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Severe Paediatric Disorders v1.184 DPP6 Tracy Lester reviewed gene: DPP6: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cleidocranial Dysplasia v1.1 CBFB Alistair Pagnamenta gene: CBFB was added
gene: CBFB was added to Cleidocranial Dysplasia. Sources: Literature
Mode of inheritance for gene: CBFB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CBFB were set to PMID: 36241386
Phenotypes for gene: CBFB were set to cleidocranial dysplasia; dental anomalies such as supernumery teeth and eruption failure; developmental delay (variable); shortening of the distal phalanges
Penetrance for gene: CBFB were set to Complete
Review for gene: CBFB was set to GREEN
gene: CBFB was marked as current diagnostic
Added comment: Beyltjens et al describe 8 individuals from 5 families (ascertained via GeneMatcher) with cleidocranial dysplasia and rare severe consequence variants in CBFB. Previous analysis of RUNX2 had been negative. CBFB encodes the core-binding factor β subunit, which can interact with RUNX2 to form a heterodimeric transcription factor - so biologically was a good candidate gene, even before the Beyltjens et al study. Aware of data in 100kGP that supports this new gene-disease association.
Sources: Literature
Dilated and arrhythmogenic cardiomyopathy v2.25 PRDM16 Mike Spiller reviewed gene: PRDM16: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autoinflammatory disorders v2.1 OGFRL1 Hannah Knight gene: OGFRL1 was added
gene: OGFRL1 was added to Autoinflammatory disorders. Sources: Literature
Mode of inheritance for gene: OGFRL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OGFRL1 were set to PMID: 38699440
Phenotypes for gene: OGFRL1 were set to Cherubism
Review for gene: OGFRL1 was set to AMBER
Added comment: PMID: 38699440 (2024) identified two different homozygous LOF mutations in two unrelated families with cherubism. Functional work carried out, but inconclusive - mouse model did not recapitulate human cherubism
Sources: Literature
Adult onset hereditary spastic paraplegia v4.3 SPG7 Sarah Leigh changed review comment from: The mode of inheritance of this gene has been updated to SPG7 following NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal, following NHS Genomic Medicine Service approval.
Adult onset hereditary spastic paraplegia v4.3 SPG7 Sarah Leigh changed review comment from: The mode of inheritance of this gene has been updated to XX following NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to SPG7 following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v4.11 RTN2 Sarah Leigh Tag Q2_24_NHS_review tag was added to gene: RTN2.
Hereditary neuropathy or pain disorder v4.11 SPTBN4 Sarah Leigh Tag Q2_24_promote_green was removed from gene: SPTBN4.
Tag Q2_24_NHS_review was removed from gene: SPTBN4.
Hereditary neuropathy or pain disorder v4.11 ABHD12 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: ABHD12.
Tag Q2_24_NHS_review tag was added to gene: ABHD12.
Hereditary neuropathy or pain disorder v4.11 AGXT Sarah Leigh Tag Q2_24_promote_green tag was added to gene: AGXT.
Tag Q2_24_NHS_review tag was added to gene: AGXT.
Hereditary neuropathy or pain disorder v4.11 APOA1 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: APOA1.
Tag Q2_24_NHS_review tag was added to gene: APOA1.
Hereditary neuropathy or pain disorder v4.11 B4GALNT1 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: B4GALNT1.
Tag Q2_24_NHS_review tag was added to gene: B4GALNT1.
Hereditary neuropathy or pain disorder v4.11 BCKDHB Sarah Leigh Tag Q2_24_promote_green tag was added to gene: BCKDHB.
Tag Q2_24_NHS_review tag was added to gene: BCKDHB.
Hereditary neuropathy or pain disorder v4.11 FXN Sarah Leigh Tag Q2_24_promote_green tag was added to gene: FXN.
Tag Q2_24_NHS_review tag was added to gene: FXN.
Hereditary neuropathy or pain disorder v4.11 GALC Sarah Leigh Tag Q2_24_promote_green tag was added to gene: GALC.
Tag Q2_24_NHS_review tag was added to gene: GALC.
Hereditary neuropathy or pain disorder v4.11 GBA2 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: GBA2.
Tag Q2_24_NHS_review tag was added to gene: GBA2.
Hereditary neuropathy or pain disorder v4.11 IARS2 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: IARS2.
Tag Q2_24_NHS_review tag was added to gene: IARS2.
Hereditary neuropathy or pain disorder v4.11 LYST Sarah Leigh Tag Q2_24_promote_green tag was added to gene: LYST.
Tag Q2_24_NHS_review tag was added to gene: LYST.
Hereditary neuropathy or pain disorder v4.11 MMACHC Sarah Leigh Tag Q2_24_promote_green tag was added to gene: MMACHC.
Tag Q2_24_NHS_review tag was added to gene: MMACHC.
Hereditary neuropathy or pain disorder v4.11 MTTP Sarah Leigh Tag Q2_24_promote_green tag was added to gene: MTTP.
Tag Q2_24_NHS_review tag was added to gene: MTTP.
Hereditary neuropathy or pain disorder v4.11 NAGA Sarah Leigh Tag Q2_24_promote_green tag was added to gene: NAGA.
Tag Q2_24_NHS_review tag was added to gene: NAGA.
Hereditary neuropathy or pain disorder v4.11 PDYN Sarah Leigh Tag Q2_24_promote_green tag was added to gene: PDYN.
Tag Q2_24_NHS_review tag was added to gene: PDYN.
Hereditary neuropathy or pain disorder v4.11 PEX10 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: PEX10.
Tag Q2_24_NHS_review tag was added to gene: PEX10.
Hereditary neuropathy or pain disorder v4.11 PEX7 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: PEX7.
Tag Q2_24_NHS_review tag was added to gene: PEX7.
Hereditary neuropathy or pain disorder v4.11 PLP1 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: PLP1.
Tag Q2_24_NHS_review tag was added to gene: PLP1.
Hereditary neuropathy or pain disorder v4.11 PMM2 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: PMM2.
Tag Q2_24_NHS_review tag was added to gene: PMM2.
Hereditary neuropathy or pain disorder v4.11 PNPLA6 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: PNPLA6.
Tag Q2_24_NHS_review tag was added to gene: PNPLA6.
Hereditary neuropathy or pain disorder v4.11 POLR3A Sarah Leigh Tag Q2_24_promote_green tag was added to gene: POLR3A.
Tag Q2_24_NHS_review tag was added to gene: POLR3A.
Hereditary neuropathy or pain disorder v4.11 SACS Sarah Leigh Tag Q2_24_promote_green tag was added to gene: SACS.
Tag Q2_24_NHS_review tag was added to gene: SACS.
Hereditary neuropathy or pain disorder v4.11 SCARB2 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: SCARB2.
Tag Q2_24_NHS_review tag was added to gene: SCARB2.
Hereditary neuropathy or pain disorder v4.11 SLC25A19 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: SLC25A19.
Tag Q2_24_NHS_review tag was added to gene: SLC25A19.
Hereditary neuropathy or pain disorder v4.11 SPTBN4 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: SPTBN4.
Tag Q2_24_NHS_review tag was added to gene: SPTBN4.
Hereditary neuropathy or pain disorder v4.11 SURF1 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: SURF1.
Tag Q2_24_NHS_review tag was added to gene: SURF1.
Hereditary neuropathy or pain disorder v4.11 TYMP Sarah Leigh Tag Q2_24_promote_green tag was added to gene: TYMP.
Tag Q2_24_NHS_review tag was added to gene: TYMP.
Hereditary neuropathy or pain disorder v4.11 XK Sarah Leigh Tag Q2_24_promote_green tag was added to gene: XK.
Tag Q2_24_NHS_review tag was added to gene: XK.
Hereditary neuropathy or pain disorder v4.11 XK Sarah Leigh reviewed gene: XK: Rating: GREEN; Mode of pathogenicity: ; Publications: 8619554, 11261514; Phenotypes: McLeod syndrome, OMIM:300842; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hereditary neuropathy or pain disorder v4.11 TYMP Sarah Leigh reviewed gene: TYMP: Rating: GREEN; Mode of pathogenicity: ; Publications: 14757860, 12177387, 9924029; Phenotypes: Mitochondrial DNA depletion syndrome 1 (MNGIE type), OMIM:603041; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 SURF1 Sarah Leigh reviewed gene: SURF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 4K, OMIM:616684, Mitochondrial complex IV deficiency, nuclear type 1, OMIM:220110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 SPTBN4 Sarah Leigh edited their review of gene: SPTBN4: Added comment: At least six SPTBN4 variants have been associated with OMIM:617519, which includes axonal and demyelinating peripheral neuropathy as one of the clinical features. Six SPTBN4 variants have been reported by PMID: 28540413;29861105 in five unrelated cases of OMIM:617519.; Changed rating: GREEN; Changed publications to: 28540413, 29861105; Changed phenotypes to: Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 SLC25A19 Sarah Leigh reviewed gene: SLC25A19: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type), OMIM:613710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 SCARB2 Sarah Leigh reviewed gene: SCARB2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Epilepsy, progressive myoclonic 4, with or without renal failure, OMIM:254900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 SACS Sarah Leigh reviewed gene: SACS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spastic ataxia, Charlevoix-Saguenay type, OMIM:270550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 POLR3A Sarah Leigh reviewed gene: POLR3A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Wiedemann-Rautenstrauch syndrome, OMIM:264090, Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism OMIM:607694; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 PNPLA6 Sarah Leigh reviewed gene: PNPLA6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Oliver-McFarlane syndrome, OMIM:275400, Spastic paraplegia 39, autosomal recessive, OMIM:612020, Boucher-Neuhauser syndrome, OMIM:215470; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 PMM2 Sarah Leigh reviewed gene: PMM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital disorder of glycosylation, type Ia, OMIM:212065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 PLP1 Sarah Leigh reviewed gene: PLP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spastic paraplegia 2, X-linked, OMIM:312920, Pelizaeus-Merzbacher disease, OMIM:312080; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hereditary neuropathy or pain disorder v4.11 PEX7 Sarah Leigh reviewed gene: PEX7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 9B, OMIM:14879; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 PEX10 Sarah Leigh reviewed gene: PEX10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Peroxisome biogenesis disorder 6A (Zellweger), OMIM:614870, Peroxisome biogenesis disorder 6B, OMIM:614871; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 PDYN Sarah Leigh reviewed gene: PDYN: Rating: GREEN; Mode of pathogenicity: ; Publications: 21035104; Phenotypes: Spinocerebellar ataxia 23, OMIM:610245; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.11 NAGA Sarah Leigh reviewed gene: NAGA: Rating: GREEN; Mode of pathogenicity: ; Publications: 8782044, 11251574; Phenotypes: Kanzaki disease, OMIM:609242; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 MTTP Sarah Leigh reviewed gene: MTTP: Rating: GREEN; Mode of pathogenicity: ; Publications: 8361539, 10446076, 8111381; Phenotypes: Abetalipoproteinemia, OMIM:200100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 MMACHC Sarah Leigh reviewed gene: MMACHC: Rating: GREEN; Mode of pathogenicity: ; Publications: 17431913, 16311595, 19370762; Phenotypes: Methylmalonic aciduria and homocystinuria, cblC type, OMIM:277400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 LYST Sarah Leigh reviewed gene: LYST: Rating: GREEN; Mode of pathogenicity: ; Publications: 9215680, 8896560, 9215679, 11857544; Phenotypes: Chediak-Higashi syndrome, OMIM:214500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 IARS2 Sarah Leigh reviewed gene: IARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, OMIM:616007; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 GBA2 Sarah Leigh reviewed gene: GBA2: Rating: GREEN; Mode of pathogenicity: ; Publications: 24252062, 23332917, 23332916; Phenotypes: Spastic paraplegia 46, autosomal recessive, OMIM:614409; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 GALC Sarah Leigh reviewed gene: GALC: Rating: GREEN; Mode of pathogenicity: ; Publications: 20886637, 21070211; Phenotypes: Krabbe disease, OMIM:245200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 FXN Sarah Leigh reviewed gene: FXN: Rating: GREEN; Mode of pathogenicity: ; Publications: 21830088, 9737785, 8596916; Phenotypes: Friedreich ataxia, OMIM:229300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 BCKDHB Sarah Leigh reviewed gene: BCKDHB: Rating: GREEN; Mode of pathogenicity: ; Publications: 14742428, 2022752, 11509994; Phenotypes: Maple syrup urine disease, type Ib,OMIM:620698; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 B4GALNT1 Sarah Leigh reviewed gene: B4GALNT1: Rating: GREEN; Mode of pathogenicity: ; Publications: 23746551; Phenotypes: Spastic paraplegia 26, autosomal recessive, OMIM:609195; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 APOA1 Sarah Leigh reviewed gene: APOA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Amyloidosis, 3 or more types, OMIM:105200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.11 AGXT Sarah Leigh reviewed gene: AGXT: Rating: GREEN; Mode of pathogenicity: ; Publications: 1961759, 10960483, 15464418; Phenotypes: Hyperoxaluria, primary, type 1, OMIM:259900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.11 ABHD12 Sarah Leigh reviewed gene: ABHD12: Rating: GREEN; Mode of pathogenicity: ; Publications: 20797687, 24697911; Phenotypes: Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract, OMIM:612674; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset hereditary spastic paraplegia v4.3 SPG7 Eleanor Williams Tag Q2_23_MOI was removed from gene: SPG7.
Hereditary neuropathy or pain disorder v4.10 SLC12A6 Eleanor Williams Tag for-review was removed from gene: SLC12A6.
Tag to_be_confirmed_NHSE was removed from gene: SLC12A6.
Tag Q4_23_promote_green was removed from gene: SLC12A6.
Tag Q4_23_NHS_review was removed from gene: SLC12A6.
Intellectual disability v6.13 ZBTB47 Eleanor Williams Tag gene-checked tag was added to gene: ZBTB47.
Intellectual disability v6.13 KDM5A Eleanor Williams Phenotypes for gene: KDM5A were changed from autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 to autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071; El Hayek-Chahrour neurodevelopmental syndrome, OMIM:620820
Intellectual disability v6.12 KDM5A Eleanor Williams Tag gene-checked was removed from gene: KDM5A.
Early onset or syndromic epilepsy v5.10 ZBTB47 Eleanor Williams Tag gene-checked tag was added to gene: ZBTB47.
Intellectual disability v6.12 TMEM63B Eleanor Williams Tag gene-checked tag was added to gene: TMEM63B.
Early onset or syndromic epilepsy v5.10 TMEM63B Eleanor Williams Tag gene-checked tag was added to gene: TMEM63B.
Childhood onset dystonia, chorea or related movement disorder v4.3 TMEM151A Eleanor Williams Tag gene-checked tag was added to gene: TMEM151A.
Ataxia and cerebellar anomalies - narrow panel v5.3 THG1L Eleanor Williams Tag gene-checked tag was added to gene: THG1L.
Intellectual disability v6.12 PPP1R3F Eleanor Williams Tag gene-checked tag was added to gene: PPP1R3F.
Early onset or syndromic epilepsy v5.10 PPP1R3F Eleanor Williams Tag gene-checked tag was added to gene: PPP1R3F.
Intellectual disability v6.12 MAST4 Eleanor Williams Tag gene-checked tag was added to gene: MAST4.
Early onset or syndromic epilepsy v5.10 MAST4 Eleanor Williams Tag gene-checked tag was added to gene: MAST4.
Retinal disorders v5.4 CFAP20 Eleanor Williams Tag gene-checked tag was added to gene: CFAP20.
Paediatric or syndromic cardiomyopathy v4.3 CAP2 Eleanor Williams Tag gene-checked tag was added to gene: CAP2.
Early onset or syndromic epilepsy v5.10 RAB5C Eleanor Williams Tag gene-checked tag was added to gene: RAB5C.
Intellectual disability v6.12 RAB5C Eleanor Williams Tag gene-checked tag was added to gene: RAB5C.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 PTPN2 Eleanor Williams Tag gene-checked tag was added to gene: PTPN2.
Intellectual disability v6.12 PABPC1 Eleanor Williams Tag gene-checked tag was added to gene: PABPC1.
Early onset or syndromic epilepsy v5.10 PABPC1 Eleanor Williams Tag gene-checked tag was added to gene: PABPC1.
Neonatal diabetes v4.6 ONECUT1 Eleanor Williams Tag gene-checked tag was added to gene: ONECUT1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 NFAT5 Eleanor Williams Tag gene-checked tag was added to gene: NFAT5.
Intellectual disability v6.12 MYH10 Eleanor Williams Tag gene-checked tag was added to gene: MYH10.
Inherited polyposis and early onset colorectal cancer - germline testing v2.11 GREM1 Eleanor Williams Tag gene-checked tag was added to gene: GREM1.
Lipodystrophy - childhood onset v4.52 EPHX1 Eleanor Williams Tag gene-checked tag was added to gene: EPHX1.
Adult onset neurodegenerative disorder v5.3 DNAJC7 Eleanor Williams Tag gene-checked tag was added to gene: DNAJC7.
Adult onset neurodegenerative disorder v5.3 DNAJC7 Eleanor Williams reviewed gene: DNAJC7: Rating: ; Mode of pathogenicity: None; Publications: 31768050, 35039179, 34233860, 32897108, 37870677, 35456894; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy or pain disorder v4.10 DHX9 Eleanor Williams Tag gene-checked tag was added to gene: DHX9.
Intellectual disability v6.12 DHX9 Eleanor Williams Tag gene-checked tag was added to gene: DHX9.
Intellectual disability v6.12 CNOT9 Eleanor Williams Tag gene-checked tag was added to gene: CNOT9.
Early onset or syndromic epilepsy v5.10 CNOT9 Eleanor Williams Tag gene-checked tag was added to gene: CNOT9.
Unexplained young onset end-stage renal disease v4.3 CFHR2 Eleanor Williams Tag gene-checked tag was added to gene: CFHR2.
Intellectual disability v6.12 CDK16 Eleanor Williams Tag gene-checked tag was added to gene: CDK16.
Structural eye disease v3.79 ARHGAP35 Eleanor Williams Tag gene-checked tag was added to gene: ARHGAP35.
Intellectual disability v6.12 ARF3 Eleanor Williams Tag gene-checked tag was added to gene: ARF3.
Early onset or syndromic epilepsy v5.10 ARF3 Eleanor Williams Tag gene-checked tag was added to gene: ARF3.
Severe microcephaly v5.7 ARF3 Eleanor Williams Tag gene-checked tag was added to gene: ARF3.
Clefting v5.3 AMOTL1 Eleanor Williams Tag gene-checked tag was added to gene: AMOTL1.
Likely inborn error of metabolism - targeted testing not possible v5.3 ATP5E Eleanor Williams Tag new-gene-name tag was added to gene: ATP5E.
Hereditary neuropathy or pain disorder v4.10 SLC12A6 Eleanor Williams commented on gene: SLC12A6
Hereditary neuropathy or pain disorder v4.10 SLC12A6 Eleanor Williams Mode of inheritance for gene: SLC12A6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.9 SURF1 Sarah Leigh Publications for gene: SURF1 were set to
Intellectual disability v6.12 MAST3 Sarah Leigh Tag Q2_24_NHS_review tag was added to gene: MAST3.
Early onset or syndromic epilepsy v5.10 MAST3 Sarah Leigh Tag Q2_24_NHS_review tag was added to gene: MAST3.
Intellectual disability v6.12 MAST3 Sarah Leigh Tag Q2_24_MOI was removed from gene: MAST3.
Intellectual disability v6.12 MAST3 Sarah Leigh Entity copied from Early onset or syndromic epilepsy v5.10
Intellectual disability v6.12 MAST3 Sarah Leigh gene: MAST3 was added
gene: MAST3 was added to Intellectual disability. Sources: Expert Review Amber,Literature
Q2_24_promote_green, Q2_24_MOI tags were added to gene: MAST3.
Mode of inheritance for gene: MAST3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAST3 were set to 34185323; 35095415
Mode of pathogenicity for gene: MAST3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Early onset or syndromic epilepsy v5.10 MAST3 Sarah Leigh changed review comment from: MAST3 variants have been associated with Developmental and epileptic encephalopathy 108 (OMIM:620115). PMID:34185323 reports five de novo missense MAST3 variants in eleven unrelated individuals with developmental and epileptic encephalopathy, with a range of seizure types. Functional studies suggest that the MAST3 variants have a gain-of-function effect.
Sources: Literature; to: MAST3 variants have been associated with Developmental and epileptic encephalopathy 108 (OMIM:620115). PMID:34185323 reports five de novo missense MAST3 variants in eleven unrelated individuals with developmental and epileptic encephalopathy, with a range of seizure types. These variants are within the serine-threonine kinases (STK) domain. PMID: 35095415 reports a further four de novo missense MAST3 variants, within the domain of unknown function (DUF). It would appear that the variants within the STK domain are associated with a neurodevelopmental disorder with a epilepsy phenotype, while variants within the DUF domain have a autistic spectrum disorder phenotype (PMID: 35095415)
Functional studies suggest that the MAST3 variants have a gain-of-function effect (PMID:34185323; 35095415).
Early onset or syndromic epilepsy v5.10 MAST3 Sarah Leigh Publications for gene: MAST3 were set to 34185323
Early onset or syndromic epilepsy v5.9 MAST3 Sarah Leigh Added comment: Comment on mode of pathogenicity: It would appear that MAST3 variants have a gain-of-function effect (PMID:34185323).
Early onset or syndromic epilepsy v5.9 MAST3 Sarah Leigh Mode of pathogenicity for gene: MAST3 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 Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Early onset or syndromic epilepsy v5.8 MAST3 Sarah Leigh Classified gene: MAST3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v5.8 MAST3 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 v5.8 MAST3 Sarah Leigh Gene: mast3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v5.7 MAST3 Sarah Leigh Tag Q2_24_promote_green tag was added to gene: MAST3.
Tag Q2_24_MOI tag was added to gene: MAST3.
Early onset or syndromic epilepsy v5.7 MAST3 Sarah Leigh gene: MAST3 was added
gene: MAST3 was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: MAST3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAST3 were set to 34185323
Mode of pathogenicity for gene: MAST3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: MAST3 was set to GREEN
Added comment: MAST3 variants have been associated with Developmental and epileptic encephalopathy 108 (OMIM:620115). PMID:34185323 reports five de novo missense MAST3 variants in eleven unrelated individuals with developmental and epileptic encephalopathy, with a range of seizure types. Functional studies suggest that the MAST3 variants have a gain-of-function effect.
Sources: Literature
Paediatric or syndromic cardiomyopathy v4.3 NEXN Hannah Robinson reviewed gene: NEXN: Rating: ; Mode of pathogenicity: None; Publications: 35166435, 33949776, 33027564, 32058062; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Limb disorders v5.4 FBXW11 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 SLC5A6 Eleanor Williams changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remainsred.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains red.
Early onset or syndromic epilepsy v5.6 ZBTB47 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: 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.
Early onset or syndromic epilepsy v5.6 U2AF2 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: 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.
Early onset or syndromic epilepsy v5.6 TRIT1 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 TMEM63B Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: 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.
Early onset or syndromic epilepsy v5.6 SHQ1 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 SHQ1 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand 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 togreenand the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 SCN8A 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 has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 RAB5C Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: 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.
Early onset or syndromic epilepsy v5.6 PTCD3 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 PPP1R3F Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'X-LINKED: hemizygous mutation in males, biallelic mutations in females'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'X-LINKED: hemizygous mutation in males, biallelic mutations in females' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 PLA2G6 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 PIP5K1C Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: 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.
Early onset or syndromic epilepsy v5.6 PIGM Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 PABPC1 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 MAST4 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: 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.
Early onset or syndromic epilepsy v5.6 LETM1 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 KDM6B Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: 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.
Early onset or syndromic epilepsy v5.6 KCNH5 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: 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.
Early onset or syndromic epilepsy v5.6 HECTD4 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 ESAM Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 EIF4A2 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 DNAJC6 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 CRELD1 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 ATP6V0C Eleanor Williams changed review comment from: 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.; to: 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.
Early onset or syndromic epilepsy v5.6 ASL Eleanor Williams 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 ARF3 Eleanor Williams changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 AGO1 Eleanor Williams changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 CNOT9 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: 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.
Early onset or syndromic epilepsy v5.6 ATP6V0C Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: 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.
Early onset or syndromic epilepsy v5.6 ASL Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 ARF3 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 AGO1 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v5.6 CACNB4 Eleanor Williams edited their review of gene: CACNB4: Changed rating: RED
Early onset or syndromic epilepsy v5.6 CACNB4 Eleanor Williams changed review comment from: The rating of this gene has been updated from green to redfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated from green to red following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 RETREG1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: RETREG1.
Tag Q4_23_NHS_review was removed from gene: RETREG1.
Childhood onset hereditary spastic paraplegia v5.3 RETREG1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 PPFIBP1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 PPFIBP1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PPFIBP1.
Childhood onset hereditary spastic paraplegia v5.3 HECTD4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HECTD4.
Childhood onset hereditary spastic paraplegia v5.3 HECTD4 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 CLDN11 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLDN11.
Childhood onset hereditary spastic paraplegia v5.3 CLDN11 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: 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.
Childhood onset hereditary spastic paraplegia v5.3 UCHL1 Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: UCHL1.
Childhood onset hereditary spastic paraplegia v5.3 UCHL1 Achchuthan Shanmugasundram changed review comment from: The mode of inheritance of this gene has been updated toBOTH monoallelic and biallelic, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 LETM1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 LETM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: LETM1.
Tag Q3_23_MOI was removed from gene: LETM1.
Childhood onset hereditary spastic paraplegia v5.3 AMFR Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: AMFR.
Childhood onset hereditary spastic paraplegia v5.3 AMFR Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 UCHL1 Achchuthan Shanmugasundram reviewed gene: UCHL1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v5.3 RETREG1 Achchuthan Shanmugasundram commented on gene: RETREG1: The rating of this gene has been updated togreenand the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 PPFIBP1 Achchuthan Shanmugasundram commented on gene: PPFIBP1: The rating of this gene has been updated togreenand the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 LETM1 Achchuthan Shanmugasundram reviewed gene: LETM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v5.3 HECTD4 Achchuthan Shanmugasundram commented on gene: HECTD4: The rating of this gene has been updated togreenand the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 CLDN11 Achchuthan Shanmugasundram commented on gene: CLDN11: The rating of this gene has been updated togreenand the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.3 AMFR Achchuthan Shanmugasundram commented on gene: AMFR: The rating of this gene has been updated togreenand the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v5.2 UCHL1 Achchuthan Shanmugasundram Mode of inheritance for gene UCHL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v5.2 RETREG1 Achchuthan Shanmugasundram Source Expert Review Green was added to RETREG1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v5.2 PPFIBP1 Achchuthan Shanmugasundram Source NHS GMS was added to PPFIBP1.
Source Expert Review Green was added to PPFIBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v5.2 LETM1 Achchuthan Shanmugasundram Source NHS GMS was added to LETM1.
Source Expert Review Green was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v5.2 HECTD4 Achchuthan Shanmugasundram Source Expert Review Green was added to HECTD4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v5.2 CLDN11 Achchuthan Shanmugasundram Source NHS GMS was added to CLDN11.
Source Expert Review Green was added to CLDN11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v5.2 AMFR Achchuthan Shanmugasundram Source NHS GMS was added to AMFR.
Source Expert Review Green was added to AMFR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.3 AFG3L2 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: AFG3L2.
Childhood onset dystonia, chorea or related movement disorder v4.3 AFG3L2 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated from green toamberfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated from green to amber following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 SHQ1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SHQ1.
Childhood onset dystonia, chorea or related movement disorder v4.3 SHQ1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 ASL Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ASL.
Tag Q4_23_NHS_review was removed from gene: ASL.
Childhood onset dystonia, chorea or related movement disorder v4.3 ASL Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 ARX Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ARX.
Childhood onset dystonia, chorea or related movement disorder v4.3 ARX Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand 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.; to: 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.
Childhood onset dystonia, chorea or related movement disorder v4.3 OCLN Achchuthan Shanmugasundram Tag Q3_23_expert_review was removed from gene: OCLN.
Tag Q3_23_demote_red was removed from gene: OCLN.
Childhood onset dystonia, chorea or related movement disorder v4.3 OCLN Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated from green toredfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated from green to red following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 TSPOAP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TSPOAP1.
Childhood onset dystonia, chorea or related movement disorder v4.3 TSPOAP1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 TMEM151A Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: 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.
Childhood onset dystonia, chorea or related movement disorder v4.3 TMEM151A Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TMEM151A.
Tag Q3_23_NHS_review was removed from gene: TMEM151A.
Childhood onset dystonia, chorea or related movement disorder v4.3 TBC1D24 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TBC1D24.
Childhood onset dystonia, chorea or related movement disorder v4.3 TBC1D24 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 SYT1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SYT1.
Childhood onset dystonia, chorea or related movement disorder v4.3 SYT1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: 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.
Childhood onset dystonia, chorea or related movement disorder v4.3 SQSTM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SQSTM1.
Childhood onset dystonia, chorea or related movement disorder v4.3 SQSTM1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 SLC30A9 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SLC30A9.
Childhood onset dystonia, chorea or related movement disorder v4.3 SLC30A9 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 SLC18A2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SLC18A2.
Childhood onset dystonia, chorea or related movement disorder v4.3 SLC18A2 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 L2HGDH Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: L2HGDH.
Childhood onset dystonia, chorea or related movement disorder v4.3 L2HGDH Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 KCNQ2 Achchuthan Shanmugasundram Tag Q3_23_expert_review was removed from gene: KCNQ2.
Tag Q3_23_demote_red was removed from gene: KCNQ2.
Childhood onset dystonia, chorea or related movement disorder v4.3 DNAJC6 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DNAJC6.
Childhood onset dystonia, chorea or related movement disorder v4.3 DNAJC6 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 KCNQ2 Achchuthan Shanmugasundram commented on gene: KCNQ2
Childhood onset dystonia, chorea or related movement disorder v4.3 TSPOAP1 Achchuthan Shanmugasundram reviewed gene: TSPOAP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v4.3 TMEM151A Achchuthan Shanmugasundram commented on gene: TMEM151A: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 TBC1D24 Achchuthan Shanmugasundram commented on gene: TBC1D24: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 SYT1 Achchuthan Shanmugasundram commented on gene: SYT1: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 SQSTM1 Achchuthan Shanmugasundram commented on gene: SQSTM1: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 SLC30A9 Achchuthan Shanmugasundram commented on gene: SLC30A9: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 SLC18A2 Achchuthan Shanmugasundram commented on gene: SLC18A2: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 SHQ1 Achchuthan Shanmugasundram reviewed gene: SHQ1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v4.3 OCLN Achchuthan Shanmugasundram reviewed gene: OCLN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset dystonia, chorea or related movement disorder v4.3 L2HGDH Achchuthan Shanmugasundram commented on gene: L2HGDH: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v4.3 DNAJC6 Achchuthan Shanmugasundram reviewed gene: DNAJC6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v4.3 ASL Achchuthan Shanmugasundram reviewed gene: ASL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v4.3 ARX Achchuthan Shanmugasundram reviewed gene: ARX: Rating: GREEN; Mode of pathogenicity: ; 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)
Childhood onset dystonia, chorea or related movement disorder v4.3 AFG3L2 Achchuthan Shanmugasundram reviewed gene: AFG3L2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset dystonia, chorea or related movement disorder v4.2 TSPOAP1 Achchuthan Shanmugasundram Source Expert Review Green was added to TSPOAP1.
Source NHS GMS was added to TSPOAP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 TMEM151A Achchuthan Shanmugasundram Source Expert Review Green was added to TMEM151A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 TBC1D24 Achchuthan Shanmugasundram Source Expert Review Green was added to TBC1D24.
Source NHS GMS was added to TBC1D24.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 SYT1 Achchuthan Shanmugasundram Source Expert Review Green was added to SYT1.
Source NHS GMS was added to SYT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 SQSTM1 Achchuthan Shanmugasundram 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)
Childhood onset dystonia, chorea or related movement disorder v4.2 SLC30A9 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC30A9.
Source NHS GMS was added to SLC30A9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 SLC18A2 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC18A2.
Source NHS GMS was added to SLC18A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 SHQ1 Achchuthan Shanmugasundram Source Expert Review Green was added to SHQ1.
Source NHS GMS was added to SHQ1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 OCLN Achchuthan Shanmugasundram Source Expert Review Red was added to OCLN.
Source NHS GMS was added to OCLN.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 L2HGDH Achchuthan Shanmugasundram Source Expert Review Green was added to L2HGDH.
Source NHS GMS was added to L2HGDH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 DNAJC6 Achchuthan Shanmugasundram Source Expert Review Green was added to DNAJC6.
Source NHS GMS was added to DNAJC6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 ASL Achchuthan Shanmugasundram Source Expert Review Green was added to ASL.
Source NHS GMS was added to ASL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 ARX Achchuthan Shanmugasundram Source Expert Review Green was added to ARX.
Source NHS GMS was added to ARX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v4.2 AFG3L2 Achchuthan Shanmugasundram Source NHS GMS was added to AFG3L2.
Source Expert Review Amber was added to AFG3L2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Arthrogryposis v6.3 ACTC1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ACTC1.
Arthrogryposis v6.3 ACTC1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: 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.
Arthrogryposis v6.3 ACTC1 Achchuthan Shanmugasundram commented on gene: ACTC1: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.
Arthrogryposis v6.2 ACTC1 Achchuthan Shanmugasundram Source NHS GMS was added to ACTC1.
Source Expert Review Green was added to ACTC1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset leukodystrophy v4.3 RNASET2 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: RNASET2.
Adult onset leukodystrophy v4.3 RNASET2 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.
Adult onset leukodystrophy v4.3 POLR1C Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: POLR1C.
Adult onset leukodystrophy v4.3 POLR1C Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.
Adult onset leukodystrophy v4.3 MARS Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: MARS.
Adult onset leukodystrophy v4.3 MARS Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.
Adult onset leukodystrophy v4.3 COL4A2 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: COL4A2.
Adult onset leukodystrophy v4.3 AARS Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: AARS.
Adult onset leukodystrophy v4.3 OCRL Achchuthan Shanmugasundram Tag Q4_23_demote_amber was removed from gene: OCRL.
Tag Q4_23_expert_review was removed from gene: OCRL.
Adult onset leukodystrophy v4.3 OCRL Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.
Adult onset leukodystrophy v4.3 HMGCL Achchuthan Shanmugasundram Tag Q4_23_demote_amber was removed from gene: HMGCL.
Tag Q4_23_expert_review was removed from gene: HMGCL.
Adult onset leukodystrophy v4.3 HMGCL Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.
Adult onset leukodystrophy v4.3 RPS6KA3 Achchuthan Shanmugasundram Tag Q3_23_expert_review was removed from gene: RPS6KA3.
Tag Q3_23_demote_red was removed from gene: RPS6KA3.
Adult onset leukodystrophy v4.3 RPS6KA3 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toredfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.
Adult onset leukodystrophy v4.3 RNF216 Achchuthan Shanmugasundram Tag Q3_23_expert_review was removed from gene: RNF216.
Tag Q3_23_demote_amber was removed from gene: RNF216.
Adult onset leukodystrophy v4.3 GCDH Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: GCDH.
Tag Q3_23_MOI was removed from gene: GCDH.
Adult onset leukodystrophy v4.3 GCDH Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated to greenand the mode of inheritance set to'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Adult onset neurodegenerative disorder v5.3 DNAJC7 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: DNAJC7.
Adult onset neurodegenerative disorder v5.3 GBA Achchuthan Shanmugasundram reviewed gene: GBA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v5.3 DNAJC7 Achchuthan Shanmugasundram reviewed gene: DNAJC7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset leukodystrophy v4.3 RPS6KA3 Achchuthan Shanmugasundram reviewed gene: RPS6KA3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v4.3 RNF216 Achchuthan Shanmugasundram commented on gene: RNF216
Adult onset leukodystrophy v4.3 RNASET2 Achchuthan Shanmugasundram reviewed gene: RNASET2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v4.3 POLR1C Achchuthan Shanmugasundram reviewed gene: POLR1C: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v4.3 OCRL Achchuthan Shanmugasundram reviewed gene: OCRL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v4.3 MARS Achchuthan Shanmugasundram reviewed gene: MARS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v4.3 HMGCL Achchuthan Shanmugasundram reviewed gene: HMGCL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v4.3 COL4A2 Achchuthan Shanmugasundram commented on gene: COL4A2
Adult onset leukodystrophy v4.3 AARS Achchuthan Shanmugasundram commented on gene: AARS
Adult onset leukodystrophy v4.3 GCDH Achchuthan Shanmugasundram reviewed gene: GCDH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v5.2 GBA Achchuthan Shanmugasundram Source Expert Review Green was added to GBA.
Mode of inheritance for gene GBA was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v5.2 DNAJC7 Achchuthan Shanmugasundram Source NHS GMS was added to DNAJC7.
Source Expert Review Green was added to DNAJC7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset leukodystrophy v4.2 RPS6KA3 Achchuthan Shanmugasundram Source Expert Review Red was added to RPS6KA3.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Adult onset leukodystrophy v4.2 RNASET2 Achchuthan Shanmugasundram Source Expert Review Amber was added to RNASET2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Adult onset leukodystrophy v4.2 POLR1C Achchuthan Shanmugasundram Source Expert Review Amber was added to POLR1C.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Adult onset leukodystrophy v4.2 OCRL Achchuthan Shanmugasundram Source Expert Review Amber was added to OCRL.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Adult onset leukodystrophy v4.2 MARS Achchuthan Shanmugasundram Source Expert Review Amber was added to MARS.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Adult onset leukodystrophy v4.2 HMGCL Achchuthan Shanmugasundram Source Expert Review Amber was added to HMGCL.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Adult onset leukodystrophy v4.2 GCDH Achchuthan Shanmugasundram Source NHS GMS was added to GCDH.
Source Expert Review Green was added to GCDH.
Mode of inheritance for gene GCDH 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)
Adult onset hereditary spastic paraplegia v4.3 UCHL1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: UCHL1.
Tag Q3_23_MOI was removed from gene: UCHL1.
Adult onset hereditary spastic paraplegia v4.3 UCHL1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Adult onset hereditary spastic paraplegia v4.3 PRNP Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PRNP.
Adult onset hereditary spastic paraplegia v4.3 PRNP Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: 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.
Adult onset hereditary spastic paraplegia v4.3 AP4S1 Achchuthan Shanmugasundram Tag for-review was removed from gene: AP4S1.
Tag to_be_confirmed_NHSE was removed from gene: AP4S1.
Adult onset hereditary spastic paraplegia v4.3 AP4S1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.
Adult onset hereditary spastic paraplegia v4.3 AP4M1 Achchuthan Shanmugasundram Tag for-review was removed from gene: AP4M1.
Tag to_be_confirmed_NHSE was removed from gene: AP4M1.
Adult onset hereditary spastic paraplegia v4.3 AP4M1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.
Adult onset hereditary spastic paraplegia v4.3 AP4B1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.
Adult onset hereditary spastic paraplegia v4.3 AP4E1 Achchuthan Shanmugasundram Tag for-review was removed from gene: AP4E1.
Tag to_be_confirmed_NHSE was removed from gene: AP4E1.
Adult onset hereditary spastic paraplegia v4.3 AP4E1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.
Adult onset hereditary spastic paraplegia v4.3 AP4B1 Achchuthan Shanmugasundram Tag for-review was removed from gene: AP4B1.
Tag to_be_confirmed_NHSE was removed from gene: AP4B1.
Adult onset hereditary spastic paraplegia v4.3 AP4B1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval. The associated phenotype has childhood onset.
Adult onset hereditary spastic paraplegia v4.3 UCHL1 Achchuthan Shanmugasundram reviewed gene: UCHL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset hereditary spastic paraplegia v4.3 PRNP Achchuthan Shanmugasundram reviewed gene: PRNP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset hereditary spastic paraplegia v4.3 AP4S1 Achchuthan Shanmugasundram reviewed gene: AP4S1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset hereditary spastic paraplegia v4.3 AP4M1 Achchuthan Shanmugasundram reviewed gene: AP4M1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset hereditary spastic paraplegia v4.3 AP4E1 Achchuthan Shanmugasundram reviewed gene: AP4E1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset hereditary spastic paraplegia v4.3 AP4B1 Achchuthan Shanmugasundram reviewed gene: AP4B1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset hereditary spastic paraplegia v4.2 UCHL1 Achchuthan Shanmugasundram Source Expert Review Green was added to UCHL1.
Mode of inheritance for gene UCHL1 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)
Adult onset hereditary spastic paraplegia v4.2 PRNP Achchuthan Shanmugasundram Source Expert Review Green was added to PRNP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset hereditary spastic paraplegia v4.2 AP4S1 Achchuthan Shanmugasundram Source Expert Review Amber was added to AP4S1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Adult onset hereditary spastic paraplegia v4.2 AP4M1 Achchuthan Shanmugasundram Source Expert Review Amber was added to AP4M1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Adult onset hereditary spastic paraplegia v4.2 AP4E1 Achchuthan Shanmugasundram Source Expert Review Amber was added to AP4E1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Adult onset hereditary spastic paraplegia v4.2 AP4B1 Achchuthan Shanmugasundram Source Expert Review Amber was added to AP4B1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Adult onset dystonia, chorea or related movement disorder v3.19 GBA Achchuthan Shanmugasundram reviewed gene: GBA: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset dystonia, chorea or related movement disorder v3.19 GBA Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: GBA.
Adult onset dystonia, chorea or related movement disorder v3.19 GBA Achchuthan Shanmugasundram Mode of inheritance for gene GBA was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v5.3 TNFRSF11A Achchuthan Shanmugasundram Tag for-review was removed from gene: TNFRSF11A.
Tag to_be_confirmed_NHSE was removed from gene: TNFRSF11A.
Skeletal dysplasia v5.3 TNFRSF11A Achchuthan Shanmugasundram 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 has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 ANAPC1 Achchuthan Shanmugasundram Tag for-review was removed from gene: ANAPC1.
Tag to_be_confirmed_NHSE was removed from gene: ANAPC1.
Skeletal dysplasia v5.3 ANAPC1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 UBA2 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 UBA2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: UBA2.
Tag Q4_23_NHS_review was removed from gene: UBA2.
Skeletal dysplasia v5.3 PSMC3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PSMC3.
Skeletal dysplasia v5.3 PSMC3 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 ERI1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance updated to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 FBXW11 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: FBXW11.
Tag Q4_23_NHS_review was removed from gene: FBXW11.
Skeletal dysplasia v5.3 FBXW11 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 ERI1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ERI1.
Tag Q4_23_NHS_review was removed from gene: ERI1.
Skeletal dysplasia v5.3 AXIN1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: AXIN1.
Skeletal dysplasia v5.3 AXIN1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance updated to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 SETD5 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SETD5.
Tag Q3_23_NHS_review was removed from gene: SETD5.
Skeletal dysplasia v5.3 SETD5 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 UBA2 Achchuthan Shanmugasundram reviewed gene: UBA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v5.3 TNFRSF11A Achchuthan Shanmugasundram reviewed gene: TNFRSF11A: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v5.3 SETD5 Achchuthan Shanmugasundram commented on gene: SETD5: The rating of this gene has been updated togreenand the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 PSMC3 Achchuthan Shanmugasundram commented on gene: PSMC3: The rating of this gene has been updated togreenand the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 FBXW11 Achchuthan Shanmugasundram reviewed gene: FBXW11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v5.3 ERI1 Achchuthan Shanmugasundram commented on gene: ERI1: The rating of this gene has been updated togreenand the mode of inheritance updated to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 AXIN1 Achchuthan Shanmugasundram commented on gene: AXIN1: The rating of this gene has been updated togreenand the mode of inheritance updated to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.
Skeletal dysplasia v5.3 ANAPC1 Achchuthan Shanmugasundram reviewed gene: ANAPC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v5.2 UBA2 Achchuthan Shanmugasundram Source NHS GMS was added to UBA2.
Source Expert Review Green was added to UBA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v5.2 TNFRSF11A Achchuthan Shanmugasundram Mode of inheritance for gene TNFRSF11A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v5.2 SETD5 Achchuthan Shanmugasundram Source Expert Review Green was added to SETD5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v5.2 PSMC3 Achchuthan Shanmugasundram Source NHS GMS was added to PSMC3.
Source Expert Review Green was added to PSMC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v5.2 FBXW11 Achchuthan Shanmugasundram Source NHS GMS was added to FBXW11.
Source Expert Review Green was added to FBXW11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v5.2 ERI1 Achchuthan Shanmugasundram Source Expert Review Green was added to ERI1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v5.2 AXIN1 Achchuthan Shanmugasundram Source NHS GMS was added to AXIN1.
Source Expert Review Green was added to AXIN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v5.2 ANAPC1 Achchuthan Shanmugasundram Source NHS GMS was added to ANAPC1.
Source Expert Review Green was added to ANAPC1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal ciliopathies v4.3 KIAA0586 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand 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 and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Skeletal ciliopathies v4.3 KIAA0586 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: KIAA0586.
Skeletal ciliopathies v4.3 PMM2 Achchuthan Shanmugasundram Tag Q3_23_expert_review was removed from gene: PMM2.
Tag Q3_23_demote_red was removed from gene: PMM2.
Skeletal ciliopathies v4.3 PMM2 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated to redfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.
Skeletal ciliopathies v4.3 PMM2 Achchuthan Shanmugasundram reviewed gene: PMM2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal ciliopathies v4.3 KIAA0586 Achchuthan Shanmugasundram reviewed gene: KIAA0586: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal ciliopathies v4.2 PMM2 Achchuthan Shanmugasundram Source Expert Review Red was added to PMM2.
Source NHS GMS was added to PMM2.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Skeletal ciliopathies v4.2 KIAA0586 Achchuthan Shanmugasundram Source Expert Review Green was added to KIAA0586.
Source NHS GMS was added to KIAA0586.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb disorders v5.4 FBXW11 Achchuthan Shanmugasundram Tag Q4_21_NHS_review was removed from gene: FBXW11.
Tag Q4_23_promote_green was removed from gene: FBXW11.
Limb disorders v5.4 FBXW11 Eleanor Williams edited their review of gene: FBXW11: Added comment: The rating of this gene has been updated togreenand the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown'following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v5.3 FBXW11 Achchuthan Shanmugasundram Source NHS GMS was added to FBXW11.
Source Expert Review Green was added to FBXW11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v5.3 SLC6A20 Achchuthan Shanmugasundram Tag Q4_23_demote_red was removed from gene: SLC6A20.
Tag Q4_23_expert_review was removed from gene: SLC6A20.
Likely inborn error of metabolism - targeted testing not possible v5.3 VPS33A Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: VPS33A.
Likely inborn error of metabolism - targeted testing not possible v5.3 VPS16 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: VPS16.
Likely inborn error of metabolism - targeted testing not possible v5.3 SEC23B Achchuthan Shanmugasundram Tag Q4_23_MOI was removed from gene: SEC23B.
Likely inborn error of metabolism - targeted testing not possible v5.3 PTCD3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PTCD3.
Likely inborn error of metabolism - targeted testing not possible v5.3 PIGM Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PIGM.
Tag Q4_23_NHS_review was removed from gene: PIGM.
Likely inborn error of metabolism - targeted testing not possible v5.3 NUS1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: NUS1.
Likely inborn error of metabolism - targeted testing not possible v5.3 MRM2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MRM2.
Likely inborn error of metabolism - targeted testing not possible v5.3 LMF1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: LMF1.
Likely inborn error of metabolism - targeted testing not possible v5.3 HSPA9 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HSPA9.
Tag Q4_23_NHS_review was removed from gene: HSPA9.
Likely inborn error of metabolism - targeted testing not possible v5.3 GRN Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: GRN.
Likely inborn error of metabolism - targeted testing not possible v5.3 GPIHBP1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: GPIHBP1.
Likely inborn error of metabolism - targeted testing not possible v5.3 EDEM3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: EDEM3.
Likely inborn error of metabolism - targeted testing not possible v5.3 CTSF Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CTSF.
Likely inborn error of metabolism - targeted testing not possible v5.3 COX5A Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: COX5A.
Likely inborn error of metabolism - targeted testing not possible v5.3 ATP5E Achchuthan Shanmugasundram Tag new-gene-name was removed from gene: ATP5E.
Tag Q4_23_promote_green was removed from gene: ATP5E.
Likely inborn error of metabolism - targeted testing not possible v5.3 ACACA Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ACACA.
Tag Q4_23_NHS_review was removed from gene: ACACA.
Likely inborn error of metabolism - targeted testing not possible v5.3 VPS33A Sarah Leigh commented on gene: VPS33A: 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.
Likely inborn error of metabolism - targeted testing not possible v5.3 VPS16 Sarah Leigh commented on gene: VPS16: 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.
Likely inborn error of metabolism - targeted testing not possible v5.3 SLC6A20 Sarah Leigh commented on gene: SLC6A20: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval. Comment from GMS: 'Demotion of a green gene - disease association refuted in OMIM, as the single variant has been classified as common in gnomAD database.'
Likely inborn error of metabolism - targeted testing not possible v5.3 SEC23B Sarah Leigh reviewed gene: SEC23B: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v5.3 PTCD3 Sarah Leigh edited their review of gene: PTCD3: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v5.3 PIGM Sarah Leigh edited their review of gene: PIGM: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v5.3 NUS1 Sarah Leigh reviewed gene: NUS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Likely inborn error of metabolism - targeted testing not possible v5.3 MRM2 Sarah Leigh edited their review of gene: MRM2: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v5.3 LMF1 Sarah Leigh commented on gene: LMF1: 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.
Likely inborn error of metabolism - targeted testing not possible v5.3 HSPA9 Sarah Leigh edited their review of gene: HSPA9: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v5.3 GRN Sarah Leigh edited their review of gene: GRN: 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 mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v5.3 GPIHBP1 Sarah Leigh commented on gene: GPIHBP1: 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.
Likely inborn error of metabolism - targeted testing not possible v5.3 EDEM3 Sarah Leigh commented on gene: EDEM3: 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.
Likely inborn error of metabolism - targeted testing not possible v5.3 CTSF Sarah Leigh edited their review of gene: CTSF: 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 mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v5.3 COX5A Sarah Leigh edited their review of gene: COX5A: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v5.3 ATP5E Sarah Leigh edited their review of gene: ATP5E: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v5.3 ACACA Sarah Leigh edited their review of gene: ACACA: 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 mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v5.2 VPS33A Achchuthan Shanmugasundram Source Expert Review Green was added to VPS33A.
Source NHS GMS was added to VPS33A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v5.2 VPS16 Achchuthan Shanmugasundram Source Expert Review Green was added to VPS16.
Source NHS GMS was added to VPS16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v5.2 SLC6A20 Achchuthan Shanmugasundram Source Expert Review Red was added to SLC6A20.
Source NHS GMS was added to SLC6A20.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Likely inborn error of metabolism - targeted testing not possible v5.2 SEC23B Achchuthan Shanmugasundram Mode of inheritance for gene SEC23B was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v5.2 PTCD3 Achchuthan Shanmugasundram Source Expert Review Green was added to PTCD3.
Source NHS GMS was added to PTCD3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v5.2 PIGM Achchuthan Shanmugasundram Source Expert Review Green was added to PIGM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v5.2 NUS1 Achchuthan Shanmugasundram Source Expert Review Green was added to NUS1.
Source NHS GMS was added to NUS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v5.2 MRM2 Achchuthan Shanmugasundram Source Expert Review Green was added to MRM2.
Source NHS GMS was added to MRM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v5.2 LMF1 Achchuthan Shanmugasundram Source Expert Review Green was added to LMF1.
Source NHS GMS was added to LMF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v5.2 HSPA9 Achchuthan Shanmugasundram Source Expert Review Green was added to HSPA9.
Source NHS GMS was added to HSPA9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v5.2 GRN Achchuthan Shanmugasundram Source Expert Review Green was added to GRN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v5.2 GPIHBP1 Achchuthan Shanmugasundram Source Expert Review Green was added to GPIHBP1.
Source NHS GMS was added to GPIHBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v5.2 EDEM3 Achchuthan Shanmugasundram Source Expert Review Green was added to EDEM3.
Source NHS GMS was added to EDEM3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v5.2 CTSF Achchuthan Shanmugasundram Source Expert Review Green was added to CTSF.
Source NHS GMS was added to CTSF.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v5.2 COX5A Achchuthan Shanmugasundram Source Expert Review Green was added to COX5A.
Source NHS GMS was added to COX5A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v5.2 ATP5E Achchuthan Shanmugasundram Source Expert Review Green was added to ATP5E.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v5.2 ACACA Achchuthan Shanmugasundram Source Expert Review Green was added to ACACA.
Source NHS GMS was added to ACACA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital disorders of glycosylation v5.3 SEC23B Achchuthan Shanmugasundram Tag Q4_23_MOI was removed from gene: SEC23B.
Congenital disorders of glycosylation v5.3 PIGM Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PIGM.
Congenital disorders of glycosylation v5.3 SEC23B Sarah Leigh edited their review of gene: SEC23B: Added comment: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital disorders of glycosylation v5.3 PIGM Sarah Leigh edited their review of gene: PIGM: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital disorders of glycosylation v5.2 SEC23B Achchuthan Shanmugasundram Source NHS GMS was added to SEC23B.
Mode of inheritance for gene SEC23B was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Congenital disorders of glycosylation v5.2 PIGM Achchuthan Shanmugasundram Source Expert Review Green was added to PIGM.
Source NHS GMS was added to PIGM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 SPI1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SPI1.
Tag Q4_23_NHS_review was removed from gene: SPI1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 TRAF3IP2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TRAF3IP2.
Tag Q4_23_NHS_review was removed from gene: TRAF3IP2.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 TFRC Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TFRC.
Tag Q4_23_NHS_review was removed from gene: TFRC.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 STAT6 Achchuthan Shanmugasundram Tag watchlist was removed from gene: STAT6.
Tag Q4_23_promote_green was removed from gene: STAT6.
Tag treatable tag was added to gene: STAT6.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 SEC61A1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SEC61A1.
Tag Q4_23_NHS_review was removed from gene: SEC61A1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 SAMD9L Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SAMD9L.
Tag Q4_23_NHS_review was removed from gene: SAMD9L.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 RELA Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: RELA.
Tag Q4_23_NHS_review was removed from gene: RELA.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 REL Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: REL.
Tag Q4_23_NHS_review was removed from gene: REL.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 RANBP2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: RANBP2.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 PTPN2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PTPN2.
Tag Q4_23_NHS_review was removed from gene: PTPN2.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 PSMB10 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PSMB10.
Tag Q4_23_NHS_review was removed from gene: PSMB10.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 POLD1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: POLD1.
Tag Q4_23_NHS_review was removed from gene: POLD1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 NLRP1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: NLRP1.
Tag Q4_23_NHS_review was removed from gene: NLRP1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 NFAT5 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: NFAT5.
Tag Q4_23_NHS_review was removed from gene: NFAT5.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 MECOM Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MECOM.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 MCTS1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MCTS1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 LYN Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: LYN.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 JAK1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: JAK1.
Tag Q4_23_NHS_review was removed from gene: JAK1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 IRF4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: IRF4.
Tag Q4_23_NHS_review was removed from gene: IRF4.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 IRF2BP2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: IRF2BP2.
Tag Q4_23_NHS_review was removed from gene: IRF2BP2.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 IL23R Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: IL23R.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 HYOU1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HYOU1.
Tag Q4_23_NHS_review was removed from gene: HYOU1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 HMOX1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HMOX1.
Tag Q4_23_NHS_review was removed from gene: HMOX1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 DUT Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: DUT.
Tag Q4_23_NHS_review was removed from gene: DUT.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CXCR2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CXCR2.
Tag Q4_23_NHS_review was removed from gene: CXCR2.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CR2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CR2.
Tag Q4_23_NHS_review was removed from gene: CR2.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CD81 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CD81.
Tag Q4_23_NHS_review was removed from gene: CD81.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CD4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CD4.
Tag Q4_23_NHS_review was removed from gene: CD4.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CBLB Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CBLB.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 AICDA Achchuthan Shanmugasundram Tag Q4_23_MOI was removed from gene: AICDA.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 OTULIN Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: OTULIN.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 DOCK11 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DOCK11.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 DIAPH1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DIAPH1.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 ARPC5 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ARPC5.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 DCLRE1B Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: DCLRE1B.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 STAT5B Achchuthan Shanmugasundram Tag for-review was removed from gene: STAT5B.
