4 Achchuthan Shanmugasundram Tag Q2_22_rating was removed from gene: PLCB4.
Clefting v3.5 GDF11 Achchuthan Shanmugasundram Tag Q4_21_rating was removed from gene: GDF11.
Clefting v3.5 SEPT9 Achchuthan Shanmugasundram Tag Q3_21_rating was removed from gene: SEPT9.
Clefting v3.5 MED12 Achchuthan Shanmugasundram Tag Q3_21_rating was removed from gene: MED12.
Tag Q3_21_expert_review was removed from gene: MED12.
Congenital myopathy v3.14 CNTN1 Eleanor Williams Tag Q3_21_NHS_review was removed from gene: CNTN1.
Congenital myopathy v3.14 CNTN1 Eleanor Williams commented on gene: CNTN1
Congenital myopathy v3.14 TNNC2 Eleanor Williams Tag Q3_21_rating was removed from gene: TNNC2.
Congenital myopathy v3.14 MYOD1 Eleanor Williams Tag Q3_21_rating was removed from gene: MYOD1.
Congenital myopathy v3.14 MYL2 Eleanor Williams Tag Q2_21_rating was removed from gene: MYL2.
Congenital myopathy v3.14 MYH8 Eleanor Williams Tag Q2_21_rating was removed from gene: MYH8.
Tag Q2_21_phenotype was removed from gene: MYH8.
Tag Q2_21_expert_review was removed from gene: MYH8.
Clefting v3.5 SF3B2 Achchuthan Shanmugasundram reviewed gene: SF3B2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Clefting v3.5 PLCB4 Achchuthan Shanmugasundram reviewed gene: PLCB4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Clefting v3.5 GDF11 Achchuthan Shanmugasundram reviewed gene: GDF11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Clefting v3.5 SEPT9 Achchuthan Shanmugasundram reviewed gene: SEPT9: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Clefting v3.5 MED12 Achchuthan Shanmugasundram reviewed gene: MED12: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Congenital myopathy v3.14 MTM1 Eleanor Williams Tag Q3_22_MOI was removed from gene: MTM1.
Congenital myopathy v3.14 MTM1 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated toX-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)following NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) following NHS Genomic Medicine Service approval.
Clefting v3.4 SF3B2 Achchuthan Shanmugasundram Source NHS GMS was added to SF3B2.
Source Expert Review Green was added to SF3B2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v3.4 SEPT9 Achchuthan Shanmugasundram Source Expert Review Amber was added to SEPT9.
Source NHS GMS was added to SEPT9.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Clefting v3.4 PLCB4 Achchuthan Shanmugasundram Source NHS GMS was added to PLCB4.
Source Expert Review Green was added to PLCB4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v3.4 MED12 Achchuthan Shanmugasundram Source NHS GMS was added to MED12.
Source Expert Review Green was added to MED12.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v3.4 GDF11 Achchuthan Shanmugasundram Source NHS GMS was added to GDF11.
Source Expert Review Green was added to GDF11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital myopathy v3.14 HNRNPA2B1 Eleanor Williams Tag for-review was removed from gene: HNRNPA2B1.
Congenital myopathy v3.14 HACD1 Eleanor Williams Tag Q2_21_rating was removed from gene: HACD1.
Congenital myopathy v3.14 COX6A2 Eleanor Williams Tag Q3_22_rating was removed from gene: COX6A2.
Congenital myopathy v3.14 ASCC3 Eleanor Williams Tag Q3_21_rating was removed from gene: ASCC3.
Congenital myopathy v3.14 TNNC2 Eleanor Williams reviewed gene: TNNC2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Congenital myopathy v3.14 MYOD1 Eleanor Williams reviewed gene: MYOD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Congenital myopathy v3.14 MYL2 Eleanor Williams reviewed gene: MYL2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Congenital myopathy v3.14 MYH8 Eleanor Williams reviewed gene: MYH8: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Congenital myopathy v3.14 MTM1 Eleanor Williams commented on gene: MTM1
Congenital myopathy v3.14 HNRNPA2B1 Eleanor Williams reviewed gene: HNRNPA2B1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Congenital myopathy v3.14 HACD1 Eleanor Williams reviewed gene: HACD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Congenital myopathy v3.14 COX6A2 Eleanor Williams reviewed gene: COX6A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Congenital myopathy v3.14 ASCC3 Eleanor Williams reviewed gene: ASCC3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Congenital myopathy v3.13 TNNC2 Eleanor Williams Source Expert Review Green was added to TNNC2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital myopathy v3.13 MYOD1 Eleanor Williams Source Expert Review Green was added to MYOD1.
Source NHS GMS was added to MYOD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital myopathy v3.13 MYL2 Eleanor Williams Source Expert Review Green was added to MYL2.
Source NHS GMS was added to MYL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital myopathy v3.13 MYH8 Eleanor Williams Source Expert Review Red was added to MYH8.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Congenital myopathy v3.13 MTM1 Eleanor Williams Mode of inheritance for gene MTM1 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)
Congenital myopathy v3.13 HNRNPA2B1 Eleanor Williams Source Expert Review Green was added to HNRNPA2B1.
Source NHS GMS was added to HNRNPA2B1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital myopathy v3.13 HACD1 Eleanor Williams Source Expert Review Green was added to HACD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital myopathy v3.13 COX6A2 Eleanor Williams Source Expert Review Green was added to COX6A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital myopathy v3.13 ASCC3 Eleanor Williams Source Expert Review Green was added to ASCC3.
Source NHS GMS was added to ASCC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Amelogenesis imperfecta v2.22 SP6 Achchuthan Shanmugasundram Tag Q3_21_rating was removed from gene: SP6.
Amelogenesis imperfecta v2.22 PEX6 Achchuthan Shanmugasundram Tag Q1_22_MOI was removed from gene: PEX6.
Amelogenesis imperfecta v2.22 PEX26 Achchuthan Shanmugasundram Tag Q3_21_rating was removed from gene: PEX26.
Amelogenesis imperfecta v2.22 SP6 Achchuthan Shanmugasundram reviewed gene: SP6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Amelogenesis imperfecta v2.22 PEX6 Achchuthan Shanmugasundram commented on gene: PEX6
Amelogenesis imperfecta v2.22 PEX26 Achchuthan Shanmugasundram reviewed gene: PEX26: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Amelogenesis imperfecta v2.21 SP6 Achchuthan Shanmugasundram Source Expert Review Green was added to SP6.
Source NHS GMS was added to SP6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Amelogenesis imperfecta v2.21 PEX6 Achchuthan Shanmugasundram Source NHS GMS was added to PEX6.
Mode of inheritance for gene PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Amelogenesis imperfecta v2.21 PEX26 Achchuthan Shanmugasundram Source Expert Review Green was added to PEX26.
Source NHS GMS was added to PEX26.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.5 PDK3 Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Red.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Red. GMS reviewers believe that there is currently insufficient evidence that variants in this gene lead to primary mitochondrial disease (disease mechanism unclear; phenotype CMT; phenotype not consistent with known PDH deficiency disorders).