Tag to_be_confirmed_NHSE was removed from gene: STAT5B.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 TRAF3IP2 Sarah Leigh reviewed gene: TRAF3IP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 TFRC Sarah Leigh reviewed gene: TFRC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 STAT6 Sarah Leigh reviewed gene: STAT6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 STAT5B Sarah Leigh reviewed gene: STAT5B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 SPI1 Sarah Leigh reviewed gene: SPI1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 SEC61A1 Sarah Leigh reviewed gene: SEC61A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 SAMD9L Sarah Leigh reviewed gene: SAMD9L: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 RELA Sarah Leigh reviewed gene: RELA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 REL Sarah Leigh reviewed gene: REL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 RANBP2 Sarah Leigh reviewed gene: RANBP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 PTPN2 Sarah Leigh reviewed gene: PTPN2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 PSMB10 Sarah Leigh edited their review of gene: PSMB10: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 POLD1 Sarah Leigh reviewed gene: POLD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 OTULIN Sarah Leigh edited their review of gene: OTULIN: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 NLRP1 Sarah Leigh reviewed gene: NLRP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 NFAT5 Sarah Leigh edited their review of gene: NFAT5: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 MECOM Sarah Leigh reviewed gene: MECOM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 MCTS1 Sarah Leigh reviewed gene: MCTS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 LYN Sarah Leigh reviewed gene: LYN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 JAK1 Sarah Leigh reviewed gene: JAK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 IRF4 Sarah Leigh reviewed gene: IRF4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 IRF2BP2 Sarah Leigh reviewed gene: IRF2BP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 IL23R Sarah Leigh reviewed gene: IL23R: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 HYOU1 Sarah Leigh reviewed gene: HYOU1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 HMOX1 Sarah Leigh reviewed gene: HMOX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 DUT Sarah Leigh reviewed gene: DUT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 DOCK11 Sarah Leigh reviewed gene: DOCK11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 DIAPH1 Sarah Leigh reviewed gene: DIAPH1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 DCLRE1B Sarah Leigh reviewed gene: DCLRE1B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CXCR2 Sarah Leigh reviewed gene: CXCR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CR2 Sarah Leigh edited their review of gene: CR2: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CD81 Sarah Leigh reviewed gene: CD81: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CD4 Sarah Leigh reviewed gene: CD4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 CBLB Sarah Leigh reviewed gene: CBLB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 ARPC5 Sarah Leigh reviewed gene: ARPC5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.3 AICDA Sarah Leigh reviewed gene: AICDA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 TRAF3IP2 Achchuthan Shanmugasundram Source NHS GMS was added to TRAF3IP2.
Source Expert Review Green was added to TRAF3IP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 TFRC Achchuthan Shanmugasundram Source NHS GMS was added to TFRC.
Source Expert Review Green was added to TFRC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 STAT6 Achchuthan Shanmugasundram Source NHS GMS was added to STAT6.
Source Expert Review Green was added to STAT6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 STAT5B Achchuthan Shanmugasundram Mode of inheritance for gene STAT5B was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 SPI1 Achchuthan Shanmugasundram Source NHS GMS was added to SPI1.
Source Expert Review Green was added to SPI1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 SEC61A1 Achchuthan Shanmugasundram Source NHS GMS was added to SEC61A1.
Source Expert Review Green was added to SEC61A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 SAMD9L Achchuthan Shanmugasundram Source Expert Review Green was added to SAMD9L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 RELA Achchuthan Shanmugasundram Source NHS GMS was added to RELA.
Source Expert Review Green was added to RELA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 REL Achchuthan Shanmugasundram Source NHS GMS was added to REL.
Source Expert Review Green was added to REL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 RANBP2 Achchuthan Shanmugasundram Source Expert Review Green was added to RANBP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 PTPN2 Achchuthan Shanmugasundram Source NHS GMS was added to PTPN2.
Source Expert Review Green was added to PTPN2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 PSMB10 Achchuthan Shanmugasundram Source NHS GMS was added to PSMB10.
Source Expert Review Green was added to PSMB10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 POLD1 Achchuthan Shanmugasundram Source NHS GMS was added to POLD1.
Source Expert Review Green was added to POLD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 OTULIN Achchuthan Shanmugasundram Mode of inheritance for gene OTULIN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 NLRP1 Achchuthan Shanmugasundram Source Expert Review Green was added to NLRP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 NFAT5 Achchuthan Shanmugasundram Source NHS GMS was added to NFAT5.
Source Expert Review Green was added to NFAT5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 MECOM Achchuthan Shanmugasundram Source NHS GMS was added to MECOM.
Source Expert Review Green was added to MECOM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 MCTS1 Achchuthan Shanmugasundram Source NHS GMS was added to MCTS1.
Source Expert Review Green was added to MCTS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 LYN Achchuthan Shanmugasundram Source NHS GMS was added to LYN.
Source Expert Review Green was added to LYN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 JAK1 Achchuthan Shanmugasundram Source NHS GMS was added to JAK1.
Source Expert Review Green was added to JAK1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 IRF4 Achchuthan Shanmugasundram Source NHS GMS was added to IRF4.
Source Expert Review Green was added to IRF4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 IRF2BP2 Achchuthan Shanmugasundram Source NHS GMS was added to IRF2BP2.
Source Expert Review Green was added to IRF2BP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 IL23R Achchuthan Shanmugasundram Source NHS GMS was added to IL23R.
Source Expert Review Green was added to IL23R.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 HYOU1 Achchuthan Shanmugasundram Source NHS GMS was added to HYOU1.
Source Expert Review Green was added to HYOU1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 HMOX1 Achchuthan Shanmugasundram Source NHS GMS was added to HMOX1.
Source Expert Review Green was added to HMOX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 DUT Achchuthan Shanmugasundram Source NHS GMS was added to DUT.
Source Expert Review Green was added to DUT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 DOCK11 Achchuthan Shanmugasundram Source NHS GMS was added to DOCK11.
Source Expert Review Green was added to DOCK11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 DIAPH1 Achchuthan Shanmugasundram Source NHS GMS was added to DIAPH1.
Source Expert Review Green was added to DIAPH1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 DCLRE1B Achchuthan Shanmugasundram Source Expert Review Amber was added to DCLRE1B.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 CXCR2 Achchuthan Shanmugasundram Source NHS GMS was added to CXCR2.
Source Expert Review Green was added to CXCR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 CR2 Achchuthan Shanmugasundram Source NHS GMS was added to CR2.
Source Expert Review Green was added to CR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 CD81 Achchuthan Shanmugasundram Source NHS GMS was added to CD81.
Source Expert Review Green was added to CD81.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 CD4 Achchuthan Shanmugasundram Source NHS GMS was added to CD4.
Source Expert Review Green was added to CD4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 CBLB Achchuthan Shanmugasundram Source NHS GMS was added to CBLB.
Source Expert Review Green was added to CBLB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 ARPC5 Achchuthan Shanmugasundram Source NHS GMS was added to ARPC5.
Source Expert Review Green was added to ARPC5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v5.2 AICDA Achchuthan Shanmugasundram Mode of inheritance for gene AICDA was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Thalassaemia and other haemoglobinopathies v1.9 HBG2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HBG2.
Thalassaemia and other haemoglobinopathies v1.9 HBG1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HBG1.
Thalassaemia and other haemoglobinopathies v1.9 HBA2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HBA2.
Thalassaemia and other haemoglobinopathies v1.9 HBG2 Sarah Leigh reviewed gene: HBG2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Thalassaemia and other haemoglobinopathies v1.9 HBG1 Sarah Leigh reviewed gene: HBG1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Thalassaemia and other haemoglobinopathies v1.9 HBA2 Sarah Leigh reviewed gene: HBA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Thalassaemia and other haemoglobinopathies v1.8 HBG2 Achchuthan Shanmugasundram Source Expert Review Green was added to HBG2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Thalassaemia and other haemoglobinopathies v1.8 HBG1 Achchuthan Shanmugasundram Source Expert Review Green was added to HBG1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Thalassaemia and other haemoglobinopathies v1.8 HBA2 Achchuthan Shanmugasundram Source Expert Review Green was added to HBA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Haemoglobinopathy trait or carrier testing v1.9 HBG2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HBG2.
Haemoglobinopathy trait or carrier testing v1.9 HBG1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HBG1.
Haemoglobinopathy trait or carrier testing v1.9 HBA2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HBA2.
Haemoglobinopathy trait or carrier testing v1.9 HBG2 Sarah Leigh reviewed gene: HBG2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Haemoglobinopathy trait or carrier testing v1.9 HBG1 Sarah Leigh reviewed gene: HBG1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Haemoglobinopathy trait or carrier testing v1.9 HBA2 Sarah Leigh reviewed gene: HBA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Haemoglobinopathy trait or carrier testing v1.8 HBG2 Achchuthan Shanmugasundram Source Expert Review Green was added to HBG2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Haemoglobinopathy trait or carrier testing v1.8 HBG1 Achchuthan Shanmugasundram Source Expert Review Green was added to HBG1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Haemoglobinopathy trait or carrier testing v1.8 HBA2 Achchuthan Shanmugasundram Source Expert Review Green was added to HBA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Neonatal diabetes v4.6 ONECUT1 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: ONECUT1.
Neonatal diabetes v4.6 CNOT1 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: CNOT1.
Neonatal diabetes v4.6 ONECUT1 Sarah Leigh reviewed gene: ONECUT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Neonatal diabetes v4.6 CNOT1 Sarah Leigh reviewed gene: CNOT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Neonatal diabetes v4.5 ONECUT1 Achchuthan Shanmugasundram Source NHS GMS was added to ONECUT1.
Source Expert Review Green was added to ONECUT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Neonatal diabetes v4.5 CNOT1 Achchuthan Shanmugasundram Source NHS GMS was added to CNOT1.
Source Expert Review Green was added to CNOT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.52 AKT2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: AKT2.
Tag Q3_23_NHS_review was removed from gene: AKT2.
Lipodystrophy - childhood onset v4.52 WRN Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: 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.
Lipodystrophy - childhood onset v4.52 WRN Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: WRN.
Tag Q3_23_NHS_review was removed from gene: WRN.
Lipodystrophy - childhood onset v4.52 PSMB8 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PSMB8.
Tag Q3_23_NHS_review was removed from gene: PSMB8.
Lipodystrophy - childhood onset v4.52 PSMB8 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: 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.
Lipodystrophy - childhood onset v4.52 PSMB4 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: 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.
Lipodystrophy - childhood onset v4.52 PSMB4 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PSMB4.
Tag Q3_23_NHS_review was removed from gene: PSMB4.
Lipodystrophy - childhood onset v4.52 POC1A Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: POC1A.
Tag Q3_23_NHS_review was removed from gene: POC1A.
Lipodystrophy - childhood onset v4.52 POC1A Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: 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.
Lipodystrophy - childhood onset v4.52 PIK3R1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toMONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; to: 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.
Lipodystrophy - childhood onset v4.52 PIK3R1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PIK3R1.
Tag Q3_23_NHS_review was removed from gene: PIK3R1.
Lipodystrophy - childhood onset v4.52 PCYT1A Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: 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.
Lipodystrophy - childhood onset v4.52 PCYT1A Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PCYT1A.
Tag Q3_23_NHS_review was removed from gene: PCYT1A.
Lipodystrophy - childhood onset v4.52 PCNT Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PCNT.
Tag Q3_23_NHS_review was removed from gene: PCNT.
Lipodystrophy - childhood onset v4.52 PCNT Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: 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.
Lipodystrophy - childhood onset v4.52 MFN2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: MFN2.
Tag Q3_23_NHS_review was removed from gene: MFN2.
Lipodystrophy - childhood onset v4.52 MFN2 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: 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.
Lipodystrophy - childhood onset v4.52 EPHX1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toMONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; to: 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.
Lipodystrophy - childhood onset v4.52 EPHX1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: EPHX1.
Tag Q3_23_NHS_review was removed from gene: EPHX1.
Lipodystrophy - childhood onset v4.52 BLM Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: BLM.
Tag Q3_23_NHS_review was removed from gene: BLM.
Lipodystrophy - childhood onset v4.52 BLM Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: 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.
Lipodystrophy - childhood onset v4.52 ALMS1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ALMS1.
Tag Q3_23_NHS_review was removed from gene: ALMS1.
Lipodystrophy - childhood onset v4.52 ALMS1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: 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.
Lipodystrophy - childhood onset v4.52 WRN Achchuthan Shanmugasundram commented on gene: WRN: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 PSMB8 Achchuthan Shanmugasundram commented on gene: PSMB8: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 PSMB4 Achchuthan Shanmugasundram commented on gene: PSMB4: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 POC1A Achchuthan Shanmugasundram commented on gene: POC1A: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 PIK3R1 Achchuthan Shanmugasundram commented on gene: PIK3R1: The rating of this gene has been updated toGreenand the mode of inheritance set toMONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 PCYT1A Achchuthan Shanmugasundram commented on gene: PCYT1A: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 PCNT Achchuthan Shanmugasundram commented on gene: PCNT: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 MFN2 Achchuthan Shanmugasundram commented on gene: MFN2: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 EPHX1 Achchuthan Shanmugasundram commented on gene: EPHX1: The rating of this gene has been updated toGreenand the mode of inheritance set toMONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 BLM Achchuthan Shanmugasundram commented on gene: BLM: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 ALMS1 Achchuthan Shanmugasundram commented on gene: ALMS1: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Lipodystrophy - childhood onset v4.52 AKT2 Achchuthan Shanmugasundram edited their review of gene: AKT2: Added comment: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. Comment from GMS: 'Should be amber. Another family is needed for AKT2 for this to be upgraded to Green. The two variants used as evidence, p.Arg467Trp and p.Arg208Lys, far too common in gnomAD to be causing a rare AD disorder.'; Changed rating: AMBER
Lipodystrophy - childhood onset v4.51 WRN Achchuthan Shanmugasundram Source Expert Review Green was added to WRN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 PSMB8 Achchuthan Shanmugasundram Source Expert Review Green was added to PSMB8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 PSMB4 Achchuthan Shanmugasundram Source Expert Review Green was added to PSMB4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 POC1A Achchuthan Shanmugasundram Source Expert Review Green was added to POC1A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 PIK3R1 Achchuthan Shanmugasundram Source Expert Review Green was added to PIK3R1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 PCYT1A Achchuthan Shanmugasundram Source Expert Review Green was added to PCYT1A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 PCNT Achchuthan Shanmugasundram Source Expert Review Green was added to PCNT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 MFN2 Achchuthan Shanmugasundram Source Expert Review Green was added to MFN2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 EPHX1 Achchuthan Shanmugasundram Source Expert Review Green was added to EPHX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 BLM Achchuthan Shanmugasundram Source Expert Review Green was added to BLM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Lipodystrophy - childhood onset v4.51 ALMS1 Achchuthan Shanmugasundram Source Expert Review Green was added to ALMS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v4.3 NOTCH3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: NOTCH3.
Tag Q4_23_expert_review was removed from gene: NOTCH3.
Paediatric disorders - additional genes v4.3 TAB2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TAB2.
Paediatric disorders - additional genes v4.3 TAB2 Sarah Leigh edited their review of gene: TAB2: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric disorders - additional genes v4.3 NOTCH3 Sarah Leigh reviewed gene: NOTCH3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paediatric disorders - additional genes v4.2 TAB2 Achchuthan Shanmugasundram Source Expert Review Green was added to TAB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v4.2 NOTCH3 Achchuthan Shanmugasundram Source Expert Review Green was added to NOTCH3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.11 FAM111A Achchuthan Shanmugasundram Tag Q4_23_demote_red was removed from gene: FAM111A.
Tag Q4_23_NHS_review was removed from gene: FAM111A.
Tag Q4_23_expert_review was removed from gene: FAM111A.
Intellectual disability v6.11 DPP6 Achchuthan Shanmugasundram Tag Q4_23_demote_red was removed from gene: DPP6.
Tag Q4_23_NHS_review was removed from gene: DPP6.
Tag Q4_23_expert_review was removed from gene: DPP6.
Intellectual disability v6.11 ZBTB47 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ZBTB47.
Intellectual disability v6.11 VCP Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: VCP.
Intellectual disability v6.11 TEFM Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TEFM.
Intellectual disability v6.11 SRSF1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SRSF1.
Intellectual disability v6.11 SHQ1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SHQ1.
Intellectual disability v6.11 RPL10 Achchuthan Shanmugasundram Tag Q4_23_MOI was removed from gene: RPL10.
Intellectual disability v6.11 RELN Achchuthan Shanmugasundram Tag Q4_23_MOI was removed from gene: RELN.
Intellectual disability v6.11 RBL2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: RBL2.
Tag Q4_23_NHS_review was removed from gene: RBL2.
Intellectual disability v6.11 RAP1B Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: RAP1B.
Intellectual disability v6.11 MYH10 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MYH10.
Intellectual disability v6.11 MAST4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MAST4.
Intellectual disability v6.11 KMT2B Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: KMT2B.
Intellectual disability v6.11 ERI1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ERI1.
Intellectual disability v6.11 COX11 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: COX11.
Intellectual disability v6.11 CLDN11 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLDN11.
Intellectual disability v6.11 CLCN6 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLCN6.
Intellectual disability v6.11 CDK16 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CDK16.
Tag Q4_23_NHS_review was removed from gene: CDK16.
Intellectual disability v6.11 CASP2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CASP2.
Intellectual disability v6.11 ARF3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ARF3.
Intellectual disability v6.11 ACACA Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ACACA.
Intellectual disability v6.11 FAR1 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: FAR1.
Intellectual disability v6.11 U2AF2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: U2AF2.
Tag Q3_23_NHS_review was removed from gene: U2AF2.
Intellectual disability v6.11 TTI1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TTI1.
Intellectual disability v6.11 TSPOAP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TSPOAP1.
Intellectual disability v6.11 TMEM63B Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TMEM63B.
Intellectual disability v6.11 SLC30A9 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SLC30A9.
Intellectual disability v6.11 RPS6KA3 Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: RPS6KA3.
Intellectual disability v6.11 RAB5C Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: RAB5C.
Intellectual disability v6.11 PSMC3 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PSMC3.
Intellectual disability v6.11 PPP1R3F Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PPP1R3F.
Intellectual disability v6.11 PIP5K1C Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PIP5K1C.
Intellectual disability v6.11 PABPC1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PABPC1.
Tag Q3_23_MOI was removed from gene: PABPC1.
Tag Q3_23_phenotype was removed from gene: PABPC1.
Intellectual disability v6.11 NR2F2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: NR2F2.
Tag Q3_23_NHS_review was removed from gene: NR2F2.
Intellectual disability v6.11 NEUROG1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: NEUROG1.
Tag Q3_23_NHS_review was removed from gene: NEUROG1.
Intellectual disability v6.11 LETM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: LETM1.
Tag Q3_23_MOI was removed from gene: LETM1.
Intellectual disability v6.11 KCNH5 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: KCNH5.
Intellectual disability v6.11 ESAM Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ESAM.
Tag Q3_23_NHS_review was removed from gene: ESAM.
Intellectual disability v6.11 EIF4A2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: EIF4A2.
Intellectual disability v6.11 DHX9 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DHX9.
Intellectual disability v6.11 DAGLA Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DAGLA.
Intellectual disability v6.11 CNOT9 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CNOT9.
Intellectual disability v6.11 ATP6V0C Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ATP6V0C.
Tag Q3_23_NHS_review was removed from gene: ATP6V0C.
Intellectual disability v6.11 AGTPBP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: AGTPBP1.
Intellectual disability v6.11 ZBTB47 Sarah Leigh edited their review of gene: ZBTB47: 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 mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 VCP Sarah Leigh reviewed gene: VCP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 U2AF2 Sarah Leigh reviewed gene: U2AF2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 TTI1 Sarah Leigh commented on gene: TTI1: 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.
Intellectual disability v6.11 TSPOAP1 Sarah Leigh edited their review of gene: TSPOAP1: 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 mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 TMEM63B Sarah Leigh reviewed gene: TMEM63B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 TEFM Sarah Leigh reviewed gene: TEFM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 SRSF1 Sarah Leigh reviewed gene: SRSF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 SLC30A9 Sarah Leigh edited their review of gene: SLC30A9: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v6.11 SHQ1 Sarah Leigh edited their review of gene: SHQ1: 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 mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 RPS6KA3 Sarah Leigh reviewed gene: RPS6KA3: Rating: GREEN; Mode of pathogenicity: ; 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)
Intellectual disability v6.11 RPL10 Sarah Leigh commented on gene: RPL10: The mode of inheritance of this gene has been updated to X-LINKED: hemizygous mutation in males, biallelic mutations in females following NHS Genomic Medicine Service approval.
Intellectual disability v6.11 RELN Sarah Leigh reviewed gene: RELN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v6.11 RBL2 Sarah Leigh commented on gene: RBL2: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Intellectual disability v6.11 RAP1B Sarah Leigh reviewed gene: RAP1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 RAB5C Sarah Leigh reviewed gene: RAB5C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 PSMC3 Sarah Leigh reviewed gene: PSMC3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 PPP1R3F Sarah Leigh reviewed gene: PPP1R3F: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v6.11 PIP5K1C Sarah Leigh reviewed gene: PIP5K1C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 PABPC1 Sarah Leigh edited their review of gene: PABPC1: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v6.11 NR2F2 Sarah Leigh reviewed gene: NR2F2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 NEUROG1 Sarah Leigh reviewed gene: NEUROG1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 MYH10 Sarah Leigh reviewed gene: MYH10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 MAST4 Sarah Leigh edited their review of gene: MAST4: 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 mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 LETM1 Sarah Leigh commented on gene: LETM1: 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.
Intellectual disability v6.11 KMT2B Sarah Leigh reviewed gene: KMT2B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v6.11 KCNH5 Sarah Leigh reviewed gene: KCNH5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 FAR1 Sarah Leigh commented on gene: FAR1: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Intellectual disability v6.11 FAM111A Sarah Leigh commented on gene: FAM111A: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.
Intellectual disability v6.11 ESAM Sarah Leigh reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 ERI1 Sarah Leigh reviewed gene: ERI1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 EIF4A2 Sarah Leigh commented on gene: EIF4A2: The rating of this gene has been updated to Green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval
Intellectual disability v6.11 DPP6 Sarah Leigh reviewed gene: DPP6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v6.11 DHX9 Sarah Leigh reviewed gene: DHX9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 DAGLA Sarah Leigh reviewed gene: DAGLA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 COX11 Sarah Leigh edited their review of gene: COX11: 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 mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 CNOT9 Sarah Leigh reviewed gene: CNOT9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 CLDN11 Sarah Leigh reviewed gene: CLDN11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 CLCN6 Sarah Leigh commented on gene: CLCN6: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Intellectual disability v6.11 CDK16 Sarah Leigh commented on gene: CDK16: The rating of this gene has been updated to green and the mode of inheritance updated to X-LINKED: hemizygous mutation in males, biallelic mutations in females following NHS Genomic Medicine Service approval.
Intellectual disability v6.11 CASP2 Sarah Leigh edited their review of gene: CASP2: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v6.11 ATP6V0C Sarah Leigh reviewed gene: ATP6V0C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 ARF3 Sarah Leigh reviewed gene: ARF3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v6.11 AGTPBP1 Sarah Leigh reviewed gene: AGTPBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 ACACA Sarah Leigh edited their review of gene: ACACA: 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 mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.10 ZBTB47 Achchuthan Shanmugasundram Source Expert Review Green was added to ZBTB47.
Source NHS GMS was added to ZBTB47.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 VCP Achchuthan Shanmugasundram Source Expert Review Green was added to VCP.
Source NHS GMS was added to VCP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 U2AF2 Achchuthan Shanmugasundram Source Expert Review Green was added to U2AF2.
Source NHS GMS was added to U2AF2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 TTI1 Achchuthan Shanmugasundram Source Expert Review Green was added to TTI1.
Source NHS GMS was added to TTI1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 TSPOAP1 Achchuthan Shanmugasundram Source Expert Review Green was added to TSPOAP1.
Source NHS GMS was added to TSPOAP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 TMEM63B Achchuthan Shanmugasundram Source Expert Review Green was added to TMEM63B.
Source NHS GMS was added to TMEM63B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 TEFM Achchuthan Shanmugasundram Source Expert Review Green was added to TEFM.
Source NHS GMS was added to TEFM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 SRSF1 Achchuthan Shanmugasundram Source Expert Review Green was added to SRSF1.
Source NHS GMS was added to SRSF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 SLC30A9 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC30A9.
Source NHS GMS was added to SLC30A9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 SHQ1 Achchuthan Shanmugasundram Source Expert Review Green was added to SHQ1.
Source NHS GMS was added to SHQ1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 RPS6KA3 Achchuthan Shanmugasundram Source NHS GMS was added to RPS6KA3.
Mode of inheritance for gene RPS6KA3 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v6.10 RPL10 Achchuthan Shanmugasundram Source NHS GMS was added to RPL10.
Mode of inheritance for gene RPL10 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v6.10 RELN Achchuthan Shanmugasundram Source NHS GMS was added to RELN.
Mode of inheritance for gene RELN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v6.10 RBL2 Achchuthan Shanmugasundram Source Expert Review Green was added to RBL2.
Source NHS GMS was added to RBL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 RAP1B Achchuthan Shanmugasundram Source Expert Review Green was added to RAP1B.
Source NHS GMS was added to RAP1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 RAB5C Achchuthan Shanmugasundram Source Expert Review Green was added to RAB5C.
Source NHS GMS was added to RAB5C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 PSMC3 Achchuthan Shanmugasundram Source Expert Review Green was added to PSMC3.
Source NHS GMS was added to PSMC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 PPP1R3F Achchuthan Shanmugasundram Source Expert Review Green was added to PPP1R3F.
Source NHS GMS was added to PPP1R3F.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 PIP5K1C Achchuthan Shanmugasundram Source Expert Review Green was added to PIP5K1C.
Source NHS GMS was added to PIP5K1C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 PABPC1 Achchuthan Shanmugasundram Source Expert Review Green was added to PABPC1.
Source NHS GMS was added to PABPC1.
Mode of inheritance for gene PABPC1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 NR2F2 Achchuthan Shanmugasundram Source Expert Review Green was added to NR2F2.
Source NHS GMS was added to NR2F2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 NEUROG1 Achchuthan Shanmugasundram Source Expert Review Green was added to NEUROG1.
Source NHS GMS was added to NEUROG1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 MYH10 Achchuthan Shanmugasundram Source Expert Review Green was added to MYH10.
Source NHS GMS was added to MYH10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 MAST4 Achchuthan Shanmugasundram Source Expert Review Green was added to MAST4.
Source NHS GMS was added to MAST4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 LETM1 Achchuthan Shanmugasundram Source Expert Review Green was added to LETM1.
Source NHS GMS was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 KMT2B Achchuthan Shanmugasundram Source Expert Review Green was added to KMT2B.
Source NHS GMS was added to KMT2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 KCNH5 Achchuthan Shanmugasundram Source Expert Review Green was added to KCNH5.
Source NHS GMS was added to KCNH5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 FAR1 Achchuthan Shanmugasundram Source NHS GMS was added to FAR1.
Mode of inheritance for gene FAR1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability v6.10 FAM111A Achchuthan Shanmugasundram Source Expert Review Red was added to FAM111A.
Source NHS GMS was added to FAM111A.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Intellectual disability v6.10 ESAM Achchuthan Shanmugasundram Source Expert Review Green was added to ESAM.
Source NHS GMS was added to ESAM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 ERI1 Achchuthan Shanmugasundram Source Expert Review Green was added to ERI1.
Source NHS GMS was added to ERI1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 EIF4A2 Achchuthan Shanmugasundram Source Expert Review Green was added to EIF4A2.
Source NHS GMS was added to EIF4A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 DPP6 Achchuthan Shanmugasundram Source Expert Review Red was added to DPP6.
Source NHS GMS was added to DPP6.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Intellectual disability v6.10 DHX9 Achchuthan Shanmugasundram Source Expert Review Green was added to DHX9.
Source NHS GMS was added to DHX9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 DAGLA Achchuthan Shanmugasundram Source Expert Review Green was added to DAGLA.
Source NHS GMS was added to DAGLA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 COX11 Achchuthan Shanmugasundram Source Expert Review Green was added to COX11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 CNOT9 Achchuthan Shanmugasundram Source Expert Review Green was added to CNOT9.
Source NHS GMS was added to CNOT9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 CLDN11 Achchuthan Shanmugasundram Source Expert Review Green was added to CLDN11.
Source NHS GMS was added to CLDN11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 CLCN6 Achchuthan Shanmugasundram Source Expert Review Green was added to CLCN6.
Source NHS GMS was added to CLCN6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 CDK16 Achchuthan Shanmugasundram Source Expert Review Green was added to CDK16.
Source NHS GMS was added to CDK16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 CASP2 Achchuthan Shanmugasundram Source Expert Review Green was added to CASP2.
Source NHS GMS was added to CASP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 ATP6V0C Achchuthan Shanmugasundram Source Expert Review Green was added to ATP6V0C.
Source NHS GMS was added to ATP6V0C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 ARF3 Achchuthan Shanmugasundram Source Expert Review Green was added to ARF3.
Source NHS GMS was added to ARF3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 AGTPBP1 Achchuthan Shanmugasundram Source Expert Review Green was added to AGTPBP1.
Source NHS GMS was added to AGTPBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 ACACA Achchuthan Shanmugasundram Source Expert Review Green was added to ACACA.
Source NHS GMS was added to ACACA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Inherited polyposis and early onset colorectal cancer - germline testing v2.11 GREM1 Achchuthan Shanmugasundram reviewed gene: GREM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Inherited polyposis and early onset colorectal cancer - germline testing v2.11 GREM1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: GREM1.
Tag Q4_23_NHS_review was removed from gene: GREM1.
Inherited polyposis and early onset colorectal cancer - germline testing v2.11 GREM1 Achchuthan Shanmugasundram Source Expert Review Green was added to GREM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v4.3 SLC22A5 Achchuthan Shanmugasundram Tag Q4_23_MOI was removed from gene: SLC22A5.
Paediatric or syndromic cardiomyopathy v4.3 TAB2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TAB2.
Paediatric or syndromic cardiomyopathy v4.3 LETM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: LETM1.
Tag Q3_23_MOI was removed from gene: LETM1.
Paediatric or syndromic cardiomyopathy v4.3 LDB3 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: LDB3.
Paediatric or syndromic cardiomyopathy v4.3 ELAC2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ELAC2.
Tag Q3_23_NHS_review was removed from gene: ELAC2.
Paediatric or syndromic cardiomyopathy v4.3 CAP2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CAP2.
Paediatric or syndromic cardiomyopathy v4.3 TAB2 Sarah Leigh edited their review of gene: TAB2: 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; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric or syndromic cardiomyopathy v4.3 SLC22A5 Sarah Leigh commented on gene: SLC22A5: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Paediatric or syndromic cardiomyopathy v4.3 LETM1 Sarah Leigh commented on gene: LETM1: 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.
Paediatric or syndromic cardiomyopathy v4.3 LDB3 Sarah Leigh reviewed gene: LDB3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy v4.3 ELAC2 Sarah Leigh reviewed gene: ELAC2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy v4.3 CAP2 Sarah Leigh reviewed gene: CAP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy v4.2 TAB2 Achchuthan Shanmugasundram Source Expert Review Green was added to TAB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v4.2 SLC22A5 Achchuthan Shanmugasundram Mode of inheritance for gene SLC22A5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy v4.2 LETM1 Achchuthan Shanmugasundram Source NHS GMS was added to LETM1.
Source Expert Review Green was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v4.2 LDB3 Achchuthan Shanmugasundram Source Expert Review Green was added to LDB3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v4.2 ELAC2 Achchuthan Shanmugasundram Source NHS GMS was added to ELAC2.
Source Expert Review Green was added to ELAC2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v4.2 CAP2 Achchuthan Shanmugasundram Source NHS GMS was added to CAP2.
Source Expert Review Green was added to CAP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v5.3 NEK8 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: NEK8.
Cystic kidney disease v5.3 SEC63 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SEC63.
Tag Q3_23_NHS_review was removed from gene: SEC63.
Cystic kidney disease v5.3 PRKCSH Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PRKCSH.
Tag Q3_23_NHS_review was removed from gene: PRKCSH.
Cystic kidney disease v5.3 SEC63 Arina Puzriakova reviewed gene: SEC63: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v5.3 PRKCSH Arina Puzriakova reviewed gene: PRKCSH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v5.3 NEK8 Arina Puzriakova reviewed gene: NEK8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v5.2 SEC63 Achchuthan Shanmugasundram Source Expert Review Green was added to SEC63.
Source NHS GMS was added to SEC63.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v5.2 PRKCSH Achchuthan Shanmugasundram Source Expert Review Green was added to PRKCSH.
Source NHS GMS was added to PRKCSH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v5.2 NEK8 Achchuthan Shanmugasundram Source Expert Review Green was added to NEK8.
Source NHS GMS was added to NEK8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.3 SLC34A3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC34A3.
Unexplained young onset end-stage renal disease v4.3 MOCOS Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MOCOS.
Unexplained young onset end-stage renal disease v4.3 YRDC Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: YRDC.
Unexplained young onset end-stage renal disease v4.3 WNK4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: WNK4.
Unexplained young onset end-stage renal disease v4.3 WDR72 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: WDR72.
Unexplained young onset end-stage renal disease v4.3 TULP3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TULP3.
Unexplained young onset end-stage renal disease v4.3 TTR Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TTR.
Unexplained young onset end-stage renal disease v4.3 TRPM6 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TRPM6.
Unexplained young onset end-stage renal disease v4.3 TPRKB Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TPRKB.
Unexplained young onset end-stage renal disease v4.3 STRADA Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: STRADA.
Unexplained young onset end-stage renal disease v4.3 SLC5A2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC5A2.
Unexplained young onset end-stage renal disease v4.3 SLC4A4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC4A4.
Unexplained young onset end-stage renal disease v4.3 SLC4A1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC4A1.
Unexplained young onset end-stage renal disease v4.3 SLC34A1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC34A1.
Unexplained young onset end-stage renal disease v4.3 SLC2A2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC2A2.
Unexplained young onset end-stage renal disease v4.3 SLC12A3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC12A3.
Unexplained young onset end-stage renal disease v4.3 SLC12A1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC12A1.
Unexplained young onset end-stage renal disease v4.3 SEC63 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SEC63.
Unexplained young onset end-stage renal disease v4.3 SCNN1G Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SCNN1G.
Unexplained young onset end-stage renal disease v4.3 SCNN1B Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SCNN1B.
Unexplained young onset end-stage renal disease v4.3 SCNN1A Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SCNN1A.
Unexplained young onset end-stage renal disease v4.3 SARS2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SARS2.
Unexplained young onset end-stage renal disease v4.3 RRAGD Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: RRAGD.
Unexplained young onset end-stage renal disease v4.3 RMND1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: RMND1.
Unexplained young onset end-stage renal disease v4.3 PRKCSH Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PRKCSH.
Unexplained young onset end-stage renal disease v4.3 PHEX Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PHEX.
Unexplained young onset end-stage renal disease v4.3 PDSS2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PDSS2.
Unexplained young onset end-stage renal disease v4.3 NR3C2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: NR3C2.
Unexplained young onset end-stage renal disease v4.3 MAGED2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MAGED2.
Unexplained young onset end-stage renal disease v4.3 LYZ Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: LYZ.
Unexplained young onset end-stage renal disease v4.3 LCAT Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: LCAT.
Unexplained young onset end-stage renal disease v4.3 KLHL3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: KLHL3.
Unexplained young onset end-stage renal disease v4.3 KCNJ16 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: KCNJ16.
Unexplained young onset end-stage renal disease v4.3 KCNJ10 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: KCNJ10.
Unexplained young onset end-stage renal disease v4.3 KCNJ1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: KCNJ1.
Unexplained young onset end-stage renal disease v4.3 IFT27 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: IFT27.
Unexplained young onset end-stage renal disease v4.3 IFT172 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: IFT172.
Unexplained young onset end-stage renal disease v4.3 IFT140 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: IFT140.
Unexplained young onset end-stage renal disease v4.3 HPRT1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HPRT1.
Unexplained young onset end-stage renal disease v4.3 HNF4A Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HNF4A.
Unexplained young onset end-stage renal disease v4.3 GSN Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: GSN.
Unexplained young onset end-stage renal disease v4.3 GON7 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: GON7.
Unexplained young onset end-stage renal disease v4.3 GNA11 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: GNA11.
Unexplained young onset end-stage renal disease v4.3 FN1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: FN1.
Unexplained young onset end-stage renal disease v4.3 FLCN Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: FLCN.
Unexplained young onset end-stage renal disease v4.3 FGA Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: FGA.
Unexplained young onset end-stage renal disease v4.3 FAM20A Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: FAM20A.
Unexplained young onset end-stage renal disease v4.3 FAH Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: FAH.
Unexplained young onset end-stage renal disease v4.3 DLG5 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: DLG5.
Unexplained young onset end-stage renal disease v4.3 DAAM2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: DAAM2.
Unexplained young onset end-stage renal disease v4.3 CYP24A1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CYP24A1.
Unexplained young onset end-stage renal disease v4.3 CUL3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CUL3.
Unexplained young onset end-stage renal disease v4.3 CNNM2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CNNM2.
Unexplained young onset end-stage renal disease v4.3 CLDN19 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLDN19.
Unexplained young onset end-stage renal disease v4.3 CLDN16 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLDN16.
Unexplained young onset end-stage renal disease v4.3 CLDN10 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLDN10.
Unexplained young onset end-stage renal disease v4.3 CLCNKB Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLCNKB.
Unexplained young onset end-stage renal disease v4.3 CFHR2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CFHR2.
Unexplained young onset end-stage renal disease v4.3 CD151 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CD151.
Unexplained young onset end-stage renal disease v4.3 CASR Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CASR.
Unexplained young onset end-stage renal disease v4.3 CA2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CA2.
Unexplained young onset end-stage renal disease v4.3 AVPR2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: AVPR2.
Unexplained young onset end-stage renal disease v4.3 ATP6V1B1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ATP6V1B1.
Unexplained young onset end-stage renal disease v4.3 ATP6V0A4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ATP6V0A4.
Unexplained young onset end-stage renal disease v4.3 ATP1A1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ATP1A1.
Unexplained young onset end-stage renal disease v4.3 APRT Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: APRT.
Unexplained young onset end-stage renal disease v4.3 APOE Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: APOE.
Unexplained young onset end-stage renal disease v4.3 APOC2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: APOC2.
Unexplained young onset end-stage renal disease v4.3 APOA2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: APOA2.
Unexplained young onset end-stage renal disease v4.3 APOA1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: APOA1.
Unexplained young onset end-stage renal disease v4.3 AP2S1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: AP2S1.
Unexplained young onset end-stage renal disease v4.3 ALG9 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ALG9.
Unexplained young onset end-stage renal disease v4.3 ALG8 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ALG8.
Unexplained young onset end-stage renal disease v4.3 ALG5 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ALG5.
Breast cancer pertinent cancer susceptibility v2.12 CDH1 Achchuthan Shanmugasundram Classified gene: CDH1 as Red List (low evidence)
Breast cancer pertinent cancer susceptibility v2.12 CDH1 Achchuthan Shanmugasundram Gene: cdh1 has been classified as Red List (Low Evidence).
Unexplained young onset end-stage renal disease v4.3 YRDC Arina Puzriakova reviewed gene: YRDC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 WNK4 Arina Puzriakova reviewed gene: WNK4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 WDR72 Arina Puzriakova reviewed gene: WDR72: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 TULP3 Arina Puzriakova reviewed gene: TULP3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 TTR Arina Puzriakova reviewed gene: TTR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Unexplained young onset end-stage renal disease v4.3 TRPM6 Arina Puzriakova reviewed gene: TRPM6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 TPRKB Arina Puzriakova reviewed gene: TPRKB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 STRADA Arina Puzriakova reviewed gene: STRADA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC5A2 Arina Puzriakova reviewed gene: SLC5A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC4A4 Arina Puzriakova reviewed gene: SLC4A4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC4A1 Arina Puzriakova reviewed gene: SLC4A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC34A3 Arina Puzriakova reviewed gene: SLC34A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC34A1 Arina Puzriakova reviewed gene: SLC34A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC2A2 Arina Puzriakova reviewed gene: SLC2A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC12A3 Arina Puzriakova reviewed gene: SLC12A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC12A1 Arina Puzriakova reviewed gene: SLC12A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SEC63 Arina Puzriakova reviewed gene: SEC63: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 SCNN1G Arina Puzriakova reviewed gene: SCNN1G: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SCNN1B Arina Puzriakova reviewed gene: SCNN1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SCNN1A Arina Puzriakova reviewed gene: SCNN1A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SARS2 Arina Puzriakova reviewed gene: SARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 RRAGD Arina Puzriakova reviewed gene: RRAGD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 RMND1 Arina Puzriakova reviewed gene: RMND1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 PRKCSH Arina Puzriakova reviewed gene: PRKCSH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 PHEX Arina Puzriakova reviewed gene: PHEX: Rating: GREEN; Mode of pathogenicity: ; 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)
Unexplained young onset end-stage renal disease v4.3 PDSS2 Arina Puzriakova reviewed gene: PDSS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 NR3C2 Arina Puzriakova reviewed gene: NR3C2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 MOCOS Arina Puzriakova reviewed gene: MOCOS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 MAGED2 Arina Puzriakova reviewed gene: MAGED2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Unexplained young onset end-stage renal disease v4.3 LYZ Arina Puzriakova reviewed gene: LYZ: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 LCAT Arina Puzriakova reviewed gene: LCAT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 KLHL3 Arina Puzriakova reviewed gene: KLHL3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 KCNJ16 Arina Puzriakova reviewed gene: KCNJ16: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 KCNJ10 Arina Puzriakova reviewed gene: KCNJ10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 KCNJ1 Arina Puzriakova reviewed gene: KCNJ1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 IFT27 Arina Puzriakova reviewed gene: IFT27: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 IFT172 Arina Puzriakova reviewed gene: IFT172: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 IFT140 Arina Puzriakova reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 HPRT1 Arina Puzriakova reviewed gene: HPRT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Unexplained young onset end-stage renal disease v4.3 HNF4A Arina Puzriakova reviewed gene: HNF4A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Unexplained young onset end-stage renal disease v4.3 GSN Arina Puzriakova reviewed gene: GSN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 GON7 Arina Puzriakova reviewed gene: GON7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 GNA11 Arina Puzriakova reviewed gene: GNA11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 FN1 Arina Puzriakova reviewed gene: FN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 FLCN Arina Puzriakova reviewed gene: FLCN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 FGA Arina Puzriakova reviewed gene: FGA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 FAM20A Arina Puzriakova reviewed gene: FAM20A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 FAH Arina Puzriakova reviewed gene: FAH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 DLG5 Arina Puzriakova reviewed gene: DLG5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 DAAM2 Arina Puzriakova reviewed gene: DAAM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CYP24A1 Arina Puzriakova reviewed gene: CYP24A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CUL3 Arina Puzriakova reviewed gene: CUL3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 CNNM2 Arina Puzriakova reviewed gene: CNNM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CLDN19 Arina Puzriakova reviewed gene: CLDN19: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CLDN16 Arina Puzriakova reviewed gene: CLDN16: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CLDN10 Arina Puzriakova reviewed gene: CLDN10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CLCNKB Arina Puzriakova reviewed gene: CLCNKB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CFHR2 Arina Puzriakova reviewed gene: CFHR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CD151 Arina Puzriakova reviewed gene: CD151: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CASR Arina Puzriakova reviewed gene: CASR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CA2 Arina Puzriakova reviewed gene: CA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 AVPR2 Arina Puzriakova reviewed gene: AVPR2: Rating: GREEN; Mode of pathogenicity: ; 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)
Unexplained young onset end-stage renal disease v4.3 ATP6V1B1 Arina Puzriakova reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 ATP6V0A4 Arina Puzriakova reviewed gene: ATP6V0A4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 ATP1A1 Arina Puzriakova reviewed gene: ATP1A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 APRT Arina Puzriakova reviewed gene: APRT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 APOE Arina Puzriakova reviewed gene: APOE: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 APOC2 Arina Puzriakova reviewed gene: APOC2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 APOA2 Arina Puzriakova reviewed gene: APOA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 APOA1 Arina Puzriakova reviewed gene: APOA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 AP2S1 Arina Puzriakova reviewed gene: AP2S1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 ALG9 Arina Puzriakova reviewed gene: ALG9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 ALG8 Arina Puzriakova reviewed gene: ALG8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Unexplained young onset end-stage renal disease v4.3 ALG5 Arina Puzriakova reviewed gene: ALG5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Unexplained young onset end-stage renal disease v4.2 YRDC Achchuthan Shanmugasundram Source Expert Review Green was added to YRDC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 WNK4 Achchuthan Shanmugasundram Source Expert Review Green was added to WNK4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 WDR72 Achchuthan Shanmugasundram Source Expert Review Green was added to WDR72.
Source NHS GMS was added to WDR72.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 TULP3 Achchuthan Shanmugasundram Source Expert Review Green was added to TULP3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 TTR Achchuthan Shanmugasundram Source Expert Review Green was added to TTR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 TRPM6 Achchuthan Shanmugasundram Source Expert Review Green was added to TRPM6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 TPRKB Achchuthan Shanmugasundram Source Expert Review Green was added to TPRKB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 STRADA Achchuthan Shanmugasundram Source Expert Review Green was added to STRADA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC5A2 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC5A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC4A4 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC4A4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC4A1 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC4A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC34A3 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC34A3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC34A1 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC34A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC2A2 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC2A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC12A3 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC12A3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC12A1 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC12A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SEC63 Achchuthan Shanmugasundram Source Expert Review Green was added to SEC63.
Source NHS GMS was added to SEC63.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SCNN1G Achchuthan Shanmugasundram Source Expert Review Green was added to SCNN1G.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SCNN1B Achchuthan Shanmugasundram Source Expert Review Green was added to SCNN1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SCNN1A Achchuthan Shanmugasundram Source Expert Review Green was added to SCNN1A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SARS2 Achchuthan Shanmugasundram Source Expert Review Green was added to SARS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 RRAGD Achchuthan Shanmugasundram Source Expert Review Green was added to RRAGD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 RMND1 Achchuthan Shanmugasundram Source Expert Review Green was added to RMND1.
Source NHS GMS was added to RMND1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 PRKCSH Achchuthan Shanmugasundram Source Expert Review Green was added to PRKCSH.
Source NHS GMS was added to PRKCSH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 PHEX Achchuthan Shanmugasundram Source Expert Review Green was added to PHEX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 PDSS2 Achchuthan Shanmugasundram Source Expert Review Green was added to PDSS2.
Source NHS GMS was added to PDSS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 NR3C2 Achchuthan Shanmugasundram Source Expert Review Green was added to NR3C2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 MOCOS Achchuthan Shanmugasundram Source Expert Review Green was added to MOCOS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 MAGED2 Achchuthan Shanmugasundram Source Expert Review Green was added to MAGED2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 LYZ Achchuthan Shanmugasundram Source Expert Review Green was added to LYZ.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 LCAT Achchuthan Shanmugasundram Source Expert Review Green was added to LCAT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 KLHL3 Achchuthan Shanmugasundram Source Expert Review Green was added to KLHL3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 KCNJ16 Achchuthan Shanmugasundram Source Expert Review Green was added to KCNJ16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 KCNJ10 Achchuthan Shanmugasundram Source Expert Review Green was added to KCNJ10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 KCNJ1 Achchuthan Shanmugasundram Source Expert Review Green was added to KCNJ1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 IFT27 Achchuthan Shanmugasundram Source Expert Review Green was added to IFT27.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 IFT172 Achchuthan Shanmugasundram Source Expert Review Green was added to IFT172.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 IFT140 Achchuthan Shanmugasundram Source Expert Review Green was added to IFT140.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 HPRT1 Achchuthan Shanmugasundram Source Expert Review Green was added to HPRT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 HNF4A Achchuthan Shanmugasundram Source Expert Review Green was added to HNF4A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 GSN Achchuthan Shanmugasundram Source Expert Review Green was added to GSN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 GON7 Achchuthan Shanmugasundram Source Expert Review Green was added to GON7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 GNA11 Achchuthan Shanmugasundram Source Expert Review Green was added to GNA11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 FN1 Achchuthan Shanmugasundram Source Expert Review Green was added to FN1.
Source NHS GMS was added to FN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 FLCN Achchuthan Shanmugasundram Source Expert Review Green was added to FLCN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 FGA Achchuthan Shanmugasundram Source Expert Review Green was added to FGA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 FAM20A Achchuthan Shanmugasundram Source Expert Review Green was added to FAM20A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 FAH Achchuthan Shanmugasundram Source Expert Review Green was added to FAH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 DLG5 Achchuthan Shanmugasundram Source Expert Review Green was added to DLG5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 DAAM2 Achchuthan Shanmugasundram Source Expert Review Green was added to DAAM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CYP24A1 Achchuthan Shanmugasundram Source Expert Review Green was added to CYP24A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CUL3 Achchuthan Shanmugasundram Source Expert Review Green was added to CUL3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CNNM2 Achchuthan Shanmugasundram Source Expert Review Green was added to CNNM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CLDN19 Achchuthan Shanmugasundram Source Expert Review Green was added to CLDN19.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CLDN16 Achchuthan Shanmugasundram Source Expert Review Green was added to CLDN16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CLDN10 Achchuthan Shanmugasundram Source Expert Review Green was added to CLDN10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CLCNKB Achchuthan Shanmugasundram Source Expert Review Green was added to CLCNKB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CFHR2 Achchuthan Shanmugasundram Source Expert Review Green was added to CFHR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CD151 Achchuthan Shanmugasundram Source Expert Review Green was added to CD151.
Source NHS GMS was added to CD151.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CASR Achchuthan Shanmugasundram Source Expert Review Green was added to CASR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CA2 Achchuthan Shanmugasundram Source Expert Review Green was added to CA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 AVPR2 Achchuthan Shanmugasundram Source Expert Review Green was added to AVPR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 ATP6V1B1 Achchuthan Shanmugasundram Source Expert Review Green was added to ATP6V1B1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 ATP6V0A4 Achchuthan Shanmugasundram Source Expert Review Green was added to ATP6V0A4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 ATP1A1 Achchuthan Shanmugasundram Source Expert Review Green was added to ATP1A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 APRT Achchuthan Shanmugasundram Source Expert Review Green was added to APRT.
Source NHS GMS was added to APRT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 APOE Achchuthan Shanmugasundram Source Expert Review Green was added to APOE.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 APOC2 Achchuthan Shanmugasundram Source Expert Review Green was added to APOC2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 APOA2 Achchuthan Shanmugasundram Source Expert Review Green was added to APOA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 APOA1 Achchuthan Shanmugasundram Source Expert Review Green was added to APOA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 AP2S1 Achchuthan Shanmugasundram Source Expert Review Green was added to AP2S1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 ALG9 Achchuthan Shanmugasundram Source Expert Review Green was added to ALG9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 ALG8 Achchuthan Shanmugasundram Source Expert Review Green was added to ALG8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 ALG5 Achchuthan Shanmugasundram Source Expert Review Green was added to ALG5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Amelogenesis imperfecta v3.3 AMBN Claire Smith edited their review of gene: AMBN: Added comment: PMID: 38058155 identifies AMBN variants that appear to cause disease in an autosomal dominant fashion.
One family has a dominant family history spanning 4 generations, and the likely causative variant in this family was also identified as monoallelic/heterozygous in 2 other apparently unrelated individuals with isolated AI.; Changed publications to: PMID: 24858907, 26502894, 38058155; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v3.79 SMG8 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: SMG8.
Tag Q4_23_NHS_review was removed from gene: SMG8.
Structural eye disease v3.79 SLC25A24 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: SLC25A24.
Tag Q4_23_NHS_review was removed from gene: SLC25A24.
Structural eye disease v3.79 RHOA Arina Puzriakova Tag Q4_23_promote_green was removed from gene: RHOA.
Tag Q4_23_NHS_review was removed from gene: RHOA.
Structural eye disease v3.79 OFD1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: OFD1.
Tag Q3_23_NHS_review was removed from gene: OFD1.
Breast cancer pertinent cancer susceptibility v2.11 CDH1 Achchuthan Shanmugasundram Classified gene: CDH1 as Amber List (moderate evidence)
Breast cancer pertinent cancer susceptibility v2.11 CDH1 Achchuthan Shanmugasundram Gene: cdh1 has been classified as Amber List (Moderate Evidence).
Structural eye disease v3.79 NUP188 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: NUP188.
Tag Q4_23_NHS_review was removed from gene: NUP188.
Structural eye disease v3.79 MIR204 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: MIR204.
Tag Q3_23_NHS_review was removed from gene: MIR204.
Breast cancer pertinent cancer susceptibility v2.10 CDH1 Achchuthan Shanmugasundram Classified gene: CDH1 as Red List (low evidence)
Breast cancer pertinent cancer susceptibility v2.10 CDH1 Achchuthan Shanmugasundram Gene: cdh1 has been classified as Red List (Low Evidence).
Breast cancer pertinent cancer susceptibility v2.9 CDH1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CDH1.
Tag Q3_23_expert_review was removed from gene: CDH1.
Structural eye disease v3.79 KIF11 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: KIF11.
Tag Q4_23_NHS_review was removed from gene: KIF11.
Structural eye disease v3.79 KIAA0586 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: KIAA0586.
Tag Q4_23_NHS_review was removed from gene: KIAA0586.
Structural eye disease v3.79 KDM6A Arina Puzriakova Tag Q4_23_promote_green was removed from gene: KDM6A.
Tag Q4_23_NHS_review was removed from gene: KDM6A.
Structural eye disease v3.79 EPHA2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: EPHA2.
Tag Q4_23_MOI was removed from gene: EPHA2.
Tag Q4_23_NHS_review was removed from gene: EPHA2.
Amelogenesis imperfecta v3.3 PLXNB2 Claire Smith changed review comment from: PMID: 38458752 Smith et al. (in press) report 8 patients in 6 families with rare biallelic pathogenic variants in PLXNB2 as a cause of a new autosomal recessive, phenotypically diverse syndrome with AI and sensorineural hearing loss as core features. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases.
Sources: Literature, Expert Review; to: PMID: 38458752 Smith et al. (in press) report 8 patients in 6 families with rare biallelic pathogenic variants in PLXNB2 as a cause of a new autosomal recessive, phenotypically diverse syndrome with AI and sensorineural hearing loss as core features. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases.
Sources: Literature, Expert Review