Possible mitochondrial disorder - nuclear genes v2.5 PDK3 Achchuthan Shanmugasundram Tag Q1_22_rating was removed from gene: PDK3.
Tag Q1_22_phenotype was removed from gene: PDK3.
Tag Q1_22_expert_review was removed from gene: PDK3.
Possible mitochondrial disorder - nuclear genes v2.5 UQCRFS1 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: UQCRFS1.
Tag Q3_22_NHS_review was removed from gene: UQCRFS1.
Possible mitochondrial disorder - nuclear genes v2.5 UQCRC2 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: UQCRC2.
Tag Q3_22_NHS_review was removed from gene: UQCRC2.
Possible mitochondrial disorder - nuclear genes v2.5 TIMMDC1 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: TIMMDC1.
Tag Q3_22_NHS_review was removed from gene: TIMMDC1.
Possible mitochondrial disorder - nuclear genes v2.5 TFAM Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: TFAM.
Tag Q3_22_NHS_review was removed from gene: TFAM.
Pituitary hormone deficiency v2.106 GHR Catherine Snow Tag Q1_23_demote_red was removed from gene: GHR.
Tag Q1_23_expert_review was removed from gene: GHR.
Pituitary hormone deficiency v2.106 BRAF Catherine Snow Tag Q3_22_rating was removed from gene: BRAF.
Tag Q3_22_NHS_review was removed from gene: BRAF.
Possible mitochondrial disorder - nuclear genes v2.5 TARS2 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: TARS2.
Tag Q3_22_NHS_review was removed from gene: TARS2.
Congenital muscular dystrophy v3.22 MYMK Eleanor Williams Tag Q3_21_rating was removed from gene: MYMK.
Tag Q3_21_expert_review was removed from gene: MYMK.
Tag Q3_21_phenotype was removed from gene: MYMK.
Congenital muscular dystrophy v3.22 JAG2 Eleanor Williams Tag Q2_21_rating was removed from gene: JAG2.
Congenital muscular dystrophy v3.22 HNRNPA2B1 Eleanor Williams Tag for-review was removed from gene: HNRNPA2B1.
Tag Q1_22_rating was removed from gene: HNRNPA2B1.
Tag Q4_22_promote_green was removed from gene: HNRNPA2B1.
Congenital muscular dystrophy v3.22 GGPS1 Eleanor Williams Tag Q4_21_rating was removed from gene: GGPS1.
Congenital muscular dystrophy v3.22 CAVIN1 Eleanor Williams Tag Q3_21_rating was removed from gene: CAVIN1.
Congenital muscular dystrophy v3.22 MYMK Eleanor Williams edited their review of gene: MYMK: Added comment: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval. MYMK will remain green on the Congenital Myopathy panel.; Changed rating: RED
Congenital muscular dystrophy v3.22 JAG2 Eleanor Williams commented on gene: JAG2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Congenital muscular dystrophy v3.22 HNRNPA2B1 Eleanor Williams reviewed gene: HNRNPA2B1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Congenital muscular dystrophy v3.22 GGPS1 Eleanor Williams reviewed gene: GGPS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Congenital muscular dystrophy v3.22 CAVIN1 Eleanor Williams reviewed gene: CAVIN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Congenital muscular dystrophy v3.21 MYMK Eleanor Williams Source Expert Review Red was added to MYMK.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Congenital muscular dystrophy v3.21 JAG2 Eleanor Williams Source Expert Review Green was added to JAG2.
Source NHS GMS was added to JAG2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital muscular dystrophy v3.21 HNRNPA2B1 Eleanor Williams Source Expert Review Green was added to HNRNPA2B1.
Source NHS GMS was added to HNRNPA2B1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital muscular dystrophy v3.21 GGPS1 Eleanor Williams Source Expert Review Green was added to GGPS1.
Source NHS GMS was added to GGPS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital muscular dystrophy v3.21 CAVIN1 Eleanor Williams Source Expert Review Green was added to CAVIN1.
Source NHS GMS was added to CAVIN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Distal myopathies v2.3 CRYAB Mafalda Gomes Tag Q4_21_MOI was removed from gene: CRYAB.
Distal myopathies v2.3 CNBP Mafalda Gomes Tag Q4_21_MOI was removed from gene: CNBP.
Tag Q4_21_rating was removed from gene: CNBP.
Distal myopathies v2.3 CRYAB Mafalda Gomes commented on gene: CRYAB
Distal myopathies v2.3 CNBP Mafalda Gomes edited their review of gene: CNBP: Added comment: The rating of this gene has been updated to Red following NHS Genomic Medicine Service approval.; Changed rating: RED
Distal myopathies v2.3 CNBP Mafalda Gomes commented on gene: CNBP
Distal myopathies v2.2 CRYAB Mafalda Gomes Source NHS GMS was added to CRYAB.
Mode of inheritance for gene CRYAB was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Distal myopathies v2.2 CNBP Mafalda Gomes Source Expert Review Red was added to CNBP.
Source NHS GMS was added to CNBP.
Mode of inheritance for gene CNBP was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Rating Changed from Green List (high evidence) to Red List (low evidence)
Congenital myaesthenic syndrome v3.5 SYT2 Mafalda Gomes Tag Q3_21_MOI was removed from gene: SYT2.
Congenital myaesthenic syndrome v3.5 SYT2 Mafalda Gomes commented on gene: SYT2
Congenital myaesthenic syndrome v3.4 SYT2 Mafalda Gomes Mode of inheritance for gene SYT2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.3 NFIA Mafalda Gomes Tag Q2_22_rating was removed from gene: NFIA.
Tag Q2_22_NHS_review was removed from gene: NFIA.
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.3 NFIA Achchuthan Shanmugasundram reviewed gene: NFIA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.2 NFIA Mafalda Gomes Source Expert Review Green was added to NFIA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ehlers Danlos syndrome with a likely monogenic cause v2.68 LTBP1 Mafalda Gomes Tag Q3_21_rating was removed from gene: LTBP1.
Ehlers Danlos syndrome with a likely monogenic cause v2.68 IPO8 Mafalda Gomes reviewed gene: IPO8: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ehlers Danlos syndrome with a likely monogenic cause v2.68 IPO8 Mafalda Gomes Tag Q2_21_rating was removed from gene: IPO8.
Ehlers Danlos syndrome with a likely monogenic cause v2.68 COL3A1 Mafalda Gomes Tag Q3_22_MOI was removed from gene: COL3A1.
Tag Q3_22_expert_review was removed from gene: COL3A1.
Ehlers Danlos syndrome with a likely monogenic cause v2.68 LTBP1 Achchuthan Shanmugasundram reviewed gene: LTBP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ehlers Danlos syndrome with a likely monogenic cause v2.68 IPO8 Achchuthan Shanmugasundram reviewed gene: IPO8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ehlers Danlos syndrome with a likely monogenic cause v2.68 COL3A1 Achchuthan Shanmugasundram commented on gene: COL3A1
Ehlers Danlos syndrome with a likely monogenic cause v2.67 COL3A1 Mafalda Gomes Mode of inheritance for gene COL3A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset hereditary spastic paraplegia v2.7 HSPD1 Mafalda Gomes Tag Q2_22_rating was removed from gene: HSPD1.
Tag Q2_22_expert_review was removed from gene: HSPD1.
Adult onset hereditary spastic paraplegia v2.7 C19orf12 Mafalda Gomes Tag Q2_22_MOI was removed from gene: C19orf12.
Adult onset hereditary spastic paraplegia v2.7 HSPD1 Mafalda Gomes reviewed gene: HSPD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset hereditary spastic paraplegia v2.7 C19orf12 Mafalda Gomes commented on gene: C19orf12
Adult onset hereditary spastic paraplegia v2.6 C19orf12 Mafalda Gomes Mode of inheritance for gene C19orf12 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal muscle channelopathy v2.4 PYGM Arina Puzriakova Tag Q2_21_rating was removed from gene: PYGM.
Tag Q2_21_phenotype was removed from gene: PYGM.
Tag Q2_21_expert_review was removed from gene: PYGM.
Skeletal muscle channelopathy v2.4 SLC2A1 Arina Puzriakova Tag Q2_21_rating was removed from gene: SLC2A1.
Tag Q2_21_phenotype was removed from gene: SLC2A1.
Tag Q2_21_expert_review was removed from gene: SLC2A1.
Skeletal muscle channelopathy v2.4 SLC1A3 Arina Puzriakova Tag Q2_21_rating was removed from gene: SLC1A3.
Tag Q2_21_phenotype was removed from gene: SLC1A3.
Tag Q2_21_expert_review was removed from gene: SLC1A3.
Skeletal muscle channelopathy v2.4 CACNA1A Arina Puzriakova Tag Q2_21_rating was removed from gene: CACNA1A.
Tag Q2_21_phenotype was removed from gene: CACNA1A.
Tag Q2_21_expert_review was removed from gene: CACNA1A.
Skeletal muscle channelopathy v2.4 ATP1A2 Arina Puzriakova Tag Q2_21_rating was removed from gene: ATP1A2.
Tag Q2_21_phenotype was removed from gene: ATP1A2.
Tag Q2_21_expert_review was removed from gene: ATP1A2.
Skeletal muscle channelopathy v2.4 PYGM Arina Puzriakova commented on gene: PYGM
Skeletal muscle channelopathy v2.4 SLC2A1 Arina Puzriakova reviewed gene: SLC2A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal muscle channelopathy v2.4 SLC1A3 Arina Puzriakova reviewed gene: SLC1A3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal muscle channelopathy v2.4 CACNA1A Arina Puzriakova reviewed gene: CACNA1A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal muscle channelopathy v2.4 ATP1A2 Arina Puzriakova reviewed gene: ATP1A2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal muscle channelopathy v2.3 SLC2A1 Arina Puzriakova Source Expert Review Red was added to SLC2A1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Skeletal muscle channelopathy v2.3 SLC1A3 Arina Puzriakova Source Expert Review Red was added to SLC1A3.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Skeletal muscle channelopathy v2.3 CACNA1A Arina Puzriakova Source Expert Review Red was added to CACNA1A.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Skeletal muscle channelopathy v2.3 ATP1A2 Arina Puzriakova Source Expert Review Red was added to ATP1A2.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Skeletal muscle channelopathy v2.2 CNBP_CCTG Arina Puzriakova Classified STR: CNBP_CCTG as Red List (low evidence)
Skeletal muscle channelopathy v2.2 CNBP_CCTG Arina Puzriakova Str: cnbp_cctg has been classified as Red List (Low Evidence).
Skeletal muscle channelopathy v2.1 CNBP_CCTG Arina Puzriakova Tag Q4_21_expert_review was removed from STR: CNBP_CCTG.
Tag Q4_21_rating was removed from STR: CNBP_CCTG.
Skeletal muscle channelopathy v2.1 CNBP_CCTG Arina Puzriakova edited their review of STR: CNBP_CCTG: Added comment: The rating of this STR has been updated to Red following NHS Genomic Medicine Service approval.; Changed rating: RED
Paediatric motor neuronopathies v2.6 AR_CAG Arina Puzriakova changed review comment from: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; to: The rating of this STR has been updated to Green following NHS Genomic Medicine Service approval.
Severe microcephaly v3.5 HHAT Arina Puzriakova Tag Q4_21_rating was removed from gene: HHAT.
Severe microcephaly v3.5 SPATA5L1 Arina Puzriakova Tag Q1_22_rating was removed from gene: SPATA5L1.
Severe microcephaly v3.5 PRIM1 Arina Puzriakova Tag Q2_21_rating was removed from gene: PRIM1.
Severe microcephaly v3.5 NCAPD3 Arina Puzriakova Tag Q2_22_rating was removed from gene: NCAPD3.
Tag Q2_22_NHS_review was removed from gene: NCAPD3.
Severe microcephaly v3.5 NAPB Arina Puzriakova Tag Q2_22_rating was removed from gene: NAPB.
Tag Q2_22_NHS_review was removed from gene: NAPB.
Severe microcephaly v3.5 HHAT Arina Puzriakova edited their review of gene: HHAT: Changed rating: GREEN
Severe microcephaly v3.5 HHAT Arina Puzriakova changed review comment from: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Severe microcephaly v3.5 DROSHA Arina Puzriakova Tag Q2_22_rating was removed from gene: DROSHA.
Severe microcephaly v3.5 CCND2 Arina Puzriakova Tag Q1_22_rating was removed from gene: CCND2.
Severe microcephaly v3.5 CCND2 Arina Puzriakova edited their review of gene: CCND2: Changed rating: GREEN
Severe microcephaly v3.5 CCND2 Arina Puzriakova changed review comment from: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v3.9 PI4KA Mafalda Gomes Tag Q1_22_phenotype was removed from gene: PI4KA.
Tag Q1_22_expert_review was removed from gene: PI4KA.
Tag Q1_22_NHS_review was removed from gene: PI4KA.
Severe microcephaly v3.5 TUBG1 Arina Puzriakova Tag Q3_22_rating was removed from gene: TUBG1.
Tag Q3_22_NHS_review was removed from gene: TUBG1.
Childhood onset hereditary spastic paraplegia v3.9 PI4KA Mafalda Gomes changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains XX.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.
Severe microcephaly v3.5 SLC38A3 Arina Puzriakova Tag Q3_22_rating was removed from gene: SLC38A3.
Severe microcephaly v3.5 NSRP1 Arina Puzriakova Tag Q3_22_rating was removed from gene: NSRP1.
Severe microcephaly v3.5 HMGB1 Arina Puzriakova Tag Q3_22_rating was removed from gene: HMGB1.
Childhood onset hereditary spastic paraplegia v3.9 TFG Mafalda Gomes Tag Q3_21_MOI was removed from gene: TFG.
Severe microcephaly v3.5 GINS3 Arina Puzriakova Tag Q3_22_rating was removed from gene: GINS3.
Severe microcephaly v3.5 CHKA Arina Puzriakova Tag Q3_22_rating was removed from gene: CHKA.