Personal communication with Roland Friedel and Christian Junquiera-Alves regarding their findings in their Plxnb2-/- mouse model after publication of human patients with PLXNB2 variants: "We had made also initial observations in the PB2 KO mouse on cochlear defects and tooth malformations that looked interesting, but we did not follow up as I focused on cerebellar development. Now these findings look in retrospect much more exciting considering your data."
Structural eye disease v3.79 CRYBB2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: CRYBB2.
Tag Q4_23_NHS_review was removed from gene: CRYBB2.
Structural eye disease v3.79 BMPR1B Arina Puzriakova Tag Q4_23_promote_green was removed from gene: BMPR1B.
Tag Q4_23_NHS_review was removed from gene: BMPR1B.
Structural eye disease v3.79 ARHGAP35 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: ARHGAP35.
Tag Q4_23_NHS_review was removed from gene: ARHGAP35.
Structural eye disease v3.79 ANK3 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: ANK3.
Tag Q4_23_NHS_review was removed from gene: ANK3.
Structural eye disease v3.79 ALX1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: ALX1.
Tag Q3_23_NHS_review was removed from gene: ALX1.
Structural eye disease v3.79 SMG8 Arina Puzriakova reviewed gene: SMG8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v3.79 SLC25A24 Arina Puzriakova reviewed gene: SLC25A24: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 RHOA Arina Puzriakova reviewed gene: RHOA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Structural eye disease v3.79 OFD1 Arina Puzriakova reviewed gene: OFD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v3.79 NUP188 Arina Puzriakova reviewed gene: NUP188: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v3.79 MIR204 Arina Puzriakova reviewed gene: MIR204: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 KIF11 Arina Puzriakova reviewed gene: KIF11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 KIAA0586 Arina Puzriakova reviewed gene: KIAA0586: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v3.79 KDM6A Arina Puzriakova reviewed gene: KDM6A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v3.79 EPHA2 Arina Puzriakova reviewed gene: EPHA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v3.79 CRYBB2 Arina Puzriakova reviewed gene: CRYBB2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 BMPR1B Arina Puzriakova reviewed gene: BMPR1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 ARHGAP35 Arina Puzriakova reviewed gene: ARHGAP35: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 ANK3 Arina Puzriakova reviewed gene: ANK3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 ALX1 Arina Puzriakova reviewed gene: ALX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v3.78 SMG8 Arina Puzriakova Source NHS GMS was added to SMG8.
Source Expert Review Green was added to SMG8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 SLC25A24 Arina Puzriakova Source Expert Review Green was added to SLC25A24.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 RHOA Arina Puzriakova Source NHS GMS was added to RHOA.
Source Expert Review Green was added to RHOA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 OFD1 Arina Puzriakova Source Expert Review Green was added to OFD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 NUP188 Arina Puzriakova Source NHS GMS was added to NUP188.
Source Expert Review Green was added to NUP188.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 MIR204 Arina Puzriakova Source Expert Review Green was added to MIR204.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 KIF11 Arina Puzriakova Source Expert Review Green was added to KIF11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 KIAA0586 Arina Puzriakova Source NHS GMS was added to KIAA0586.
Source Expert Review Green was added to KIAA0586.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 KDM6A Arina Puzriakova Source Expert Review Green was added to KDM6A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 EPHA2 Arina Puzriakova Source Expert Review Green was added to EPHA2.
Mode of inheritance for gene EPHA2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 CRYBB2 Arina Puzriakova Source Expert Review Green was added to CRYBB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 BMPR1B Arina Puzriakova Source NHS GMS was added to BMPR1B.
Source Expert Review Green was added to BMPR1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 ARHGAP35 Arina Puzriakova Source NHS GMS was added to ARHGAP35.
Source Expert Review Green was added to ARHGAP35.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 ANK3 Arina Puzriakova Source NHS GMS was added to ANK3.
Source Expert Review Green was added to ANK3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 ALX1 Arina Puzriakova Source Expert Review Green was added to ALX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Breast cancer pertinent cancer susceptibility v2.9 ATRIP Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ATRIP.
Tag Q4_23_expert_review was removed from gene: ATRIP.
Amelogenesis imperfecta v3.3 PLXNB2 Claire Smith gene: PLXNB2 was added
gene: PLXNB2 was added to Amelogenesis imperfecta. Sources: Literature,Expert Review
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to PMID: 38458752
Phenotypes for gene: PLXNB2 were set to Amelogenesis imperfecta; sensorineural hearing loss
Penetrance for gene: PLXNB2 were set to unknown
Review for gene: PLXNB2 was set to GREEN
Added comment: PMID: 38458752 Smith et al. (in press) report 8 patients in 6 families with rare biallelic pathogenic variants in PLXNB2 as a cause of a new autosomal recessive, phenotypically diverse syndrome with AI and sensorineural hearing loss as core features. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases.
Sources: Literature, Expert Review
Breast cancer pertinent cancer susceptibility v2.9 CDH1 Arina Puzriakova edited their review of gene: CDH1: Added comment: After NHS Genomic Medicine Service consideration, this gene has not been made Green and has been rated as Red. Additional comments from reviewing GLHs: 'There is a well established association of this gene withpredisposition to lobular breast cancer, but it presents huge problems when it is identified outside the context of a relevant family history. The UK Cancer genetics community do not want to add this gene to any general breast cancer susceptibility panels hence are extremely reluctant to test this gene outside of the already existing R215 criteria'; Changed rating: RED; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Breast cancer pertinent cancer susceptibility v2.9 ATRIP Arina Puzriakova edited their review of gene: ATRIP: Added comment: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber. Additional comments from reviewing GLHs: 'Whilst the referenced paper does support an association with breast cancer, more studies are needed before we can consider adding this gene to any panel. The referenced paper itself comments that further replication in larger datasets is necessary to provide figures on lifetime risk, to better define the association with breast cancer and the clinic-pathological characteristics of tumors in variant carriers . Without this important information, it is too early to add the gene to a breast cancer susceptibility panel'; Changed rating: AMBER; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v5.4 RPE65 Arina Puzriakova Tag Q4_23_MOI was removed from gene: RPE65.
Retinal disorders v5.4 PYGM Arina Puzriakova Tag Q3_23_promote_green was removed from gene: PYGM.
Tag Q3_23_NHS_review was removed from gene: PYGM.
Retinal disorders v5.4 NBAS Arina Puzriakova Tag Q3_23_promote_green was removed from gene: NBAS.
Tag Q3_23_NHS_review was removed from gene: NBAS.
Retinal disorders v5.4 MVK Arina Puzriakova Tag Q4_23_promote_green was removed from gene: MVK.
Tag Q4_23_NHS_review was removed from gene: MVK.
Retinal disorders v5.4 MPDZ Arina Puzriakova Tag Q3_23_promote_green was removed from gene: MPDZ.
Tag Q3_23_NHS_review was removed from gene: MPDZ.
Retinal disorders v5.4 MIR204 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: MIR204.
Tag Q3_23_NHS_review was removed from gene: MIR204.
Retinal disorders v5.4 MCOLN1 Arina Puzriakova Phenotypes for gene: MCOLN1 were changed from to Mucolipidosis IV, OMIM:252650
Retinal disorders v5.3 MCOLN1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: MCOLN1.
Retinal disorders v5.3 DYNC2H1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: DYNC2H1.
Retinal disorders v5.3 CTNND1 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: CTNND1.
Retinal disorders v5.3 CFAP20 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: CFAP20.
Retinal disorders v5.3 RPE65 Arina Puzriakova Mode of inheritance for gene RPE65 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinal disorders v5.3 PYGM Arina Puzriakova Source NHS GMS was added to PYGM.
Source Expert Review Green was added to PYGM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 NBAS Arina Puzriakova Source Expert Review Green was added to NBAS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 MVK Arina Puzriakova Source Expert Review Green was added to MVK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 MPDZ Arina Puzriakova Source NHS GMS was added to MPDZ.
Source Expert Review Green was added to MPDZ.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 MIR204 Arina Puzriakova Source Expert Review Green was added to MIR204.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 MCOLN1 Arina Puzriakova Source NHS GMS was added to MCOLN1.
Source Expert Review Green was added to MCOLN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 DYNC2H1 Arina Puzriakova Source NHS GMS was added to DYNC2H1.
Source Expert Review Green was added to DYNC2H1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 CTNND1 Arina Puzriakova Source NHS GMS was added to CTNND1.
Source Expert Review Green was added to CTNND1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 CFAP20 Arina Puzriakova Source NHS GMS was added to CFAP20.
Source Expert Review Green was added to CFAP20.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.2 RPE65 Arina Puzriakova edited their review of gene: RPE65: Added comment: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinal disorders v5.2 PYGM Arina Puzriakova reviewed gene: PYGM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v5.2 NBAS Arina Puzriakova reviewed gene: NBAS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v5.2 MVK Arina Puzriakova reviewed gene: MVK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v5.2 MPDZ Arina Puzriakova reviewed gene: MPDZ: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v5.2 MIR204 Arina Puzriakova reviewed gene: MIR204: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v5.2 MCOLN1 Arina Puzriakova reviewed gene: MCOLN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v5.2 DYNC2H1 Arina Puzriakova reviewed gene: DYNC2H1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v5.2 CTNND1 Arina Puzriakova reviewed gene: CTNND1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v5.2 CFAP20 Arina Puzriakova reviewed gene: CFAP20: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 SCN8A Achchuthan Shanmugasundram Tag for-review was removed from gene: SCN8A.
Tag to_be_confirmed_NHSE was removed from gene: SCN8A.
Early onset or syndromic epilepsy v5.6 CACNB4 Achchuthan Shanmugasundram Tag Q4_23_demote_red was removed from gene: CACNB4.
Tag Q4_23_expert_review was removed from gene: CACNB4.
Early onset or syndromic epilepsy v5.6 ZBTB47 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ZBTB47.
Early onset or syndromic epilepsy v5.6 TRIT1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TRIT1.
Early onset or syndromic epilepsy v5.6 SHQ1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SHQ1.
Early onset or syndromic epilepsy v5.6 PTCD3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PTCD3.
Early onset or syndromic epilepsy v5.6 PLA2G6 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PLA2G6.
Early onset or syndromic epilepsy v5.6 PIGM Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PIGM.
Early onset or syndromic epilepsy v5.6 MAST4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MAST4.
Early onset or syndromic epilepsy v5.6 HECTD4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HECTD4.
Early onset or syndromic epilepsy v5.6 ASL Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ASL.
Tag Q4_23_NHS_review was removed from gene: ASL.
Early onset or syndromic epilepsy v5.6 ARF3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ARF3.
Bilateral congenital or childhood onset cataracts v4.14 LETM1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: LETM1.
Tag Q3_23_MOI was removed from gene: LETM1.
Bilateral congenital or childhood onset cataracts v4.14 EPHA2 Arina Puzriakova Tag Q4_23_MOI was removed from gene: EPHA2.
Early onset or syndromic epilepsy v5.6 AGO1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: AGO1.
Bilateral congenital or childhood onset cataracts v4.14 LETM1 Arina Puzriakova reviewed gene: LETM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bilateral congenital or childhood onset cataracts v4.14 EPHA2 Arina Puzriakova reviewed gene: EPHA2: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Bilateral congenital or childhood onset cataracts v4.13 LETM1 Arina Puzriakova Source NHS GMS was added to LETM1.
Source Expert Review Green was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Bilateral congenital or childhood onset cataracts v4.13 EPHA2 Arina Puzriakova Source NHS GMS was added to EPHA2.
Mode of inheritance for gene EPHA2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 U2AF2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: U2AF2.
Early onset or syndromic epilepsy v5.6 TMEM63B Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TMEM63B.
White matter disorders and cerebral calcification - narrow panel v4.3 PPFIBP1 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: PPFIBP1.
White matter disorders and cerebral calcification - narrow panel v4.3 ESAM Arina Puzriakova Tag Q3_23_promote_green was removed from gene: ESAM.
Early onset or syndromic epilepsy v5.6 RAB5C Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: RAB5C.
Early onset or syndromic epilepsy v5.6 PPP1R3F Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PPP1R3F.
Early onset or syndromic epilepsy v5.6 PIP5K1C Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PIP5K1C.
White matter disorders and cerebral calcification - narrow panel v4.3 PPFIBP1 Arina Puzriakova reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v4.3 ESAM Arina Puzriakova reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 PABPC1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PABPC1.
Tag Q3_23_MOI was removed from gene: PABPC1.
White matter disorders and cerebral calcification - narrow panel v4.2 PPFIBP1 Arina Puzriakova Source Expert Review Green was added to PPFIBP1.
Source NHS GMS was added to PPFIBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v4.2 ESAM Arina Puzriakova Source Expert Review Green was added to ESAM.
Source NHS GMS was added to ESAM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.6 LETM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: LETM1.
Tag Q3_23_MOI was removed from gene: LETM1.
Early onset or syndromic epilepsy v5.6 KDM6B Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: KDM6B.
Early onset or syndromic epilepsy v5.6 KCNH5 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: KCNH5.
Intellectual disability v6.9 DPP6 Arina Puzriakova Phenotypes for gene: DPP6 were changed from autosomal dominant microcephaly and mental retardation; Mental retardation, autosomal dominant 33, 616311 to Intellectual developmental disorder, autosomal dominant 33, OMIM:616311
Early onset or syndromic epilepsy v5.6 ESAM Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ESAM.
Early onset or syndromic epilepsy v5.6 EIF4A2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: EIF4A2.
Early onset or syndromic epilepsy v5.6 DNAJC6 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DNAJC6.
Severe microcephaly v5.7 DPP6 Arina Puzriakova Phenotypes for gene: DPP6 were changed from MCPH; primary microcephaly; autosomal dominant microcephaly and mental retardation; Mental retardation, autosomal dominant 33, 616311 to Intellectual developmental disorder, autosomal dominant 33, OMIM:616311
Intellectual disability v6.8 TTI1 Arina Puzriakova Added comment: Comment on phenotypes: Relevant phenotype now listed in OMIM (Neurodevelopmental disorder with microcephaly and movement abnormalities, OMIM:620445)
Intellectual disability v6.8 TTI1 Arina Puzriakova Phenotypes for gene: TTI1 were changed from neurodevelopmental disorder with microcephaly to Neurodevelopmental disorder with microcephaly and movement abnormalities, OMIM:620445
Severe microcephaly v5.6 DPP6 Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: DPP6.
Severe microcephaly v5.6 TTI1 Arina Puzriakova Added comment: Comment on phenotypes: Relevant phenotype now listed in OMIM (Neurodevelopmental disorder with microcephaly and movement abnormalities, OMIM:620445)
Severe microcephaly v5.6 TTI1 Arina Puzriakova Phenotypes for gene: TTI1 were changed from neurodevelopmental disorder with microcephaly to Neurodevelopmental disorder with microcephaly and movement abnormalities, OMIM:620445
Severe microcephaly v5.5 TTI1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: TTI1.
Severe microcephaly v5.5 PPFIBP1 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: PPFIBP1.
Early onset or syndromic epilepsy v5.6 CRELD1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CRELD1.
Severe microcephaly v5.5 NSD2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: NSD2.
Severe microcephaly v5.5 MECP2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: MECP2.
Severe microcephaly v5.5 KMT2B Arina Puzriakova Tag Q4_23_promote_green was removed from gene: KMT2B.
Severe microcephaly v5.5 BUB1 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: BUB1.
Severe microcephaly v5.5 ATP6V0C Arina Puzriakova Tag Q3_23_promote_green was removed from gene: ATP6V0C.
Tag Q3_23_NHS_review was removed from gene: ATP6V0C.
Severe microcephaly v5.5 ARF3 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: ARF3.
Early onset or syndromic epilepsy v5.6 CNOT9 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CNOT9.
Early onset or syndromic epilepsy v5.6 ATP6V0C Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ATP6V0C.
Tag Q3_23_NHS_review was removed from gene: ATP6V0C.
Severe microcephaly v5.5 TTI1 Arina Puzriakova Source Expert Review Green was added to TTI1.
Source NHS GMS was added to TTI1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 PPFIBP1 Arina Puzriakova Source Expert Review Green was added to PPFIBP1.
Source NHS GMS was added to PPFIBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 NSD2 Arina Puzriakova Source Expert Review Green was added to NSD2.
Source NHS GMS was added to NSD2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 MECP2 Arina Puzriakova Source Expert Review Green was added to MECP2.
Source NHS GMS was added to MECP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 KMT2B Arina Puzriakova Source Expert Review Green was added to KMT2B.
Source NHS GMS was added to KMT2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 DPP6 Arina Puzriakova Source Expert Review Amber was added to DPP6.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Severe microcephaly v5.5 BUB1 Arina Puzriakova Source Expert Review Green was added to BUB1.
Source NHS GMS was added to BUB1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 ATP6V0C Arina Puzriakova Source Expert Review Green was added to ATP6V0C.
Source NHS GMS was added to ATP6V0C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 ARF3 Arina Puzriakova Source Expert Review Green was added to ARF3.
Source NHS GMS was added to ARF3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.4 DPP6 Arina Puzriakova reviewed gene: DPP6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v5.4 TTI1 Arina Puzriakova reviewed gene: TTI1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v5.4 PPFIBP1 Arina Puzriakova reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v5.4 NSD2 Arina Puzriakova reviewed gene: NSD2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe microcephaly v5.4 MECP2 Arina Puzriakova reviewed gene: MECP2: Rating: GREEN; Mode of pathogenicity: ; 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)
Severe microcephaly v5.4 KMT2B Arina Puzriakova commented on gene: KMT2B: The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Severe microcephaly v5.4 BUB1 Arina Puzriakova edited their review of gene: BUB1: 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; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v5.4 ATP6V0C Arina Puzriakova reviewed gene: ATP6V0C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe microcephaly v5.4 ARF3 Arina Puzriakova reviewed gene: ARF3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v5.6 SLC5A6 Eleanor Williams reviewed gene: SLC5A6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v5.6 ZBTB47 Eleanor Williams reviewed gene: ZBTB47: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 U2AF2 Eleanor Williams reviewed gene: U2AF2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 TRIT1 Eleanor Williams edited their review of gene: TRIT1: Added comment: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Early onset or syndromic epilepsy v5.6 TMEM63B Eleanor Williams reviewed gene: TMEM63B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 SHQ1 Eleanor Williams reviewed gene: SHQ1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 SCN8A Eleanor Williams reviewed gene: SCN8A: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 RAB5C Eleanor Williams reviewed gene: RAB5C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 PTCD3 Eleanor Williams reviewed gene: PTCD3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 PPP1R3F Eleanor Williams reviewed gene: PPP1R3F: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early onset or syndromic epilepsy v5.6 PLA2G6 Eleanor Williams reviewed gene: PLA2G6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 PIP5K1C Eleanor Williams reviewed gene: PIP5K1C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 PIGM Eleanor Williams reviewed gene: PIGM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 PABPC1 Eleanor Williams reviewed gene: PABPC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 MAST4 Eleanor Williams reviewed gene: MAST4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 LETM1 Eleanor Williams reviewed gene: LETM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 KDM6B Eleanor Williams reviewed gene: KDM6B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 KCNH5 Eleanor Williams reviewed gene: KCNH5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 HECTD4 Eleanor Williams reviewed gene: HECTD4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 ESAM Eleanor Williams reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 EIF4A2 Eleanor Williams reviewed gene: EIF4A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 DNAJC6 Eleanor Williams reviewed gene: DNAJC6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 CRELD1 Eleanor Williams reviewed gene: CRELD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 CNOT9 Eleanor Williams reviewed gene: CNOT9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 CACNB4 Eleanor Williams reviewed gene: CACNB4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v5.6 ATP6V0C Eleanor Williams reviewed gene: ATP6V0C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 ASL Eleanor Williams edited their review of gene: ASL: Added comment: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 ARF3 Eleanor Williams reviewed gene: ARF3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v5.6 AGO1 Eleanor Williams reviewed gene: AGO1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v5.5 ZBTB47 Achchuthan Shanmugasundram Source NHS GMS was added to ZBTB47.
Source Expert Review Green was added to ZBTB47.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 U2AF2 Achchuthan Shanmugasundram Source NHS GMS was added to U2AF2.
Source Expert Review Green was added to U2AF2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 TRIT1 Achchuthan Shanmugasundram Source NHS GMS was added to TRIT1.
Source Expert Review Green was added to TRIT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 TMEM63B Achchuthan Shanmugasundram Source NHS GMS was added to TMEM63B.
Source Expert Review Green was added to TMEM63B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 SLC5A6 Achchuthan Shanmugasundram Source NHS GMS was added to SLC5A6.
Early onset or syndromic epilepsy v5.5 SHQ1 Achchuthan Shanmugasundram Source NHS GMS was added to SHQ1.
Source Expert Review Green was added to SHQ1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 SCN8A Achchuthan Shanmugasundram Mode of inheritance for gene SCN8A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.5 RAB5C Achchuthan Shanmugasundram Source NHS GMS was added to RAB5C.
Source Expert Review Green was added to RAB5C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 PTCD3 Achchuthan Shanmugasundram Source NHS GMS was added to PTCD3.
Source Expert Review Green was added to PTCD3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 PPP1R3F Achchuthan Shanmugasundram Source NHS GMS was added to PPP1R3F.
Source Expert Review Green was added to PPP1R3F.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 PLA2G6 Achchuthan Shanmugasundram Source NHS GMS was added to PLA2G6.
Source Expert Review Green was added to PLA2G6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 PIP5K1C Achchuthan Shanmugasundram Source NHS GMS was added to PIP5K1C.
Source Expert Review Green was added to PIP5K1C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 PIGM Achchuthan Shanmugasundram Source Expert Review Green was added to PIGM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 PABPC1 Achchuthan Shanmugasundram Source NHS GMS was added to PABPC1.
Source Expert Review Green was added to PABPC1.
Mode of inheritance for gene PABPC1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 MAST4 Achchuthan Shanmugasundram Source NHS GMS was added to MAST4.
Source Expert Review Green was added to MAST4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 LETM1 Achchuthan Shanmugasundram Source NHS GMS was added to LETM1.
Source Expert Review Green was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 KDM6B Achchuthan Shanmugasundram Source Expert Review Green was added to KDM6B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 KCNH5 Achchuthan Shanmugasundram Source Expert Review Green was added to KCNH5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 HECTD4 Achchuthan Shanmugasundram Source Expert Review Green was added to HECTD4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 ESAM Achchuthan Shanmugasundram Source NHS GMS was added to ESAM.
Source Expert Review Green was added to ESAM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 EIF4A2 Achchuthan Shanmugasundram Source NHS GMS was added to EIF4A2.
Source Expert Review Green was added to EIF4A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 DNAJC6 Achchuthan Shanmugasundram Source Expert Review Green was added to DNAJC6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 CRELD1 Achchuthan Shanmugasundram Source NHS GMS was added to CRELD1.
Source Expert Review Green was added to CRELD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 CNOT9 Achchuthan Shanmugasundram Source NHS GMS was added to CNOT9.
Source Expert Review Green was added to CNOT9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 CACNB4 Achchuthan Shanmugasundram Source Expert Review Red was added to CACNB4.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Early onset or syndromic epilepsy v5.5 ATP6V0C Achchuthan Shanmugasundram Source NHS GMS was added to ATP6V0C.
Source Expert Review Green was added to ATP6V0C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 ASL Achchuthan Shanmugasundram Source NHS GMS was added to ASL.
Source Expert Review Green was added to ASL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 ARF3 Achchuthan Shanmugasundram Source NHS GMS was added to ARF3.
Source Expert Review Green was added to ARF3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 AGO1 Achchuthan Shanmugasundram Source NHS GMS was added to AGO1.
Source Expert Review Green was added to AGO1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Distal myopathies v4.3 SMPX Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SMPX.
Tag Q3_23_MOI was removed from gene: SMPX.
Distal myopathies v4.3 SMPX Eleanor Williams reviewed gene: SMPX: Rating: GREEN; Mode of pathogenicity: ; 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)
Distal myopathies v4.2 SMPX Achchuthan Shanmugasundram Source Expert Review Green was added to SMPX.
Source NHS GMS was added to SMPX.
Mode of inheritance for gene SMPX 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)
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary ataxia with onset in adulthood v5.3 UCHL1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: UCHL1.
Tag Q3_23_MOI was removed from gene: UCHL1.
Hereditary ataxia with onset in adulthood v5.3 TDP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TDP1.
Hereditary ataxia with onset in adulthood v5.3 UCHL1 Eleanor Williams reviewed gene: UCHL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v5.3 TDP1 Eleanor Williams reviewed gene: TDP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v5.2 UCHL1 Achchuthan Shanmugasundram Source Expert Review Green was added to UCHL1.
Mode of inheritance for gene UCHL1 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)
Hereditary ataxia with onset in adulthood v5.2 TDP1 Achchuthan Shanmugasundram Source Expert Review Green was added to TDP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.3 ZC4H2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ZC4H2.
Clefting v5.3 TRRAP Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TRRAP.
Clefting v5.3 STAG2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: STAG2.
Clefting v5.3 SMARCA4 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SMARCA4.
Clefting v5.3 PGM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PGM1.
Clefting v5.3 PGAP3 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PGAP3.
Clefting v5.3 KAT6B Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: KAT6B.
Clefting v5.3 HNRNPK Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: HNRNPK.
Clefting v5.3 GLI2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: GLI2.
Clefting v5.3 CNTNAP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CNTNAP1.
Clefting v5.3 AMOTL1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: AMOTL1.
Clefting v5.3 ALX1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ALX1.
Clefting v5.3 ZC4H2 Sarah Leigh reviewed gene: ZC4H2: Rating: GREEN; Mode of pathogenicity: ; 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)
Clefting v5.3 TRRAP Sarah Leigh reviewed gene: TRRAP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v5.3 STAG2 Sarah Leigh reviewed gene: STAG2: Rating: GREEN; Mode of pathogenicity: ; 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)
Clefting v5.3 SMARCA4 Sarah Leigh reviewed gene: SMARCA4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v5.3 PGM1 Sarah Leigh reviewed gene: PGM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v5.3 PGAP3 Sarah Leigh reviewed gene: PGAP3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v5.3 KAT6B Sarah Leigh reviewed gene: KAT6B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Clefting v5.3 HNRNPK Sarah Leigh reviewed gene: HNRNPK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v5.3 GLI2 Sarah Leigh reviewed gene: GLI2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v5.3 CNTNAP1 Sarah Leigh reviewed gene: CNTNAP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v5.3 AMOTL1 Sarah Leigh reviewed gene: AMOTL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v5.3 ALX1 Sarah Leigh edited their review of gene: ALX1: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v5.2 ZC4H2 Achchuthan Shanmugasundram Source Expert Review Green was added to ZC4H2.
Source NHS GMS was added to ZC4H2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 TRRAP Achchuthan Shanmugasundram Source Expert Review Green was added to TRRAP.
Source NHS GMS was added to TRRAP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 STAG2 Achchuthan Shanmugasundram Source Expert Review Green was added to STAG2.
Source NHS GMS was added to STAG2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 SMARCA4 Achchuthan Shanmugasundram Source Expert Review Green was added to SMARCA4.
Source NHS GMS was added to SMARCA4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 PGM1 Achchuthan Shanmugasundram Source Expert Review Green was added to PGM1.
Source NHS GMS was added to PGM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 PGAP3 Achchuthan Shanmugasundram Source Expert Review Green was added to PGAP3.
Source NHS GMS was added to PGAP3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 KAT6B Achchuthan Shanmugasundram Source Expert Review Green was added to KAT6B.
Source NHS GMS was added to KAT6B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 HNRNPK Achchuthan Shanmugasundram Source Expert Review Green was added to HNRNPK.
Source NHS GMS was added to HNRNPK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 GLI2 Achchuthan Shanmugasundram Source Expert Review Green was added to GLI2.
Source NHS GMS was added to GLI2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 CNTNAP1 Achchuthan Shanmugasundram Source Expert Review Green was added to CNTNAP1.
Source NHS GMS was added to CNTNAP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 AMOTL1 Achchuthan Shanmugasundram Source Expert Review Green was added to AMOTL1.
Source NHS GMS was added to AMOTL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 ALX1 Achchuthan Shanmugasundram Source Expert Review Green was added to ALX1.
Source NHS GMS was added to ALX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.3 THG1L Achchuthan Shanmugasundram Tag watchlist was removed from gene: THG1L.
Tag Q4_23_promote_green was removed from gene: THG1L.
Tag Q4_23_NHS_review was removed from gene: THG1L.
Ataxia and cerebellar anomalies - narrow panel v5.3 DLG4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: DLG4.
Ataxia and cerebellar anomalies - narrow panel v5.3 ASL Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ASL.
Tag Q4_23_NHS_review was removed from gene: ASL.
Ataxia and cerebellar anomalies - narrow panel v5.3 UCHL1 Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: UCHL1.
Ataxia and cerebellar anomalies - narrow panel v5.3 LETM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: LETM1.
Tag Q3_23_MOI was removed from gene: LETM1.
Ataxia and cerebellar anomalies - narrow panel v5.3 DNAJC3 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DNAJC3.
Ataxia and cerebellar anomalies - narrow panel v5.3 DAGLA Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DAGLA.
Ataxia and cerebellar anomalies - narrow panel v5.3 AGTPBP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: AGTPBP1.
Ataxia and cerebellar anomalies - narrow panel v5.3 UCHL1 Sarah Leigh commented on gene: UCHL1: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Ataxia and cerebellar anomalies - narrow panel v5.3 THG1L Sarah Leigh reviewed gene: THG1L: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v5.3 LETM1 Sarah Leigh commented on gene: LETM1: 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.
Ataxia and cerebellar anomalies - narrow panel v5.3 DNAJC3 Sarah Leigh reviewed gene: DNAJC3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v5.3 DLG4 Sarah Leigh reviewed gene: DLG4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v5.3 DAGLA Sarah Leigh reviewed gene: DAGLA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v5.3 ASL Sarah Leigh reviewed gene: ASL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v5.3 AGTPBP1 Sarah Leigh reviewed gene: AGTPBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v5.2 UCHL1 Achchuthan Shanmugasundram Mode of inheritance for gene UCHL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v5.2 THG1L Achchuthan Shanmugasundram Source Expert Review Green was added to THG1L.
Source NHS GMS was added to THG1L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.2 LETM1 Achchuthan Shanmugasundram Source Expert Review Green was added to LETM1.
Source NHS GMS was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.2 DNAJC3 Achchuthan Shanmugasundram Source Expert Review Green was added to DNAJC3.
Source NHS GMS was added to DNAJC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.2 DLG4 Achchuthan Shanmugasundram Source Expert Review Green was added to DLG4.
Source NHS GMS was added to DLG4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.2 DAGLA Achchuthan Shanmugasundram Source Expert Review Green was added to DAGLA.
Source NHS GMS was added to DAGLA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.2 ASL Achchuthan Shanmugasundram Source Expert Review Green was added to ASL.
Source NHS GMS was added to ASL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.2 AGTPBP1 Achchuthan Shanmugasundram Source Expert Review Green was added to AGTPBP1.
Source NHS GMS was added to AGTPBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v4.4 TAMM41 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: TAMM41.
Rhabdomyolysis and metabolic muscle disorders v4.4 PNPLA2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: PNPLA2.
Rhabdomyolysis and metabolic muscle disorders v4.4 ISCU Arina Puzriakova Phenotypes for gene: ISCU were changed from Myopathy with lactic acidosis, hereditary 255125 to Myopathy with lactic acidosis, hereditary, OMIM:255125
Rhabdomyolysis and metabolic muscle disorders v4.3 ISCU Arina Puzriakova Tag for-review was removed from gene: ISCU.
Tag to_be_confirmed_NHSE was removed from gene: ISCU.
Rhabdomyolysis and metabolic muscle disorders v4.3 ABHD5 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: ABHD5.
Rhabdomyolysis and metabolic muscle disorders v4.3 ABHD5 Arina Puzriakova edited their review of gene: ABHD5: Changed rating: GREEN
Rhabdomyolysis and metabolic muscle disorders v4.3 ABHD5 Arina Puzriakova changed review comment from: The mode of inheritance of this gene has been updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; to: 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.
Mitochondrial disorders v6.4 ANO10 Achchuthan Shanmugasundram Tag Q3_23_expert_review was removed from gene: ANO10.
Tag Q2_24_demote_amber tag was added to gene: ANO10.
Tag Q2_24_expert_review tag was added to gene: ANO10.
Mitochondrial disorders v6.4 BTD Achchuthan Shanmugasundram Tag Q3_23_expert_review was removed from gene: BTD.
Tag Q2_24_demote_amber tag was added to gene: BTD.
Tag Q2_24_expert_review tag was added to gene: BTD.
Rhabdomyolysis and metabolic muscle disorders v4.3 ISCU Arina Puzriakova edited their review of gene: ISCU: Added comment: The mode of inheritance of this gene has been updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v4.3 TAMM41 Arina Puzriakova reviewed gene: TAMM41: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v4.3 PNPLA2 Arina Puzriakova reviewed gene: PNPLA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v4.3 ABHD5 Arina Puzriakova reviewed gene: ABHD5: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v4.2 TAMM41 Arina Puzriakova Source Expert Review Green was added to TAMM41.
Source NHS GMS was added to TAMM41.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v4.2 PNPLA2 Arina Puzriakova Source Expert Review Green was added to PNPLA2.
Source NHS GMS was added to PNPLA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v4.2 ISCU Arina Puzriakova Source NHS GMS was added to ISCU.
Mode of inheritance for gene ISCU was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v4.2 ABHD5 Arina Puzriakova Source Expert Review Green was added to ABHD5.
Source NHS GMS was added to ABHD5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v5.4 HECTD4 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: HECTD4.
Malformations of cortical development v5.4 COL4A2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: COL4A2.
Tag Q4_23_NHS_review was removed from gene: COL4A2.
Intellectual disability v6.7 CASP2 Arina Puzriakova Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, OMIM:620653
DDG2P v4.3 CASP2 Arina Puzriakova Phenotypes for gene: CASP2 were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, OMIM:620653
Malformations of cortical development v5.4 COL4A1 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: COL4A1.
Tag Q4_23_NHS_review was removed from gene: COL4A1.
Malformations of cortical development v5.4 CASP2 Arina Puzriakova Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder, MONDO:0700092; hereditary cerebral malformation, MONDO:0957008 to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, OMIM:620653
Malformations of cortical development v5.3 CASP2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: CASP2.