Tag Q3_22_MOI was removed from gene: CHKA.
Childhood onset hereditary spastic paraplegia v3.9 SPATA5L1 Mafalda Gomes Tag Q1_22_rating was removed from gene: SPATA5L1.
Severe microcephaly v3.5 ATP6V0A1 Arina Puzriakova Tag Q3_22_rating was removed from gene: ATP6V0A1.
Childhood onset hereditary spastic paraplegia v3.9 HSPD1 Mafalda Gomes Tag Q2_22_rating was removed from gene: HSPD1.
Childhood onset hereditary spastic paraplegia v3.9 C19orf12 Mafalda Gomes Tag Q2_22_MOI was removed from gene: C19orf12.
Severe microcephaly v3.5 SPATA5L1 Arina Puzriakova reviewed gene: SPATA5L1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v3.5 PRIM1 Arina Puzriakova commented on gene: PRIM1: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Severe microcephaly v3.5 NCAPD3 Arina Puzriakova commented on gene: NCAPD3: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Severe microcephaly v3.5 NAPB Arina Puzriakova edited their review of gene: NAPB: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Severe microcephaly v3.5 HHAT Arina Puzriakova commented on gene: HHAT
Severe microcephaly v3.5 DROSHA Arina Puzriakova reviewed gene: DROSHA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v3.5 CCND2 Arina Puzriakova commented on gene: CCND2
Severe microcephaly v3.5 TUBG1 Arina Puzriakova edited their review of gene: TUBG1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Severe microcephaly v3.5 SLC38A3 Arina Puzriakova reviewed gene: SLC38A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v3.5 NSRP1 Arina Puzriakova edited their review of gene: NSRP1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Severe microcephaly v3.5 HMGB1 Arina Puzriakova edited their review of gene: HMGB1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Severe microcephaly v3.5 GINS3 Arina Puzriakova reviewed gene: GINS3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v3.5 CHKA Arina Puzriakova reviewed gene: CHKA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v3.5 ATP6V0A1 Arina Puzriakova reviewed gene: ATP6V0A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset hereditary spastic paraplegia v3.9 AIMP1 Mafalda Gomes Tag Q3_21_MOI was removed from gene: AIMP1.
Childhood onset hereditary spastic paraplegia v3.9 ACER3 Mafalda Gomes Tag Q1_22_rating was removed from gene: ACER3.
Severe microcephaly v3.4 TUBG1 Arina Puzriakova Source Expert Review Green was added to TUBG1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v3.4 SPATA5L1 Arina Puzriakova Source Expert Review Green was added to SPATA5L1.
Source NHS GMS was added to SPATA5L1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v3.4 SLC38A3 Arina Puzriakova Source Expert Review Green was added to SLC38A3.
Source NHS GMS was added to SLC38A3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v3.4 PRIM1 Arina Puzriakova Source Expert Review Green was added to PRIM1.
Source NHS GMS was added to PRIM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v3.4 NSRP1 Arina Puzriakova Source Expert Review Green was added to NSRP1.
Source NHS GMS was added to NSRP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v3.4 NCAPD3 Arina Puzriakova Source Expert Review Green was added to NCAPD3.
Source NHS GMS was added to NCAPD3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v3.4 NAPB Arina Puzriakova Source Expert Review Green was added to NAPB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v3.4 HMGB1 Arina Puzriakova Source Expert Review Green was added to HMGB1.
Source NHS GMS was added to HMGB1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v3.4 HHAT Arina Puzriakova Source Expert Review Green was added to HHAT.
Source NHS GMS was added to HHAT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v3.4 GINS3 Arina Puzriakova Source Expert Review Green was added to GINS3.
Source NHS GMS was added to GINS3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v3.4 DROSHA Arina Puzriakova Source Expert Review Green was added to DROSHA.
Source NHS GMS was added to DROSHA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v3.4 CHKA Arina Puzriakova Source Expert Review Green was added to CHKA.
Source NHS GMS was added to CHKA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v3.4 CCND2 Arina Puzriakova Source Expert Review Green was added to CCND2.
Source NHS GMS was added to CCND2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v3.4 ATP6V0A1 Arina Puzriakova Source Expert Review Green was added to ATP6V0A1.
Source NHS GMS was added to ATP6V0A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v3.9 ABHD16A Mafalda Gomes Tag Q4_21_rating was removed from gene: ABHD16A.
Childhood onset hereditary spastic paraplegia v3.9 TMEM63C Mafalda Gomes Tag Q3_22_rating was removed from gene: TMEM63C.
Childhood onset hereditary spastic paraplegia v3.9 TAF8 Mafalda Gomes Tag Q3_22_rating was removed from gene: TAF8.
Rhabdomyolysis and metabolic muscle disorders v2.5 SGCA Arina Puzriakova Tag Q1_22_rating was removed from gene: SGCA.
Rhabdomyolysis and metabolic muscle disorders v2.5 SCN4A Arina Puzriakova Tag Q1_22_rating was removed from gene: SCN4A.
Childhood onset hereditary spastic paraplegia v3.9 NSRP1 Mafalda Gomes Tag Q3_22_rating was removed from gene: NSRP1.
Rhabdomyolysis and metabolic muscle disorders v2.5 GMPPB Arina Puzriakova Tag Q3_21_rating was removed from gene: GMPPB.
Rhabdomyolysis and metabolic muscle disorders v2.5 FDX2 Arina Puzriakova Tag Q3_21_rating was removed from gene: FDX2.
Rhabdomyolysis and metabolic muscle disorders v2.5 CPT2 Arina Puzriakova Tag Q1_22_MOI was removed from gene: CPT2.
Childhood onset hereditary spastic paraplegia v3.9 NDUFA12 Mafalda Gomes Tag Q3_22_rating was removed from gene: NDUFA12.
Rhabdomyolysis and metabolic muscle disorders v2.5 CAV3 Arina Puzriakova Tag Q3_21_MOI was removed from gene: CAV3.
Rhabdomyolysis and metabolic muscle disorders v2.5 TSEN54 Arina Puzriakova Tag Q2_21_rating was removed from gene: TSEN54.
Tag Q2_21_expert_review was removed from gene: TSEN54.
Childhood onset hereditary spastic paraplegia v3.9 KPNA3 Mafalda Gomes Tag Q3_22_rating was removed from gene: KPNA3.
Rhabdomyolysis and metabolic muscle disorders v2.5 PHKB Arina Puzriakova Tag Q4_21_rating was removed from gene: PHKB.
Tag Q4_21_phenotype was removed from gene: PHKB.
Tag Q2_22_expert_review was removed from gene: PHKB.
Rhabdomyolysis and metabolic muscle disorders v2.5 FKTN Arina Puzriakova Tag Q3_22_rating was removed from gene: FKTN.
Tag Q3_22_expert_review was removed from gene: FKTN.