Malformations of cortical development v5.3 HECTD4 Arina Puzriakova Source Expert Review Green was added to HECTD4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v5.3 COL4A2 Arina Puzriakova Source NHS GMS was added to COL4A2.
Source Expert Review Green was added to COL4A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v5.3 COL4A1 Arina Puzriakova Source NHS GMS was added to COL4A1.
Source Expert Review Green was added to COL4A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v5.3 CASP2 Arina Puzriakova Source NHS GMS was added to CASP2.
Source Expert Review Green was added to CASP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v5.2 HECTD4 Arina Puzriakova commented on gene: HECTD4: 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.
Malformations of cortical development v5.2 COL4A2 Arina Puzriakova reviewed gene: COL4A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v5.2 COL4A1 Arina Puzriakova reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v5.2 CASP2 Arina Puzriakova reviewed gene: CASP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.4 HPDL Achchuthan Shanmugasundram Tag for-review was removed from gene: HPDL.
Tag to_be_confirmed_NHSE was removed from gene: HPDL.
Mitochondrial disorders v6.4 PTCD3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PTCD3.
Mitochondrial disorders v6.4 TEFM Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TEFM.
Tag Q4_23_NHS_review was removed from gene: TEFM.
Mitochondrial disorders v6.4 TAMM41 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TAMM41.
Tag Q4_23_NHS_review was removed from gene: TAMM41.
Mitochondrial disorders v6.4 SLC52A3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC52A3.
Tag Q4_23_MOI was removed from gene: SLC52A3.
Mitochondrial disorders v6.4 SLC52A2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC52A2.
Mitochondrial disorders v6.4 SLC25A36 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC25A36.
Tag Q4_23_NHS_review was removed from gene: SLC25A36.
Mitochondrial disorders v6.4 MRM2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MRM2.
Mitochondrial disorders v6.4 HADHB Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HADHB.
Mitochondrial disorders v6.4 COX5A Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: COX5A.
Mitochondrial disorders v6.4 COX11 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: COX11.
Mitochondrial disorders v6.4 ATP5E Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ATP5E.
Mitochondrial disorders v6.4 SLC25A24 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SLC25A24.
Mitochondrial disorders v6.4 SLC25A20 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SLC25A20.
Mitochondrial disorders v6.4 SLC22A5 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SLC22A5.
Mitochondrial disorders v6.4 QARS Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: QARS.
Mitochondrial disorders v6.4 PPOX Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PPOX.
Mitochondrial disorders v6.4 PLA2G6 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PLA2G6.
Mitochondrial disorders v6.4 PITRM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PITRM1.
Mitochondrial disorders v6.4 PANK2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PANK2.
Mitochondrial disorders v6.4 OXCT1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: OXCT1.
Hydrocephalus v4.6 HYLS1 Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: HYLS1.
Hydrocephalus v4.6 MYMK Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: MYMK.
Hydrocephalus v4.6 ERF Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: ERF.
Hydrocephalus v4.6 MYMK Arina Puzriakova reviewed gene: MYMK: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hydrocephalus v4.6 HYLS1 Arina Puzriakova reviewed gene: HYLS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hydrocephalus v4.6 ERF Arina Puzriakova reviewed gene: ERF: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hydrocephalus v4.5 MYMK Arina Puzriakova Source Expert Review Amber was added to MYMK.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Hydrocephalus v4.5 ERF Arina Puzriakova Source Expert Review Red was added to ERF.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Mitochondrial disorders v6.4 TEFM Sarah Leigh edited their review of gene: TEFM: Changed rating: GREEN
Mitochondrial disorders v6.4 TAMM41 Sarah Leigh edited their review of gene: TAMM41: Changed rating: GREEN
Mitochondrial disorders v6.4 SLC25A36 Sarah Leigh edited their review of gene: SLC25A36: Changed rating: GREEN
Mitochondrial disorders v6.4 QARS Sarah Leigh edited their review of gene: QARS: Changed rating: GREEN
Mitochondrial disorders v6.4 PPOX Sarah Leigh edited their review of gene: PPOX: Changed rating: GREEN
Mitochondrial disorders v6.4 PANK2 Sarah Leigh edited their review of gene: PANK2: Changed rating: GREEN
Mitochondrial disorders v6.4 OXCT1 Sarah Leigh edited their review of gene: OXCT1: Changed rating: GREEN
Mitochondrial disorders v6.4 HADHB Sarah Leigh edited their review of gene: HADHB: Changed rating: GREEN
Holoprosencephaly - NOT chromosomal v4.9 DISP1 Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: DISP1.
Holoprosencephaly - NOT chromosomal v4.9 DISP1 Arina Puzriakova 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 demoted to Amber following NHS Genomic Medicine Service approval.
Holoprosencephaly - NOT chromosomal v4.9 DISP1 Arina Puzriakova reviewed gene: DISP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Holoprosencephaly - NOT chromosomal v4.8 DISP1 Arina Puzriakova Source Expert Review Amber was added to DISP1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Mitochondrial disorders v6.3 TEFM Sarah Leigh reviewed gene: TEFM: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 TAMM41 Sarah Leigh reviewed gene: TAMM41: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 SLC52A3 Sarah Leigh commented on gene: SLC52A3: The rating of this gene has been updated to green and the mode of inheritance updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Mitochondrial disorders v6.3 SLC52A2 Sarah Leigh edited their review of gene: SLC52A2: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 SLC25A36 Sarah Leigh reviewed gene: SLC25A36: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 SLC25A24 Sarah Leigh commented on gene: SLC25A24: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Mitochondrial disorders v6.3 SLC25A20 Sarah Leigh edited their review of gene: SLC25A20: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 SLC22A5 Sarah Leigh commented on gene: SLC22A5: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Mitochondrial disorders v6.3 QARS Sarah Leigh reviewed gene: QARS: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 PTCD3 Sarah Leigh edited their review of gene: PTCD3: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 PPOX Sarah Leigh edited their review of gene: PPOX: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 PLA2G6 Sarah Leigh commented on gene: PLA2G6: 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.
Mitochondrial disorders v6.3 PITRM1 Sarah Leigh edited their review of gene: PITRM1: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 PANK2 Sarah Leigh reviewed gene: PANK2: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 OXCT1 Sarah Leigh edited their review of gene: OXCT1: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 MRM2 Sarah Leigh edited their review of gene: MRM2: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 HPDL Sarah Leigh edited their review of gene: HPDL: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 HADHB Sarah Leigh edited their review of gene: HADHB: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 COX5A Sarah Leigh edited their review of gene: COX5A: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 COX11 Sarah Leigh edited their review of gene: COX11: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 ATP5E Sarah Leigh edited their review of gene: ATP5E: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.2 TEFM Achchuthan Shanmugasundram Source NHS GMS was added to TEFM.
Source Expert Review Green was added to TEFM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 TAMM41 Achchuthan Shanmugasundram Source NHS GMS was added to TAMM41.
Source Expert Review Green was added to TAMM41.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 SLC52A3 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC52A3.
Mode of inheritance for gene SLC52A3 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)
Mitochondrial disorders v6.2 SLC52A2 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC52A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 SLC25A36 Achchuthan Shanmugasundram Source NHS GMS was added to SLC25A36.
Source Expert Review Green was added to SLC25A36.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 SLC25A24 Achchuthan Shanmugasundram Source NHS GMS was added to SLC25A24.
Source Expert Review Green was added to SLC25A24.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 SLC25A20 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC25A20.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 SLC22A5 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC22A5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 QARS Achchuthan Shanmugasundram Source NHS GMS was added to QARS.
Source Expert Review Green was added to QARS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 PTCD3 Achchuthan Shanmugasundram Source Expert Review Green was added to PTCD3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 PPOX Achchuthan Shanmugasundram Source Expert Review Green was added to PPOX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 PLA2G6 Achchuthan Shanmugasundram Source NHS GMS was added to PLA2G6.
Source Expert Review Green was added to PLA2G6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 PITRM1 Achchuthan Shanmugasundram Source NHS GMS was added to PITRM1.
Source Expert Review Green was added to PITRM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 PANK2 Achchuthan Shanmugasundram Source NHS GMS was added to PANK2.
Source Expert Review Green was added to PANK2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 OXCT1 Achchuthan Shanmugasundram Source Expert Review Green was added to OXCT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 MRM2 Achchuthan Shanmugasundram Source Expert Review Green was added to MRM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 HPDL Achchuthan Shanmugasundram Source NHS GMS was added to HPDL.
Source Expert Review Green was added to HPDL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 HADHB Achchuthan Shanmugasundram Source Expert Review Green was added to HADHB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 COX5A Achchuthan Shanmugasundram Source NHS GMS was added to COX5A.
Source Expert Review Green was added to COX5A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 COX11 Achchuthan Shanmugasundram Source Expert Review Green was added to COX11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 ATP5E Achchuthan Shanmugasundram Source NHS GMS was added to ATP5E.
Source Expert Review Green was added to ATP5E.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.6 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from Neurodevelopmental disorder with hypotonia, neuropathy, and deafness MIM#617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
Early onset or syndromic epilepsy v5.4 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from Neurodevelopmental disorder with hypotonia, neuropathy, and deafness MIM#617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
Monogenic hearing loss v4.41 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, 617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
DDG2P v4.2 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, NEUROPATHY, AND DEAFNESS, OMIM:617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
Hereditary neuropathy v1.478 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, 617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
Hereditary neuropathy or pain disorder v4.8 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, 617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
Hereditary neuropathy or pain disorder v4.7 SPTBN4 Arina Puzriakova Tag for-review was removed from gene: SPTBN4.
Tag to_be_confirmed_NHSE was removed from gene: SPTBN4.
Hereditary neuropathy or pain disorder v4.7 NEMF Arina Puzriakova Phenotypes for gene: NEMF were changed from Hypotonia; Axonal neuropathy; Ataxia; Abnormal brain imaging; Global developmental delay; Intellectual disability; Kyphosis; Scoliosis; Tremor; Respiratory distress to Intellectual developmental disorder with speech delay and axonal peripheral neuropathy, OMIM:619099
Hereditary neuropathy or pain disorder v4.6 NEMF Arina Puzriakova Tag watchlist was removed from gene: NEMF.
Tag for-review was removed from gene: NEMF.
Tag to_be_confirmed_NHSE was removed from gene: NEMF.
Hereditary neuropathy or pain disorder v4.6 SYT2 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: SYT2.
Hereditary neuropathy or pain disorder v4.6 SPTAN1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: SPTAN1.
Hereditary neuropathy or pain disorder v4.6 SARS Arina Puzriakova Tag Q4_23_promote_green was removed from gene: SARS.
Tag Q4_23_NHS_review was removed from gene: SARS.
Hereditary neuropathy or pain disorder v4.6 PPOX Arina Puzriakova Phenotypes for gene: PPOX were changed from Porphyria variegata, 176200; Skin photosensitivity. Acute episodes similar to AIP to Porphyria variegata, OMIM:176200; Sensory neuropathy, HP:0000763
Hereditary neuropathy or pain disorder v4.5 PPOX Arina Puzriakova Tag Q3_23_MOI was removed from gene: PPOX.
Hereditary neuropathy or pain disorder v4.5 ITPR3 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: ITPR3.
Hereditary neuropathy or pain disorder v4.5 DNAJC3 Arina Puzriakova Phenotypes for gene: DNAJC3 were changed from Cerebellar ataxia, neuropathy with SNCV, hearing loss, diabetes mellitus; Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, 616192 to Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, OMIM:616192
Hereditary neuropathy or pain disorder v4.4 DNAJC3 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: DNAJC3.
Hereditary neuropathy or pain disorder v4.4 DHX9 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: DHX9.
Hereditary neuropathy or pain disorder v4.4 DHTKD1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: DHTKD1.
Hereditary neuropathy or pain disorder v4.4 AGTPBP1 Arina Puzriakova Phenotypes for gene: AGTPBP1 were changed from Early onset cerebellar atrophy, developmental delay, and feeding and respiratory difficulties, severe motor neuronopathy; Neurodegeneration, childhood-onset, with cerebellar atrophy, 618276 to Neurodegeneration, childhood-onset, with cerebellar atrophy, OMIM:618276
Hereditary neuropathy or pain disorder v4.3 AGTPBP1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: AGTPBP1.
Hereditary neuropathy or pain disorder v4.3 SPTBN4 Arina Puzriakova edited their review of gene: SPTBN4: 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
Hereditary neuropathy or pain disorder v4.3 NEMF Arina Puzriakova edited their review of gene: NEMF: 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 mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.3 SYT2 Arina Puzriakova reviewed gene: SYT2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.3 SPTAN1 Arina Puzriakova reviewed gene: SPTAN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.3 SLC12A6 Arina Puzriakova edited their review of gene: SLC12A6: 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; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.3 SARS Arina Puzriakova reviewed gene: SARS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.3 PPOX Arina Puzriakova reviewed gene: PPOX: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.3 ITPR3 Arina Puzriakova reviewed gene: ITPR3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.3 DNAJC3 Arina Puzriakova reviewed gene: DNAJC3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.3 DHX9 Arina Puzriakova edited their review of gene: DHX9: 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; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.3 DHTKD1 Arina Puzriakova reviewed gene: DHTKD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.3 AGTPBP1 Arina Puzriakova reviewed gene: AGTPBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.2 SYT2 Arina Puzriakova Source Expert Review Green was added to SYT2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 SPTBN4 Arina Puzriakova Source NHS GMS was added to SPTBN4.
Source Expert Review Green was added to SPTBN4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 SPTAN1 Arina Puzriakova Source NHS GMS was added to SPTAN1.
Source Expert Review Green was added to SPTAN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 SLC12A6 Arina Puzriakova Source Expert Review Green was added to SLC12A6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 SARS Arina Puzriakova Source NHS GMS was added to SARS.
Source Expert Review Green was added to SARS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 PPOX Arina Puzriakova Mode of inheritance for gene PPOX was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.2 NEMF Arina Puzriakova Source NHS GMS was added to NEMF.
Source Expert Review Green was added to NEMF.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 ITPR3 Arina Puzriakova Source NHS GMS was added to ITPR3.
Source Expert Review Green was added to ITPR3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 DNAJC3 Arina Puzriakova Source Expert Review Green was added to DNAJC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 DHX9 Arina Puzriakova Source NHS GMS was added to DHX9.
Source Expert Review Green was added to DHX9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 DHTKD1 Arina Puzriakova Source Expert Review Green was added to DHTKD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 AGTPBP1 Arina Puzriakova Source Expert Review Green was added to AGTPBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb disorders v5.2 ISCA-37467-Gain Arina Puzriakova edited their review of Region: ISCA-37467-Gain: Added comment: The rating of this region has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v6.5 ISCA-46292-Loss Arina Puzriakova reviewed Region: ISCA-46292-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Severe microcephaly v5.3 ISCA-46743-Loss Arina Puzriakova reviewed Region: ISCA-46743-Loss: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v6.5 ISCA-46743-Loss Arina Puzriakova changed review comment from: The rating of this region 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. Evidence: multiple unrelated cases curated in ClinGen plus several others - sufficient evidence for this region. Phenotype: syndromic intellectual disability (congenital anomalies, behavioural problems and facial dysmorphism), seizures in about 30%. Modulated phenotype in females is reported.; to: The rating of this region 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. Evidence: two cases (PMID: 30158690; 33758131) with intragenic STAG2 deletions but listed as sufficient evidence in ClinGen. Region encompasses STAG2 and some of XIAP. Phenotype: holoprosencephaly and/or developmental delay/ID based on LOF of STAG2 gene. Affected females are reported.
Early onset or syndromic epilepsy v5.3 ISCA-46743-Gain Arina Puzriakova changed review comment from: The rating of this region 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. Evidence: multiple unrelated cases curated in ClinGen plus several others - sufficient evidence for this region. Phenotype: syndromic intellectual disability (congenital anomalies, behavioural problems and facial dysmorphism). Modulated phenotype in females is reported.; to: The rating of this region 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. Evidence: multiple unrelated cases curated in ClinGen plus several others - sufficient evidence for this region. Phenotype: syndromic intellectual disability (congenital anomalies, behavioural problems and facial dysmorphism), seizures in about 30%. Modulated phenotype in females is reported.
Intellectual disability v6.5 ISCA-46743-Gain Arina Puzriakova reviewed Region: ISCA-46743-Gain: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Holoprosencephaly - NOT chromosomal v4.7 ISCA-46743-Loss Arina Puzriakova reviewed Region: ISCA-46743-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v6.5 ISCA-46743-Loss Arina Puzriakova reviewed Region: ISCA-46743-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v5.3 ISCA-46743-Gain Arina Puzriakova reviewed Region: ISCA-46743-Gain: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v6.5 ISCA-46292-Loss Arina Puzriakova Publications for Region: ISCA-46292-Loss were set to
Limb disorders v5.2 ISCA-37467-Gain Arina Puzriakova Tag Q3_23_promote_green was removed from Region: ISCA-37467-Gain.
Intellectual disability v6.4 ISCA-46743-Loss Arina Puzriakova Publications for Region: ISCA-46743-Loss were set to
Severe microcephaly v5.3 ISCA-46743-Loss Arina Puzriakova Publications for Region: ISCA-46743-Loss were set to
Holoprosencephaly - NOT chromosomal v4.7 ISCA-46743-Loss Arina Puzriakova Publications for Region: ISCA-46743-Loss were set to
Early onset or syndromic epilepsy v5.3 ISCA-46743-Gain Arina Puzriakova Publications for Region: ISCA-46743-Gain were set to
Intellectual disability v6.3 ISCA-46743-Gain Arina Puzriakova Publications for Region: ISCA-46743-Gain were set to
Limb disorders v5.2 ISCA-37467-Gain Arina Puzriakova Haploinsufficiency Score for ISCA-37467-Gain was changed from None to .
Source Expert Review Green was added to Region: ISCA-37467-Gain.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.2 ISCA-46292-Loss Arina Puzriakova Region: ISCA-46292-Loss was added
Region: ISCA-46292-Loss was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46292-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Severe microcephaly v5.2 ISCA-46743-Loss Arina Puzriakova Region: ISCA-46743-Loss was added
Region: ISCA-46743-Loss was added to Severe microcephaly. Sources: ClinGen,Expert Review Amber
Mode of inheritance for Region: ISCA-46743-Loss was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Holoprosencephaly - NOT chromosomal v4.6 ISCA-46743-Loss Arina Puzriakova Region: ISCA-46743-Loss was added
Region: ISCA-46743-Loss was added to Holoprosencephaly - NOT chromosomal. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46743-Loss was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v6.2 ISCA-46743-Loss Arina Puzriakova Region: ISCA-46743-Loss was added
Region: ISCA-46743-Loss was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46743-Loss was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early onset or syndromic epilepsy v5.2 ISCA-46743-Gain Arina Puzriakova Region: ISCA-46743-Gain was added
Region: ISCA-46743-Gain was added to Early onset or syndromic epilepsy. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46743-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)
Intellectual disability v6.2 ISCA-46743-Gain Arina Puzriakova Region: ISCA-46743-Gain was added
Region: ISCA-46743-Gain was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46743-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)
Rare multisystem ciliopathy Super panel v15.3 Arina Puzriakova Panel version 15.2 has been signed off on 2024-05-01
Hypotonic infant v29.2 Arina Puzriakova Panel version 29.1 has been signed off on 2024-05-01
Cystic renal disease v8.4 Eleanor Williams Panel version 8.3 has been signed off on 2024-05-01
Hereditary ataxia and cerebellar anomalies - childhood onset v15.3 Eleanor Williams Panel version 15.2 has been signed off on 2024-05-01
Sudden unexplained death or survivors of a cardiac event v19.74 Arina Puzriakova Panel version 19.73 has been signed off on 2024-05-01
Childhood onset leukodystrophy v19.3 Eleanor Williams Panel version 19.2 has been signed off on 2024-05-01
Unexplained death in infancy and sudden unexplained death in childhood v9.8 Arina Puzriakova Panel version 9.7 has been signed off on 2024-05-01
Cerebral malformation v11.3 Eleanor Williams Panel version 11.2 has been signed off on 2024-05-01
Other rare neuromuscular disorders v21.3 Eleanor Williams Panel version 21.2 has been signed off on 2024-05-01
Paediatric disorders v45.3 Arina Puzriakova Panel version 45.2 has been signed off on 2024-05-01
Short QT syndrome v3.12 Achchuthan Shanmugasundram Panel version 3.11 has been signed off on 2024-05-01
Progressive cardiac conduction disease v2.8 Achchuthan Shanmugasundram Panel version 2.7 has been signed off on 2024-05-01
Catecholaminergic polymorphic VT v4.6 Achchuthan Shanmugasundram Panel version 4.5 has been signed off on 2024-05-01
Hypertrophic cardiomyopathy v4.9 Achchuthan Shanmugasundram Panel version 4.8 has been signed off on 2024-05-01
Autoinflammatory disorders v2.1 Eleanor Williams Panel version 2.0 has been signed off on 2024-05-01
Autoinflammatory disorders v2.0 Eleanor Williams promoted panel to version 2.0
Brugada syndrome and cardiac sodium channel disease v3.10 Achchuthan Shanmugasundram Panel version 3.9 has been signed off on 2024-05-01
Unexplained young onset end-stage renal disease v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2024-05-01
Differences in sex development v4.6 Achchuthan Shanmugasundram Panel version 4.5 has been signed off on 2024-05-01
Unexplained young onset end-stage renal disease v4.0 Eleanor Williams promoted panel to version 4.0
Arrhythmogenic right ventricular cardiomyopathy v3.11 Achchuthan Shanmugasundram Panel version 3.10 has been signed off on 2024-05-01
Cystic kidney disease v5.1 Eleanor Williams Panel version 5.0 has been signed off on 2024-05-01
Cystic kidney disease v5.0 Eleanor Williams promoted panel to version 5.0
Arthrogryposis v6.1 Achchuthan Shanmugasundram Panel version 6.0 has been signed off on 2024-05-01
Arthrogryposis v6.0 Achchuthan Shanmugasundram promoted panel to version 6.0
Retinal disorders v5.1 Eleanor Williams Panel version 5.0 has been signed off on 2024-05-01
Retinal disorders v5.0 Eleanor Williams promoted panel to version 5.0
Distal myopathies v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2024-05-01
Distal myopathies v4.0 Arina Puzriakova promoted panel to version 4.0
Severe microcephaly v5.1 Achchuthan Shanmugasundram Panel version 5.0 has been signed off on 2024-05-01
Malformations of cortical development v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Malformations of cortical development v5.0 Arina Puzriakova promoted panel to version 5.0
Ophthalmological ciliopathies v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2024-05-01
Rhabdomyolysis and metabolic muscle disorders v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2024-05-01
Severe microcephaly v5.0 Achchuthan Shanmugasundram promoted panel to version 5.0
Rhabdomyolysis and metabolic muscle disorders v4.0 Arina Puzriakova promoted panel to version 4.0
Neurological ciliopathies v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2024-05-01
Rare syndromic craniosynostosis or isolated multisuture synostosis v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Rare syndromic craniosynostosis or isolated multisuture synostosis v5.0 Arina Puzriakova promoted panel to version 5.0
Ophthalmological ciliopathies v4.0 Eleanor Williams promoted panel to version 4.0
Skeletal ciliopathies v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2024-05-01
Neurological ciliopathies v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Neurological segmental overgrowth v2.13 Ivone Leong Panel version 2.12 has been signed off on 2024-05-01
Congenital myaesthenic syndrome v4.6 Ivone Leong Panel version 4.5 has been signed off on 2024-05-01
Ataxia and cerebellar anomalies - narrow panel v5.1 Achchuthan Shanmugasundram Panel version 5.0 has been signed off on 2024-05-01
Childhood onset dystonia, chorea or related movement disorder v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2024-05-01
Ataxia and cerebellar anomalies - narrow panel v5.0 Achchuthan Shanmugasundram promoted panel to version 5.0
Skeletal ciliopathies v4.0 Arina Puzriakova promoted panel to version 4.0
Limb disorders v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
White matter disorders and cerebral calcification - narrow panel v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2024-05-01
Congenital myopathy v4.38 Ivone Leong Panel version 4.37 has been signed off on 2024-05-01
Childhood onset dystonia, chorea or related movement disorder v4.0 Eleanor Williams promoted panel to version 4.0
White matter disorders and cerebral calcification - narrow panel v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Congenital muscular dystrophy v4.24 Ivone Leong Panel version 4.23 has been signed off on 2024-05-01
DDG2P v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2024-05-01
Hereditary neuropathy or pain disorder v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2024-05-01
Limb disorders v5.0 Arina Puzriakova promoted panel to version 5.0
Hereditary neuropathy or pain disorder v4.0 Eleanor Williams promoted panel to version 4.0
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.33 Ivone Leong Panel version 4.32 has been signed off on 2024-05-01
DDG2P v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Paediatric motor neuronopathies v3.7 Ivone Leong Panel version 3.6 has been signed off on 2024-05-01
Adult onset leukodystrophy v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2024-05-01
Paediatric disorders - additional genes v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2024-05-01
Adult onset leukodystrophy v4.0 Eleanor Williams promoted panel to version 4.0
Mitochondrial disorders v6.1 Arina Puzriakova Panel version 6.0 has been signed off on 2024-05-01
Familial hypoparathyroidism v2.15 Ivone Leong Panel version 2.14 has been signed off on 2024-05-01
Paediatric disorders - additional genes v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Skeletal dysplasia v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Skeletal dysplasia v5.0 Arina Puzriakova promoted panel to version 5.0
Possible mitochondrial disorder - nuclear genes v3.106 Ivone Leong Panel version 3.105 has been signed off on 2024-05-01
Clefting v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Paediatric or syndromic cardiomyopathy v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2024-05-01
Childhood onset hereditary spastic paraplegia v5.1 Eleanor Williams Panel version 5.0 has been signed off on 2024-05-01
Mitochondrial disorder with complex IV deficiency v3.21 Ivone Leong Panel version 3.20 has been signed off on 2024-05-01
Clefting v5.0 Arina Puzriakova promoted panel to version 5.0
Childhood onset hereditary spastic paraplegia v5.0 Eleanor Williams promoted panel to version 5.0
Respiratory ciliopathies including non-CF bronchiectasis v3.11 Ivone Leong Panel version 3.10 has been signed off on 2024-05-01
Adult onset hereditary spastic paraplegia v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2024-05-01
Adult onset hereditary spastic paraplegia v4.0 Eleanor Williams promoted panel to version 4.0
Laterality disorders and isomerism v3.10 Ivone Leong Panel version 3.9 has been signed off on 2024-05-01
Mitochondrial disorders v6.0 Arina Puzriakova promoted panel to version 6.0
Paediatric or syndromic cardiomyopathy v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Mitochondrial disorders v5.0 Arina Puzriakova promoted panel to version 5.0
Renal ciliopathies v3.6 Ivone Leong Panel version 3.5 has been signed off on 2024-05-01
Fetal anomalies v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2024-05-01
Early onset or syndromic epilepsy v5.1 Achchuthan Shanmugasundram Panel version 5.0 has been signed off on 2024-05-01
Fetal anomalies v4.0 Arina Puzriakova promoted panel to version 4.0
Holoprosencephaly - NOT chromosomal v4.5 Ivone Leong Panel version 4.4 has been signed off on 2024-05-01
Adult onset neurodegenerative disorder v5.1 Eleanor Williams Panel version 5.0 has been signed off on 2024-05-01
Adult onset neurodegenerative disorder v5.0 Eleanor Williams promoted panel to version 5.0
Early onset or syndromic epilepsy v5.0 Achchuthan Shanmugasundram promoted panel to version 5.0
Long QT syndrome v3.8 Ivone Leong Panel version 3.7 has been signed off on 2024-05-01
Hereditary ataxia with onset in adulthood v5.1 Eleanor Williams Panel version 5.0 has been signed off on 2024-05-01
Likely inborn error of metabolism - targeted testing not possible v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Primary immunodeficiency or monogenic inflammatory bowel disease v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Dilated and arrhythmogenic cardiomyopathy v2.25 Ivone Leong Panel version 2.23 has been signed off on 2024-05-01
Hereditary ataxia with onset in adulthood v5.0 Eleanor Williams promoted panel to version 5.0
Primary immunodeficiency or monogenic inflammatory bowel disease v5.0 Arina Puzriakova promoted panel to version 5.0
Intellectual disability v6.1 Achchuthan Shanmugasundram Panel version 6.0 has been signed off on 2024-05-01
Monogenic hearing loss v4.40 Ivone Leong Panel version 4.39 has been signed off on 2024-05-01
Likely inborn error of metabolism - targeted testing not possible v5.0 Arina Puzriakova promoted panel to version 5.0
Confirmed Fanconi anaemia or Bloom syndrome v2.6 Ivone Leong Panel version 2.5 has been signed off on 2024-05-01
Congenital disorders of glycosylation v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Intellectual disability v6.0 Achchuthan Shanmugasundram promoted panel to version 6.0
Congenital disorders of glycosylation v5.0 Arina Puzriakova promoted panel to version 5.0
Dilated and arrhythmogenic cardiomyopathy v2.24 Ivone Leong Panel version 2.23 has been signed off on 2024-02-01
Paediatric disorders v35.1834 Achchuthan Shanmugasundram Changed child panels to: Intellectual disability; Early onset or syndromic epilepsy; Likely inborn error of metabolism - targeted testing not possible; Clefting; Skeletal dysplasia; Monogenic hearing loss; Limb disorders; DDG2P; Skeletal ciliopathies; Neurological ciliopathies; Paediatric disorders - additional genes; Ophthalmological ciliopathies; Renal ciliopathies
Unexplained death in infancy and sudden unexplained death in childhood v6.430 Eleanor Williams Changed child panels to: Early onset or syndromic epilepsy; Likely inborn error of metabolism - targeted testing not possible; Hypertrophic cardiomyopathy; Catecholaminergic polymorphic VT; Paediatric or syndromic cardiomyopathy; Short QT syndrome; Arrhythmogenic right ventricular cardiomyopathy; Brugada syndrome and cardiac sodium channel disease; Long QT syndrome; Dilated and arrhythmogenic cardiomyopathy; Progressive cardiac conduction disease
Confirmed Fanconi anaemia or Bloom syndrome v2.5 Ivone Leong List of related panels changed from R229; R258 to R229; R258; Confirmed Fanconi anaemia or Bloom syndrome - mutation testing; Cytopenia - Fanconi breakage testing indicated
Differences in sex development v4.5 Ivone Leong Panel name changed from Disorders of sex development to Differences in sex development
List of related panels changed from R146 to R146; Disorders of sex development
Intellectual disability v5.558 Arina Puzriakova Panel name changed from Intellectual disability - microarray and sequencing to Intellectual disability
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; Intellectual disability; 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 - microarray and sequencing; R29
Intellectual disability v5.557 DIP2B Dmitrijs Rots reviewed gene: DIP2B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.557 ADGRL1 Dmitrijs Rots gene: ADGRL1 was added
gene: ADGRL1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: ADGRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADGRL1 were set to PubMed: 35907405
Phenotypes for gene: ADGRL1 were set to Developmental delay, behavioral abnormalities, and neuropsychiatric disorders
Review for gene: ADGRL1 was set to GREEN
Added comment: More than 10 cases described in PubMed: 35907405
Sources: Literature
Hypertrophic cardiomyopathy v4.7 SVIL Dmitrijs Rots gene: SVIL was added
gene: SVIL was added to Hypertrophic cardiomyopathy. Sources: Literature
Mode of inheritance for gene: SVIL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SVIL were set to PMID: 36778260
Phenotypes for gene: SVIL were set to HCM
Review for gene: SVIL was set to AMBER
Added comment: In the novel paper described:"the excess burden is even greater at 15.3-fold (95% CI: 5.7-41.3; P:7x10−7) when restricting the analysis to high confidence LoF variants affecting the predominant SVIL transcript in LV (ENST00000375400) (Supplementary Table 6b). In one family, the SVIL LoF variant (p.(Gln255*)) was carried by two cousins with HCM (parents deceased), providing some evidence of co-segregation. Taken together, these data support SVIL as a novel HCM disease gene."
Strong statistical evidence + one family segregating.
Sources: Literature
Familial non syndromic congenital heart disease v1.80 FLT4 Dmitrijs Rots edited their review of gene: FLT4: Added comment: Statistically proven 30582441 enrichment in multiple affected cases. Enough for green rating.; Changed phenotypes to: Congenital heart defect; Set current diagnostic: yes
Familial non syndromic congenital heart disease v1.80 FLT4 Dmitrijs Rots reviewed gene: FLT4: Rating: GREEN; Mode of pathogenicity: None; Publications: 30582441; Phenotypes: Congenital; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Thrombophilia with a likely monogenic cause v2.5 PLG Zornitza Stark reviewed gene: PLG: Rating: AMBER; Mode of pathogenicity: None; Publications: 35244080, 27976734; Phenotypes: Dysplasminogenemia, MIM# 217090; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Familial breast cancer v1.20 BARD1 Dmitrijs Rots edited their review of gene: BARD1: Added comment: PMID: 37592023 metaanlysis also reports significant association with breast cancer; Changed publications to: PMID: 37592023
Familial breast cancer v1.20 BARD1 Dmitrijs Rots reviewed gene: BARD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v5.31 SLC35A3 Hannah Knight reviewed gene: SLC35A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28777481, 24031089, 28328131, 33416188; Phenotypes: Arthrogryposis, impaired intellectual development, and seizures, 615553 (3), Autosomal recessive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.557 ZNFX1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ZNFX1.
Early onset or syndromic epilepsy v4.196 ZNFX1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ZNFX1.
Early onset or syndromic epilepsy v4.196 YIF1B Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: YIF1B.
Severe microcephaly v4.88 YIF1B Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: YIF1B.
Early onset or syndromic epilepsy v4.196 TRIT1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TRIT1.
Ataxia and cerebellar anomalies - narrow panel v4.64 SVBP Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: SVBP.
Intellectual disability v5.557 RNPC3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: RNPC3.
Mitochondrial disorders v4.169 PITRM1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: PITRM1.
Likely inborn error of metabolism - targeted testing not possible v4.137 PITRM1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: PITRM1.
Intellectual disability v5.557 FILIP1 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: FILIP1.
Arthrogryposis v5.31 FILIP1 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: FILIP1.
Intellectual disability v5.557 OTUD7A Achchuthan Shanmugasundram Tag gene-checked was removed from gene: OTUD7A.
Early onset or syndromic epilepsy v4.196 OTUD7A Achchuthan Shanmugasundram Tag gene-checked was removed from gene: OTUD7A.
Hypertrophic cardiomyopathy v4.7 ALPK3 Dmitrijs Rots commented on gene: ALPK3: As described by Luis Lopes, should be BOTH monoallelic and biallelic on this panel.
Intellectual disability v5.557 CEP295 Achchuthan Shanmugasundram Phenotypes for gene: CEP295 were changed from Seckel syndrome 11, OMIM # 620767 to Seckel syndrome 11, OMIM:620767
Intellectual disability v5.556 CEP295 Achchuthan Shanmugasundram Classified gene: CEP295 as Amber List (moderate evidence)
Intellectual disability v5.556 CEP295 Achchuthan Shanmugasundram Gene: cep295 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.555 CEP295 Achchuthan Shanmugasundram reviewed gene: CEP295: Rating: AMBER; Mode of pathogenicity: None; Publications: 38154379; Phenotypes: Seckel syndrome 11, OMIM:620767; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.555 DOCK4 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: DOCK4.
Intellectual disability v5.555 DOCK4 Achchuthan Shanmugasundram Classified gene: DOCK4 as Amber List (moderate evidence)
Intellectual disability v5.555 DOCK4 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, PMID:38526744 reported seven unrelated individuals with heterozygous variants and with developmental delay or intellectual disability, of which four had ID. Three of them with ID had heterozygous variants, while one had compound heterozygous variants. There is also some functional evidence available.

Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.555 DOCK4 Achchuthan Shanmugasundram Gene: dock4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.554 DOCK4 Achchuthan Shanmugasundram Phenotypes for gene: DOCK4 were changed from neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.554 DOCK4 Achchuthan Shanmugasundram Phenotypes for gene: DOCK4 were changed from DOCK4-related neurodevelopmental disorder (MONDO:0060490) to neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.553 DOCK4 Achchuthan Shanmugasundram reviewed gene: DOCK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 38526744; Phenotypes: neuronevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.553 GTF3C5 Achchuthan Shanmugasundram Publications for gene: GTF3C5 were set to 38520561; 35503477
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark, PMID:35503477 reported a proband with profound developmental delay and PMID:38520561 reported three families with syndromic intellectual disability (ID was mild in one family). There is also functional evidence and evidence from zebrafish model in support of the disease association.

Hence, the gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: As reviewed by Zornitza Stark, PMID:35503477 reported a proband with profound developmental delay and PMID:38520561 reported three families with syndromic intellectual disability (ID was mild in one family). There is also functional evidence and evidence from zebrafish model in support of the disease association.

Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram edited their review of gene: GTF3C5: Changed publications to: 35503477, 38520561
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram Classified gene: GTF3C5 as Amber List (moderate evidence)
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, PMID:35503477 reported a proband with profound developmental delay and PMID:38520561 reported three families with syndromic intellectual disability (ID was mild in one family). There is also functional evidence and evidence from zebrafish model in support of the disease association.

Hence, the gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram Gene: gtf3c5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.551 GTF3C5 Achchuthan Shanmugasundram Phenotypes for gene: GTF3C5 were changed from neurodevelopmental disorder MONDO:0700092, GTF3C5-related to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.550 GTF3C5 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: GTF3C5.
Intellectual disability v5.550 GTF3C5 Achchuthan Shanmugasundram reviewed gene: GTF3C5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal ciliopathies v3.23 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Childhood onset dystonia, chorea or related movement disorder v3.78 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Neurological ciliopathies v3.20 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Ophthalmological ciliopathies v3.7 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Intellectual disability v5.550 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Rare multisystem ciliopathy disorders v1.172 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
DDG2P v3.90 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome to Stromme syndrome, OMIM:243605
Fetal anomalies v3.169 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605 to Stromme syndrome, OMIM:243605
Unexplained young onset end-stage renal disease v3.42 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
CAKUT v1.177 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; bilateral renal hypoplasia; Duodenal atresia; Hydronephrosis to Stromme syndrome, OMIM:243605
Limb disorders v4.23 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Polydactyly; Stromme syndrome 243605 to Stromme syndrome, OMIM:243605
Severe microcephaly v4.88 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from MPD; microcephalic primordial dwarfism; Stromme syndrome, 243605; Microcephaly to Stromme syndrome, OMIM:243605; Microcephalic primordial dwarfism
Intellectual disability v5.549 GMNN Arina Puzriakova Phenotypes for gene: GMNN were changed from Meier-Gorlin syndrome 6, 616835 to Meier-Gorlin syndrome 6, OMIM:616835
Clefting v4.111 GMNN Arina Puzriakova Phenotypes for gene: GMNN were changed from Meier-Gorlin syndrome 6, 616835 to Meier-Gorlin syndrome 6, OMIM:616835
Severe microcephaly v4.87 GMNN Arina Puzriakova Phenotypes for gene: GMNN were changed from MPD; microcephalic primordial dwarfism; Meier-Gorlin syndrome 6, 616835; MGORS6; primordial dwarfism to Meier-Gorlin syndrome 6, OMIM:616835; Microcephalic primordial dwarfism
Intellectual disability v5.548 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from Growth retardation with deafness and mental retardation due to IGF1 deficiency, 608747; INSULIN-LIKE GROWTH FACTOR I DEFICIENCY (IGF1 DEFICIENCY) to Insulin-like growth factor I deficiency, OMIM:608747
Monogenic hearing loss v4.39 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from Growth retardation with deafness and mental retardation due to IGF1 deficiency,608747; GrowthretardationwithdeafnessandmentalretardationduetoIGF1deficiency,608747 to Insulin-like growth factor I deficiency, OMIM:608747
DDG2P v3.89 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from INSULIN-LIKE GROWTH FACTOR I DEFICIENCY 608747 to Insulin-like growth factor I deficiency, OMIM:608747
Fetal anomalies v3.168 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from INSULIN-LIKE GROWTH FACTOR I DEFICIENCY to Insulin-like growth factor I deficiency, OMIM:608747
IUGR and IGF abnormalities v1.69 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from Growth retardation with deafness and mental retardation due to IGF1 deficiency, 608747; Insulin-Like Growth Factor I Deficiency to Insulin-like growth factor I deficiency, OMIM:608747
Silver Russell syndrome v1.13 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from Growth retardation with deafness and mental retardation due to IGF1 deficiency 608747 to Insulin-like growth factor I deficiency, OMIM:608747
Severe microcephaly v4.86 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from Growth retardation with deafness and mental retardation due to IGF1 deficiency, 608747; MPD; microcephalic primordial dwarfism to Insulin-like growth factor I deficiency, OMIM:608747; Microcephalic primordial dwarfism
Intellectual disability v5.547 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from LIG4 syndrome, OMIM:606593 to LIG4 syndrome, OMIM:606593
Haematological malignancies cancer susceptibility v4.5 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from Class: miscellaneous; Ligase IV syndrome; Lymphoma; ALL to LIG4 syndrome, OMIM:606593; Ligase IV syndrome; Lymphoma; ALL
Intellectual disability v5.547 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from LIG4 syndrome, 606593{Multiple myeloma, resistance to}, 254500Severe combined immunodeficiency with sensitivity to ionizing radiation, 602450; LIG4 SYNDROME to LIG4 syndrome, OMIM:606593
Growth failure in early childhood v3.95 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from microcephaly, growth retardation, immunodeficiency, developmental delay to LIG4 syndrome, OMIM:606593; microcephaly, growth retardation, immunodeficiency, developmental delay
Fetal anomalies v3.167 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from SEVERE COMBINED IMMUNODEFICIENCY AUTOSOMAL RECESSIVE T-CELL-NEGATIVE/B-CELL-NEGATIVE/NK-CELL-POSITIVE WITH SENSITIVITY TO IONIZING RADIATION; LIG4 SYNDROME to LIG4 syndrome, OMIM:606593
Cytopenia - NOT Fanconi anaemia v3.34 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from 606593 LIG4 syndrome to LIG4 syndrome, OMIM:606593
IUGR and IGF abnormalities v1.68 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from microcephaly, growth retardation, immunodeficiency, developmental delay to LIG4 syndrome, OMIM:606593; microcephaly, growth retardation, immunodeficiency, developmental delay
Haematological malignancies for rare disease v1.18 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from Class: miscellaneous; Ligase IV syndrome; Lymphoma; ALL to LIG4 syndrome, OMIM:606593; Class: miscellaneous; Ligase IV syndrome; Lymphoma; ALL
Infantile enterocolitis & monogenic inflammatory bowel disease v1.44 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from SCID; LIG4 syndrome 606593 to LIG4 syndrome, OMIM:606593
Severe microcephaly v4.85 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from MPD; microcephalic primordial dwarfism; LIG4 syndrome, 606593; microcephaly to LIG4 syndrome, OMIM:606593; Microcephalic primordial dwarfism
Intellectual disability v5.546 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from Meier-Gorlin syndrome 1, 224690; MEIER-GORLIN SYNDROME 1 to Meier-Gorlin syndrome 1, OMIM:224690
Skeletal dysplasia v4.65 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from Meier-Gorlin syndrome 1 224690; Meier-Gorlin syndrome 1 224690 to Meier-Gorlin syndrome 1, OMIM:224690
Fetal anomalies v3.166 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from MEIER-GORLIN SYNDROME 1 to Meier-Gorlin syndrome 1, OMIM:224690
Limb disorders v4.22 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from Meier-Gorlin syndrome 1 to Meier-Gorlin syndrome 1, OMIM:224690
Deafness and congenital structural abnormalities v1.27 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from Bilateral Microtia; 224690; Meier Gorlin EPS; causes microtia and syndromic features; Meier-Gorlin syndrome 1 to Meier-Gorlin syndrome 1, OMIM:224690; Bilateral Microtia
IUGR and IGF abnormalities v1.67 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from microtia, beaked nose, patellar aplasia/hypoplasia, mammary hypoplasia, micrognathia to Meier-Gorlin syndrome 1, OMIM:224690; microtia, beaked nose, patellar aplasia/hypoplasia, mammary hypoplasia, micrognathia
Severe microcephaly v4.84 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from MPD; microcephalic primordial dwarfism; Meier-Gorlin syndrome 1, 224690 to Meier-Gorlin syndrome 1, OMIM:224690; Microcephalic primordial dwarfism
Intellectual disability v5.545 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from Meier-Gorlin syndrome 2, 613800 to Meier-Gorlin syndrome 2, OMIM:613800
Fetal anomalies v3.165 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from MEIER-GORLIN SYNDROME 2 to Meier-Gorlin syndrome 2, OMIM:613800
Skeletal dysplasia v4.64 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from Meier-Gorlin syndrome 2 613800; Meier-Gorlin syndrome 2 613800 to Meier-Gorlin syndrome 2, OMIM:613800
Deafness and congenital structural abnormalities v1.26 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from Bilateral Microtia; 613800; Meier-Gorlin EPS; causes syndromic features to Meier-Gorlin syndrome 2, OMIM:613800; Bilateral Microtia
IUGR and IGF abnormalities v1.66 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia to Meier-Gorlin syndrome 2, OMIM:613800; micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia
Severe microcephaly v4.83 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from MPD; microcephalic primordial dwarfism; Meier-Gorlin syndrome 2, 613800 to Meier-Gorlin syndrome 2, OMIM:613800; Microcephalic primordial dwarfism
Breast cancer pertinent cancer susceptibility v2.8 PTEN Dmitrijs Rots reviewed gene: PTEN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: PHTS; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Growth failure in early childhood v3.94 PAPPA2 Melissa Connolly reviewed gene: PAPPA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31555216, Durkie et al, 2024 https://www.acgs.uk.com/media/12533/uk-practice-guidelines-for-variant-classification-v12-2024.pdf; Phenotypes: Short stature, dysmorphism, mild microcephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Growth failure in early childhood v3.94 PAPPA2 Melissa Connolly Deleted their review
Growth failure in early childhood v3.94 PAPPA2 Melissa Connolly reviewed gene: PAPPA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31555216, Durkie et al, 2024 https://www.acgs.uk.com/media/12533/uk-practice-guidelines-for-variant-classification-v12-2024.pdf; Phenotypes: Short stature, frontal bossing, prognathism, juvenile cataracts; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.31 COASY Achchuthan Shanmugasundram Classified gene: COASY as Amber List (moderate evidence)
Arthrogryposis v5.31 COASY Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for promoting this gene to green rating in the next GMS review.
Arthrogryposis v5.31 COASY Achchuthan Shanmugasundram Gene: coasy has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.30 COASY Achchuthan Shanmugasundram Phenotypes for gene: COASY were changed from Pontocerebellar hypoplasia, type 12, OMIM:618266; pontocerebellar hypoplasia, type 12, MONDO:0032643 to Neurodegeneration with brain iron accumulation 6, OMIM:615643; Pontocerebellar hypoplasia, type 12, OMIM:618266; arthrogryposis, MONDO:0008779
Arthrogryposis v5.29 COASY Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: COASY.
Tag Q2_24_NHS_review tag was added to gene: COASY.
Arthrogryposis v5.29 COASY Achchuthan Shanmugasundram reviewed gene: COASY: Rating: GREEN; Mode of pathogenicity: None; Publications: 30089828, 35499143, 36495139; Phenotypes: Neurodegeneration with brain iron accumulation 6, OMIM:615643, Pontocerebellar hypoplasia, type 12, OMIM:618266, arthrogryposis, MONDO:0008779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.29 PIP5K1C Achchuthan Shanmugasundram Phenotypes for gene: PIP5K1C were changed from Lethal congenital contractural syndrome 3 611369 to Lethal congenital contractural syndrome 3, OMIM:611369
Arthrogryposis v5.28 PIP5K1C Achchuthan Shanmugasundram Publications for gene: PIP5K1C were set to 17701898
Arthrogryposis v5.27 PIP5K1C Achchuthan Shanmugasundram Classified gene: PIP5K1C as Amber List (moderate evidence)
Arthrogryposis v5.27 PIP5K1C Achchuthan Shanmugasundram Added comment: Comment on list classification: As there are three unrelated cases with biallelic variants (two unrelated cases with the same homozygous variant and two foetuses from one family with compound heterozygous variants), this gene can be promoted to green rating in the next GMS update.
Arthrogryposis v5.27 PIP5K1C Achchuthan Shanmugasundram Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.26 PIP5K1C Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: PIP5K1C.
Tag Q2_24_NHS_review tag was added to gene: PIP5K1C.
Arthrogryposis v5.26 PIP5K1C Achchuthan Shanmugasundram reviewed gene: PIP5K1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 17701898, 38491417; Phenotypes: Lethal congenital contractural syndrome 3, OMIM:611369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.26 TRIP4 Achchuthan Shanmugasundram reviewed gene: TRIP4: Rating: AMBER; Mode of pathogenicity: None; Publications: 31794073; Phenotypes: Spinal muscular atrophy with congenital bone fractures 1, OMIM:616866, ?Muscular dystrophy, congenital, Davignon-Chauveau type, OMIM:617066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.26 COASY Achchuthan Shanmugasundram Publications for gene: COASY were set to 11980892; 25778941; 24360804; 27021474; 28489334; 30089828; 36495139
Ectodermal dysplasia v3.29 TWIST2 Dmitrijs Rots gene: TWIST2 was added
gene: TWIST2 was added to Ectodermal dysplasia. Sources: Expert Review
Mode of inheritance for gene: TWIST2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TWIST2 were set to Focal facial dermal dysplasia 3, Setleis type
Review for gene: TWIST2 was set to GREEN
Added comment: Included as differential for ectodermal dysplasia
Sources: Expert Review
Arthrogryposis v5.25 SLC18A3 Achchuthan Shanmugasundram Classified gene: SLC18A3 as Amber List (moderate evidence)
Arthrogryposis v5.25 SLC18A3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, PMID:34943989 reports an additional patient with compound heterozygous variants in SLC18A3 gene and presenting with arthrogryposis congenital (AMC). Hence, there is sufficient evidence available for promoting this gene to green rating in the next GMS review.
Arthrogryposis v5.25 SLC18A3 Achchuthan Shanmugasundram Gene: slc18a3 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.24 SLC18A3 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: SLC18A3.
Tag Q2_24_NHS_review tag was added to gene: SLC18A3.
Arthrogryposis v5.24 SLC18A3 Achchuthan Shanmugasundram edited their review of gene: SLC18A3: Changed phenotypes to: Myasthenic syndrome, congenital, 21, presynaptic, OMIM:617239, arthrogryposis, MONDO:0008779
Arthrogryposis v5.24 SLC18A3 Achchuthan Shanmugasundram Phenotypes for gene: SLC18A3 were changed from Myasthenic syndrome, congenital, 21, presynaptic, 617239; arthrogryposis to Myasthenic syndrome, congenital, 21, presynaptic, OMIM:617239; arthrogryposis, MONDO:0008779
Arthrogryposis v5.23 SLC18A3 Achchuthan Shanmugasundram Publications for gene: SLC18A3 were set to 28188302; 27590285; 31059209
Arthrogryposis v5.22 SLC18A3 Achchuthan Shanmugasundram reviewed gene: SLC18A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v4.63 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from Meier-Gorlin syndrome 3 613803; Meier-Gorlin syndrome 3 613803 to Meier-Gorlin syndrome 3, OMIM:613803
Intellectual disability v5.544 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from Meier-Gorlin syndrome 3, 613803 to Meier-Gorlin syndrome 3, OMIM:613803
Fetal anomalies v3.164 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from MEIER-GORLIN SYNDROME 3 to Meier-Gorlin syndrome 3, OMIM:613803
Deafness and congenital structural abnormalities v1.25 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from Bilateral Microtia; 613803; Meier-Gorlin EPS; causes syndromic features; Meier-Gorlin syndrome 3 to Meier-Gorlin syndrome 3, OMIM:613803; Bilateral Microtia
IUGR and IGF abnormalities v1.65 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia to Meier-Gorlin syndrome 3, OMIM:613803; micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia
Severe microcephaly v4.82 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from MPD; microcephalic primordial dwarfism; Meier-Gorlin syndrome 3, 613803 to Meier-Gorlin syndrome 3, OMIM:613803; Microcephalic primordial dwarfism
Insulin resistance (including lipodystrophy) v1.17 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from Microcephalic osteodysplastic primordial dwarfism, type II 210720; Osteodysplastic Primordial Dwarfism of Majewski Tyoe 2; Severe Insulin Resistance to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720; Insulin resistance, HP:0000855
IUGR and IGF abnormalities v1.64 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from Seckel syndrome, MOPD type II - growth restrction, microcephaly, prominent nose, micrognathia, squeaky voice, insulin resistance to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
Limb disorders v4.21 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from Microcephalic osteodysplastic primordial dwarfism, type II 210720 to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
Skeletal dysplasia v4.62 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from Microcephalic osteodysplastic primordial dwarfism, type II 210720 to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
DDG2P v3.88 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE II 210720 to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
Fetal anomalies v3.163 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE II to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
Intellectual disability v5.543 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from Microcephalic osteodysplastic primordial dwarfism, type II, 210720 -3; MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE II to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
Growth failure in early childhood v3.94 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from MOPDII; Seckel syndrome, MOPD type II - growth restrction, microcephaly, prominent nose, micrognathia, squeaky voice, insulin resistance, 210720 to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
Severe microcephaly v4.81 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from MPD; microcephalic primordial dwarfism; Microcephalic Osteodysplastic Primordial Dwarfism; Microcephalic osteodysplastic primordial dwarfism, type II, 210720 to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720; Microcephalic primordial dwarfism
Retinal disorders v4.90 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Lowry-Wood syndrome, OMIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710; Roifman syndrome, OMIM:616651 to Lowry-Wood syndrome, OMIM:226960; Roifman syndrome, OMIM:616651
Intellectual disability v5.542 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Gene2Phenotype confirmed gene with ID HPO to Lowry-Wood syndrome, OMIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710; Roifman syndrome, OMIM:616651
Early onset or syndromic epilepsy v4.196 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Microcephalic osteodysplastic primordial dwarfism, type I 210710 to Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710
Growth failure in early childhood v3.93 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from MOPD I to Lowry-Wood syndrome, OMIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710
Fetal anomalies v3.162 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE I to Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710
Cytopenia - NOT Fanconi anaemia v3.33 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Roifman syndrome, 616651; Microcephalic osteodysplastic primordial dwarfism, type I, 210710 to Roifman syndrome, OMIM:616651
Bleeding and platelet disorders v3.10 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Microcephalic osteodysplastic primordial dwarfism, type I / Roifman syndrome to Roifman syndrome, OMIM:616651
Inherited bleeding disorders v1.178 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Platelet disorder; Roifman Syndrome with thrombocytopenia and Primary immunodeficiency to Roifman syndrome, OMIM:616651; Roifman Syndrome with thrombocytopenia and Primary immunodeficiency
Skeletal dysplasia v4.61 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Roifman syndrome 616651; Microcephalic osteodysplastic primordial dwarfism, type I 210710 to Lowry-Wood syndrome, OMIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710; Roifman syndrome, OMIM:616651
Limb disorders v4.20 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Microcephalic osteodysplastic primordial dwarfism, type I 210710; Roifman syndrome 616651 to Lowry-Wood syndrome, OMIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710; Roifman syndrome, OMIM:616651
Primary immunodeficiency or monogenic inflammatory bowel disease v4.202 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly, short stature; Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly; Combined immunodeficiencies with associated or syndromic features to Roifman syndrome, OMIM:616651; Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly
COVID-19 research v1.142 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly; Combined immunodeficiencies with associated or syndromic features; Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly, short stature to Roifman syndrome, OMIM:616651; Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly
Severe microcephaly v4.80 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Microcephalic osteodysplastic primordial dwarfism, type I; Microcephalic osteodysplastic primordial dwarfism, type I, 210710; MPD; microcephalic primordial dwarfism to Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710; Lowry-Wood syndrome, OMIM:226960; Microcephalic primordial dwarfism
Intellectual disability v5.541 TRAIP Arina Puzriakova Phenotypes for gene: TRAIP were changed from Seckel syndrome 9, 616777 to Seckel syndrome 9, OMIM:616777
Cerebral vascular malformations v3.16 TRAIP Arina Puzriakova Phenotypes for gene: TRAIP were changed from Seckel syndrome 9 616777 to Seckel syndrome 9, OMIM:616777
Fetal anomalies v3.161 TRAIP Arina Puzriakova Phenotypes for gene: TRAIP were changed from Seckel syndrome 9 to Seckel syndrome 9, OMIM:616777
Severe microcephaly v4.79 TRAIP Arina Puzriakova Phenotypes for gene: TRAIP were changed from MPD; microcephalic primordial dwarfism; Seckel syndrome 9, 616777; Microcephaly to Seckel syndrome 9, OMIM:616777; Microcephalic primordial dwarfism
Mitochondrial disorders v4.169 XRCC4 Arina Puzriakova Mode of inheritance for gene: XRCC4 was changed from to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.169 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from Short stature, microcephaly, and endocrine dysfunction 616541 to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541
Growth failure in early childhood v3.92 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from short stature, microcephaly, hypothyroidism, diabetes mellitus, progressive ataxia, hypergonadotrophic hypogonadism to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541
Fetal anomalies v3.160 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from PRIMORDIAL DWARFISM to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541
Skeletal dysplasia v4.60 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from Short stature, microcephaly, and endocrine dysfunction 616541 to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541
Intellectual disability v5.540 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from PRIMORDIAL DWARFISM to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541
IUGR and IGF abnormalities v1.63 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from short stature, microcephaly, hypothyroidism, diabetes mellitus, progressive ataxia, hypergonadotrophic hypogonadism to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541; Short stature, microcephaly, hypothyroidism, diabetes mellitus, progressive ataxia, hypergonadotrophic hypogonadism
Severe microcephaly v4.78 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from MPD; microcephalic primordial dwarfism; Short stature, microcephaly, and endocrine dysfunction, 616541 to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541; Microcephalic primordial dwarfism
Severe microcephaly v4.77 ATRIP Arina Puzriakova Publications for gene: ATRIP were set to
Severe microcephaly v4.76 ATRIP Arina Puzriakova Mode of inheritance for gene: ATRIP was changed from to BIALLELIC, autosomal or pseudoautosomal
Growth failure in early childhood v3.91 ATRIP Arina Puzriakova Phenotypes for gene: ATRIP were changed from microcephaly, micrognathia, small ear lobes, dental crowding to Microcephalic primordial dwarfism; Microcephaly, micrognathia, small ear lobes, dental crowding
Severe microcephaly v4.75 ATRIP Arina Puzriakova Phenotypes for gene: ATRIP were changed from MPD; microcephalic primordial dwarfism; severe microcephaly (-10 SD), micrognathia, dental crowding, small earlobes, delayed bone age, and symmetric dwarfism to Microcephalic primordial dwarfism; Severe microcephaly (-10 SD), micrognathia, dental crowding, small earlobes, delayed bone age, and symmetric dwarfism
Intellectual disability v5.539 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from MEIER-GORLIN SYNDROME 5 to Meier-Gorlin syndrome 5, OMIM:613805
Growth failure in early childhood v3.90 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from ?Meier-Gorlin syndrome 5, 613805; patellar hypoplasia/aplasia, microtia, meier-gorlin syndrome, mammary hypoplasia to Meier-Gorlin syndrome 5, OMIM:613805; patellar hypoplasia/aplasia, microtia, meier-gorlin syndrome, mammary hypoplasia
Skeletal dysplasia v4.59 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from Meier-Gorlin syndrome 5 613805 to Meier-Gorlin syndrome 5, OMIM:613805
Fetal anomalies v3.159 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from MEIER-GORLIN SYNDROME 5 to Meier-Gorlin syndrome 5, OMIM:613805
Deafness and congenital structural abnormalities v1.24 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from Bilateral Microtia; 613805; Meier-Gorlin syndrome 5, 613805; Neurology panel; Bilateral Microtia, 613805; Causes Meier-Gorlin EPS; syndromic features to Meier-Gorlin syndrome 5, OMIM:613805; Bilateral Microtia
IUGR and IGF abnormalities v1.62 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from patellar hypoplasia/aplasia, microtia, meier-gorlin syndrome, mammary hypoplasia to Meier-Gorlin syndrome 5, OMIM:613805; patellar hypoplasia/aplasia, microtia, meier-gorlin syndrome, mammary hypoplasia
Severe microcephaly v4.74 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from MPD; microcephalic primordial dwarfism; ?Meier-Gorlin syndrome 5, 613805 to Meier-Gorlin syndrome 5, OMIM:613805; Microcephalic primordial dwarfism
Severe microcephaly v4.73 CENPE Arina Puzriakova Phenotypes for gene: CENPE were changed from ?Microcephaly 13, primary, autosomal recessive, 616051; MPD; microcephalic primordial dwarfism to ?Microcephaly 13, primary, autosomal recessive, OMIM:616051; Microcephalic primordial dwarfism
Intellectual disability v5.538 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from MEIER-GORLIN SYNDROME 4 to Meier-Gorlin syndrome 4, OMIM:613804
Skeletal dysplasia v4.58 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from Meier-Gorlin syndrome 4 613804 to Meier-Gorlin syndrome 4, OMIM:613804
Fetal anomalies v3.158 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from MEIER-GORLIN SYNDROME 4 to Meier-Gorlin syndrome 4, OMIM:613804
Deafness and congenital structural abnormalities v1.23 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from Bilateral Microtia; 613804; Meier-Gorlin syndrome 4, 613804; Causes Meier-Gorlin EPS; syndromic features; Short stature, small head size, the ears may be low-set or rotated backward (+/-microtia). Additional features can include a small mouth (microstomia), an underdeveloped lower jaw (micrognathia), full lips, and a narrow nose with a high nasal bridge to Meier-Gorlin syndrome 4, OMIM:613804; Short stature, small head size, the ears may be low-set or rotated backward (+/-microtia). Additional features can include a small mouth (microstomia), an underdeveloped lower jaw (micrognathia), full lips, and a narrow nose with a high nasal bridge
IUGR and IGF abnormalities v1.61 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from micrognathia, microtia, patellar hypoplasia/aplasia, mammary hypoplasia to Meier-Gorlin syndrome 4, OMIM:613804; micrognathia, microtia, patellar hypoplasia/aplasia, mammary hypoplasia
Severe microcephaly v4.72 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from MPD; microcephalic primordial dwarfism; Meier-Gorlin syndrome 4, 613804 to Meier-Gorlin syndrome 4, OMIM:613804; Microcephalic primordial dwarfism
Monogenic diabetes v2.58 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome to Bloom syndrome, OMIM:210900
Pigmentary skin disorders v3.12 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome to Bloom syndrome, OMIM:210900
Primary ovarian insufficiency v1.68 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome 210900 to Bloom syndrome, OMIM:210900
IUGR and IGF abnormalities v1.60 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome, 210900 to Bloom syndrome, OMIM:210900
Haematological malignancies for rare disease v1.17 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Class: BM failure syndrome (typ AR); Bloom syndrome; leukaemia; lymphoma; skin squamous cell; other tumour types; Lymphoma; ALL; MDS; AML; Leukaemia; Carcinomas to Bloom syndrome, OMIM:210900; Class: BM failure syndrome (typ AR); Bloom syndrome; leukaemia; lymphoma; skin squamous cell; other tumour types; Lymphoma; ALL; MDS; AML; Leukaemia; Carcinomas
Severe microcephaly v4.71 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome, OMIM:210900 to Bloom syndrome, OMIM:210900; Microcephalic primordial dwarfism
Hereditary haemorrhagic telangiectasia v3.6 ATR Arina Puzriakova Phenotypes for gene: ATR were changed from Cutaneous telangiectasia and cancer syndrome, familial, 614564 (biallelic) to ?Cutaneous telangiectasia and cancer syndrome, familial, OMIM:614564
Intellectual disability v5.537 ATR Arina Puzriakova Phenotypes for gene: ATR were changed from Seckel syndrome 1, 210600Cutaneous telangiectasia and cancer syndrome, familial, 614564; SECKEL SYNDROME TYPE 1 (SCKL1) to Seckel syndrome 1, OMIM:210600
Clefting v4.110 ATR Arina Puzriakova Phenotypes for gene: ATR were changed from SECKEL SYNDROME 1; SCKL1 to Seckel syndrome 1, OMIM:210600
Clefting v4.110 ATR Arina Puzriakova Mode of inheritance for gene: ATR was changed from to BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v4.70 ATR Arina Puzriakova Publications for gene: ATR were set to
Severe microcephaly v4.69 ATR Arina Puzriakova Phenotypes for gene: ATR were changed from MPD; microcephalic primordial dwarfism; Seckel syndrome 1, 210600; MICROCEPHALIC PRIMORDIAL DWARFISM I to Seckel syndrome 1, OMIM:210600; Microcephalic primordial dwarfism
Intellectual disability v5.536 FEM1B Zornitza Stark edited their review of gene: FEM1B: Added comment: Five individuals reported now with same recurrent missense variant, NM_015322.5:c.377G>A NP_056137.1:p.(Arg126Gln). Affected individuals shared a severe neurodevelopmental disorder with behavioral phenotypes and a variable set of malformations, including brain anomalies, clubfeet, skeletal abnormalities, and facial dysmorphism. Overexpression of the the FEM1BR126Q variant but not FEM1B wild-type protein, during mouse brain development, resulted in delayed neuronal migration of the target cells.; Changed rating: GREEN; Changed publications to: 31036916, 38465576; Changed phenotypes to: Syndromic disease MONDO:0002254, FEM1B-related
Fetal anomalies v3.157 USP14 Zornitza Stark gene: USP14 was added
gene: USP14 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: USP14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP14 were set to 38469793
Phenotypes for gene: USP14 were set to Syndromic disease MONDO:0002254, USP14-related
Review for gene: USP14 was set to AMBER
Added comment: PMID 38469793: biallelic USP14 variants in four individuals from three unrelated families: one fetus, a newborn with a syndromic NDD, and two siblings affected by a progressive neurological disease. Specifically, the two siblings from the latter family carried two compound heterozygous variants c.8T>C p.(Leu3Pro) and c.988C>T p.(Arg330*), while the fetus had a homozygous frameshift c.899_902del p.(Lys300Serfs*24) variant and the newborn patient harbored a homozygous frameshift c.233_236del p.(Leu78Glnfs*11) variant. The fetus and the newborn had extensive brain malformations.
Sources: Literature
Intellectual disability v5.536 RNU4-2 Zornitza Stark gene: RNU4-2 was added
gene: RNU4-2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: RNU4-2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNU4-2 were set to 38645094
Phenotypes for gene: RNU4-2 were set to Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related
Review for gene: RNU4-2 was set to GREEN
Added comment: Over 100 individuals reported with NND and heterozygous variants in a 18 bp region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and Stem III). The vast majority of individuals (77.3%) have the same highly recurrent single base-pair insertion (n.64_65insT). Variants in this region likely explain 0.41% of individuals with NDD.
Sources: Literature
Intellectual disability v5.536 ACBD6 Arina Puzriakova Added comment: Comment on phenotypes: This gene now has a relevant phenotype listed in OMIM (MIM# 620785)
Intellectual disability v5.536 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Childhood onset dystonia, chorea or related movement disorder v3.77 ACBD6 Arina Puzriakova Added comment: Comment on phenotypes: This gene now has a relevant phenotype listed in OMIM (MIM# 620785)
Childhood onset dystonia, chorea or related movement disorder v3.77 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Childhood onset hereditary spastic paraplegia v4.43 ACBD6 Arina Puzriakova Added comment: Comment on phenotypes: This gene now has a relevant phenotype listed in OMIM (MIM# 620785)
Childhood onset hereditary spastic paraplegia v4.43 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Severe microcephaly v4.68 ACBD6 Arina Puzriakova Added comment: Comment on phenotypes: This gene now has a relevant phenotype listed in OMIM (MIM# 620785)
Severe microcephaly v4.68 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Ataxia and cerebellar anomalies - narrow panel v4.64 ACBD6 Arina Puzriakova Added comment: Comment on phenotypes: This gene now has a relevant phenotype listed in OMIM (MIM# 620785)
Ataxia and cerebellar anomalies - narrow panel v4.64 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Paediatric disorders - additional genes v3.10 PLD1 Arina Puzriakova changed review comment from: Comment on list classification: This Green gene was signed off in Nov 2022 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.; to: Comment on list classification: This Green gene was signed off in Mar 2023 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.
Fetal anomalies v3.157 PLD1 Arina Puzriakova changed review comment from: Comment on list classification: This Green gene was signed off in Nov 2022 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.; to: Comment on list classification: This Green gene was signed off in Mar 2023 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.
Paediatric disorders - additional genes v3.10 PLD1 Arina Puzriakova Classified gene: PLD1 as Green List (high evidence)
Paediatric disorders - additional genes v3.10 PLD1 Arina Puzriakova Added comment: Comment on list classification: This Green gene was signed off in Nov 2022 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.
Paediatric disorders - additional genes v3.10 PLD1 Arina Puzriakova Gene: pld1 has been classified as Green List (High Evidence).
Fetal anomalies v3.157 PLD1 Arina Puzriakova Classified gene: PLD1 as Green List (high evidence)
Fetal anomalies v3.157 PLD1 Arina Puzriakova Added comment: Comment on list classification: This Green gene was signed off in Nov 2022 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.
Fetal anomalies v3.157 PLD1 Arina Puzriakova Gene: pld1 has been classified as Green List (High Evidence).
Fetal anomalies v3.156 PLD1 Arina Puzriakova Tag Q2_24_demote_red tag was added to gene: PLD1.
Tag Q2_24_expert_review tag was added to gene: PLD1.
Paediatric disorders - additional genes v3.9 PLD1 Arina Puzriakova Tag Q2_24_demote_red tag was added to gene: PLD1.
Tag Q2_24_expert_review tag was added to gene: PLD1.
Paediatric disorders - additional genes v3.9 PLD1 Arina Puzriakova commented on gene: PLD1: Copied review from Paediatric or syndromic cardiomyopathy (749) v3.43 panel:

Jesse Hayesmoore (Oxford Regional Genetics Laboratory)
Red List (low evidence)

"On the basis of functional data described in PMIDs: 27799408 and 33645542, PLD1 certainly seems to be a plausible functional candidate for causality of cardiac valvular defects. The main paper linking this gene with congenital heart disease / cardiomyopathy is Lahrouchi et al. (2021; PMID: 33645542; note this also includes the same 2 cases as described in Ta-Shma et al. 2017 PMID: 27799408). The paper presents 19 families with severe fetal- / neonatal-onset congenital heart (mainly valvular) defects and 2 with cardiomyopathy where affected babies were homozygous or compound heterozygous for PLD1 variants. The paper also provides some functional analysis of missense variants detected, showing that many but not all of them result significant loss of PLD1 function. Unfortunately, the paper does not include a LOD score, and there is very little cosegregation data presented for any of the variants. In addition, 4 of the 31 variants they promote as pathogenic for autosomal recessive disease are detected in multiple homozygous individuals on gnomAD, which I think provides significant evidence that they might not be pathogenic for a severe autosomal recessive condition. Most notably, 1 of the variants (i.e. I668F), which the authors promote as a pathogenic Ashkenazi Jewish founder variant (but which is also fairly frequent in non-Finnish Europeans) is detected in 7 homozygotes on gnomAD and was found to have ~80% loss of PLD1 function in their assay. This suggests that significant loss of function of this gene (i.e. down to 20%) might not be causative of a severe recessive condition (that is not to say that total or near total loss of function is not causative). Three other of the variants promoted as pathogenic in this article are also detected in homozygotes on gnomAD.

I think one of the major pieces of missing information required to make a full assessment of this gene’s linkage to disease is that is unknown how frequent biallelic (apparently loss of function) variant genotypes are in the general population or in healthy control individuals. Although homozygosity for any one variant can be determined from gnomAD, compound heterozygosity (which is likely to represent the vast majority of biallelic genotypes) cannot be assessed on gnomAD, and I can find no record in the literature of this being assessed in a normal control cohort. Without this information, we cannot know whether biallelic PLD1 genotypes are specific to babies with this severe phenotype. Without knowing this, and in the absence of any significant cosegregation data for any variant, there is no reasonable basis upon which one can conclude that this is a valid autosomal recessive gene for the phenotype. Without such validation, PVS1 cannot be applied for any apparent loss of function variant. Given this, and the general lack of cosegregation data for any one variant, I do not believe there is any PLD1 variant reported in the literature that could be classified as anything but uncertain significance (if not benign or likely benign) on the basis of current variant classification guidelines. Also, there are only two cases of biallelic variants in neonates where the primary phenotype is cardiomyopathy, and of these only one was dilated cardiomyopathy (the other was histiocytoid cardiomyopathy). Hence, the evidence linking this gene to cardiomyopathy is even weaker than it is for valvular defects. I, therefore, do not feel there is sufficient evidence to justify this gene being tested as part of the R135 paediatric cardiomyopathy gene panel.

Other papers (e.g. PMIDs: 33142350, 35380090, 36923242, 37770978) reporting a link between PLD1 genotypes and early onset cardiac disease (not cardiomyopathy) have been published. However, again, I do not think there is sufficient data in the articles to allow any of the variants detected to be confidently classified as anything but VUS according to current variant classification guidelines."
Created: 31 Jan 2024, 12:04 p.m. | Last Modified: 31 Jan 2024, 12:17 p.m
Paediatric or syndromic cardiomyopathy v3.47 PLD1 Arina Puzriakova Classified gene: PLD1 as Green List (high evidence)
Paediatric or syndromic cardiomyopathy v3.47 PLD1 Arina Puzriakova Added comment: Comment on list classification: This Green gene was signed off in Nov 2022 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.
Paediatric or syndromic cardiomyopathy v3.47 PLD1 Arina Puzriakova Gene: pld1 has been classified as Green List (High Evidence).
Fetal anomalies v3.156 PLD1 Arina Puzriakova commented on gene: PLD1: Copied review from Paediatric or syndromic cardiomyopathy (749) v3.43 panel:

Jesse Hayesmoore (Oxford Regional Genetics Laboratory)
Red List (low evidence)

"On the basis of functional data described in PMIDs: 27799408 and 33645542, PLD1 certainly seems to be a plausible functional candidate for causality of cardiac valvular defects. The main paper linking this gene with congenital heart disease / cardiomyopathy is Lahrouchi et al. (2021; PMID: 33645542; note this also includes the same 2 cases as described in Ta-Shma et al. 2017 PMID: 27799408). The paper presents 19 families with severe fetal- / neonatal-onset congenital heart (mainly valvular) defects and 2 with cardiomyopathy where affected babies were homozygous or compound heterozygous for PLD1 variants. The paper also provides some functional analysis of missense variants detected, showing that many but not all of them result significant loss of PLD1 function. Unfortunately, the paper does not include a LOD score, and there is very little cosegregation data presented for any of the variants. In addition, 4 of the 31 variants they promote as pathogenic for autosomal recessive disease are detected in multiple homozygous individuals on gnomAD, which I think provides significant evidence that they might not be pathogenic for a severe autosomal recessive condition. Most notably, 1 of the variants (i.e. I668F), which the authors promote as a pathogenic Ashkenazi Jewish founder variant (but which is also fairly frequent in non-Finnish Europeans) is detected in 7 homozygotes on gnomAD and was found to have ~80% loss of PLD1 function in their assay. This suggests that significant loss of function of this gene (i.e. down to 20%) might not be causative of a severe recessive condition (that is not to say that total or near total loss of function is not causative). Three other of the variants promoted as pathogenic in this article are also detected in homozygotes on gnomAD.

I think one of the major pieces of missing information required to make a full assessment of this gene’s linkage to disease is that is unknown how frequent biallelic (apparently loss of function) variant genotypes are in the general population or in healthy control individuals. Although homozygosity for any one variant can be determined from gnomAD, compound heterozygosity (which is likely to represent the vast majority of biallelic genotypes) cannot be assessed on gnomAD, and I can find no record in the literature of this being assessed in a normal control cohort. Without this information, we cannot know whether biallelic PLD1 genotypes are specific to babies with this severe phenotype. Without knowing this, and in the absence of any significant cosegregation data for any variant, there is no reasonable basis upon which one can conclude that this is a valid autosomal recessive gene for the phenotype. Without such validation, PVS1 cannot be applied for any apparent loss of function variant. Given this, and the general lack of cosegregation data for any one variant, I do not believe there is any PLD1 variant reported in the literature that could be classified as anything but uncertain significance (if not benign or likely benign) on the basis of current variant classification guidelines. Also, there are only two cases of biallelic variants in neonates where the primary phenotype is cardiomyopathy, and of these only one was dilated cardiomyopathy (the other was histiocytoid cardiomyopathy). Hence, the evidence linking this gene to cardiomyopathy is even weaker than it is for valvular defects. I, therefore, do not feel there is sufficient evidence to justify this gene being tested as part of the R135 paediatric cardiomyopathy gene panel.

Other papers (e.g. PMIDs: 33142350, 35380090, 36923242, 37770978) reporting a link between PLD1 genotypes and early onset cardiac disease (not cardiomyopathy) have been published. However, again, I do not think there is sufficient data in the articles to allow any of the variants detected to be confidently classified as anything but VUS according to current variant classification guidelines."
Created: 31 Jan 2024, 12:04 p.m. | Last Modified: 31 Jan 2024, 12:17 p.m
Paediatric or syndromic cardiomyopathy v3.46 PLD1 Arina Puzriakova Tag Q2_24_demote_red tag was added to gene: PLD1.
Tag Q2_24_expert_review tag was added to gene: PLD1.
Tag Q2_24_NHS_review tag was added to gene: PLD1.
Early onset or syndromic epilepsy v4.195 GLI3 Arina Puzriakova Mode of inheritance for gene: GLI3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v4.194 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Skeletal ciliopathies v3.22 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Joubert Syndrome and Senior-Loken Syndrome 24 gene panel to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Childhood onset dystonia, chorea or related movement disorder v3.76 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Joubert Syndrome and Senior-Loken Syndrome 24 gene panel to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Neurological ciliopathies v3.19 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Joubert Syndrome and Senior-Loken Syndrome 24 gene panel to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Ophthalmological ciliopathies v3.6 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Joubert Syndrome and Senior-Loken Syndrome 24 gene panel to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Rare multisystem ciliopathy disorders v1.171 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Joubert Syndrome and Senior-Loken Syndrome 24 gene panel to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Growth failure in early childhood v3.89 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Pallister-Hall syndrome to Pallister-Hall syndrome, OMIM:146510
Clefting v4.109 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Pallister-Hall syndrome, 146510 to Pallister-Hall syndrome, OMIM:146510
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.180 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Greig cephalopolysyndactyly syndrome 175700; 175700 to Greig cephalopolysyndactyly syndrome, OMIM:175700
Unexplained young onset end-stage renal disease v3.41 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Pallister-Hall syndrome; Pallister-Hall syndrome 146510 to Pallister-Hall syndrome, OMIM:146510
CAKUT v1.176 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Pallister-Hall syndrome to Pallister-Hall syndrome, OMIM:146510
Unexplained kidney failure in young people v1.119 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Pallister-Hall syndrome 146510 to Pallister-Hall syndrome, OMIM:146510
Fetal anomalies v3.156 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from PALLISTER-HALL SYNDROME; GREIG CEPHALOPOLYSYNDACTYLY SYNDROME; PREAXIAL POLYDACTYLY TYPE IV; POSTAXIAL POLYDACTYLY TYPE A to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510; Polydactyly, postaxial, types A1 and B, OMIM:174200; Polydactyly, preaxial, type IV, OMIM:174700
Skeletal dysplasia v4.57 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Greig cephalopolysyndactyly syndrome 175700; Polydactyly, postaxial, types A1 and B 174200; Polydactyly, preaxial, type IV 174700; Pallister-Hall syndrome 146510; {Hypothalamic hamartomas, somatic} 241800 to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510; Polydactyly, postaxial, types A1 and B, OMIM:174200; Polydactyly, preaxial, type IV, OMIM:174700
Limb disorders v4.19 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Greig cephalopolysyndactyly syndrome 175700; Pallister-Hall syndrome 146510; Polydactyly, postaxial, types A1 and B 174200; Polydactyly, preaxial, type IV 174700; {Hypothalamic hamartomas, somatic} 241800; Polydactyly to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510; Polydactyly, postaxial, types A1 and B, OMIM:174200; Polydactyly, preaxial, type IV, OMIM:174700
Pituitary hormone deficiency v3.12 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Greig cephalopolysyndactyly syndrome (175700); Pallister-Hall syndrome (146510) to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Intellectual disability v5.535 GLI3 Arina Puzriakova Tag Q2_24_demote_amber tag was added to gene: GLI3.
Tag Q2_24_NHS_review tag was added to gene: GLI3.
Intellectual disability v5.535 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Greig cephalopolysyndactyly syndrome, 175700Pallister-Hall syndrome, 146510Polydactyly, preaxial, type IV, 174700Polydactyly, postaxial, types A1 and B, 174200{Hypothalamic hamartomas, somatic}, 241800; GREIG CEPHALOPOLYSYNDACTYLY SYNDROME to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Intellectual disability v5.534 GLI3 Arina Puzriakova Publications for gene: GLI3 were set to
Intellectual disability v5.533 GLI3 Arina Puzriakova Classified gene: GLI3 as Green List (high evidence)
Intellectual disability v5.533 GLI3 Arina Puzriakova Added comment: Comment on list classification: Reassessed in view of the Red review by Tracy Lester on this Green gene

Rarely, individuals with Greig cephalopolysyndactyly syndrome or GLI3-Related Pallister-Hall syndrome have been found to have intellectual disability (PMID: 12414818; 14708104; 14608643; 34296525). This is usually observed in the most severely affected individuals and those with large deletions encompassing GLI3. The majority of patients have normal psychomotor development or only some mild delays. All GLI3-related disorders are more likely to be recognised in context of other features such as skeletal abnormalities.