Childhood onset hereditary spastic paraplegia v3.9 PI4KA Mafalda Gomes reviewed gene: PI4KA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset hereditary spastic paraplegia v3.9 TFG Mafalda Gomes commented on gene: TFG
Childhood onset hereditary spastic paraplegia v3.9 SPATA5L1 Mafalda Gomes reviewed gene: SPATA5L1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset hereditary spastic paraplegia v3.9 HSPD1 Mafalda Gomes reviewed gene: HSPD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset hereditary spastic paraplegia v3.9 C19orf12 Mafalda Gomes commented on gene: C19orf12
Childhood onset hereditary spastic paraplegia v3.9 AIMP1 Mafalda Gomes commented on gene: AIMP1
Childhood onset hereditary spastic paraplegia v3.9 ACER3 Mafalda Gomes edited their review of gene: ACER3: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Childhood onset hereditary spastic paraplegia v3.9 ACER3 Mafalda Gomes commented on gene: ACER3
Childhood onset hereditary spastic paraplegia v3.9 ABHD16A Mafalda Gomes reviewed gene: ABHD16A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset hereditary spastic paraplegia v3.9 TMEM63C Mafalda Gomes commented on gene: TMEM63C: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v3.9 TMEM63C Mafalda Gomes reviewed gene: TMEM63C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset hereditary spastic paraplegia v3.9 TAF8 Mafalda Gomes commented on gene: TAF8: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v3.9 TAF8 Mafalda Gomes reviewed gene: TAF8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset hereditary spastic paraplegia v3.9 NSRP1 Mafalda Gomes commented on gene: NSRP1: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v3.9 NSRP1 Mafalda Gomes reviewed gene: NSRP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset hereditary spastic paraplegia v3.9 NDUFA12 Mafalda Gomes commented on gene: NDUFA12: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v3.9 NDUFA12 Mafalda Gomes reviewed gene: NDUFA12: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset hereditary spastic paraplegia v3.9 KPNA3 Mafalda Gomes commented on gene: KPNA3
Rhabdomyolysis and metabolic muscle disorders v2.5 SGCA Arina Puzriakova edited their review of gene: SGCA: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Rhabdomyolysis and metabolic muscle disorders v2.5 SCN4A Arina Puzriakova edited their review of gene: SCN4A: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Rhabdomyolysis and metabolic muscle disorders v2.5 GMPPB Arina Puzriakova reviewed gene: GMPPB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Rhabdomyolysis and metabolic muscle disorders v2.5 FDX2 Arina Puzriakova reviewed gene: FDX2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Rhabdomyolysis and metabolic muscle disorders v2.5 CPT2 Arina Puzriakova commented on gene: CPT2: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Rhabdomyolysis and metabolic muscle disorders v2.5 CAV3 Arina Puzriakova commented on gene: CAV3
Rhabdomyolysis and metabolic muscle disorders v2.5 TSEN54 Arina Puzriakova commented on gene: TSEN54: The rating of this gene has been updated to Red following NHS Genomic Medicine Service approval.
Rhabdomyolysis and metabolic muscle disorders v2.5 PHKB Arina Puzriakova reviewed gene: PHKB: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Rhabdomyolysis and metabolic muscle disorders v2.5 FKTN Arina Puzriakova reviewed gene: FKTN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Rhabdomyolysis and metabolic muscle disorders v2.4 TSEN54 Arina Puzriakova Source Expert Review Red was added to TSEN54.
Source NHS GMS was added to TSEN54.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Rhabdomyolysis and metabolic muscle disorders v2.4 SGCA Arina Puzriakova Source Expert Review Green was added to SGCA.
Source NHS GMS was added to SGCA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v2.4 SCN4A Arina Puzriakova Source Expert Review Green was added to SCN4A.
Source NHS GMS was added to SCN4A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v2.4 PHKB Arina Puzriakova Source Expert Review Red was added to PHKB.
Source NHS GMS was added to PHKB.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Rhabdomyolysis and metabolic muscle disorders v2.4 GMPPB Arina Puzriakova Source Expert Review Green was added to GMPPB.
Source NHS GMS was added to GMPPB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v2.4 FKTN Arina Puzriakova Source Expert Review Red was added to FKTN.
Source NHS GMS was added to FKTN.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Rhabdomyolysis and metabolic muscle disorders v2.4 FDX2 Arina Puzriakova Source Expert Review Green was added to FDX2.
Source NHS GMS was added to FDX2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v2.4 CPT2 Arina Puzriakova Source NHS GMS was added to CPT2.
Mode of inheritance for gene CPT2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v2.4 CAV3 Arina Puzriakova Source NHS GMS was added to CAV3.
Mode of inheritance for gene CAV3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary ataxia with onset in adulthood v3.10 GLRB Mafalda Gomes Tag Q3_21_expert_review was removed from gene: GLRB.
Tag Q3_21_phenotype was removed from gene: GLRB.
Tag Q2_22_rating was removed from gene: GLRB.
Hereditary ataxia with onset in adulthood v3.10 PRDX3 Mafalda Gomes Tag Q1_22_rating was removed from gene: PRDX3.
Hereditary ataxia with onset in adulthood v3.10 PEX6 Mafalda Gomes Tag Q1_22_MOI was removed from gene: PEX6.
Hereditary ataxia with onset in adulthood v3.10 NKX2-1 Mafalda Gomes Tag Q1_22_MOI was removed from gene: NKX2-1.
Hereditary ataxia with onset in adulthood v3.10 CLCN2 Mafalda Gomes Tag Q4_21_MOI was removed from gene: CLCN2.
Hereditary ataxia with onset in adulthood v3.10 STUB1 Mafalda Gomes Tag Q3_22_MOI was removed from gene: STUB1.
Hereditary ataxia with onset in adulthood v3.10 GLRB Mafalda Gomes reviewed gene: GLRB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary ataxia with onset in adulthood v3.10 PRDX3 Mafalda Gomes reviewed gene: PRDX3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary ataxia with onset in adulthood v3.10 PEX6 Mafalda Gomes commented on gene: PEX6
Hereditary ataxia with onset in adulthood v3.10 NKX2-1 Mafalda Gomes commented on gene: NKX2-1
Hereditary ataxia with onset in adulthood v3.10 CLCN2 Mafalda Gomes commented on gene: CLCN2
Hereditary ataxia with onset in adulthood v3.10 STUB1 Mafalda Gomes commented on gene: STUB1
Paroxysmal central nervous system disorders v2.3 KCNMA1 Arina Puzriakova Tag Q1_22_MOI was removed from gene: KCNMA1.
Paroxysmal central nervous system disorders v2.3 KCNMA1 Arina Puzriakova commented on gene: KCNMA1
Paroxysmal central nervous system disorders v2.2 KCNMA1 Arina Puzriakova Mode of inheritance for gene KCNMA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v3.9 STUB1 Mafalda Gomes Mode of inheritance for gene STUB1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v3.9 PRDX3 Mafalda Gomes Source NHS GMS was added to PRDX3.
Source Expert Review Green was added to PRDX3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary ataxia with onset in adulthood v3.9 PEX6 Mafalda Gomes Mode of inheritance for gene PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v3.9 NKX2-1 Mafalda Gomes Mode of inheritance for gene NKX2-1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v3.9 CLCN2 Mafalda Gomes Mode of inheritance for gene CLCN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v3.8 TMEM63C Mafalda Gomes Source Expert Review Green was added to TMEM63C.