Overall, I therefore agree that this gene could be demoted to Amber at the next GMS panel update.
Intellectual disability v5.533 GLI3 Arina Puzriakova Gene: gli3 has been classified as Green List (High Evidence).
Pigmentary skin disorders v3.11 BLM Dmitrijs Rots gene: BLM was added
gene: BLM was added to Pigmentary skin disorders. Sources: Expert Review
Mode of inheritance for gene: BLM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BLM were set to PMID: 32972601
Phenotypes for gene: BLM were set to Bloom syndrome
Penetrance for gene: BLM were set to Complete
Review for gene: BLM was set to GREEN
Added comment: Included in the review PMID: 32972601 as differential for cafe-au-lait
Sources: Expert Review
Pigmentary skin disorders v3.11 SMARCB1 Dmitrijs Rots gene: SMARCB1 was added
gene: SMARCB1 was added to Pigmentary skin disorders. Sources: Expert Review
Mode of inheritance for gene: SMARCB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCB1 were set to PMID: 32972601
Phenotypes for gene: SMARCB1 were set to Schwannomatosis-1, susceptibility to
Penetrance for gene: SMARCB1 were set to Incomplete
Review for gene: SMARCB1 was set to GREEN
Added comment: Included in the review PMID: 32972601 as differential for cafe-au-lait
Sources: Expert Review
Intellectual disability v5.532 CPA6 Arina Puzriakova Tag refuted tag was added to gene: CPA6.
Intellectual disability v5.532 CPA6 Arina Puzriakova commented on gene: CPA6
Severe microcephaly v4.67 SASS6 Zornitza Stark edited their review of gene: SASS6: Added comment: Two additional families:

PMID: 38501757
1x compound het for a fs and +3 splice variant.

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

PMID: 36739862
1x family, compound het for 2 missense
Functional studies not performed; Changed rating: GREEN; Changed publications to: 24951542, 30639237, 38501757, 36739862
Intellectual disability v5.532 KCNB2 Zornitza Stark gene: KCNB2 was added
gene: KCNB2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: KCNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNB2 were set to 38503299
Phenotypes for gene: KCNB2 were set to neurodevelopmental disorder MONDO:0700092, KCNB2-related
Review for gene: KCNB2 was set to GREEN
Added comment: 7 individuals, all missense
5 de novo + 1x inherited from father who has hypotonia + 1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature
Intellectual disability v5.532 GTF3C5 Zornitza Stark gene: GTF3C5 was added
gene: GTF3C5 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: GTF3C5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C5 were set to 38520561; 35503477
Phenotypes for gene: GTF3C5 were set to neurodevelopmental disorder MONDO:0700092, GTF3C5-related
Review for gene: GTF3C5 was set to GREEN
Added comment: 4 families/probands with syndromic ID. Loss of function is the expected mechanism.
PMID: 38520561 - Biallelic variants identified (3 missense & 1 stopgain) in 4 individuals from 3 families presenting with multisystem developmental syndrome including the features: growth retardation, developmental delay, intellectual disability, dental anomalies, cerebellar malformations, delayed bone age, skeletal anomalies, and facial dysmorphism. Gene-disease relationship supported by: reduced protein expression in patient cells, yeast assays, and a zebrafish model
PMID: 35503477 - 1 proband with biallelic missense variants and hypomelanosis of Ito, seizures, growth retardation, abnormal brain MRI, developmental delay, and facial dysmorphism
Sources: Literature
Intellectual disability v5.532 DOCK4 Zornitza Stark gene: DOCK4 was added
gene: DOCK4 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: DOCK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DOCK4 were set to 38526744
Phenotypes for gene: DOCK4 were set to DOCK4-related neurodevelopmental disorder (MONDO:0060490)
Review for gene: DOCK4 was set to GREEN
Added comment: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities. Two of the individuals are reportedly compound heterozygous.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).
Sources: Literature
Intellectual disability v5.532 PLXNB2 Zornitza Stark gene: PLXNB2 was added
gene: PLXNB2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to 38458752
Phenotypes for gene: PLXNB2 were set to Syndromic disease MONDO:0002254, PLXNB2 -related
Review for gene: PLXNB2 was set to GREEN
Added comment: 8 individuals from 6 families with core features of amelogenesis imperfecta and sensorineural hearing loss. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. WES and WGS identified biallelic pathogenic variants in PLXNB2 (missense, nonsense, splice and a multiexon deletion variants). Variants segregated with disease.

PLXNB2 is a large transmembrane semaphorin receptor protein, and semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Plxnb2 expression was detected in differentiating ameloblasts in mice. Human phenotype overlaps with that seen in Plxnb2 knockout mice.
Sources: Literature
Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: KIAA1024L.
Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available for the association of this gene to green rating in the next GMS review.; to: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram Classified gene: KIAA1024L as Amber List (moderate evidence)
Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of this gene to green rating in the next GMS review.
Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram Gene: kiaa1024l has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.37 KIAA1024L Achchuthan Shanmugasundram commented on gene: KIAA1024L: The new gene name for KIAA1024L is MINAR2 and 'new-gene-name' tag has been added to flag this.
Monogenic hearing loss v4.37 KIAA1024L Achchuthan Shanmugasundram gene: KIAA1024L was added
gene: KIAA1024L was added to Monogenic hearing loss. Sources: Literature
new-gene-name tags were added to gene: KIAA1024L.
Mode of inheritance for gene: KIAA1024L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA1024L were set to 35727972
Phenotypes for gene: KIAA1024L were set to Deafness, autosomal recessive 120, OMIM:620238
Review for gene: KIAA1024L was set to GREEN
Added comment: PMID:35727972 reported 13 patients from four unrelated families with non-syndromic sensorineural hearing loss. Four of these patients had prelingual onset of severe to profound, progressive bilateral hearing loss. The other nine patients had congenital onset of severe to profound bilateral hearing loss, which was not progressive on one patient, while data was not available for the other.

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

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

This gene has also been associated with relevant phenotype in OMIM (MIM #620238).
Sources: Literature
Intellectual disability v5.532 CEP295 Zornitza Stark edited their review of gene: CEP295: Changed rating: GREEN
Intellectual disability v5.532 CEP295 Zornitza Stark gene: CEP295 was added
gene: CEP295 was added to Intellectual disability - microarray and sequencing. Sources: Expert Review
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Expert Review
Ataxia and cerebellar anomalies - narrow panel v4.63 ATP2B3 Achchuthan Shanmugasundram Classified gene: ATP2B3 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.63 ATP2B3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Ataxia and cerebellar anomalies - narrow panel v4.63 ATP2B3 Achchuthan Shanmugasundram Gene: atp2b3 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.62 ATP2B3 Achchuthan Shanmugasundram Publications for gene: ATP2B3 were set to
Ataxia and cerebellar anomalies - narrow panel v4.61 ATP2B3 Achchuthan Shanmugasundram Phenotypes for gene: ATP2B3 were changed from Spinocerebellar ataxia, X-linked 1 to ?Spinocerebellar ataxia, X-linked 1, OMIM:302500
Ataxia and cerebellar anomalies - narrow panel v4.60 ATP2B3 Achchuthan Shanmugasundram Mode of inheritance for gene: ATP2B3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ataxia and cerebellar anomalies - narrow panel v4.59 ATP2B3 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: ATP2B3.
Ataxia and cerebellar anomalies - narrow panel v4.59 ATP2B3 Achchuthan Shanmugasundram changed review comment from: There are six unrelated cases reported with X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood in three of these cases, while detailed clinical information was not available for the other three cases. There is also functional evidence available.

This gene has already been associated with ataxia in OMIM (MIM #302500), but not yet with any phenotypes in Gene2Phenotype.; to: There are six unrelated cases reported with five different X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood in three of these cases, while detailed clinical information was not available for the other three cases. There is also functional evidence available.

This gene has already been associated with ataxia in OMIM (MIM #302500), but not yet with any phenotypes in Gene2Phenotype.
Ataxia and cerebellar anomalies - narrow panel v4.59 ATP2B3 Achchuthan Shanmugasundram reviewed gene: ATP2B3: Rating: GREEN; Mode of pathogenicity: None; Publications: 25953895, 28807751, 36207321; Phenotypes: ?Spinocerebellar ataxia, X-linked 1, OMIM:302500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Hereditary ataxia with onset in adulthood v4.34 ATP2B3 Achchuthan Shanmugasundram changed review comment from: There are six unrelated cases reported with X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood inn three of these cases, while detailed clinical information was not available for the other three cases.; to: There are six unrelated cases reported with X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood in three of these cases, while detailed clinical information was not available for the other three cases.
Hereditary ataxia with onset in adulthood v4.34 ATP2B3 Achchuthan Shanmugasundram Phenotypes for gene: ATP2B3 were changed from Spinocerebellar ataxia, X-linked 1; X-linked spinocerebellar ataxia, 302500 to ?Spinocerebellar ataxia, X-linked 1, OMIM:302500
Hereditary ataxia with onset in adulthood v4.33 ATP2B3 Achchuthan Shanmugasundram Publications for gene: ATP2B3 were set to
Hereditary ataxia with onset in adulthood v4.32 ATP2B3 Achchuthan Shanmugasundram Mode of inheritance for gene: ATP2B3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Hereditary ataxia with onset in adulthood v4.31 ATP2B3 Achchuthan Shanmugasundram commented on gene: ATP2B3: There are six unrelated cases reported with X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood inn three of these cases, while detailed clinical information was not available for the other three cases.
Hereditary ataxia with onset in adulthood v4.31 ATP2B3 Achchuthan Shanmugasundram edited their review of gene: ATP2B3: Changed phenotypes to: ?Spinocerebellar ataxia, X-linked 1, OMIM:302500
Hereditary ataxia with onset in adulthood v4.31 ATP2B3 Achchuthan Shanmugasundram reviewed gene: ATP2B3: Rating: AMBER; Mode of pathogenicity: None; Publications: 25953895, 28807751, 36207321; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.532 SMAD3 Achchuthan Shanmugasundram changed review comment from: Two out of six cases with single nucleotide variants from DECIPHER database (https://www.deciphergenomics.org/gene/SMAD3/patient-overlap/snvs )were reported with global developmental delay. However, intellectual disability or global developmental delay were not reported as clinical presentations in patients with Loeys-Dietz syndrome 3 (MIM #613795).; to: Two out of six cases with single nucleotide variants from DECIPHER database (https://www.deciphergenomics.org/gene/SMAD3/patient-overlap/snvs) were reported with global developmental delay. However, intellectual disability or global developmental delay were not reported as clinical presentations in patients with Loeys-Dietz syndrome 3 (MIM #613795). Hence the rating should remain amber with current evidence.
Intellectual disability v5.532 SMAD3 Achchuthan Shanmugasundram reviewed gene: SMAD3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Neurological segmental overgrowth v2.12 MAX Achchuthan Shanmugasundram Classified gene: MAX as Amber List (moderate evidence)
Neurological segmental overgrowth v2.12 MAX Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by James Poulter, there is sufficient evidence available (three unrelated cases with the same p.Arg60Gln variant and functional studies) for the promotion of this gene to green rating in the next GMS update.
Neurological segmental overgrowth v2.12 MAX Achchuthan Shanmugasundram Gene: max has been classified as Amber List (Moderate Evidence).
Neurological segmental overgrowth v2.11 MAX Achchuthan Shanmugasundram changed review comment from: PMID:38141607 reported three individuals with the same recurrent de novo germline variant in the MAX gene (p.Arg60Gln). Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.; to: PMID:38141607 reported three individuals with the same recurrent de novo germline variant in the MAX gene (p.Arg60Gln). Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.

This gene has been associated with relevant phenotypes in OMIM (MIM #620712).
Neurological segmental overgrowth v2.11 MAX Achchuthan Shanmugasundram Phenotypes for gene: MAX were changed from Macrocephaly; Polydactyly; delayed ophthalmic development; autism to Polydactyly-macrocephaly syndrome, OMIM:620712
Neurological segmental overgrowth v2.10 MAX Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: MAX.
Tag Q2_24_NHS_review tag was added to gene: MAX.
Neurological segmental overgrowth v2.10 MAX Achchuthan Shanmugasundram changed review comment from: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

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

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.; to: PMID:38141607 reported three individuals with the same recurrent de novo germline variant in the MAX gene (p.Arg60Gln). Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Neurological segmental overgrowth v2.10 MAX Achchuthan Shanmugasundram Publications for gene: MAX were set to PMID:38141607
Neurological segmental overgrowth v2.9 MAX Achchuthan Shanmugasundram commented on gene: MAX: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

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

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Neurological segmental overgrowth v2.9 MAX Achchuthan Shanmugasundram reviewed gene: MAX: Rating: GREEN; Mode of pathogenicity: None; Publications: 38141607; Phenotypes: Polydactyly-macrocephaly syndrome, OMIM:620712; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.532 ZFX Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with phenotype in OMIM (MIM #301118), but not yet in Gene2Phenotype.
Intellectual disability v5.532 ZFX Achchuthan Shanmugasundram Phenotypes for gene: ZFX were changed from X-linked neurodevelopmental disorder with recurrent facial gestalt to Intellectual developmental disorder, X-linked syndromic 37, OMIM:301118
Hereditary neuropathy or pain disorder v3.94 CADM3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Ian Berry, there are now five unrelated families with peripheral neuropathy and with one of the two reported missense variants in heterozygous state. Hence, this gene can be promoted to green rating in the next GMS update.; to: Comment on list classification: As reviewed by Ian Berry, there are now at least nine probands with peripheral neuropathy and with one of the two reported missense variants in heterozygous state. Hence, this gene can be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v3.94 CADM3 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: CADM3.
Tag Q2_24_NHS_review tag was added to gene: CADM3.
Hereditary neuropathy or pain disorder v3.94 CADM3 Achchuthan Shanmugasundram Classified gene: CADM3 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.94 CADM3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Ian Berry, there are now five unrelated families with peripheral neuropathy and with one of the two reported missense variants in heterozygous state. Hence, this gene can be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v3.94 CADM3 Achchuthan Shanmugasundram Gene: cadm3 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.93 CADM3 Achchuthan Shanmugasundram Publications for gene: CADM3 were set to 33889941
Hereditary neuropathy or pain disorder v3.92 CADM3 Achchuthan Shanmugasundram reviewed gene: CADM3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe Paediatric Disorders v1.184 PRNP Tracy Lester reviewed gene: PRNP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Monogenic hearing loss v4.36 GRXCR2 Sadaf Naz reviewed gene: GRXCR2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 33528103, PMID:24619944; Phenotypes: #615837: Deafness, autosomal recessive 101; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Paediatric or syndromic cardiomyopathy v3.46 CASZ1 Achchuthan Shanmugasundram Classified gene: CASZ1 as Amber List (moderate evidence)
Paediatric or syndromic cardiomyopathy v3.46 CASZ1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Ludmila Volozonoka, there is sufficient evidence available (three unrelated cases and some functional studies) for the promotion of this gene to green rating in the next GMS update.
Paediatric or syndromic cardiomyopathy v3.46 CASZ1 Achchuthan Shanmugasundram Gene: casz1 has been classified as Amber List (Moderate Evidence).
Paediatric or syndromic cardiomyopathy v3.45 CASZ1 Achchuthan Shanmugasundram Phenotypes for gene: CASZ1 were changed from Pediatric Dilated Cardiomyopathy; Pediatric LVNC to dilated cardiomyopathy, MONDO:0005021; left ventricular noncompaction, MONDO:0018901
Paediatric or syndromic cardiomyopathy v3.44 CASZ1 Achchuthan Shanmugasundram changed review comment from: PMID:28099117 reported a patient with a novel heterozygous CASZ1 variant (p.K351X) and with dilated cardiomyopathy (DCM). The variant co-segregated with DCM, which was transmitted in an autosomal dominant pattern with complete penetrance. The functional characterisation of the variant with a luciferase reporter assay showed that the variant had no transcriptional activity.

PMID:31268246 reported the identification of a previously unreported de novo heterozygous frameshift variant (p.Val815Profs*14) in CASZ1 in an 11-month-old Chinese boy with DCM and left ventricular noncompaction cardiomyopathy (LVNC).

PMID:36293425 reported a girl with a new de novo frameshift variant (p.Trp1261GlyfsTer29) in CASZ1 gene. DCM was diagnosed for the first time at the age of three months and she died at the age of 1 year 10 months with a diagnosis of dilated cardiomyopathy and decompensation, systemic multiple organ failure, post-anoxic brain damage and gastrointestinal and vaginal bleeding.; to: PMID:28099117 reported a patient with a novel heterozygous CASZ1 variant (p.K351X) and with dilated cardiomyopathy (DCM). The variant co-segregated with DCM, which was transmitted in an autosomal dominant pattern with complete penetrance. The functional characterisation of the variant with a luciferase reporter assay showed that the variant had no transcriptional activity.

PMID:31268246 reported the identification of a previously unreported de novo heterozygous frameshift variant (p.Val815Profs*14) in CASZ1 in an 11-month-old Chinese boy with DCM and left ventricular noncompaction cardiomyopathy (LVNC).

PMID:36293425 reported a girl with a new de novo frameshift variant (p.Trp1261GlyfsTer29) in CASZ1 gene. DCM was diagnosed for the first time at the age of three months and she died at the age of 1 year 10 months with a diagnosis of dilated cardiomyopathy and decompensation, systemic multiple organ failure, post-anoxic brain damage and gastrointestinal and vaginal bleeding.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Paediatric or syndromic cardiomyopathy v3.44 CASZ1 Achchuthan Shanmugasundram edited their review of gene: CASZ1: Changed phenotypes to: dilated cardiomyopathy, MONDO:0005021, left ventricular noncompaction, MONDO:0018901
Paediatric or syndromic cardiomyopathy v3.44 CASZ1 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: CASZ1.
Paediatric or syndromic cardiomyopathy v3.44 CASZ1 Achchuthan Shanmugasundram reviewed gene: CASZ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28099117, 31268246, 36293425; Phenotypes: dilated cardiomyopathy, MONDO:0005021; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v4.89 MT-ATP6 Achchuthan Shanmugasundram Tag Q2_24_NHS_review tag was added to gene: MT-ATP6.
Retinal disorders v4.89 SLC37A3 Achchuthan Shanmugasundram Tag Q2_24_NHS_review tag was added to gene: SLC37A3.
Retinal disorders v4.89 SLC37A3 Achchuthan Shanmugasundram Classified gene: SLC37A3 as Amber List (moderate evidence)
Retinal disorders v4.89 SLC37A3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Siying Lin, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Retinal disorders v4.89 SLC37A3 Achchuthan Shanmugasundram Gene: slc37a3 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.88 SLC37A3 Achchuthan Shanmugasundram Phenotypes for gene: SLC37A3 were changed from Retinitis pigmentosa; No OMIM entry to retinitis pigmentosa, MONDO:0019200
Retinal disorders v4.87 SLC37A3 Achchuthan Shanmugasundram Publications for gene: SLC37A3 were set to 28041643
Retinal disorders v4.86 SLC37A3 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: SLC37A3.
Retinal disorders v4.86 SLC37A3 Achchuthan Shanmugasundram reviewed gene: SLC37A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: retinitis pigmentosa, MONDO:0019200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.86 MT-ATP6 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: MT-ATP6.
Retinal disorders v4.86 MT-ATP6 Achchuthan Shanmugasundram Classified gene: MT-ATP6 as Amber List (moderate evidence)
Retinal disorders v4.86 MT-ATP6 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is ample evidence available for the association of MT-ATP6 gene with retinitis pigmentosa. Hence, this gene can be promoted to green rating in the next GMS review.
Retinal disorders v4.86 MT-ATP6 Achchuthan Shanmugasundram Gene: mt-atp6 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.85 MT-ATP6 Achchuthan Shanmugasundram Phenotypes for gene: MT-ATP6 were changed from Retinitis pigmentosa to NARP syndrome, MONDO:0010794
Retinal disorders v4.84 MT-ATP6 Achchuthan Shanmugasundram Publications for gene: MT-ATP6 were set to
Retinal disorders v4.83 MT-ATP6 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: MT-ATP6.
Retinal disorders v4.83 MT-ATP6 Achchuthan Shanmugasundram reviewed gene: MT-ATP6: Rating: GREEN; Mode of pathogenicity: None; Publications: 11843698, 17568559, 19124644, 22819295, 23266623, 24118886, 27015314, 29054413, 29224958, 36809201; Phenotypes: NARP syndrome, MONDO:0010794; Mode of inheritance: MITOCHONDRIAL
Primary immunodeficiency or monogenic inflammatory bowel disease v4.201 PTCRA Achchuthan Shanmugasundram Classified gene: PTCRA as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.201 PTCRA Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.201 PTCRA Achchuthan Shanmugasundram Gene: ptcra has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.200 PTCRA Achchuthan Shanmugasundram Phenotypes for gene: PTCRA were changed from Autoimmunity; elevated TCRgamma/delta T cells; lymphopenia; low TREC to Autoimmunity, HP:0002960; lymphopenia, MONDO:0003783
Primary immunodeficiency or monogenic inflammatory bowel disease v4.199 PTCRA Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: PTCRA.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.199 PTCRA Achchuthan Shanmugasundram reviewed gene: PTCRA: Rating: GREEN; Mode of pathogenicity: None; Publications: 38422122; Phenotypes: Autoimmunity, HP:0002960, lymphopenia, MONDO:0003783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.92 GAN Arina Puzriakova Publications for gene: GAN were set to 1106248
Hereditary neuropathy or pain disorder v3.91 GAN Arina Puzriakova Classified gene: GAN as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.91 GAN Arina Puzriakova Added comment: Comment on list classification: This gene should be promoted to Green at the next GMS panel update as the scope of this panel has now been expanded to include complex cases of neuropathy.
Biallelic variants in the GAN gene cause giant axonal neuropathy. This childhood onset polyneuropathy results in progressive neurodegeneration of both the peripheral and central nervous systems. More than 10 unrelated cases have been reported in the literature which is sufficient for making this gene Green (PMIDs: 18595793; 19231187; 20949505; 27852232; 36866531)
Hereditary neuropathy or pain disorder v3.91 GAN Arina Puzriakova Gene: gan has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.531 GAN Arina Puzriakova changed review comment from: Comment on list classification: Biallelic variants in the GAN gene cause giant axonal neuropathy, characterised by abnormalities in the peripheral and central nervous systems. Though extent of CNS involvement can vary, intellectual disability has been reported in at least 3 unrelated cases to date (PMID: 18595793; 19231187). Therefore, this gene should be promoted to Green at the next GMS panel update.; to: Comment on list classification: Biallelic variants in the GAN gene cause giant axonal neuropathy, characterised by abnormalities in the peripheral and central nervous systems. Though extent of CNS involvement can vary, intellectual disability has been reported in at least 3 unrelated cases (PMID: 18595793; 19231187). Therefore, this gene should be promoted to Green at the next GMS panel update.
Intellectual disability v5.531 GAN Arina Puzriakova Tag Q2_24_promote_green tag was added to gene: GAN.
Tag Q2_24_NHS_review tag was added to gene: GAN.
Intellectual disability v5.531 GAN Arina Puzriakova Publications for gene: GAN were set to
Intellectual disability v5.530 GAN Arina Puzriakova Classified gene: GAN as Amber List (moderate evidence)
Intellectual disability v5.530 GAN Arina Puzriakova Added comment: Comment on list classification: Biallelic variants in the GAN gene cause giant axonal neuropathy, characterised by abnormalities in the peripheral and central nervous systems. Though extent of CNS involvement can vary, intellectual disability has been reported in at least 3 unrelated cases to date (PMID: 18595793; 19231187). Therefore, this gene should be promoted to Green at the next GMS panel update.
Intellectual disability v5.530 GAN Arina Puzriakova Gene: gan has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.22 COASY Hannah Knight reviewed gene: COASY: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 35499143; Phenotypes: Pontocerebellar hypoplasia type 12; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.22 PIP5K1C Hannah Knight reviewed gene: PIP5K1C: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38491417; Phenotypes: Lethal congenital contractural syndrome 3 611369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.90 GAN Arina Puzriakova Tag Q2_24_promote_green tag was added to gene: GAN.
Tag Q2_24_NHS_review tag was added to gene: GAN.
Arthrogryposis v5.22 SLC18A3 Hannah Knight reviewed gene: SLC18A3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34943989; Phenotypes: Myasthenic syndrome, congenital, 21, presynaptic; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.22 TRIP4 Hannah Knight reviewed gene: TRIP4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31794073; Phenotypes: Spinal muscular atrophy with congenital bone fractures 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.529 GAN Arina Puzriakova Mode of inheritance for gene: GAN was changed from to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.528 GAN Arina Puzriakova Phenotypes for gene: GAN were changed from to Giant axonal neuropathy-1, OMIM:256850
Hereditary neuropathy v1.477 GAN Arina Puzriakova Phenotypes for gene: GAN were changed from Giant axonal neuropathy-1 to Giant axonal neuropathy-1, OMIM:256850
Hereditary neuropathy or pain disorder v3.90 GAN Arina Puzriakova Phenotypes for gene: GAN were changed from Giant axonal neuropathy-1 to Giant axonal neuropathy-1, OMIM:256850
Intellectual disability v5.527 SEPHS1 Arina Puzriakova Classified gene: SEPHS1 as Amber List (moderate evidence)
Intellectual disability v5.527 SEPHS1 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Intellectual disability v5.527 SEPHS1 Arina Puzriakova Gene: sephs1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.526 SEPHS1 Arina Puzriakova Classified gene: SEPHS1 as Amber List (moderate evidence)
Intellectual disability v5.526 SEPHS1 Arina Puzriakova Gene: sephs1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.525 SEPHS1 Arina Puzriakova gene: SEPHS1 was added
gene: SEPHS1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Q2_24_promote_green tags were added to gene: SEPHS1.
Mode of inheritance for gene: SEPHS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SEPHS1 were set to 38531365
Phenotypes for gene: SEPHS1 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: SEPHS1 was set to GREEN
Added comment: Mullegama et al. (2024) reported 9 individuals from 8 families with developmental delay, growth and feeding problems, hypotonia, and dysmorphic features, all with heterozygous missense variants in SEPHS1. Eight individuals shared different missense variants at the same p.Arg371 residue in SEPHS1 (p.Arg371Trp, p.Arg371Gln, and p.Arg371Gly); seven of these variants were confirmed as de novo (one unknown). Functional studies showed that variants at the Arg371 residue impact direct protein-protein interactions of SEPSH1 and enhance cell proliferation by modulating ROS homeostasis.
Sources: Literature
Fetal anomalies v3.155 GRM1 Arina Puzriakova Classified gene: GRM1 as Red List (low evidence)
Fetal anomalies v3.155 GRM1 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Zornitza Stark. Could not find any evidence of prenatal phenotypes in patients with GRM1 variants.
Fetal anomalies v3.155 GRM1 Arina Puzriakova Gene: grm1 has been classified as Red List (Low Evidence).
Stickler syndrome v4.4 LRP2 Arina Puzriakova Classified gene: LRP2 as Red List (low evidence)
Stickler syndrome v4.4 LRP2 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.

Only a single family reported with features overlapping those of Stickler syndrome (PMID:23992033), mainly based on their ocular phenotype, including high myopia, vitreous changes, cataract and esotropia. LRP2 variants are typically associated with Donnai-Barrow syndrome and facio-oculo-acoustico-renal syndrome which are not relevant to this panel.
Stickler syndrome v4.4 LRP2 Arina Puzriakova Gene: lrp2 has been classified as Red List (Low Evidence).
Cytopenia - NOT Fanconi anaemia v3.32 FCGR3B Arina Puzriakova Classified gene: FCGR3B as Red List (low evidence)
Cytopenia - NOT Fanconi anaemia v3.32 FCGR3B Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.

Also note review from Helen Brittain (Genomics England Clinical Team) on 100K panel Cytopenias and congenital anaemias (159) from 9 Mar 2017:

"Relevant phenotype affects neutrophils only, on a transient basis owing to presence of antibodies in mother and antigen in fetus (as a result of different genetic factors in father and mother.). Therefore not a germline condition associated with mutations in the child."
Cytopenia - NOT Fanconi anaemia v3.32 FCGR3B Arina Puzriakova Gene: fcgr3b has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.19 ADAMTS2 Arina Puzriakova Classified gene: ADAMTS2 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.19 ADAMTS2 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.19 ADAMTS2 Arina Puzriakova Gene: adamts2 has been classified as Red List (Low Evidence).
Dilated and arrhythmogenic cardiomyopathy v2.22 MYZAP Arina Puzriakova Tag Q2_24_promote_green tag was added to gene: MYZAP.
Dilated and arrhythmogenic cardiomyopathy v2.22 MYZAP Arina Puzriakova Deleted their comment
Dilated and arrhythmogenic cardiomyopathy v2.22 MYZAP Arina Puzriakova Publications for gene: MYZAP were set to 34899865; 20093627; 35840178
Dilated and arrhythmogenic cardiomyopathy v2.21 MYZAP Arina Puzriakova Classified gene: MYZAP as Amber List (moderate evidence)
Dilated and arrhythmogenic cardiomyopathy v2.21 MYZAP Arina Puzriakova Added comment: Comment on list classification: New gene added to the panel by Aleš Maver. MYZAP is not yet associated with any phenotype in OMIM or Gene2Phenoype. At least three unrelated families have been reported with biallelic LOF variants in MYZAP and a phenotype of DCM (PMIDs: 34899865; 35840178; 38436102). Studies in zebrafish and mice demonstrate the link between MYZAP and cardiomyopathy (PMIDs: 20093627; 24698889). Overall, the evidence is sufficient to promote this gene to Green at the next GMS panel update.
Dilated and arrhythmogenic cardiomyopathy v2.21 MYZAP Arina Puzriakova Gene: myzap has been classified as Amber List (Moderate Evidence).
Dilated and arrhythmogenic cardiomyopathy v2.21 MYZAP Arina Puzriakova Classified gene: MYZAP as Amber List (moderate evidence)
Dilated and arrhythmogenic cardiomyopathy v2.21 MYZAP Arina Puzriakova Added comment: Comment on list classification: New gene added to the panel by Aleš Maver. MYZAP is not yet associated with any phenotype in OMIM or Gene2Phenoype. At least three unrelated families have been reported with biallelic LOF variants in MYZAP and a phenotype of DCM (PMIDs: 34899865; 35840178; 38436102). Studies in zebrafish and mice demonstrate the link between MYZAP and cardiomyopathy (PMIDs: 20093627; 24698889). Overall, the evidence is sufficient to promote this gene to Green at the next GMS panel update.
Dilated and arrhythmogenic cardiomyopathy v2.21 MYZAP Arina Puzriakova Gene: myzap has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism (GMS) v3.18 NDNF Arina Puzriakova Classified gene: NDNF as Green List (high evidence)
Hypogonadotropic hypogonadism (GMS) v3.18 NDNF Arina Puzriakova Added comment: Comment on list classification: Gene was re-reviewed in light of an Amber review by Zornitza Stark (Australian Genomics) on a Green gene. At least five unrelated cases have been reported, as well as mouse and zebrafish studies showing Ndnf deficiency leads to anomalies in GnRH neuron migration. Pedigree analysis does indicate variable expressivity and incomplete penetrance, although this is relatively common in dominant forms of HH. Furthermore, inclusion of NDNF on this panel has already been reviewed and approved by the NHS specialist group and therefore the Green rating is being maintained.
Hypogonadotropic hypogonadism (GMS) v3.18 NDNF Arina Puzriakova Gene: ndnf has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism (GMS) v3.17 NDNF Arina Puzriakova Phenotypes for gene: NDNF were changed from Congenital hypogonadotropic hypogonadism (CHH); Hypogonadotropic hypogonadism 25 with anosmia, 618841 to Hypogonadotropic hypogonadism 25 with anosmia, OMIM:618841
Hypogonadotropic hypogonadism (GMS) v3.16 NDNF Arina Puzriakova Publications for gene: NDNF were set to 31883645
Hypogonadotropic hypogonadism (GMS) v3.15 NDNF Arina Puzriakova commented on gene: NDNF: PMID: 36245975 (2022) - another male patient with idiopathic hypogonadotropin hypogonadism identified harbouring a paternally inherited NDNF variant (c.1439T>A, p.Ile480Asn)
Hereditary spastic paraplegia v1.311 RTN2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As there are sufficient number of cases with biallelic variants and lower limb spasticity, the MOI has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'.
Hereditary spastic paraplegia v1.311 RTN2 Achchuthan Shanmugasundram Mode of inheritance for gene: RTN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.310 RTN2 Achchuthan Shanmugasundram Phenotypes for gene: RTN2 were changed from Spastic paraplegia 12, autosomal dominant to Spastic paraplegia 12, autosomal dominant, OMIM:604805; distal hereditary motor neuropathy, MONDO:0018894; Lower limb spasticity, HP:0002061
Hereditary spastic paraplegia v1.309 RTN2 Achchuthan Shanmugasundram Publications for gene: RTN2 were set to Montenegro et al. (2012)
Hereditary spastic paraplegia v1.308 RTN2 Achchuthan Shanmugasundram reviewed gene: RTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38527963; Phenotypes: distal hereditary motor neuropathy, MONDO:0018894, Lower limb spasticity, HP:0002061; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v4.42 RTN2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As there are sufficient number of cases with biallelic variants and lower limb spasticity, the MOI should be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS update.
Childhood onset hereditary spastic paraplegia v4.42 RTN2 Achchuthan Shanmugasundram Mode of inheritance for gene: RTN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Childhood onset hereditary spastic paraplegia v4.41 RTN2 Achchuthan Shanmugasundram Phenotypes for gene: RTN2 were changed from Spastic paraplegia 12, autosomal dominant, 604805 to Spastic paraplegia 12, autosomal dominant, OMIM:604805; distal hereditary motor neuropathy, MONDO:0018894; Lower limb spasticity, HP:0002061
Childhood onset hereditary spastic paraplegia v4.40 RTN2 Achchuthan Shanmugasundram Publications for gene: RTN2 were set to 22232211; 24123792; 28362824
Childhood onset hereditary spastic paraplegia v4.39 RTN2 Achchuthan Shanmugasundram Tag Q2_24_MOI tag was added to gene: RTN2.
Tag Q2_24_NHS_review tag was added to gene: RTN2.
Hereditary neuropathy or pain disorder v3.89 RTN2 Achchuthan Shanmugasundram changed review comment from: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

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

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

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

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

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

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Sources: Literature
Childhood onset hereditary spastic paraplegia v4.39 RTN2 Achchuthan Shanmugasundram reviewed gene: RTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38527963; Phenotypes: distal hereditary motor neuropathy, MONDO:0018894, Lower limb spasticity, HP:0002061; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.89 RTN2 Achchuthan Shanmugasundram changed review comment from: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

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

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

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

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

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

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Sources: Literature
Rare genetic inflammatory skin disorders v3.18 COL5A2 Arina Puzriakova Classified gene: COL5A2 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.18 COL5A2 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.18 COL5A2 Arina Puzriakova Gene: col5a2 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.17 COL5A1 Arina Puzriakova Classified gene: COL5A1 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.17 COL5A1 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.17 COL5A1 Arina Puzriakova Gene: col5a1 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.16 COL4A5 Arina Puzriakova Classified gene: COL4A5 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.16 COL4A5 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.16 COL4A5 Arina Puzriakova Gene: col4a5 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.15 COL4A4 Arina Puzriakova Classified gene: COL4A4 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.15 COL4A4 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.15 COL4A4 Arina Puzriakova Gene: col4a4 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.14 COL4A3 Arina Puzriakova Classified gene: COL4A3 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.14 COL4A3 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.14 COL4A3 Arina Puzriakova Gene: col4a3 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.13 COL3A1 Arina Puzriakova Classified gene: COL3A1 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.13 COL3A1 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.13 COL3A1 Arina Puzriakova Gene: col3a1 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.12 COL1A2 Arina Puzriakova Classified gene: COL1A2 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.12 COL1A2 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.12 COL1A2 Arina Puzriakova Gene: col1a2 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.11 COL1A1 Arina Puzriakova Classified gene: COL1A1 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.11 COL1A1 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.11 COL1A1 Arina Puzriakova Gene: col1a1 has been classified as Red List (Low Evidence).
Autoinflammatory disorders v1.17 IL17RA Arina Puzriakova Tag watchlist tag was added to gene: IL17RA.
Autoinflammatory disorders v1.17 IL17RA Arina Puzriakova Classified gene: IL17RA as Amber List (moderate evidence)
Autoinflammatory disorders v1.17 IL17RA Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Lauma Freimane (Children's Clinical University Hospital). Biallelic variants have been found patients with immunodeficiency, presenting as chronic mucocutaneous candidiasis (PMID: 21350122).

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine implicated in diverse autoimmune and inflammatory disorders such as psoriasis and Kawasaki disease so it is plausible that the interleukin-17A receptor (IL-17RA) could contribute to the same pathway.

Literature review did reveal multiple mouse models where IL-17RA was shown to promote the inflammatory response (PMID: 38060620; 30364284; 35844540; 38451335); however, there is no evidence of human cases where a variant in the IL17RA gene caused an autoinflammatory disorder. Therefore rating as Amber with a watchlist tag, awaiting further evidence.
Autoinflammatory disorders v1.17 IL17RA Arina Puzriakova Gene: il17ra has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.199 IL17RA Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Candidiasis, familial, 5;Chronic mucocutaneous candidiasis (CMC);Immunodeficiency 51, 613953;Defects in Intrinsic and Innate Immunity;CMC, folliculitis;Defects in Intrinsic and Innate Immunity
Primary immunodeficiency or monogenic inflammatory bowel disease v4.199 IL17RA Arina Puzriakova Phenotypes for gene: IL17RA were changed from Candidiasis, familial, 5; Chronic mucocutaneous candidiasis (CMC); Immunodeficiency 51, 613953; Defects in Intrinsic and Innate Immunity; CMC, folliculitis; Defects in Intrinsic and Innate Immunity to Immunodeficiency 51, OMIM:613953
Autoinflammatory disorders v1.16 IL17RA Arina Puzriakova Phenotypes for gene: IL17RA were changed from Immunodeficiency-51 to Immunodeficiency 51, OMIM:613953
Likely inborn error of metabolism - targeted testing not possible v4.137 ADA Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Combined B and T cell defect;Adenosine deaminase deficiency (Disorders of purine metabolism);SCID;Infantile enterocolitis & monogenic inflammatory bowel disease
Likely inborn error of metabolism - targeted testing not possible v4.137 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700 to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Likely inborn error of metabolism - targeted testing not possible v4.136 ADA Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Combined B and T cell defect;Adenosine deaminase deficiency (Disorders of purine metabolism);SCID;Infantile enterocolitis & monogenic inflammatory bowel disease
Likely inborn error of metabolism - targeted testing not possible v4.136 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Combined B and T cell defect; Adenosine deaminase deficiency (Disorders of purine metabolism); SCID; Infantile enterocolitis & monogenic inflammatory bowel disease to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Primary immunodeficiency or monogenic inflammatory bowel disease v4.198 ADA Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Severe combined immunodeficiency due to ADA deficiency (some mosiacism noted);Severe combined immunodeficiency due to ADA deficiency, 102700;T-B- SCID;T-B+ SCID;Adenosine deaminase (ADA) deficiency;Atypical Severe Combined Immunodeficiency (Atypical SCID);Omenn syndrome;Severe combined immunodeficiency (SCID);Low NK, bone defects, may have pulmonary alveolar proteinosis, cognitive defects;Immunodeficiencies affecting cellular and humoral immunity
Primary immunodeficiency or monogenic inflammatory bowel disease v4.198 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Severe combined immunodeficiency due to ADA deficiency (some mosiacism noted); Severe combined immunodeficiency due to ADA deficiency, 102700; T-B- SCID; T-B+ SCID; Adenosine deaminase (ADA) deficiency; Atypical Severe Combined Immunodeficiency (Atypical SCID); Omenn syndrome; Severe combined immunodeficiency (SCID); Low NK, bone defects, may have pulmonary alveolar proteinosis, cognitive defects; Immunodeficiencies affecting cellular and humoral immunity to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Fetal anomalies v3.154 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Combined B and T cell defect; Adenosine deaminase deficiency (Disorders of purine metabolism); SCID; Infantile enterocolitis & monogenic inflammatory bowel disease to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Fetal anomalies v3.153 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from ADENOSINE DEAMINASE DEFICIENCY to Combined B and T cell defect; Adenosine deaminase deficiency (Disorders of purine metabolism); SCID; Infantile enterocolitis & monogenic inflammatory bowel disease
Undiagnosed metabolic disorders v1.617 ADA Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Adenosine deaminase deficiency (Disorders of purine metabolism);Combined B and T cell defect;Infantile enterocolitis & monogenic inflammatory bowel disease;SCID
Undiagnosed metabolic disorders v1.617 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Adenosine deaminase deficiency (Disorders of purine metabolism); Combined B and T cell defect; Infantile enterocolitis & monogenic inflammatory bowel disease; SCID to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Intellectual disability v5.524 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Severe combined immunodeficiency due to ADA deficiency, 102700; Adenosine deaminase deficiency, partial, 102700 to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Severe combined immunodeficiency with adenosine deaminase deficiency v1.3 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700 to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700
Severe combined immunodeficiency with adenosine deaminase deficiency v1.2 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Autoinflammatory disorders v1.15 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from T(-), B(-), NK(-) severe combin immunodeficiency to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Bleeding and platelet disorders v3.9 GP6 Arina Puzriakova Phenotypes for gene: GP6 were changed from 614201 Bleeding disorder, platelet-type, 11 to Bleeding disorder, platelet-type, 11, OMIM:614201
Inherited bleeding disorders v1.177 GP6 Arina Puzriakova Phenotypes for gene: GP6 were changed from Bleeding diathesis due to glycoprotein VI deficiency to Bleeding disorder, platelet-type, 11, OMIM:614201
Autoinflammatory disorders v1.14 GP6 Arina Puzriakova Phenotypes for gene: GP6 were changed from Platlet-type bleeding disorder-11 to Bleeding disorder, platelet-type, 11, OMIM:614201
Autoinflammatory disorders v1.13 GP6 Arina Puzriakova Classified gene: GP6 as Red List (low evidence)
Autoinflammatory disorders v1.13 GP6 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Lauma Freimane (Children's Clinical University Hospital). Biallelic variants are associated with bleeding disorder caused by defective platelet activation and aggregation in response to collagen. Could not find evidence of an autoinflammatory component observed in patients and therefore rating as Red on this panel
Autoinflammatory disorders v1.13 GP6 Arina Puzriakova Gene: gp6 has been classified as Red List (Low Evidence).
Autoinflammatory disorders v1.12 ADA Arina Puzriakova Classified gene: ADA as Red List (low evidence)
Autoinflammatory disorders v1.12 ADA Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Lauma Freimane (Children's Clinical University Hospital). Biallelic variants are associated with partial ADA deficiency or severe combined immunodeficiency (SCID) due to ADA deficiency with multiple unrelated cases reported.

Despite ADA null mice displaying severe pulmonary inflammation, could not find evidence of an autoinflammatory component observed in patients and therefore rating as Red on this panel
Autoinflammatory disorders v1.12 ADA Arina Puzriakova Gene: ada has been classified as Red List (Low Evidence).
Hereditary neuropathy or pain disorder v3.89 RTN2 Achchuthan Shanmugasundram Classified gene: RTN2 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.89 RTN2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of RTN2 biallelic variants with distal hereditary motor neuropathy. Hence, this gene should be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v3.89 RTN2 Achchuthan Shanmugasundram Gene: rtn2 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.88 RTN2 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: RTN2.
Hereditary neuropathy or pain disorder v3.88 RTN2 Achchuthan Shanmugasundram gene: RTN2 was added
gene: RTN2 was added to Hereditary neuropathy or pain disorder. Sources: Literature
Mode of inheritance for gene: RTN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RTN2 were set to 38527963
Phenotypes for gene: RTN2 were set to distal hereditary motor neuropathy, MONDO:0018894
Review for gene: RTN2 was set to GREEN
Added comment: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

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

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

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Sources: Literature
Fetal anomalies v3.152 NRXN2 Sarah Leigh Classified gene: NRXN2 as Red List (low evidence)
Fetal anomalies v3.152 NRXN2 Sarah Leigh Added comment: Comment on list classification: There insufficient evidence between NRXN2 variants and autism for this gene to be rated amber.
Fetal anomalies v3.152 NRXN2 Sarah Leigh Gene: nrxn2 has been classified as Red List (Low Evidence).
Iron metabolism disorders - NOT common HFE mutations v2.6 CYBRD1 Sarah Leigh Publications for gene: CYBRD1 were set to 15338274; 27884173
Iron metabolism disorders - NOT common HFE mutations v2.5 CYBRD1 Sarah Leigh edited their review of gene: CYBRD1: Added comment: It would appear that there are no CYBRD1 rare SNVs associated with iron metabolism.  However, PMID: 37632052 concludes that the coexistence of minor alleles of HDAC3 rs976552 and CYBRD1 rs884409 is linked with higher prevalence of hepatocellular carcinoma.

Furthermore, HFE p.C282Y variant together with the CYBRD1 polymorphism rs884409 reduces CYBRD1 promoter activity by 30% (PMID: 19673882).; Changed rating: AMBER
Bilateral congenital or childhood onset cataracts v4.12 LIM2 Arina Puzriakova changed review comment from: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with congenital cataracts due to a recurrent heterozygous LIM2 p.R130C variant (PMIDs: 32202185; 33078099; 33708862; 33923544; 35736209). These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.; to: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with cataracts due to a recurrent heterozygous LIM2 p.R130C variant (PMIDs: 32202185; 33078099; 33708862; 33923544; 35736209). These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.
Bilateral congenital or childhood onset cataracts v4.12 LIM2 Arina Puzriakova changed review comment from: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with congenital cataracts due to a recurrent LIM2 p.R130C variant (PMIDs: 32202185; 33078099; 33708862; 33923544; 35736209). These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.; to: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with congenital cataracts due to a recurrent heterozygous LIM2 p.R130C variant (PMIDs: 32202185; 33078099; 33708862; 33923544; 35736209). These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.
Bilateral congenital or childhood onset cataracts v4.12 LIM2 Arina Puzriakova Tag recurrent-variant tag was added to gene: LIM2.
Tag Q2_24_MOI tag was added to gene: LIM2.
Bilateral congenital or childhood onset cataracts v4.12 LIM2 Arina Puzriakova changed review comment from: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with congenital cataracts due to a recurrent LIM2 p.R130C variant. These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.; to: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with congenital cataracts due to a recurrent LIM2 p.R130C variant (PMIDs: 32202185; 33078099; 33708862; 33923544; 35736209). These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.
Bilateral congenital or childhood onset cataracts v4.12 LIM2 Arina Puzriakova Added comment: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with congenital cataracts due to a recurrent LIM2 p.R130C variant. These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.
Bilateral congenital or childhood onset cataracts v4.12 LIM2 Arina Puzriakova Mode of inheritance for gene: LIM2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.87 CADM3 Ian Berry reviewed gene: CADM3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38074074, 33889941; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bilateral congenital or childhood onset cataracts v4.11 LIM2 Arina Puzriakova Publications for gene: LIM2 were set to Ponnam et al (2008) Mol Vis 14:1204-1208; Pras et al (2002) Am J Hum genet 70:1363-7
Bilateral congenital or childhood onset cataracts v4.10 LIM2 Arina Puzriakova Phenotypes for gene: LIM2 were changed from Cortical Pulverulent Cataract; Cataract 19, 615277 to Cataract 19, multiple types, OMIM:615277
Structural eye disease v3.77 LIM2 Arina Puzriakova Phenotypes for gene: LIM2 were changed from Cataract 19, 615277 to Cataract 19, multiple types, OMIM:615277
Intellectual disability v5.523 FRYL Arina Puzriakova Classified gene: FRYL as Amber List (moderate evidence)
Intellectual disability v5.523 FRYL Arina Puzriakova Added comment: Comment on list classification: Rating Amber as overall the evidence is borderline. Only one recent study (PMID:38479391) has reported an disease association for FRYL, with variable phenotypes and results from functional studies, as well as variants in other genes in several cases. Additional studies are required to conclusively corroborate causality (added watchlist tag).
Intellectual disability v5.523 FRYL Arina Puzriakova Gene: fryl has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.522 FRYL Arina Puzriakova gene: FRYL was added
gene: FRYL was added to Intellectual disability - microarray and sequencing. Sources: Literature
watchlist tags were added to gene: FRYL.
Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRYL were set to 38479391
Phenotypes for gene: FRYL were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: FRYL was set to AMBER
Added comment: New association linking this gene to disease which is not yet listed in OMIM or Gene2Phenotype. There are no sequence variants in Decipher and ClinVar shows only a single pathogenic frameshift variant (c.1224del, p.Lys409fs) for FRYL-associated neurodevelopmental disorder, amongst multiple SNVs which are mostly missense VUS or B/LB.

Pan et al., 2024 (PMID: 38479391) reported 14 individuals with heterozygous variant in FRYL who presented with DD/ID, dysmorphic features, and other congenital anomalies in multiple systems. Except for DD/ID which was the only universal feature, observed phenotypes were variable and nonspecific.

Variants were confirmed de novo in all except one individual (duo testing excluded paternal inheritance although it was present at low frequency in gnomAD). Variant types include missense (5), fs/stop-gain (8) and canonical splice (1). Modelling 4/5 patient missense variants using flies showed that only one serves as a severe LoF variant, two others behave as partial LoF variants, and one variant had no functional impact (only variant not confirmed as de novo indicating this is a VUS). Four individuals also had P/LP variants in other genes (SF3B4, DHCR7, SLC6A19, SDHA) which could at least partially explain their phenotypes, and a further four harboured additional VUSs.
Sources: Literature
RASopathies v1.81 RRAS Sarah Leigh Classified gene: RRAS as Green List (high evidence)
RASopathies v1.81 RRAS Sarah Leigh Gene: rras has been classified as Green List (High Evidence).
RASopathies v1.80 RRAS Sarah Leigh Tag Q2_24_promote_green was removed from gene: RRAS.
RASopathies v1.80 RRAS Sarah Leigh Tag Q2_24_promote_green tag was added to gene: RRAS.
Fetal anomalies v3.151 RRAS Sarah Leigh Tag Q2_24_promote_green tag was added to gene: RRAS.
Cytopenia - NOT Fanconi anaemia v3.31 RRAS Sarah Leigh Tag Q2_24_promote_green tag was added to gene: RRAS.
RASopathies v1.80 RRAS Sarah Leigh Publications for gene: RRAS were set to 24705357
RASopathies v1.79 RRAS Sarah Leigh edited their review of gene: RRAS: Added comment: RRAS variants have not associated with a phenotype in OMIM or MONDO, but Gen2Phen lists a strong association between RRAS variants and RRAS-related atypical Noonan syndrome. Three germline RRAS variants have been reported (PMID: 24705357; 32815881; 34935735), associated with a RASopathy, which includes myelodysplastic syndrome and contributes to leukaemogenesis.; Changed rating: GREEN; Changed publications to: 24705357, 32815881, 34935735
Fetal anomalies v3.151 RRAS Sarah Leigh edited their review of gene: RRAS: Added comment: RRAS variants have not associated with a phenotype in OMIM or MONDO, but Gen2Phen lists a strong association between RRAS variants and RRAS-related atypical Noonan syndrome. Three germline RRAS variants have been reported (PMID: 24705357; 32815881; 34935735), associated with a RASopathy, which includes myelodysplastic syndrome and contributes to leukaemogenesis.; Changed rating: GREEN; Changed publications to: 24705357, 32815881, 34935735
Cytopenia - NOT Fanconi anaemia v3.31 RRAS Sarah Leigh Publications for gene: RRAS were set to 34935735
Cytopenia - NOT Fanconi anaemia v3.30 RRAS Sarah Leigh commented on gene: RRAS: RRAS variants have not associated with a phenotype in OMIM or MONDO, but Gen2Phen lists a strong association between RRAS variants and RRAS-related atypical Noonan syndrome. Three germline RRAS variants have been reported (PMID: 24705357; 32815881; 34935735), associated with a RASopathy, which includes myelodysplastic syndrome and contributes to leukaemogenesis.
RASopathies v1.79 RRAS Sarah Leigh Added comment: Comment on phenotypes: Phenotype from Gen2Phen
RASopathies v1.79 RRAS Sarah Leigh Phenotypes for gene: RRAS were changed from Noonan syndrome to RRAS-related atypical Noonan syndrome
Fetal anomalies v3.151 RRAS Sarah Leigh Added comment: Comment on phenotypes: Phenotype from Gen2Phen
Fetal anomalies v3.151 RRAS Sarah Leigh Phenotypes for gene: RRAS were changed from ATYPICAL NOONAN SYNDROME to RRAS-related atypical Noonan syndrome
Fetal anomalies v3.150 RRAS Sarah Leigh Publications for gene: RRAS were set to
Cytopenia - NOT Fanconi anaemia v3.30 RRAS Sarah Leigh edited their review of gene: RRAS: Added comment: RRAS variants have not associated with a phenotype in OMIM or MONDO, but Gen2Phen lists a strong association between RRAS variants and RRAS-related atypical Noonan syndrome. Three germline RRAS variants have been reported (PMID: 24705357; 32815881; 34935735), associated with a RASopathy, which includes myelodysplastic syndrome and contributes to leukaemogenesis.; Changed rating: GREEN; Changed publications to: 24705357, 32815881, 34935735; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cytopenia - NOT Fanconi anaemia v3.30 RRAS Sarah Leigh Added comment: Comment on phenotypes: RRAS-related atypical Noonan syndrome phenotype from Gen2Phen
Cytopenia - NOT Fanconi anaemia v3.30 RRAS Sarah Leigh Phenotypes for gene: RRAS were changed from Pediatric Myelodysplastic Syndrome to RRAS-related atypical Noonan syndrome
Cytopenia - NOT Fanconi anaemia v3.29 RRAS Sarah Leigh Publications for gene: RRAS were set to PMID: 34935735
Cytopenia - NOT Fanconi anaemia v3.28 RRAS Sarah Leigh Classified gene: RRAS as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v3.28 RRAS Sarah Leigh Gene: rras has been classified as Amber List (Moderate Evidence).
Hereditary ataxia with onset in adulthood v4.31 NAA60 Sarah Leigh commented on gene: NAA60: NAA60 should be green on the Hereditary ataxia with onset in adulthood as four of the families described in table 1 (PMID: 38480682), also displayed either cerebellar syndrome (which often includes ataxia) or cerebellar ataxia (personal communication from Helen Brittain (Genomics England Clinical Fellow).
Adult onset neurodegenerative disorder v4.47 NAA60 Sarah Leigh changed review comment from: To date, NAA60 variants are not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38480682 reports six NAA60 variants in six unrelated cases with an autosomal recessive primary familial brain calcification (PFBC). Table 2 in PMID: 38480682 outlines the extent of the calcification seen in the patient's CT scans. Functional studies show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro, and loss of function by the NAA60 variants results in a reduced level of surface SLC20A2, thereby, reducing the extracellular phosphate uptake. The authors conclude, that this study provides a possible biochemical explanation of the involvement of NAA60 variants in PFBC development (PMID: 38480682).
Sources: Literature; to: To date, NAA60 variants are not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38480682 reports six NAA60 variants in six unrelated cases with an autosomal recessive primary familial brain calcification (PFBC); signs of Parkinsonian presentation was evident in three families reported. Table 2 in PMID: 38480682 outlines the extent of the calcification seen in the patient's CT scans. Functional studies show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro, and loss of function by the NAA60 variants results in a reduced level of surface SLC20A2, thereby, reducing the extracellular phosphate uptake. The authors conclude, that this study provides a possible biochemical explanation of the involvement of NAA60 variants in PFBC development (PMID: 38480682).
Sources: Literature
Hereditary ataxia with onset in adulthood v4.31 NAA60 Sarah Leigh Tag Q2_24_MOI tag was added to gene: NAA60.
Adult onset neurodegenerative disorder v4.47 NAA60 Sarah Leigh Tag Q2_24_MOI tag was added to gene: NAA60.
White matter disorders and cerebral calcification - narrow panel v3.35 NAA60 Sarah Leigh Tag Q2_24_MOI tag was added to gene: NAA60.
Hereditary ataxia with onset in adulthood v4.31 NAA60 Sarah Leigh Entity copied from White matter disorders and cerebral calcification - narrow panel v3.35
Hereditary ataxia with onset in adulthood v4.31 NAA60 Sarah Leigh gene: NAA60 was added
gene: NAA60 was added to Hereditary ataxia with onset in adulthood. Sources: Literature,Expert Review Amber
Q2_24_promote_green, Q2_24_NHS_review tags were added to gene: NAA60.
Mode of inheritance for gene: NAA60 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAA60 were set to 38480682
Phenotypes for gene: NAA60 were set to NAA60 associated autosomal recessive primary familial brain calcifications
Adult onset neurodegenerative disorder v4.47 NAA60 Sarah Leigh Entity copied from White matter disorders and cerebral calcification - narrow panel v3.35
Adult onset neurodegenerative disorder v4.47 NAA60 Sarah Leigh gene: NAA60 was added
gene: NAA60 was added to Adult onset neurodegenerative disorder. Sources: Literature,Expert Review Amber
Q2_24_promote_green, Q2_24_NHS_review tags were added to gene: NAA60.
Mode of inheritance for gene: NAA60 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAA60 were set to 38480682
Phenotypes for gene: NAA60 were set to NAA60 associated autosomal recessive primary familial brain calcifications
White matter disorders and cerebral calcification - narrow panel v3.35 NAA60 Sarah Leigh changed review comment from: To date, NAA60 variants are not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38480682 reports six NAA60 variants in six unrelated cases with an autosomal recessive primary familial brain calcification (PFBC). Table 2 in PMID: 38480682 outlines the extent of the calcification seen in the patient's CT scans. Functional studies show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro, and loss of function by the NAA60 variants results in a reduced level of surface SLC20A2, thereby, reducing the extracellular phosphate uptake. The authors conclude, that this study provides a possible biochemical explanation of the involvement of NAA60 variants in PFBC development (PMID: 38480682).
Sources: Literature; to: To date, NAA60 variants are not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38480682 reports six NAA60 variants in six unrelated cases with an autosomal recessive primary familial brain calcification (PFBC). Table 2 in PMID: 38480682 outlines the extent of the calcification seen in the patient's CT scans. Functional studies show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro, and loss of function by the NAA60 variants results in a reduced level of surface SLC20A2, thereby, reducing the extracellular phosphate uptake. The authors conclude, that this study provides a possible biochemical explanation of the involvement of NAA60 variants in PFBC development (PMID: 38480682).
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v3.35 NAA60 Sarah Leigh Mode of inheritance for gene: NAA60 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v4.30 BTD Achchuthan Shanmugasundram Phenotypes for gene: BTD were changed from Biotinidase deficiency, OMIM:253260 to Biotinidase deficiency, OMIM:253260; optic atrophy, MONDO:0003608
Optic neuropathy v4.29 BTD Achchuthan Shanmugasundram edited their review of gene: BTD: Changed phenotypes to: Biotinidase deficiency, OMIM:253260, optic atrophy, MONDO:0003608
Optic neuropathy v4.29 BTD Achchuthan Shanmugasundram Classified gene: BTD as Amber List (moderate evidence)
Optic neuropathy v4.29 BTD Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Optic neuropathy v4.29 BTD Achchuthan Shanmugasundram Gene: btd has been classified as Amber List (Moderate Evidence).
Optic neuropathy v4.28 BTD Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: BTD.
Optic neuropathy v4.28 BTD Achchuthan Shanmugasundram gene: BTD was added
gene: BTD was added to Optic neuropathy. Sources: Literature
Mode of inheritance for gene: BTD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BTD were set to 26203071; 29025919; 32235217; 33364171
Phenotypes for gene: BTD were set to Biotinidase deficiency, OMIM:253260
Review for gene: BTD was set to GREEN
Added comment: PMID:26203071 - A 22-year-old man presented with a disabling extensive myelopathy and bilateral optic neuropathy which mimicked the findings of a (seronegative) neuromyelitis optica. A novel homozygous BTD variant (p.Ala439Asp) and a known variant (c.1413T>C/ p.Cys471Cys) were identified in this patient.

PMID:29025919 - Two unrelated individuals with adult-onset biotinidase deficiency had severe, but reversible optic neuropathy. They were identified with compound heterozygous variants (patient 1: p.Phe232Cys/ p.Leu440Pro; patient 2: p.Gln456His/ p.Arg538Cys).

PMID:32235217 - A 49-year-old man was reported with progressive optic atrophy, peripheral neuropathy, and systemic weakness and fatigue due to biotinidase deficiency. This patient was reported with compound heterozygous variants (p.Ala171Thr/ p.Asp444His)

PMID:33364171 - Two adult brothers were reported with biallelic BTD variants. Both of them presented with lower limb neuropathy and one had progressive optic neuropathy.
Sources: Literature
Possible mitochondrial disorder - nuclear genes v3.105 SLIRP Achchuthan Shanmugasundram Classified gene: SLIRP as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.105 SLIRP Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with compound heterozygous SLIRP variants and the gene should be rated red.
Possible mitochondrial disorder - nuclear genes v3.105 SLIRP Achchuthan Shanmugasundram Gene: slirp has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.104 SLIRP Achchuthan Shanmugasundram reviewed gene: SLIRP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v3.15 COL5A1 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: COL5A1.
Cerebral vascular malformations v3.15 COL5A1 Achchuthan Shanmugasundram Classified gene: COL5A1 as Amber List (moderate evidence)
Cerebral vascular malformations v3.15 COL5A1 Achchuthan Shanmugasundram Gene: col5a1 has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v3.14 COL5A1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence available for the association of heterozygous COL5A1 variants with this panel. However, there are only two cases reported with compound heterozygous variants. Hence the MOI should be set as 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'.
Cerebral vascular malformations v3.14 COL5A1 Achchuthan Shanmugasundram Mode of inheritance for gene: COL5A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v3.13 COL5A1 Achchuthan Shanmugasundram Phenotypes for gene: COL5A1 were changed from Fibromuscular dysplasia, multifocal to Ehlers-Danlos syndrome, classic type, 1, OMIM:130000; Fibromuscular dysplasia, multifocal, OMIM:619329
Cerebral vascular malformations v3.12 COL5A1 Achchuthan Shanmugasundram Publications for gene: COL5A1 were set to PMID: 32938213
Cerebral vascular malformations v3.11 COL5A1 Achchuthan Shanmugasundram edited their review of gene: COL5A1: Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v3.11 COL5A1 Achchuthan Shanmugasundram edited their review of gene: COL5A1: Changed phenotypes to: Ehlers-Danlos syndrome, classic type, 1, OMIM:130000, Fibromuscular dysplasia, multifocal, OMIM:619329
Cerebral vascular malformations v3.11 COL5A1 Achchuthan Shanmugasundram changed review comment from: PMID:17053184 - Of 15 patients from seven families with spontaneous cervical artery dissections (CAD) recruited in this study, two patients from a family carried a rare variant in COL5A1 (p.Asp192Asn). One of them also carried a rare variant in COL5A2.

PMID:31903434 - Among 43 patients with cervical artery dissection (CeAD) analysed in this study, one patient had classic Ehlers Danlos syndrome due to two different missense variants in COL5A1 (p.Arg65Trp and p.Val172Phe), while another patient had missense variants in COL5A2 (p.Pro1103Leu) and COL5A1 (p.Thr1757Met).

PMID:32938213 - Four unrelated individuals were reported with the same heterozygous variant in COL5A1 (p.Gly514Ser) and they presented with arterial aneurysms, dissections, tortuosity, and mFMD affecting multiple arteries. The existence of a common haplotype among all four probands suggest founder effect.

PMID:33189937 - A 22-year-old patient with intracranial aneurysm and mild connective tissue manifestations reminiscent of EDS was identified with two COL5A1 missense variants in trans configuration (p.Gly530Ser and p.Pro1379Ser).

PMID:35911880; to: PMID:17053184 - Of 15 patients from seven families with spontaneous cervical artery dissections (CAD) recruited in this study, two patients from a family carried a rare variant in COL5A1 (p.Asp192Asn). One of them also carried a rare variant in COL5A2.

PMID:31903434 - Among 43 patients with cervical artery dissection (CeAD) analysed in this study, one patient had classic Ehlers Danlos syndrome due to two different missense variants in COL5A1 (p.Arg65Trp and p.Val172Phe), while another patient had missense variants in COL5A2 (p.Pro1103Leu) and COL5A1 (p.Thr1757Met).

PMID:32938213 - Four unrelated individuals were reported with the same heterozygous variant in COL5A1 (p.Gly514Ser) and they presented with arterial aneurysms, dissections, tortuosity, and mFMD affecting multiple arteries. The existence of a common haplotype among all four probands suggest founder effect.

PMID:33189937 - A 22-year-old patient with intracranial aneurysm and mild connective tissue manifestations reminiscent of EDS was identified with two COL5A1 missense variants in trans configuration (p.Gly530Ser and p.Pro1379Ser).

PMID:35911880 - A female was reported with postpartum arterial dissection involving all four cervicocephalic arteries resulting in acute cerebral infarction. She was identified with a heterozygous COL5A1 gene variant (p.Asp1648Gly).

This gene has been associated with relevant phenotypes in OMIM and Gene2Phenotype.
Cerebral vascular malformations v3.11 COL5A1 Achchuthan Shanmugasundram reviewed gene: COL5A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 17053184, 31903434, 32938213, 33189937, 35911880; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v4.36 GRAP Achchuthan Shanmugasundram commented on gene: GRAP: As reviewed by Barbara Vona, two unrelated families were reported with the same homozygous missense variant. There is some functional data available as well.

This gene has been associated with relevant phenotype in OMIM (MIM #618456).
Monogenic hearing loss v4.36 GRAP Achchuthan Shanmugasundram Classified gene: GRAP as Red List (low evidence)
Monogenic hearing loss v4.36 GRAP Achchuthan Shanmugasundram Gene: grap has been classified as Red List (Low Evidence).
Monogenic hearing loss v4.35 GRAP Achchuthan Shanmugasundram Phenotypes for gene: GRAP were changed from Non-syndromic hearing loss to Deafness, autosomal recessive 114, OMIM:618456
Monogenic hearing loss v4.34 GRAP Achchuthan Shanmugasundram reviewed gene: GRAP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 114, OMIM:618456; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.34 GRAP Achchuthan Shanmugasundram Publications for gene: GRAP were set to PMID: 30610177
Proteinuric renal disease v4.12 RCAN1 Achchuthan Shanmugasundram commented on gene: RCAN1: As reviewed by Zornitza Stark, whole-genome sequencing performed on 320 individuals from 201 families with familial and sporadic nephrotic syndrome (NS)/ focal segmental glomerulosclerosis (FSGS) identified two variants in RCAN1 gene in two families with autosomal dominant FSGS/ steroid-resistant nephrotic syndrome (SRNS). In addition, there is some functional data available.

This gene has not been associated with any phenotypes either in OMIM or in Gene2Phenotype.

This gene can be rated amber with current evidence.
Proteinuric renal disease v4.12 RCAN1 Achchuthan Shanmugasundram Classified gene: RCAN1 as Amber List (moderate evidence)
Proteinuric renal disease v4.12 RCAN1 Achchuthan Shanmugasundram Gene: rcan1 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v4.11 RCAN1 Achchuthan Shanmugasundram Phenotypes for gene: RCAN1 were changed from FSGS; proteinuria to focal segmental glomerulosclerosis, MONDO:0100313; nephrotic syndrome, MONDO:0005377
Proteinuric renal disease v4.10 RCAN1 Achchuthan Shanmugasundram reviewed gene: RCAN1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: focal segmental glomerulosclerosis, MONDO:0100313, nephrotic syndrome, MONDO:0005377; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Proteinuric renal disease v4.10 PRDM15 Achchuthan Shanmugasundram Classified gene: PRDM15 as Amber List (moderate evidence)
Proteinuric renal disease v4.10 PRDM15 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (six unrelated individuals with three different biallelic variants, mouse and Xenopus models and functional data) for the promotion of this gene to green rating in the next GMS update.
Proteinuric renal disease v4.10 PRDM15 Achchuthan Shanmugasundram Gene: prdm15 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v4.9 PRDM15 Achchuthan Shanmugasundram Phenotypes for gene: PRDM15 were changed from Steroid resistant nephrotic syndrome; Holoprosencephaly to steroid-resistant nephrotic syndrome, MONDO:0044765
Proteinuric renal disease v4.8 PRDM15 Achchuthan Shanmugasundram Publications for gene: PRDM15 were set to 31950080
Proteinuric renal disease v4.7 PRDM15 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: PRDM15.
Proteinuric renal disease v4.7 PRDM15 Achchuthan Shanmugasundram reviewed gene: PRDM15: Rating: GREEN; Mode of pathogenicity: None; Publications: 33593823; Phenotypes: steroid-resistant nephrotic syndrome, MONDO:0044765; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v4.27 PDXK Achchuthan Shanmugasundram Classified gene: PDXK as Amber List (moderate evidence)
Optic neuropathy v4.27 PDXK Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated cases and functional studies) for the promotion of this gene to green rating in the next GMS update.
Optic neuropathy v4.27 PDXK Achchuthan Shanmugasundram Gene: pdxk has been classified as Amber List (Moderate Evidence).
Optic neuropathy v4.26 PDXK Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: PDXK.
Hereditary neuropathy or pain disorder v3.87 PDXK Achchuthan Shanmugasundram Classified gene: PDXK as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.87 PDXK Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated cases and functional studies) for the promotion of this gene to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v3.87 PDXK Achchuthan Shanmugasundram Gene: pdxk has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.86 PDXK Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: PDXK.
Optic neuropathy v4.26 PDXK Achchuthan Shanmugasundram gene: PDXK was added
gene: PDXK was added to Optic neuropathy. Sources: Literature
Mode of inheritance for gene: PDXK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDXK were set to 31187503; 32522499
Phenotypes for gene: PDXK were set to Neuropathy, hereditary motor and sensory, type VIC, with optic atrophy, OMIM:618511
Review for gene: PDXK was set to GREEN
Added comment: PMID:31187503 - Five individuals from two unrelated families were reported with biallelic PDXK variants and with primary axonal polyneuropathy and optic atrophy. This association was also supported by results from cell-based functional assays. The biochemical profile can be rescued with PLP supplementation associated with clinical improvement.

PMID:32522499 - Two affected siblings with a novel biallelic missense PDXK variant were reported with a similar phenotype as reported in PMID:31187503 with earlier onset. Functional analysis showed that this variant leads to almost complete loss of PDXK enzymatic activity and low PLP levels.

This gene has been associated with relevant phenotypes in OMIM (MIM #618511), but not yet in Gene2Phenotype.
Sources: Literature
Hereditary neuropathy or pain disorder v3.86 PDXK Achchuthan Shanmugasundram gene: PDXK was added
gene: PDXK was added to Hereditary neuropathy or pain disorder. Sources: Literature
Mode of inheritance for gene: PDXK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDXK were set to 31187503; 32522499
Phenotypes for gene: PDXK were set to Neuropathy, hereditary motor and sensory, type VIC, with optic atrophy, OMIM:618511
Review for gene: PDXK was set to GREEN
Added comment: PMID:31187503 - Five individuals from two unrelated families were reported with biallelic PDXK variants and with primary axonal polyneuropathy and optic atrophy. This association was also supported by results from cell-based functional assays. The biochemical profile can be rescued with PLP supplementation associated with clinical improvement.

PMID:32522499 - Two affected siblings with a novel biallelic missense PDXK variant were reported with a similar phenotype as reported in PMID:31187503 with earlier onset. Functional analysis showed that this variant leads to almost complete loss of PDXK enzymatic activity and low PLP levels.

This gene has been associated with relevant phenotypes in OMIM (MIM #618511), but not yet in Gene2Phenotype.
Sources: Literature
Fetal anomalies v3.149 NRXN2 Sarah Leigh Publications for gene: NRXN2 were set to
Fetal hydrops v1.64 FZD6 Irina Adamena gene: FZD6 was added
gene: FZD6 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: FZD6 was set to Unknown
Publications for gene: FZD6 were set to PMID: 33082562
Phenotypes for gene: FZD6 were set to Nonimmune hydrops fetalis
Review for gene: FZD6 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 GLMN Irina Adamena gene: GLMN was added
gene: GLMN was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: GLMN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GLMN were set to PMID: 33082562
Phenotypes for gene: GLMN were set to Nonimmune hydrops fetalis
Review for gene: GLMN was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 ITGA9 Irina Adamena gene: ITGA9 was added
gene: ITGA9 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: ITGA9 was set to Unknown
Publications for gene: ITGA9 were set to PMID: 33082562
Phenotypes for gene: ITGA9 were set to Nonimmune hydrops fetalis
Review for gene: ITGA9 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Hereditary neuropathy or pain disorder v3.84 SPG7 Sarah Leigh changed review comment from: SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive (OMIM:607259) and have a definitive association with the same condition on the Eye panel at Gen2Phen. Various phenotypic features are apparent in cases of OMIM:607259. Peripheral neuropathy has been reported in at least three cases (PMID: 35096021, in the review on this panel by Williams Kirsty), and optical neuropathy has been reported in many more cases (as mentioned in PMID:35243150).; to: SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive (OMIM:607259) and have a definitive association with the same condition on the Eye panel at Gen2Phen. Various phenotypic features are apparent in cases of OMIM:607259. Peripheral neuropathy has been reported in at least three cases (PMID: 35096021, in the review on this panel by Kirsty Williams), and optical neuropathy has been reported in many more cases (as mentioned in PMID:35243150).
Fetal hydrops v1.64 CANT1 Irina Adamena gene: CANT1 was added
gene: CANT1 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: CANT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CANT1 were set to PMID: 33082562
Phenotypes for gene: CANT1 were set to Nonimmune hydrops fetalis
Review for gene: CANT1 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 PTH1R Irina Adamena reviewed gene: PTH1R: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 GPI Irina Adamena gene: GPI was added
gene: GPI was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: GPI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPI were set to PMID: 33082562
Phenotypes for gene: GPI were set to Nonimmune hydrops fetalis
Review for gene: GPI was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 G6PD Irina Adamena gene: G6PD was added
gene: G6PD was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: G6PD was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: G6PD were set to PMID: 33082562
Phenotypes for gene: G6PD were set to Nonimmune hydrops fetalis
Review for gene: G6PD was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 RPL15 Irina Adamena gene: RPL15 was added
gene: RPL15 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: RPL15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL15 were set to PMID: 33082562
Phenotypes for gene: RPL15 were set to Nonimmune hydrops fetalis
Review for gene: RPL15 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 PRF1 Irina Adamena gene: PRF1 was added
gene: PRF1 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: PRF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRF1 were set to PMID: 33082562
Phenotypes for gene: PRF1 were set to Nonimmune hydrops fetalis
Review for gene: PRF1 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 GATA1 Irina Adamena reviewed gene: GATA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal hydrops v1.64 SEC23B Irina Adamena gene: SEC23B was added
gene: SEC23B was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: SEC23B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEC23B were set to PMID: 33082562
Phenotypes for gene: SEC23B were set to Nonimmune hydrops fetalis
Review for gene: SEC23B was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 CDAN1 Irina Adamena reviewed gene: CDAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 SPTB Irina Adamena gene: SPTB was added
gene: SPTB was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: SPTB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPTB were set to PMID: 33082562
Phenotypes for gene: SPTB were set to Nonimmune hydrops fetalis
Review for gene: SPTB was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 SLC4A1 Irina Adamena gene: SLC4A1 was added
gene: SLC4A1 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: SLC4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC4A1 were set to PMID: 33082562
Phenotypes for gene: SLC4A1 were set to Nonimmune hydrops fetalis
Review for gene: SLC4A1 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Congenital muscular dystrophy v4.23 FHL1 Sarah Leigh changed review comment from: In response to Zornitza Starks' review, are the phenotypes of Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset (OMIM:300717) and/or Reducing body myopathy, X-linked 1b, with late childhood or adult onset (OMIM:300718), which are associated with FHL1 variants, appropriate for this panel - Congenital muscular dystrophy (R79)?; to: In response to Zornitza Starks' review, Helen Brittain (Genomics England Clinical Fellow) was asked the following question: are the phenotypes of Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset (OMIM:300717) and/or Reducing body myopathy, X-linked 1b, with late childhood or adult onset (OMIM:300718), which are associated with FHL1 variants, appropriate for this panel - Congenital muscular dystrophy (R79)?
Helen Brittain replied that in PMID: 19181672, the patients present with weakness and a raised CK - this would make clinicians think of a muscular dystrophy primarily. Although technically it may be a myopathy, I think it is enough of a mimic to be included on both the dystrophy and myopathy panels. Therefore this gene should remain green on Congenital muscular dystrophy
Fetal hydrops v1.64 SGPL1 Irina Adamena reviewed gene: SGPL1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 GBE1 Irina Adamena reviewed gene: GBE1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 MT-TL1 Irina Adamena gene: MT-TL1 was added
gene: MT-TL1 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene gene: MT-TL1 was set to MITOCHONDRIAL
Publications for gene: MT-TL1 were set to PMID: 33082562
Phenotypes for gene: MT-TL1 were set to Nonimmune hydrops fetalis
Review for gene: MT-TL1 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 MT-TE Irina Adamena gene: MT-TE was added
gene: MT-TE was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene gene: MT-TE was set to MITOCHONDRIAL
Publications for gene: MT-TE were set to PMID: 33082562
Phenotypes for gene: MT-TE were set to Nonimmune hydrops fetalis
Review for gene: MT-TE was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 MVK Irina Adamena reviewed gene: MVK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 MGAT2 Irina Adamena gene: MGAT2 was added
gene: MGAT2 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: MGAT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MGAT2 were set to PMID: 33082562
Phenotypes for gene: MGAT2 were set to Nonimmune hydrops fetalis
Review for gene: MGAT2 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 SLC17A5 Irina Adamena reviewed gene: SLC17A5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 GLB1 Irina Adamena reviewed gene: GLB1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 GUSB Irina Adamena reviewed gene: GUSB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 GALNS Irina Adamena reviewed gene: GALNS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 SCN5A Irina Adamena gene: SCN5A was added
gene: SCN5A was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: SCN5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN5A were set to PMID: 33082562
Phenotypes for gene: SCN5A were set to Nonimmune hydrops fetalis
Review for gene: SCN5A was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 KCNH2 Irina Adamena gene: KCNH2 was added
gene: KCNH2 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: KCNH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNH2 were set to PMID: 33082562
Phenotypes for gene: KCNH2 were set to Nonimmune hydrops fetalis
Review for gene: KCNH2 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 ALPK3 Irina Adamena gene: ALPK3 was added
gene: ALPK3 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: ALPK3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALPK3 were set to PMID: 33082562
Phenotypes for gene: ALPK3 were set to Nonimmune hydrops fetalis
Review for gene: ALPK3 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 MYH7 Irina Adamena gene: MYH7 was added
gene: MYH7 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: MYH7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYH7 were set to PMID: 33082562
Phenotypes for gene: MYH7 were set to Nonimmune hydrops fetalis
Review for gene: MYH7 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 LAMB2 Irina Adamena gene: LAMB2 was added
gene: LAMB2 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: LAMB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAMB2 were set to PMID: 33082562
Phenotypes for gene: LAMB2 were set to Nonimmune hydrops fetalis
Review for gene: LAMB2 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v3.34 NAA60 Sarah Leigh Classified gene: NAA60 as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v3.34 NAA60 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
White matter disorders and cerebral calcification - narrow panel v3.34 NAA60 Sarah Leigh Gene: naa60 has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - narrow panel v3.33 NAA60 Sarah Leigh gene: NAA60 was added
gene: NAA60 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Q2_24_promote_green, Q2_24_NHS_review tags were added to gene: NAA60.
Mode of inheritance for gene: NAA60 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NAA60 were set to 38480682
Phenotypes for gene: NAA60 were set to NAA60 associated autosomal recessive primary familial brain calcifications
Review for gene: NAA60 was set to GREEN
Added comment: To date, NAA60 variants are not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38480682 reports six NAA60 variants in six unrelated cases with an autosomal recessive primary familial brain calcification (PFBC). Table 2 in PMID: 38480682 outlines the extent of the calcification seen in the patient's CT scans. Functional studies show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro, and loss of function by the NAA60 variants results in a reduced level of surface SLC20A2, thereby, reducing the extracellular phosphate uptake. The authors conclude, that this study provides a possible biochemical explanation of the involvement of NAA60 variants in PFBC development (PMID: 38480682).
Sources: Literature
Fetal hydrops v1.64 CDC42 Irina Adamena gene: CDC42 was added
gene: CDC42 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: CDC42 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDC42 were set to PMID: 33082562
Phenotypes for gene: CDC42 were set to Nonimmune hydrops fetalis
Review for gene: CDC42 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 SLC30A5 Irina Adamena changed review comment from: Four affected children with homozygous loss of function variants in SLC30A5 gene with cardiomyopathy, hydrops fetalis, or cystic hygroma.; to: Four affected children with homozygous loss of function variants in SLC30A5 gene with cardiomyopathy, hydrops fetalis, or cystic hygroma (PMID: 33547425).
Fetal hydrops v1.64 ANGPT2 Irina Adamena reviewed gene: ANGPT2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34876502; Phenotypes: Hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 SLC30A5 Irina Adamena reviewed gene: SLC30A5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33547425; Phenotypes: hydrops fetalis, cardiomyopathy, cystic hygroma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.33 NLRP12 Achchuthan Shanmugasundram Classified gene: NLRP12 as Amber List (moderate evidence)
Monogenic hearing loss v4.33 NLRP12 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated cases) for the association of NLRP12 with sensorineural hearing loss and hence this gene can be promoted to green rating in the next GMS review.
Monogenic hearing loss v4.33 NLRP12 Achchuthan Shanmugasundram Gene: nlrp12 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.32 NLRP12 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: NLRP12.
Monogenic hearing loss v4.32 NLRP12 Achchuthan Shanmugasundram changed review comment from: PMID:18230725 - Two unrelated families from Guadeloupe were reported with a periodic fever syndrome and with monoallelic NLRP12 variants. Of these, twin boys from family 1 had bilateral sensorineural hearing loss.

PMID:24064030 - Six unrelated Italian patients were reported with familial cold autoinflammatory syndrome 2 and NLRP12 variants, of which one patient had sensorineural hearing loss.

PMID:31820221 - Three cases presenting with NLRP12 - autoinflammatory disorder were reported, where one had sensorineural deafness.
Sources: Literature; to: PMID:18230725 - Two unrelated families from Guadeloupe were reported with a periodic fever syndrome and with monoallelic NLRP12 variants. Of these, twin boys from family 1 had bilateral sensorineural hearing loss.

PMID:24064030 - Six unrelated Italian patients were reported with familial cold autoinflammatory syndrome 2 and NLRP12 variants, of which one patient had sensorineural hearing loss.

PMID:31820221 - Three cases presenting with NLRP12 - autoinflammatory disorder were reported, where one had sensorineural deafness.

NLRP12 has been associated with Familial cold autoinflammatory syndrome 2 (MIM #611762) in OMIM and sensorineural deafness has been listed as one of the clinical presentations of this phenotype.

Sources: Literature
Monogenic hearing loss v4.32 NLRP12 Achchuthan Shanmugasundram gene: NLRP12 was added
gene: NLRP12 was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: NLRP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NLRP12 were set to 18230725; 24064030; 31820221
Phenotypes for gene: NLRP12 were set to Familial cold autoinflammatory syndrome 2, OMIM:611762; sensorineural hearing loss disorder, MONDO:0020678
Review for gene: NLRP12 was set to GREEN
Added comment: PMID:18230725 - Two unrelated families from Guadeloupe were reported with a periodic fever syndrome and with monoallelic NLRP12 variants. Of these, twin boys from family 1 had bilateral sensorineural hearing loss.

PMID:24064030 - Six unrelated Italian patients were reported with familial cold autoinflammatory syndrome 2 and NLRP12 variants, of which one patient had sensorineural hearing loss.

PMID:31820221 - Three cases presenting with NLRP12 - autoinflammatory disorder were reported, where one had sensorineural deafness.
Sources: Literature
Childhood solid tumours v4.18 KDM3B Achchuthan Shanmugasundram Classified gene: KDM3B as Amber List (moderate evidence)
Childhood solid tumours v4.18 KDM3B Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there are four cases reported with KDM3B variants and with cancer, of which three cases are childhood solid tumours (two cases with Wilms tumour and one case with Hodgkin lymphoma), while the fourth case had acute myeloid leukaemia in childhood.

Hence, this gene can be promoted to green rating in the next GMS review.
Childhood solid tumours v4.18 KDM3B Achchuthan Shanmugasundram Gene: kdm3b has been classified as Amber List (Moderate Evidence).
Childhood solid tumours v4.17 KDM3B Achchuthan Shanmugasundram Phenotypes for gene: KDM3B were changed from Diets-Jongmans syndrome to Diets-Jongmans syndrome, OMIM:618846
Childhood solid tumours v4.16 KDM3B Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: KDM3B.
Childhood solid tumours v4.16 KDM3B Achchuthan Shanmugasundram reviewed gene: KDM3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 30885698, 30929739; Phenotypes: Diets-Jongmans syndrome, OMIM:618846; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.521 DENND5B Sarah Leigh Classified gene: DENND5B as Amber List (moderate evidence)
Intellectual disability v5.521 DENND5B 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 v5.521 DENND5B Sarah Leigh Gene: dennd5b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.520 DENND5B Sarah Leigh Tag Q2_24_promote_green tag was added to gene: DENND5B.
Tag Q2_24_NHS_review tag was added to gene: DENND5B.
Early onset or syndromic epilepsy v4.193 DENND5B Sarah Leigh Classified gene: DENND5B as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.193 DENND5B Sarah Leigh Gene: dennd5b has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.192 DENND5B Sarah Leigh edited their review of gene: DENND5B: Changed rating: AMBER
Early onset or syndromic epilepsy v4.192 DENND5B Sarah Leigh gene: DENND5B was added
gene: DENND5B was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: DENND5B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DENND5B were set to 38387458
Phenotypes for gene: DENND5B were set to DENND5B associated neurodevelopmental disorder
Review for gene: DENND5B was set to GREEN
Added comment: DENND5B variants have not previously been associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38387458 reports five de novo missense variants in five unrelated cases. The carriers of these DENND5B variants have a neurodevelopmental disorder, which is characterized by psychomotor delay (5/5 cases), intellectual disability, ranging from severe to mild (3/5 cases, although one of the negative cases was a 2 year old child, who was considered to be too young to make the assessment, although the DD/intellectual disability phenotype was considered to be moderate in this case), epilepsy (2/5 cases) and hypotonia (4/5 cases). The authors of PMID: 38387458 also report the functional effects of the DENND5B variants, which revealed defective intracellular vesicle trafficking, with significant impairment of lipid uptake and distribution. They conclude that this effect is likely to be caused by the predicted disruption of protein folding in the variant DENND5B peptide.
Sources: Literature
Intellectual disability v5.520 DENND5B Sarah Leigh gene: DENND5B was added
gene: DENND5B was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: DENND5B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DENND5B were set to 38387458
Phenotypes for gene: DENND5B were set to DENND5B associated neurodevelopmental disorder
Review for gene: DENND5B was set to GREEN
Added comment: DENND5B variants have not previously been associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38387458 reports five de novo missense variants in five unrelated cases. The carriers of these DENND5B variants have a neurodevelopmental disorder, which is characterized by psychomotor delay (5/5 cases), intellectual disability, ranging from severe to mild (3/5 cases, although one of the negative cases was a 2 year old child, who was considered to be too young to make the assessment, although the DD/intellectual disability phenotype was considered to be moderate in this case), epilepsy (2/5 cases) and hypotonia (4/5 cases). The authors of PMID: 38387458 also report the functional effects of the DENND5B variants, which revealed defective intracellular vesicle trafficking, with significant impairment of lipid uptake and distribution. They conclude that this effect is likely to be caused by the predicted disruption of protein folding in the variant DENND5B peptide.
Sources: Literature
Intellectual disability v5.519 TBC1D2B Sarah Leigh Tag watchlist was removed from gene: TBC1D2B.
Tag Q2_24_promote_green tag was added to gene: TBC1D2B.
Tag Q2_24_NHS_review tag was added to gene: TBC1D2B.
Intellectual disability v5.519 TBC1D2B Sarah Leigh Classified gene: TBC1D2B as Amber List (moderate evidence)
Intellectual disability v5.519 TBC1D2B 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 v5.519 TBC1D2B Sarah Leigh Gene: tbc1d2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.518 TBC1D2B Sarah Leigh reviewed gene: TBC1D2B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v4.191 TBC1D2B Sarah Leigh edited their review of gene: TBC1D2B: Added comment: TBC1D2B variants have been associated with Neurodevelopmental disorder with seizures and gingival overgrowth (OMIM:619323) and as definitive Gen2Phen gene for TBC1D2B-related neurodevelopmental disorder. So far, 11 TBC1D2B variants have been reported in 8 unrelated families. Global developmental delay (HP:0001263) was reported in 5/8 families, mental deterioration (HP:0001268) was seen in 5/8 families and seizures (HP:0001250) were reported in 8/8 families (four of these were controlled with medication)(PMID: 38374468).; Changed rating: GREEN
Intellectual disability v5.518 TBC1D2B Sarah Leigh Publications for gene: TBC1D2B were set to 32623794
Early onset or syndromic epilepsy v4.191 TBC1D2B Sarah Leigh Publications for gene: TBC1D2B were set to 32623794
Intellectual disability v5.517 TBC1D2B Sarah Leigh Phenotypes for gene: TBC1D2B were changed from Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality to Neurodevelopmental disorder with seizures and gingival overgrowth, OMIM:619323; neurodevelopmental disorder with seizures and gingival overgrowth, MONDO:0859148
Early onset or syndromic epilepsy v4.190 TBC1D2B Sarah Leigh Phenotypes for gene: TBC1D2B were changed from Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality to Neurodevelopmental disorder with seizures and gingival overgrowth, OMIM:619323; neurodevelopmental disorder with seizures and gingival overgrowth, MONDO:0859148
Ichthyosis and erythrokeratoderma v3.28 DBR1 Achchuthan Shanmugasundram Classified gene: DBR1 as Amber List (moderate evidence)
Ichthyosis and erythrokeratoderma v3.28 DBR1 Achchuthan Shanmugasundram Gene: dbr1 has been classified as Amber List (Moderate Evidence).
Ichthyosis and erythrokeratoderma v3.27 DBR1 Achchuthan Shanmugasundram Tag founder-effect tag was added to gene: DBR1.
Ichthyosis and erythrokeratoderma v3.27 DBR1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark, the same variant was identified in four different families and haplotype analysis suggests this to be a founder variant.; to: Comment on list classification: As reviewed by Zornitza Stark, the same variant was identified in four different families and haplotype analysis suggests this to be a founder variant. There is functional data available. This gene can only be rated amber with the current evidence.