Source NHS GMS was added to TMEM63C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v3.8 TFG Mafalda Gomes Mode of inheritance for gene TFG was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v3.8 TAF8 Mafalda Gomes Source Expert Review Green was added to TAF8.
Source NHS GMS was added to TAF8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v3.8 SPATA5L1 Mafalda Gomes Source Expert Review Green was added to SPATA5L1.
Source NHS GMS was added to SPATA5L1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v3.8 NSRP1 Mafalda Gomes Source Expert Review Green was added to NSRP1.
Source NHS GMS was added to NSRP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v3.8 NDUFA12 Mafalda Gomes Source Expert Review Green was added to NDUFA12.
Source NHS GMS was added to NDUFA12.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v3.8 KPNA3 Mafalda Gomes Source Expert Review Green was added to KPNA3.
Source NHS GMS was added to KPNA3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v3.8 HSPD1 Mafalda Gomes Source Expert Review Green was added to HSPD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v3.8 C19orf12 Mafalda Gomes Mode of inheritance for gene C19orf12 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v3.8 AIMP1 Mafalda Gomes Mode of inheritance for gene AIMP1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v3.8 ACER3 Mafalda Gomes Source Expert Review Green was added to ACER3.
Source NHS GMS was added to ACER3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v3.8 ABHD16A Mafalda Gomes Source Expert Review Green was added to ABHD16A.
Source NHS GMS was added to ABHD16A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.5 SSBP1 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: SSBP1.
Tag Q3_22_NHS_review was removed from gene: SSBP1.
Possible mitochondrial disorder - nuclear genes v2.5 SDHB Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: SDHB.
Tag Q3_22_NHS_review was removed from gene: SDHB.
Possible mitochondrial disorder - nuclear genes v2.5 SDHA Achchuthan Shanmugasundram Tag Q3_22_MOI was removed from gene: SDHA.
Tag Q3_22_NHS_review was removed from gene: SDHA.
Possible mitochondrial disorder - nuclear genes v2.5 POLRMT Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: POLRMT.
Tag Q3_22_NHS_review was removed from gene: POLRMT.
Possible mitochondrial disorder - nuclear genes v2.5 NSUN3 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: NSUN3.
Tag Q3_22_NHS_review was removed from gene: NSUN3.
Possible mitochondrial disorder - nuclear genes v2.5 NFS1 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: NFS1.
Possible mitochondrial disorder - nuclear genes v2.5 NDUFB10 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: NDUFB10.
Tag Q3_22_NHS_review was removed from gene: NDUFB10.
Possible mitochondrial disorder - nuclear genes v2.5 NDUFA8 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: NDUFA8.
Tag Q3_22_NHS_review was removed from gene: NDUFA8.
Possible mitochondrial disorder - nuclear genes v2.5 NDUFA13 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: NDUFA13.
Tag Q3_22_NHS_review was removed from gene: NDUFA13.
Possible mitochondrial disorder - nuclear genes v2.5 NDUFA12 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: NDUFA12.
Tag Q3_22_NHS_review was removed from gene: NDUFA12.
Possible mitochondrial disorder - nuclear genes v2.5 LYRM4 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: LYRM4.
Tag Q3_22_NHS_review was removed from gene: LYRM4.
Possible mitochondrial disorder - nuclear genes v2.5 LIG3 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: LIG3.
Possible mitochondrial disorder - nuclear genes v2.5 COX6A2 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: COX6A2.
Tag Q3_22_NHS_review was removed from gene: COX6A2.
Possible mitochondrial disorder - nuclear genes v2.5 CLPB Achchuthan Shanmugasundram Tag Q4_21_MOI was removed from gene: CLPB.
Tag Q3_22_NHS_review was removed from gene: CLPB.
Possible mitochondrial disorder - nuclear genes v2.5 ATP5G3 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: ATP5G3.
Tag Q3_22_NHS_review was removed from gene: ATP5G3.
Possible mitochondrial disorder - nuclear genes v2.5 ATP5A1 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: ATP5A1.
Tag Q3_22_NHS_review was removed from gene: ATP5A1.
Possible mitochondrial disorder - nuclear genes v2.5 ACO2 Achchuthan Shanmugasundram Tag Q2_22_MOI was removed from gene: ACO2.
Possible mitochondrial disorder - nuclear genes v2.5 PDK3 Achchuthan Shanmugasundram reviewed gene: PDK3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 UQCRFS1 Achchuthan Shanmugasundram reviewed gene: UQCRFS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 UQCRC2 Achchuthan Shanmugasundram reviewed gene: UQCRC2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 TIMMDC1 Achchuthan Shanmugasundram reviewed gene: TIMMDC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 TFAM Achchuthan Shanmugasundram reviewed gene: TFAM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 TARS2 Achchuthan Shanmugasundram reviewed gene: TARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 SSBP1 Achchuthan Shanmugasundram reviewed gene: SSBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 SDHB Achchuthan Shanmugasundram reviewed gene: SDHB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 SDHA Achchuthan Shanmugasundram commented on gene: SDHA
Possible mitochondrial disorder - nuclear genes v2.5 POLRMT Achchuthan Shanmugasundram reviewed gene: POLRMT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 NSUN3 Achchuthan Shanmugasundram reviewed gene: NSUN3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 NFS1 Achchuthan Shanmugasundram reviewed gene: NFS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 NDUFB10 Achchuthan Shanmugasundram reviewed gene: NDUFB10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 NDUFA8 Achchuthan Shanmugasundram reviewed gene: NDUFA8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 NDUFA13 Achchuthan Shanmugasundram reviewed gene: NDUFA13: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 NDUFA12 Achchuthan Shanmugasundram reviewed gene: NDUFA12: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 LYRM4 Achchuthan Shanmugasundram reviewed gene: LYRM4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 LIG3 Achchuthan Shanmugasundram reviewed gene: LIG3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 COX6A2 Achchuthan Shanmugasundram reviewed gene: COX6A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 CLPB Achchuthan Shanmugasundram commented on gene: CLPB
Possible mitochondrial disorder - nuclear genes v2.5 ATP5G3 Achchuthan Shanmugasundram reviewed gene: ATP5G3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 ATP5A1 Achchuthan Shanmugasundram reviewed gene: ATP5A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Possible mitochondrial disorder - nuclear genes v2.5 ACO2 Achchuthan Shanmugasundram commented on gene: ACO2
Possible mitochondrial disorder - nuclear genes v2.4 UQCRFS1 Achchuthan Shanmugasundram Source Expert Review Green was added to UQCRFS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.4 UQCRC2 Achchuthan Shanmugasundram Source Expert Review Green was added to UQCRC2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.4 TIMMDC1 Achchuthan Shanmugasundram Source Expert Review Green was added to TIMMDC1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.4 TFAM Achchuthan Shanmugasundram Source Expert Review Green was added to TFAM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.4 TARS2 Achchuthan Shanmugasundram Source Expert Review Green was added to TARS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.4 SSBP1 Achchuthan Shanmugasundram Source Expert Review Green was added to SSBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.4 SDHB Achchuthan Shanmugasundram Source Expert Review Green was added to SDHB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.4 SDHA Achchuthan Shanmugasundram Mode of inheritance for gene SDHA was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v2.4 POLRMT Achchuthan Shanmugasundram Source Expert Review Green was added to POLRMT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.4 NSUN3 Achchuthan Shanmugasundram Source Expert Review Green was added to NSUN3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.4 NFS1 Achchuthan Shanmugasundram Source Expert Review Green was added to NFS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.4 NDUFB10 Achchuthan Shanmugasundram Source Expert Review Green was added to NDUFB10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.4 NDUFA8 Achchuthan Shanmugasundram Source Expert Review Green was added to NDUFA8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.4 NDUFA13 Achchuthan Shanmugasundram Source Expert Review Green was added to NDUFA13.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.4 NDUFA12 Achchuthan Shanmugasundram Source Expert Review Green was added to NDUFA12.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.4 LYRM4 Achchuthan Shanmugasundram Source Expert Review Green was added to LYRM4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.4 LIG3 Achchuthan Shanmugasundram Source NHS GMS was added to LIG3.
Source Expert Review Green was added to LIG3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.4 COX6A2 Achchuthan Shanmugasundram Source Expert Review Green was added to COX6A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.4 CLPB Achchuthan Shanmugasundram Mode of inheritance for gene CLPB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v2.4 ATP5G3 Achchuthan Shanmugasundram Source Expert Review Green was added to ATP5G3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.4 ATP5A1 Achchuthan Shanmugasundram Source Expert Review Green was added to ATP5A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v2.4 ACO2 Achchuthan Shanmugasundram Mode of inheritance for gene ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial DNA maintenance disorder v2.3 TFAM Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: TFAM.
Tag Q3_22_NHS_review was removed from gene: TFAM.
Mitochondrial DNA maintenance disorder v2.3 SSBP1 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: SSBP1.
Tag Q3_22_NHS_review was removed from gene: SSBP1.
Mitochondrial DNA maintenance disorder v2.3 LIG3 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: LIG3.
Mitochondrial DNA maintenance disorder v2.3 TFAM Achchuthan Shanmugasundram reviewed gene: TFAM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Mitochondrial DNA maintenance disorder v2.3 SSBP1 Achchuthan Shanmugasundram reviewed gene: SSBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Mitochondrial DNA maintenance disorder v2.3 LIG3 Achchuthan Shanmugasundram reviewed gene: LIG3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Mitochondrial DNA maintenance disorder v2.2 TFAM Achchuthan Shanmugasundram Source Expert Review Green was added to TFAM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial DNA maintenance disorder v2.2 SSBP1 Achchuthan Shanmugasundram Source Expert Review Green was added to SSBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial DNA maintenance disorder v2.2 LIG3 Achchuthan Shanmugasundram Source Expert Review Green was added to LIG3.
Source NHS GMS was added to LIG3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v3.6 XPNPEP3 Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.

Note from GMS reviewers: The phenotype arising from mutation of this gene is not that of mitochondrial disease. Not sure there is sufficient evidence that this can be classified as primary mitochondrial disease, but may be appropriate to include elsewhere in white matter disorders panel (C&S).
Mitochondrial disorders v3.6 XPNPEP3 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: XPNPEP3.
Tag Q2_21_phenotype was removed from gene: XPNPEP3.
Tag Q2_21_expert_review was removed from gene: XPNPEP3.
Mitochondrial disorders v3.6 PDK3 Achchuthan Shanmugasundram Tag Q1_22_phenotype was removed from gene: PDK3.
Tag Q2_22_rating was removed from gene: PDK3.
Tag Q2_22_expert_review was removed from gene: PDK3.
Mitochondrial disorders v3.6 PDK3 Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Red.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Red.

Note from GMS reviewers: Phenotype from mutations from this gene is not that of Mitochondrial disease - appropriate to be green on Neuropathy panel(NT). Not sure there is sufficient evidence that this can be classified as primary mitochondrial disease, but may be appropriate to include elsewhere in white matter disorders panel (C&S).
Paediatric motor neuronopathies v2.6 AR Arina Puzriakova Tag Q2_21_rating was removed from gene: AR.
Tag Q2_21_MOI was removed from gene: AR.
Paediatric motor neuronopathies v2.6 AR_CAG Arina Puzriakova Classified STR: AR_CAG as Green List (high evidence)
Paediatric motor neuronopathies v2.6 AR_CAG Arina Puzriakova Str: ar_cag has been classified as Green List (High Evidence).
Paediatric motor neuronopathies v2.5 AR Arina Puzriakova commented on gene: AR: The rating of this gene has been updated to Red and the mode of inheritance set to 'Other' following NHS Genomic Medicine Service approval.
Mitochondrial disorders v3.6 MARS2 Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Green.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Green.

Comment from GMS reviewers: If AR spastic ataxia cases due to rearrangement/duplication variants are included this is a green gene (NT), There looks to be sufficient evidence - include spastic ataxia OMIM #611390(C&S)
Paediatric motor neuronopathies v2.4 AR Arina Puzriakova Source NHS GMS was added to AR.
Source Expert Review Red was added to AR.
Mode of inheritance for gene AR was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to Other
Rating Changed from Green List (high evidence) to Red List (low evidence)
Mitochondrial disorders v3.6 MARS2 Achchuthan Shanmugasundram Tag Q2_22_rating was removed from gene: MARS2.
Tag Q2_22_expert_review was removed from gene: MARS2.
Paediatric motor neuronopathies v2.3 AR_CAG Arina Puzriakova Tag Q2_21_rating was removed from STR: AR_CAG.
Paediatric motor neuronopathies v2.3 AR_CAG Arina Puzriakova edited their review of STR: AR_CAG: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Mitochondrial disorders v3.6 COX14 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated to Amber following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Amber following NHS Genomic Medicine Service approval.
Mitochondrial disorders v3.6 COX14 Achchuthan Shanmugasundram Tag Q2_22_rating was removed from gene: COX14.
Tag Q2_22_expert_review was removed from gene: COX14.
Mitochondrial disorders v3.6 TARS2 Achchuthan Shanmugasundram Tag Q4_21_rating was removed from gene: TARS2.
Mitochondrial disorders v3.6 SSBP1 Achchuthan Shanmugasundram Tag Q1_22_rating was removed from gene: SSBP1.
Neurological ciliopathies v2.6 ZNF423 Arina Puzriakova Tag Q3_22_rating was removed from gene: ZNF423.
Tag Q3_22_expert_review was removed from gene: ZNF423.
Neurological ciliopathies v2.6 ZNF423 Arina Puzriakova changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber. Additional comments from reviewing GLHs: "Chaki paper from 2012 has not been well-replicated in the decade since. Some individual reports but nothing convincing. Lack of clear biallelic LOF variants reported in humans"
Mitochondrial disorders v3.6 NFS1 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: NFS1.
Mitochondrial disorders v3.6 NDUFA12 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: NDUFA12.
Mitochondrial disorders v3.6 NAXD Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: NAXD.
Mitochondrial disorders v3.6 LIG3 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: LIG3.
Neurological ciliopathies v2.6 LAMA1 Arina Puzriakova Tag Q3_21_rating was removed from gene: LAMA1.
Tag Q3_21_expert_review was removed from gene: LAMA1.
Mitochondrial disorders v3.6 KIAA0391 Achchuthan Shanmugasundram Tag Q4_21_rating was removed from gene: KIAA0391.
Neurological ciliopathies v2.6 ZNF423 Arina Puzriakova edited their review of gene: ZNF423: Added comment: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.; Changed rating: AMBER
Neurological ciliopathies v2.6 LAMA1 Arina Puzriakova edited their review of gene: LAMA1: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Neurological ciliopathies v2.5 LAMA1 Arina Puzriakova Source Expert Review Green was added to LAMA1.
Source NHS GMS was added to LAMA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v3.6 CLPB Achchuthan Shanmugasundram Tag Q4_21_MOI was removed from gene: CLPB.
Mitochondrial disorders v3.6 ACO2 Achchuthan Shanmugasundram Tag Q2_22_MOI was removed from gene: ACO2.
Mitochondrial disorders v3.6 UQCRFS1 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: UQCRFS1.
Mitochondrial disorders v3.6 UQCRC2 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: UQCRC2.
Mitochondrial disorders v3.6 TIMMDC1 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: TIMMDC1.
Mitochondrial disorders v3.6 TFAM Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: TFAM.
Adult onset neurodegenerative disorder v3.49 TTR Arina Puzriakova Tag Q1_23_promote_green was removed from gene: TTR.
Mitochondrial disorders v3.6 SDHB Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: SDHB.
Adult onset neurodegenerative disorder v3.49 TREX1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: TREX1.
Adult onset neurodegenerative disorder v3.49 LAMB1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: LAMB1.
Mitochondrial disorders v3.6 SDHA Achchuthan Shanmugasundram Tag Q3_22_MOI was removed from gene: SDHA.
Adult onset neurodegenerative disorder v3.49 GSN Arina Puzriakova Tag Q1_23_promote_green was removed from gene: GSN.
Mitochondrial disorders v3.6 POLRMT Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: POLRMT.
Adult onset neurodegenerative disorder v3.49 GLA Arina Puzriakova Tag Q1_23_promote_green was removed from gene: GLA.
Adult onset neurodegenerative disorder v3.49 CTSA Arina Puzriakova Tag Q1_23_promote_green was removed from gene: CTSA.
Mitochondrial disorders v3.6 NSUN3 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: NSUN3.
Adult onset neurodegenerative disorder v3.49 COL4A2 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: COL4A2.
Adult onset neurodegenerative disorder v3.49 COL4A1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: COL4A1.
Adult onset neurodegenerative disorder v3.49 SOD1 Arina Puzriakova Tag Q3_21_MOI was removed from gene: SOD1.
Mitochondrial disorders v3.6 NDUFC2 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: NDUFC2.
Adult onset neurodegenerative disorder v3.49 FIG4 Arina Puzriakova Tag Q3_21_MOI was removed from gene: FIG4.
Adult onset neurodegenerative disorder v3.49 CLCN2 Arina Puzriakova Tag Q4_21_MOI was removed from gene: CLCN2.
Adult onset neurodegenerative disorder v3.49 C19orf12 Arina Puzriakova Tag Q2_22_MOI was removed from gene: C19orf12.
Adult onset neurodegenerative disorder v3.49 XK Arina Puzriakova Tag Q3_22_rating was removed from gene: XK.
Adult onset neurodegenerative disorder v3.49 STUB1 Arina Puzriakova Tag Q3_22_rating was removed from gene: STUB1.
Tag Q3_22_MOI was removed from gene: STUB1.
Tag Q3_22_expert_review was removed from gene: STUB1.
Mitochondrial disorders v3.6 NDUFB10 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: NDUFB10.
Mitochondrial disorders v3.6 NDUFA8 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: NDUFA8.
Adult onset neurodegenerative disorder v3.49 CST3 Arina Puzriakova reviewed gene: CST3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset neurodegenerative disorder v3.49 TTR Arina Puzriakova reviewed gene: TTR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset neurodegenerative disorder v3.49 TREX1 Arina Puzriakova reviewed gene: TREX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset neurodegenerative disorder v3.49 LAMB1 Arina Puzriakova reviewed gene: LAMB1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset neurodegenerative disorder v3.49 GSN Arina Puzriakova reviewed gene: GSN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset neurodegenerative disorder v3.49 GLA Arina Puzriakova reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset neurodegenerative disorder v3.49 CTSA Arina Puzriakova reviewed gene: CTSA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset neurodegenerative disorder v3.49 COL4A2 Arina Puzriakova reviewed gene: COL4A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset neurodegenerative disorder v3.49 COL4A1 Arina Puzriakova reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset neurodegenerative disorder v3.49 SOD1 Arina Puzriakova commented on gene: SOD1
Adult onset neurodegenerative disorder v3.49 FIG4 Arina Puzriakova commented on gene: FIG4
Adult onset neurodegenerative disorder v3.49 CLCN2 Arina Puzriakova commented on gene: CLCN2: The mode of inheritance of this gene has been updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Adult onset neurodegenerative disorder v3.49 C19orf12 Arina Puzriakova commented on gene: C19orf12
Adult onset neurodegenerative disorder v3.49 XK Arina Puzriakova edited their review of gene: XK: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Adult onset neurodegenerative disorder v3.49 STUB1 Arina Puzriakova reviewed gene: STUB1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Mitochondrial disorders v3.6 NDUFA13 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: NDUFA13.
Adult onset neurodegenerative disorder v3.48 XK Arina Puzriakova Source NHS GMS was added to XK.
Source Expert Review Green was added to XK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v3.48 TTR Arina Puzriakova Source NHS GMS was added to TTR.
Source Expert Review Green was added to TTR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v3.48 TREX1 Arina Puzriakova Source NHS GMS was added to TREX1.
Source Expert Review Green was added to TREX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v3.48 STUB1 Arina Puzriakova Source Expert Review Green was added to STUB1.
Mode of inheritance for gene STUB1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Red List (low evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v3.48 SOD1 Arina Puzriakova Mode of inheritance for gene SOD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v3.48 LAMB1 Arina Puzriakova Source NHS GMS was added to LAMB1.
Source Expert Review Green was added to LAMB1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v3.48 GSN Arina Puzriakova Source NHS GMS was added to GSN.
Source Expert Review Green was added to GSN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v3.48 GLA Arina Puzriakova Source NHS GMS was added to GLA.
Source Expert Review Green was added to GLA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v3.48 FIG4 Arina Puzriakova Mode of inheritance for gene FIG4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v3.48 CTSA Arina Puzriakova Source NHS GMS was added to CTSA.
Source Expert Review Green was added to CTSA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v3.48 CST3 Arina Puzriakova Source NHS GMS was added to CST3.