The 'founder-effect' tag is added to this gene.
Ichthyosis and erythrokeratoderma v3.27 DBR1 Achchuthan Shanmugasundram Classified gene: DBR1 as No list
Ichthyosis and erythrokeratoderma v3.27 DBR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, the same variant was identified in four different families and haplotype analysis suggests this to be a founder variant.
Ichthyosis and erythrokeratoderma v3.27 DBR1 Achchuthan Shanmugasundram Gene: dbr1 has been removed from the panel.
Ichthyosis and erythrokeratoderma v3.26 DBR1 Achchuthan Shanmugasundram edited their review of gene: DBR1: Changed phenotypes to: ichthyosis, MONDO:0019269
Ichthyosis and erythrokeratoderma v3.26 DBR1 Achchuthan Shanmugasundram Phenotypes for gene: DBR1 were changed from Ichthyosis (MONDO#0019269), DBR1-related to ichthyosis, MONDO:0019269
Ichthyosis and erythrokeratoderma v3.25 DBR1 Achchuthan Shanmugasundram reviewed gene: DBR1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: inherited ichthyosis, MONDO:0015947; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ehlers Danlos syndrome with a likely monogenic cause v3.12 ADAMTSL2 Achchuthan Shanmugasundram Classified gene: ADAMTSL2 as Amber List (moderate evidence)
Ehlers Danlos syndrome with a likely monogenic cause v3.12 ADAMTSL2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, six families were reported with the same monoallelic variant and with Ehlers-Danlos syndrome. However, there is no functional data and it is not clear whether it is a founder variant. Hence, this gene can only be rated amber with the current evidence in this panel.
Ehlers Danlos syndrome with a likely monogenic cause v3.12 ADAMTSL2 Achchuthan Shanmugasundram Gene: adamtsl2 has been classified as Amber List (Moderate Evidence).
Ehlers Danlos syndrome with a likely monogenic cause v3.11 ADAMTSL2 Achchuthan Shanmugasundram reviewed gene: ADAMTSL2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Ehlers-Danlos syndrome, MONDO:0020066; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital adrenal hypoplasia v3.11 KDM1A Achchuthan Shanmugasundram Phenotypes for gene: KDM1A were changed from Food-dependent Cushing syndrome (FDCS) to Cleft palate, psychomotor retardation, and distinctive facial features, OMIM:616728; congenital adrenal hyperplasia, MONDO:0018479
Congenital adrenal hypoplasia v3.10 KDM1A Achchuthan Shanmugasundram Classified gene: KDM1A as Red List (low evidence)
Congenital adrenal hypoplasia v3.10 KDM1A Achchuthan Shanmugasundram Gene: kdm1a has been classified as Red List (Low Evidence).
Congenital adrenal hypoplasia v3.9 KDM1A Achchuthan Shanmugasundram reviewed gene: KDM1A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cleft palate, psychomotor retardation, and distinctive facial features, OMIM:616728, congenital adrenal hyperplasia, MONDO:0018479; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare genetic inflammatory skin disorders v3.10 GNB1 Achchuthan Shanmugasundram Classified gene: GNB1 as Amber List (moderate evidence)
Rare genetic inflammatory skin disorders v3.10 GNB1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there are five cases reported with cutaneous mastocytosis.

Cutaneous mastocytosis has also been reported as one of the clinical presentations of the OMIM phenotype Intellectual developmental disorder, autosomal dominant 42 (MIM #616973).

Hence, this gene can be promoted to green rating in the next GMS review.
Rare genetic inflammatory skin disorders v3.10 GNB1 Achchuthan Shanmugasundram Gene: gnb1 has been classified as Amber List (Moderate Evidence).
Rare genetic inflammatory skin disorders v3.9 GNB1 Achchuthan Shanmugasundram Phenotypes for gene: GNB1 were changed from Cutaneous mastocytosis; Intellectual developmental disorder, autosomal dominant 42 to Intellectual developmental disorder, autosomal dominant 42, OMIM:616973; cutaneous mastocytosis, MONDO:0019023
Rare genetic inflammatory skin disorders v3.8 GNB1 Achchuthan Shanmugasundram Publications for gene: GNB1 were set to 35119134
Rare genetic inflammatory skin disorders v3.7 GNB1 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: GNB1.
Rare genetic inflammatory skin disorders v3.7 GNB1 Achchuthan Shanmugasundram reviewed gene: GNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29174093, 30194818, 35119134; Phenotypes: Intellectual developmental disorder, autosomal dominant 42, OMIM:616973, cutaneous mastocytosis, MONDO:0019023; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Thoracic aortic aneurysm or dissection (GMS) v3.11 SECISBP2 Achchuthan Shanmugasundram Tag Q2_24_NHS_review tag was added to gene: SECISBP2.
Thoracic aortic aneurysm or dissection (GMS) v3.11 SECISBP2 Achchuthan Shanmugasundram Classified gene: SECISBP2 as Amber List (moderate evidence)
Thoracic aortic aneurysm or dissection (GMS) v3.11 SECISBP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (four unrelated cases and animal models) for the promotion of this gene to green rating in the next GMS review.
Thoracic aortic aneurysm or dissection (GMS) v3.11 SECISBP2 Achchuthan Shanmugasundram Gene: secisbp2 has been classified as Amber List (Moderate Evidence).
Thoracic aortic aneurysm or dissection (GMS) v3.10 SECISBP2 Achchuthan Shanmugasundram Phenotypes for gene: SECISBP2 were changed from Growth retardation; sensorineural hearing loss; muscular dystrophy; thoracic aortic aneurysm; raised circulating thyroxine and low plasma selenium to Thyroid hormone metabolism, abnormal, 1, OMIM:609698; thoracic aortic aneurysm
Thoracic aortic aneurysm or dissection (GMS) v3.9 SECISBP2 Achchuthan Shanmugasundram Publications for gene: SECISBP2 were set to PMID 38042913; PMID 21084748
Thoracic aortic aneurysm or dissection (GMS) v3.8 SECISBP2 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: SECISBP2.
Thoracic aortic aneurysm or dissection (GMS) v3.8 SECISBP2 Achchuthan Shanmugasundram reviewed gene: SECISBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38042913; Phenotypes: Thyroid hormone metabolism, abnormal, 1, OMIM:609698; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.83 RP1L1 Arina Puzriakova Added comment: Comment on mode of inheritance: This gene is associated with occult macular dystrophy (monoallelic variants) and retinitis pigmentosa (biallelic variants) (https://omim.org/entry/608581) with sufficient cases reported for each phenotype. Currently the monoallelic phenotype is not represented on any GMS panels.

Following curation and consultation with the Genomics England clinical team, there was agreement that macular dystrophy is part of the phenotypic target for this panel. Based on previous reviews, it is not clear why the monoallelic MOI was overwritten and therefore this gene will be flagged for specialist review to determine whether the MOI should stay as 'biallelic' or be updated to 'both mono- and biallelic'.
Retinal disorders v4.83 RP1L1 Arina Puzriakova Mode of inheritance for gene: RP1L1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.82 RP1L1 Arina Puzriakova Tag Q2_24_MOI tag was added to gene: RP1L1.
Tag Q2_24_expert_review tag was added to gene: RP1L1.
Monogenic hearing loss v4.31 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051; 32631815
Monogenic hearing loss v4.31 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051; 32631815
Monogenic hearing loss v4.31 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051; 32631815
Monogenic hearing loss v4.31 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051; 32631815
Monogenic hearing loss v4.31 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051; 32631815
Monogenic hearing loss v4.30 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051; 32631815
Monogenic hearing loss v4.30 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051
Monogenic hearing loss v4.29 RIPOR2 Achchuthan Shanmugasundram Phenotypes for gene: RIPOR2 were changed from Deafness, autosomal dominant 21, OMIM:607017; ?Deafness, autosomal recessive 104, OMIM:616515 to Deafness, autosomal dominant 21, OMIM:607017; ?Deafness, autosomal recessive 104, OMIM:616515
Monogenic hearing loss v4.29 RIPOR2 Achchuthan Shanmugasundram Phenotypes for gene: RIPOR2 were changed from ?Deafness, autosomal recessive 104 , OMIM:616515 to Deafness, autosomal dominant 21, OMIM:607017; ?Deafness, autosomal recessive 104, OMIM:616515
Monogenic hearing loss v4.28 RIPOR2 Achchuthan Shanmugasundram Classified gene: RIPOR2 as Amber List (moderate evidence)
Monogenic hearing loss v4.28 RIPOR2 Achchuthan Shanmugasundram Added comment: Comment on list classification: Only one variant was reported with both monoallelic and biallelic inheritance. There is some functional data for both modes of inheritance. Although there are 12 unrelated cases reported with the same monoallelic variant, this variant was suggested to be founder variant. Hence, this gene can only be rated amber with the current evidence for both modes of inheritance.
Monogenic hearing loss v4.28 RIPOR2 Achchuthan Shanmugasundram Gene: ripor2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.27 RIPOR2 Achchuthan Shanmugasundram changed review comment from: Biallelic variants:
PMID:24958875 reported six affected members from a single Turkish family with a homozygous splice site variant in the RIPOR2 gene (c.102-1G-A) and with deafness. In addition, morpholino knockdown of the orthologous gene in zebrafish embryos resulted in a significant reduction in the number of saccular hair cells and neuromasts, and caused hearing loss.

Monoallelic variants:
PMID:32631815 reported a heterozygous 12 nucleotide in-frame deletion (c.1696_1707del, p.Gln566_Lys569del) in RIPOR2 that was detected in 12 families of Dutch origin with non-syndromic hearing loss.

In total, the variant was detected in 59/63 affected participants, but also in five unaffected subjects from three family. Age of onset was highly variable, from congenital to 70 years (mean age: 30.6 years) - unaffected family members who harboured the variant were aged 23, 40, 49, 50, and 51 years, respectively. The authors speculated that the four affected subjects without the variant represent phenocopies. The presence of an identical variant in 12 families of common origin, as well as haplotype analysis, indicates a founder effect.

Functional analysis of this variant showed aberrant localisation of RIPOR2 variant protein in early postnatal mouse hair cells, ex vivo; and failure to rescue the stereocilia defects of Ripor2 knockout mice, in contrast to the rescue effect observed in cells expressing wild-type RIPOR2.; to: Biallelic variants:
PMID:24958875 reported six affected members from a single Turkish family with a homozygous splice site variant in the RIPOR2 gene (c.102-1G-A) and with deafness. In addition, morpholino knockdown of the orthologous gene in zebrafish embryos resulted in a significant reduction in the number of saccular hair cells and neuromasts, and caused hearing loss.

Monoallelic variants:
PMID:32631815 reported a heterozygous 12 nucleotide in-frame deletion (c.1696_1707del, p.Gln566_Lys569del) in RIPOR2 that was detected in 12 families of Dutch origin with non-syndromic hearing loss.

In total, the variant was detected in 59/63 affected participants, but also in five unaffected subjects from three family. Age of onset was highly variable, from congenital to 70 years (mean age: 30.6 years) - unaffected family members who harboured the variant were aged 23, 40, 49, 50, and 51 years, respectively. The authors speculated that the four affected subjects without the variant represent phenocopies. The presence of an identical variant in 12 families of common origin, as well as haplotype analysis, indicates a founder effect. Hence, the 'founder-effect' tag was added.

Functional analysis of this variant showed aberrant localisation of RIPOR2 variant protein in early postnatal mouse hair cells, ex vivo; and failure to rescue the stereocilia defects of Ripor2 knockout mice, in contrast to the rescue effect observed in cells expressing wild-type RIPOR2.
Monogenic hearing loss v4.27 RIPOR2 Achchuthan Shanmugasundram edited their review of gene: RIPOR2: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v4.27 RIPOR2 Achchuthan Shanmugasundram Tag founder-effect tag was added to gene: RIPOR2.
Monogenic hearing loss v4.27 RIPOR2 Achchuthan Shanmugasundram reviewed gene: RIPOR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24958875, 32631815; Phenotypes: Deafness, autosomal dominant 21, OMIM:607017, ?Deafness, autosomal recessive 104, OMIM:616515; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe Paediatric Disorders v1.184 CNTNAP2 Tracy Lester reviewed gene: CNTNAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.515 ASCC3 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Intellectual developmental disorder, autosomal recessive 81, OMIM:620700)
Intellectual disability v5.515 ASCC3 Arina Puzriakova Phenotypes for gene: ASCC3 were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to Intellectual developmental disorder, autosomal recessive 81, OMIM:620700
DDG2P v3.86 ASCC3 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Intellectual developmental disorder, autosomal recessive 81, OMIM:620700)
DDG2P v3.86 ASCC3 Arina Puzriakova Phenotypes for gene: ASCC3 were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to Intellectual developmental disorder, autosomal recessive 81, OMIM:620700
Congenital myopathy v4.37 ASCC3 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Intellectual developmental disorder, autosomal recessive 81, OMIM:620700)
Congenital myopathy v4.37 ASCC3 Arina Puzriakova Phenotypes for gene: ASCC3 were changed from congenital myopathy, MONDO:0019952 to Intellectual developmental disorder, autosomal recessive 81, OMIM:620700
Intellectual disability v5.514 ASCC3 Arina Puzriakova Tag gene-checked was removed from gene: ASCC3.
DDG2P v3.85 ASCC3 Arina Puzriakova Tag gene-checked was removed from gene: ASCC3.
Congenital myopathy v4.36 ASCC3 Arina Puzriakova Tag gene-checked was removed from gene: ASCC3.
Renal ciliopathies v3.5 DLG5 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Yuksel-Vogel-Bauser syndrome, OMIM:620703)
Renal ciliopathies v3.5 DLG5 Arina Puzriakova Phenotypes for gene: DLG5 were changed from DLG5-associated developmental disorder (monoallelic); DLG5-associated developmental disorder (biallelic) to Yuksel-Vogel-Bauser syndrome, OMIM:620703
Unexplained young onset end-stage renal disease v3.40 DLG5 Arina Puzriakova Phenotypes for gene: DLG5 were changed from DLG5-associated developmental disorder (monoallelic); DLG5-associated developmental disorder (biallelic) to Yuksel-Vogel-Bauser syndrome, OMIM:620703
Renal ciliopathies v3.4 DLG5 Arina Puzriakova Tag gene-checked was removed from gene: DLG5.
Intellectual disability v5.514 PTRHD1 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, OMIM:620747)
Intellectual disability v5.514 PTRHD1 Arina Puzriakova Phenotypes for gene: PTRHD1 were changed from Intellectual disability; Parkinsonism to Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, OMIM:620747
Parkinson Disease and Complex Parkinsonism v1.121 PTRHD1 Arina Puzriakova Phenotypes for gene: PTRHD1 were changed from Intellectual disability; Parkinsonism to Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, OMIM:620747
Intellectual disability v5.513 PTRHD1 Arina Puzriakova Tag gene-checked was removed from gene: PTRHD1.
DDG2P v3.85 FZD5 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Microphthalmia/coloboma 11, OMIM:620731)
DDG2P v3.85 FZD5 Arina Puzriakova Phenotypes for gene: FZD5 were changed from Autosomal Dominant Coloboma to Microphthalmia/coloboma 11, OMIM:620731
Structural eye disease v3.76 FZD5 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Microphthalmia/coloboma 11, OMIM:620731)
Structural eye disease v3.76 FZD5 Arina Puzriakova Phenotypes for gene: FZD5 were changed from Coloboma, None to Microphthalmia/coloboma 11, OMIM:620731
Fetal anomalies v3.147 FZD5 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Microphthalmia/coloboma 11, OMIM:620731)
Fetal anomalies v3.147 FZD5 Arina Puzriakova Phenotypes for gene: FZD5 were changed from Autosomal Dominant Coloboma to Microphthalmia/coloboma 11, OMIM:620731
Ocular coloboma v1.47 FZD5 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Microphthalmia/coloboma 11, OMIM:620731)
Ocular coloboma v1.47 FZD5 Arina Puzriakova Phenotypes for gene: FZD5 were changed from Coloboma to Microphthalmia/coloboma 11, OMIM:620731
Structural eye disease v3.75 FZD5 Arina Puzriakova Tag gene-checked was removed from gene: FZD5.
DDG2P v3.84 FZD5 Arina Puzriakova Tag gene-checked was removed from gene: FZD5.
Ocular coloboma v1.46 FZD5 Arina Puzriakova Tag gene-checked was removed from gene: FZD5.
Intellectual disability v5.513 SLC32A1 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Developmental and epileptic encephalopathy 114, OMIM:620774)
Intellectual disability v5.513 SLC32A1 Arina Puzriakova Phenotypes for gene: SLC32A1 were changed from developmental and epileptic encephalopathy, MONDO:0100062 to Developmental and epileptic encephalopathy 114, OMIM:620774
Early onset or syndromic epilepsy v4.188 SLC32A1 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has relevant phenotypes listed in OMIM (Developmental and epileptic encephalopathy 114, OMIM:620774 and Generalized epilepsy with febrile seizures plus, type 12, OMIM:620755)
Early onset or syndromic epilepsy v4.188 SLC32A1 Arina Puzriakova Phenotypes for gene: SLC32A1 were changed from developmental and epileptic encephalopathy, MONDO:0100062; generalized epilepsy with febrile seizures plus, MONDO:0018214 to Developmental and epileptic encephalopathy 114, OMIM:620774; Generalized epilepsy with febrile seizures plus, type 12, OMIM:620755
DDG2P v3.84 SLC32A1 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Developmental and epileptic encephalopathy 114, OMIM:620774)
DDG2P v3.84 SLC32A1 Arina Puzriakova Phenotypes for gene: SLC32A1 were changed from SLC32A1-associated developmental and epileptic encephalopathy to Developmental and epileptic encephalopathy 114, OMIM:620774
Intellectual disability v5.512 SLC32A1 Arina Puzriakova Tag gene-checked was removed from gene: SLC32A1.
Early onset or syndromic epilepsy v4.187 SLC32A1 Arina Puzriakova Tag gene-checked was removed from gene: SLC32A1.
DDG2P v3.83 SLC32A1 Arina Puzriakova Tag gene-checked was removed from gene: SLC32A1.
DDG2P v3.83 BRD4 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a phenotype listed in OMIM (Cornelia de Lange syndrome 6, OMIM:620568)
DDG2P v3.83 BRD4 Arina Puzriakova Phenotypes for gene: BRD4 were changed from CORNELIA DE LANGE-LIKE SYNDROME to Cornelia de Lange syndrome 6, OMIM:620568
Severe microcephaly v4.67 BRD4 Arina Puzriakova Phenotypes for gene: BRD4 were changed from Cornelia de Lange-like syndrome, MONDO:0016033 to Cornelia de Lange syndrome 6, OMIM:620568
Intellectual disability v5.512 BRD4 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a phenotype listed in OMIM (Cornelia de Lange syndrome 6, OMIM:620568)
Intellectual disability v5.512 BRD4 Arina Puzriakova Phenotypes for gene: BRD4 were changed from Intellectual disability; Microcephaly; Abnormal heart morphology; Abnormality of the face to Cornelia de Lange syndrome 6, OMIM:620568
DDG2P v3.82 BRD4 Arina Puzriakova Tag gene-checked was removed from gene: BRD4.
Intellectual disability v5.511 BRD4 Arina Puzriakova Tag gene-checked was removed from gene: BRD4.
Intellectual disability v5.511 CAPRIN1 Arina Puzriakova Publications for gene: CAPRIN1 were set to 23849776; 35979925; 36136249
Early onset or syndromic epilepsy v4.187 CAPRIN1 Arina Puzriakova Publications for gene: CAPRIN1 were set to 35979925
DDG2P v3.82 CAPRIN1 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636)
DDG2P v3.82 CAPRIN1 Arina Puzriakova Phenotypes for gene: CAPRIN1 were changed from Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636 to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636
Intellectual disability v5.510 CAPRIN1 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a phenotype listed in OMIM (Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636)
Intellectual disability v5.510 CAPRIN1 Arina Puzriakova Phenotypes for gene: CAPRIN1 were changed from Global developmental delay; Delayed speech and language development; Intellectual disability; Autistic behaviour; Seizures to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636
Early onset or syndromic epilepsy v4.186 CAPRIN1 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a phenotype listed in OMIM (Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636)
Early onset or syndromic epilepsy v4.186 CAPRIN1 Arina Puzriakova Phenotypes for gene: CAPRIN1 were changed from Global developmental delay; Delayed speech and language development; Intellectual disability; Autistic behavior; Seizures to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636
Intellectual disability v5.509 CAPRIN1 Arina Puzriakova Tag gene-checked was removed from gene: CAPRIN1.
Early onset or syndromic epilepsy v4.185 CAPRIN1 Arina Puzriakova Tag gene-checked was removed from gene: CAPRIN1.
DDG2P v3.81 CAPRIN1 Arina Puzriakova Phenotypes for gene: CAPRIN1 were changed from AUTISM OR INTELLECTUAL DISABILITY to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636
DDG2P v3.80 CAPRIN1 Arina Puzriakova Tag gene-checked was removed from gene: CAPRIN1.
Ataxia and cerebellar anomalies - narrow panel v4.59 CAPRIN1 Arina Puzriakova Phenotypes for gene: CAPRIN1 were changed from Cerebellar ataxia, MONDO:0000437; Early-onset ataxia to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636
DDG2P v3.80 WNK3 Arina Puzriakova Tag gene-checked was removed from gene: WNK3.
DDG2P v3.80 WNK3 Arina Puzriakova Phenotypes for gene: WNK3 were changed from WNK3-related neurodevelopmental disorder to WNK3-related neurodevelopmental disorder; Prieto syndrome, OMIM:309610
Autism v0.36 WNK3 Arina Puzriakova Tag gene-checked was removed from gene: WNK3.
Early onset or syndromic epilepsy v4.185 WNK3 Arina Puzriakova Tag gene-checked was removed from gene: WNK3.
Intellectual disability v5.509 WNK3 Arina Puzriakova Phenotypes for gene: WNK3 were changed from X-linked intellectual disability, MONDO:0100284 to Prieto syndrome, OMIM:309610; Intellectual disability, MONDO:0001071
Early onset or syndromic epilepsy v4.185 WNK3 Arina Puzriakova Phenotypes for gene: WNK3 were changed from X-linked intellectual disability, MONDO:0100284 to Prieto syndrome, OMIM:309610; Intellectual disability, MONDO:0001071
Intellectual disability v5.508 WNK3 Arina Puzriakova Tag gene-checked was removed from gene: WNK3.
Malformations of cortical development v4.26 WNK3 Arina Puzriakova Phenotypes for gene: WNK3 were changed from Intellectual disability, MONDO:0001071 to Prieto syndrome, OMIM:309610; Intellectual disability, MONDO:0001071
Malformations of cortical development v4.25 WNK3 Arina Puzriakova Tag gene-checked was removed from gene: WNK3.
Intellectual disability v5.508 C12orf4 Arina Puzriakova Phenotypes for gene: C12orf4 were changed from Autosomal recessive intellectual disability to Intellectual developmental disorder, autosomal recessive 66, OMIM:618221
Severe Paediatric Disorders v1.183 C12orf4 Arina Puzriakova Phenotypes for gene: C12orf4 were changed from Mental retardation, autosomal recessive 66, 618221 to Intellectual developmental disorder, autosomal recessive 66, OMIM:618221
Severe Paediatric Disorders v1.182 C12orf4 Arina Puzriakova commented on gene: C12orf4
Intellectual disability v5.507 C12orf4 Arina Puzriakova commented on gene: C12orf4
Severe Paediatric Disorders v1.182 C12orf4 Arina Puzriakova Tag new-gene-name tag was added to gene: C12orf4.
Intellectual disability v5.507 C12orf4 Arina Puzriakova Tag new-gene-name tag was added to gene: C12orf4.
Mosaic skin disorders - deep sequencing v2.47 MVD Arina Puzriakova Tag Q2_24_promote_green tag was added to gene: MVD.
Mosaic skin disorders - deep sequencing v2.47 MVD Arina Puzriakova Classified gene: MVD as Amber List (moderate evidence)
Mosaic skin disorders - deep sequencing v2.47 MVD Arina Puzriakova Added comment: Comment on list classification: At least 5 individuals reported (PMID: 30942823; 33491095) which meets the criteria for classifying this gene-disease association as Green at the next GMS panel update.
Mosaic skin disorders - deep sequencing v2.47 MVD Arina Puzriakova Gene: mvd has been classified as Amber List (Moderate Evidence).
Mosaic skin disorders - deep sequencing v2.46 MVD Arina Puzriakova commented on gene: MVD
Mosaic skin disorders - deep sequencing v2.46 MVD Arina Puzriakova Publications for gene: MVD were set to 30942823
Mosaic skin disorders - deep sequencing v2.45 MVD Arina Puzriakova Phenotypes for gene: MVD were changed from Linear porokeratosis to Porokeratosis 7, multiple types, OMIM:614714
Rare genetic inflammatory skin disorders v3.7 MVD Arina Puzriakova Phenotypes for gene: MVD were changed from POROKERATOSIS 7, MULTIPLE TYPES, OMIM:614714 to Porokeratosis 7, multiple types, OMIM:614714
Familial disseminated superficial actinic porokeratosis v1.3 MVD Arina Puzriakova Phenotypes for gene: MVD were changed from Porokeratosis 7, multiple types, 614714; actinic/non-actinic disseminated superficial porokeratosis; POROK7; DSAP/DSP to Porokeratosis 7, multiple types, OMIM:614714
Skeletal dysplasia v4.55 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Incontinentia pigmenti 308300; Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency 300301 to Ectodermal dysplasia and immunodeficiency 1, OMIM:300291
Primary lymphoedema v3.11 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency 300301 to Ectodermal dysplasia and immunodeficiency 1, OMIM:300291
Intellectual disability v5.507 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Incontinentia pigmenti, type II, 308300Ectodermal dysplasia, hypohidrotic, with immune deficiency, 300291Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency, 300301Immunodeficiency, isolated, 300584{Atypical mycobacteriosis, familial}, 300636Invasive pneumococcal disease, recurrent isolated, 2, 300640; INCONTINENTIA PIGMENTI (IP) to Incontinentia pigmenti, OMIM:308300
Incontinentia pigmenti v1.2 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from to Incontinentia pigmenti, OMIM:308300
Structural eye disease v3.75 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Incontinentia pigmenti, IP, 308300 to Incontinentia pigmenti, OMIM:308300
Retinal disorders v4.82 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Incontinentia pigmenti, 308300 to Incontinentia pigmenti, OMIM:308300
Early onset or syndromic epilepsy v4.184 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Incontinentia pigmenti, 308300 to Incontinentia pigmenti, OMIM:308300
Mosaic skin disorders - deep sequencing v2.44 IKBKG Arina Puzriakova changed review comment from: Comment on list classification: Incontinentia pigmenti (IP) is a X-linked dominant disorder associated with variants in the IKBKG gene. IP is mostly lethal in males in utero, and only very rare surviving male cases have somatic mosaicism. Phenotypically, cutaneous lesions manifest in Blaschkoid distribution.

Overall 'R327 Mosaic skin disorders - deep sequencing' represents the most likely diagnostic route for these cases and therefore a Green rating on this panel would be appropriate.; to: Comment on list classification: Incontinentia pigmenti (IP) is a X-linked dominant disorder associated with variants in the IKBKG gene. IP is mostly lethal in males in utero, and only very rare surviving male cases have somatic mosaicism. Phenotypically, cutaneous lesions manifest in Blaschkoid distribution.

Overall 'R327 Mosaic skin disorders - deep sequencing' represents a plausible route for referral and diagnosis for these cases and therefore a Green rating on this panel would be appropriate.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.197 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Immunodeficiency 33, 300636; Ectodermal dysplasia, hypohidrotic, with immune deficiency 300291; Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency, 300301; Immunodeficiency, isolated, 300584; Invasive pneumococcal disease, recurrent isolated, 2,300640; Defects of TLR/NFkappa-B signalling; Anhidrotic ectodermal dysplasia (in some), various infections (bacteria, mycobacteria, viruses and fungi), colitis, conical teeth, variable defects of skin, hair and teeth, monocyte dysfunction; Combined immunodeficiencies with associated or syndromic features to Ectodermal dysplasia and immunodeficiency 1, OMIM:300291; Immunodeficiency 33, OMIM:300636
Rare genetic inflammatory skin disorders v3.6 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Incontinentia pigmenti; Incontinentia pigmenti, Ectodermal dysplasia to Incontinentia pigmenti, OMIM:308300
Ectodermal dysplasia without a known gene mutation v1.28 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Incontinentia pigmenti, type II, 308300; Ectodermal dysplasia, hypohidrotic, with immune deficiency, 300291; Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency, 300301; Immunodeficiency, isolated, 300584; {Atypical mycobacteriosis, familial}, 300636:Invasive pneumococcal disease, recurrent isolated, 2, 300640; Ectodermal Dysplasia, Hypohidrotic, With Immune Deficiency to Ectodermal dysplasia and immunodeficiency 1, OMIM:300291
Ectodermal dysplasia v3.29 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Ectodermal Dysplasia, Hypohidrotic, With Immune Deficiency; Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency, 300301; {Atypical mycobacteriosis, familial}, 300636:Invasive pneumococcal disease, recurrent isolated, 2, 300640; Immunodeficiency, isolated, 300584; Ectodermal dysplasia, hypohidrotic, with immune deficiency, 300291; Incontinentia pigmenti, type II, 308300 to Ectodermal dysplasia and immunodeficiency 1, OMIM:300291
Gastrointestinal epithelial barrier disorders v1.75 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Immunodeficiency 33, 300636; Immunodeficiency, isolated, 300584 to Ectodermal dysplasia and immunodeficiency 1, OMIM:300291
Infantile enterocolitis & monogenic inflammatory bowel disease v1.43 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Ectodermal X-linked dysplasia, hypohidrotic, with immune deficiency 300291 to Ectodermal dysplasia and immunodeficiency 1, OMIM:300291
Mosaic skin disorders - deep sequencing v2.44 IKBKG Arina Puzriakova Classified gene: IKBKG as Amber List (moderate evidence)
Mosaic skin disorders - deep sequencing v2.44 IKBKG Arina Puzriakova Added comment: Comment on list classification: Incontinentia pigmenti (IP) is a X-linked dominant disorder associated with variants in the IKBKG gene. IP is mostly lethal in males in utero, and only very rare surviving male cases have somatic mosaicism. Phenotypically, cutaneous lesions manifest in Blaschkoid distribution.

Overall 'R327 Mosaic skin disorders - deep sequencing' represents the most likely diagnostic route for these cases and therefore a Green rating on this panel would be appropriate.
Mosaic skin disorders - deep sequencing v2.44 IKBKG Arina Puzriakova Gene: ikbkg has been classified as Amber List (Moderate Evidence).
Mosaic skin disorders - deep sequencing v2.43 IKBKG Arina Puzriakova Tag somatic tag was added to gene: IKBKG.
Tag Q2_24_promote_green tag was added to gene: IKBKG.
Mosaic skin disorders - deep sequencing v2.43 IKBKG Arina Puzriakova Publications for gene: IKBKG were set to
Mosaic skin disorders - deep sequencing v2.42 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Ectodermal dysplasia and immunodeficiency 1, 300291; Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency, 300301; Incontinentia pigmenti, 308300 to Incontinentia pigmenti, OMIM:308300
Retinal disorders v4.81 SAMD7 Arina Puzriakova commented on gene: SAMD7
Rare genetic inflammatory skin disorders v3.5 ADAMTS2 Dmitrijs Rots reviewed gene: ADAMTS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Thoracic aortic aneurysm or dissection (GMS) v3.8 SECISBP2 krishna chatterjee gene: SECISBP2 was added
gene: SECISBP2 was added to Thoracic aortic aneurysm or dissection (GMS). Sources: Literature
Mode of inheritance for gene: SECISBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SECISBP2 were set to PMID 38042913; PMID 21084748
Phenotypes for gene: SECISBP2 were set to Growth retardation; sensorineural hearing loss; muscular dystrophy; thoracic aortic aneurysm; raised circulating thyroxine and low plasma selenium
Penetrance for gene: SECISBP2 were set to Complete
Review for gene: SECISBP2 was set to GREEN
Added comment: Biallelic defects in this gene cause a multi system disorder with deficiency of most human selenoproteins. Phenotypes listed here are associated with a biochemical signature of elevated circulating T4 (thyroxine) and low plasma selenium.

Since some pathogenic variants can be in non-coding regions and cryptic, we suggest a high index of suspicion even in cases of aortic aneurysm with an apparently monoallelic SECISBP2 defect. In such cases, we advocate measuring circulating T4 and selenium; if these biomarker levels are abnormal a cryptic mutation on the other allele should be sought.
Sources: Literature
Childhood onset hereditary spastic paraplegia v4.39 RTN2 Nour Elkhateeb reviewed gene: RTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38527963; Phenotypes: Weakness in the distal upper and lower limbs, Lower limb spasticity, Hyperreflexia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.308 RTN2 Nour Elkhateeb changed review comment from: A recent publication has been described seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven consanguineous families with distal hereditary motor neuropathy (dHMN) with pyramidal features.; to: A recent publication has been described seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven consanguineous families with distal hereditary motor neuropathy (dHMN) with pyramidal features.
Hereditary spastic paraplegia v1.308 RTN2 Nour Elkhateeb changed review comment from: A recent publication has described seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven consanguineous families with distal hereditary motor neuropathy (dHMN) with pyramidal features.; to: A recent publication has been described seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven consanguineous families with distal hereditary motor neuropathy (dHMN) with pyramidal features.
Hereditary spastic paraplegia v1.308 RTN2 Nour Elkhateeb reviewed gene: RTN2: Rating: ; Mode of pathogenicity: None; Publications: PMID: 38527963; Phenotypes: Weakness in the distal upper and lower limbs, Lower limb spasticity, Hyperreflexia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia v1.332 FGF14 Evan Reid reviewed gene: FGF14: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMC10844931; Phenotypes: Adult onset cerebellar ataxia, adult onsent episodic ataxia, cerebellar oculomotor disturbances, vestibulopathy, peripheral neuropathy, dysautonomia, spasticity, parkinsonism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hydrocephalus v4.4 HYLS1 Arina Puzriakova Tag founder-effect tag was added to gene: HYLS1.
Intellectual disability v5.506 ZFX Tracy Lester reviewed gene: ZFX: Rating: GREEN; Mode of pathogenicity: None; Publications: 38325380; Phenotypes: Intellectual disability, developmental delay, behavioural abnormalities, hypotonia, dysmorphic facies; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v5.506 CLEC16A Arina Puzriakova Tag Q1_24_promote_green tag was added to gene: CLEC16A.
Intellectual disability v5.506 GLI3 Tracy Lester reviewed gene: GLI3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cystic kidney disease v4.24 CLCN5 John Sayer gene: CLCN5 was added
gene: CLCN5 was added to Cystic kidney disease. Sources: Literature
Mode of inheritance for gene: CLCN5 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: CLCN5 were set to 7922301; 37641036
Phenotypes for gene: CLCN5 were set to cystic kdiney disease; cortical cysts; medullary cysts; nephrocalcinosis; low molecular weight proteinuria; hypercalciuria
Penetrance for gene: CLCN5 were set to Complete
Review for gene: CLCN5 was set to GREEN
Added comment: Oliver Wrong noted kidney cysts in 33% of his cohort and I think Dent disease is such a difficult diagnosis to make, adding it to the cystic panel will identify new cases presenting with mild cystic kidney disease
Sources: Literature
Growth failure in early childhood v3.87 ISCA-37406-Loss Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: PMID: 10573006 death in infancy, accessory spleens, hypoplastic left heart, abnormal pulmonary lobulation, renal agenesis (patient 1), severe neonatal seizures (patient 2). PMID 16783566: failure to thrive, life-threatening malformations, and/or critical infections, and all died in infancy (5 weeks, 7 months, and 9 months, respectivelyFrom Genetics Home Reference: short stature, moderate to severe intellectual disability, distinctive facial features, and broad thumbs and first toes;610543
Growth failure in early childhood v3.87 ISCA-37406-Loss Arina Puzriakova Phenotypes for Region: ISCA-37406-Loss were changed from PMID: 10573006 death in infancy, accessory spleens, hypoplastic left heart, abnormal pulmonary lobulation, renal agenesis (patient 1), severe neonatal seizures (patient 2). PMID 16783566: failure to thrive, life-threatening malformations, and/or critical infections, and all died in infancy (5 weeks, 7 months, and 9 months, respectivelyFrom Genetics Home Reference: short stature, moderate to severe intellectual disability, distinctive facial features, and broad thumbs and first toes; 610543 to Chromosome 16p13.3 deletion syndrome, OMIM:610543
Growth failure in early childhood v3.86 ISCA-37397-Loss Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: uterine didelphys;language delay;Hyptonia;prematurity;clinodactyly;ADHD;Goldenhar syndrome;developmental delay;611867;diaphragmatic hernia;DiGeorge syndrome (DGS);velocardiofacial syndrome;mild skeletal abnormalities;Seizures;global developmental delay;prenatal and postnatal growth delay;micropephaly;cardiovascular defects
Growth failure in early childhood v3.86 ISCA-37397-Loss Arina Puzriakova Phenotypes for Region: ISCA-37397-Loss were changed from uterine didelphys; language delay; Hyptonia; prematurity; clinodactyly; ADHD; Goldenhar syndrome; developmental delay; 611867; diaphragmatic hernia; DiGeorge syndrome (DGS); velocardiofacial syndrome; mild skeletal abnormalities; Seizures; global developmental delay; prenatal and postnatal growth delay; micropephaly; cardiovascular defects to Chromosome 22q11.2 deletion syndrome, distal, OMIM:611867
Growth failure in early childhood v3.85 ISCA-37392-Loss Arina Puzriakova Triplosensitivity Score for ISCA-37392-Loss was changed from to None.
Phenotypes for Region: ISCA-37392-Loss were changed from 194050; Williams syndrome to Williams-Beuren syndrome, OMIM:194050
Growth failure in early childhood v3.82 RBBP8 Arina Puzriakova Publications for gene: RBBP8 were updated from 24389050, 21998596 to 24389050; 21998596
Growth failure in early childhood v3.81 LIG4 Arina Puzriakova Publications for gene: LIG4 were updated from 11779494, 16088910, to 11779494; 16088910
Growth failure in early childhood v3.80 LIG1 Arina Puzriakova Publications for gene: LIG1 were updated from 1581963, 1351188 to 1581963; 1351188
Growth failure in early childhood v3.79 H19 Arina Puzriakova Mode of inheritance for gene: H19 was changed from Other - please specifiy in evaluation comments to Other
Growth failure in early childhood v3.76 RAPSN Arina Puzriakova Phenotypes for gene: RAPSN were changed from Fetal Akinesia Deformation Sequence; Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency, 608931Myasthenic syndrome, congenital, associated with facial dysmorphism and acetylcholine receptordeficiency, 608931Fetal akinesia deformation sequence, 208150 to Fetal akinesia deformation sequence 2, OMIM:618388; Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency, OMIM:616326
Growth failure in early childhood v3.75 ORC6 Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia
Growth failure in early childhood v3.75 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from Meier-Gorlin syndrome 3, 613803; Meier-Gorlin; micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia to Meier-Gorlin syndrome 3, OMIM:613803
Growth failure in early childhood v3.74 ORC4 Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia
Growth failure in early childhood v3.74 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from Meier-Gorlin; Meier-Gorlin syndrome 2, 613800; micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia to Meier-Gorlin syndrome 2, OMIM:613800
Growth failure in early childhood v3.73 ORC1 Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: microtia, beaked nose, patellar aplasia/hypoplasia, mammary hypoplasia, micrognathia
Growth failure in early childhood v3.73 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from microtia, beaked nose, patellar aplasia/hypoplasia, mammary hypoplasia, micrognathia; Meier-Gorlin; Meier-Gorlin syndrome 1, 224690 to Meier-Gorlin syndrome 1, OMIM:224690
Growth failure in early childhood v3.72 FANCM Arina Puzriakova Phenotypes for gene: FANCM were changed from Fanconi anemia, complementation group M, 614087; Fanconi Anemia; Fanconi anemia to Fanconi anemia, complementation group M, 614087
Growth failure in early childhood v3.71 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from micrognathia, microtia, patellar hypoplasia/aplasia, mammary hypoplasia; Meier-Gorlin syndrome 4, 613804; Meier-Gorlin to Meier-Gorlin syndrome 4, OMIM:613804
Growth failure in early childhood v3.70 PLK4 Arina Puzriakova Phenotypes for gene: PLK4 were changed from Microcephaly and chorioretinopathy, autosomal recessive, 2, OMIM:616171; microcephaly and chorioretinopathy 2, MONDO:0014516 to Microcephaly and chorioretinopathy, autosomal recessive, 2, OMIM:616171
Growth failure in early childhood v3.69 INTS1 Arina Puzriakova Phenotypes for gene: INTS1 were changed from Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies, OMIM:618571, MONDO:0032817 to Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies, OMIM:618571
Growth failure in early childhood v3.68 HMGA2 Arina Puzriakova Phenotypes for gene: HMGA2 were changed from Silver-Russell syndrome 5, OMIM:618908; Silver-Russell syndrome 5, MONDO:0020795 to Silver-Russell syndrome 5, OMIM:618908
Growth failure in early childhood v3.67 COG4 Arina Puzriakova Phenotypes for gene: COG4 were changed from Saul-Wilson syndrome, OMIM:618150; microcephalic osteodysplastic dysplasia, Saul-Wilson type, MONDO:0019407 to Saul-Wilson syndrome, OMIM:618150
Growth failure in early childhood v3.66 ANAPC1 Arina Puzriakova Phenotypes for gene: ANAPC1 were changed from Rothmund Thomson syndrome type 1, OMIM:618625, MONDO:0016368 to Rothmund Thomson syndrome type 1, OMIM:618625
Growth failure in early childhood v3.65 ZNF668 Arina Puzriakova Phenotypes for gene: ZNF668 were changed from DNA damage repair defect; microcephaly; growth deficiency; severe global developmental delay; brain malformation; facial dysmorphism to Neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies, OMIM:620194
Growth failure in early childhood v3.64 VPS50 Arina Puzriakova Phenotypes for gene: VPS50 were changed from Neonatal cholestatic liver disease; Failure to thrive; Profound global developmental delay; Postnatal microcephaly; Seizures; Abnormality of the corpus callosum to Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis, OMIM:619685
Growth failure in early childhood v3.63 SETD5 Arina Puzriakova Phenotypes for gene: SETD5 were changed from Mental retardation, autosomal dominant 23, OMIM:615761; growth retardation; bone fragility to Intellectual developmental disorder, autosomal dominant 23, OMIM:615761
Growth failure in early childhood v3.62 ZFP57 Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes include: IUGR;Multi Locus Imprinting Disturbance
Growth failure in early childhood v3.62 ZFP57 Arina Puzriakova Phenotypes for gene: ZFP57 were changed from Diabetes mellitus, transient neonatal 1 OMIM:601410; diabetes mellitus, transient neonatal, 1MONDO:0011073; IUGR; Multi Locus Imprinting Disturbance to Diabetes mellitus, transient neonatal 1, OMIM:601410
Growth failure in early childhood v3.61 UBE2T Arina Puzriakova Phenotypes for gene: UBE2T were changed from Falcon anemia; 616435 Fanconi anemia, complementation group T; Fanconi anemia, complementation group T, 616435 to Fanconi anemia, complementation group T, OMIM:616435
Growth failure in early childhood v3.60 TRIM37 Arina Puzriakova Phenotypes for gene: TRIM37 were changed from Mulibery Nanism, 253250; Mulibrey nanism to Mulibrey nanism, OMIM:253250
Growth failure in early childhood v3.59 TOP3A Arina Puzriakova Phenotypes for gene: TOP3A were changed from MGRISCE2 (Bloom-like syndrome) 618097; Microcephaly, growth restriction, and increased sister chromatid exchange 2; 618097 MGRISCE2 (Bloom-like syndrome) to Microcephaly, growth restriction, and increased sister chromatid exchange 2, OMIM:618097
Intellectual disability v5.506 SRCAP Arina Puzriakova Phenotypes for gene: SRCAP were changed from Floating-Harbor syndrome, 136140; FLOATING-HARBOR SYNDROME to Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, OMIM:619595; Floating-Harbor syndrome, OMIM:136140
Growth failure in early childhood v3.58 SRCAP Arina Puzriakova Phenotypes for gene: SRCAP were changed from Floating Harbor; Floating-Harbor syndrome, 136140 to Floating-Harbor syndrome, OMIM:136140
Growth failure in early childhood v3.57 SPRED2 Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes (overwritten): developmental delay;intellectual disability;cardiac defects;short stature;skeletal anomalies;a typical facial gestalt
Growth failure in early childhood v3.57 SPRED2 Arina Puzriakova Phenotypes for gene: SPRED2 were changed from developmental delay; intellectual disability; cardiac defects; short stature; skeletal anomalies; a typical facial gestalt to Noonan syndrome 14, OMIM:619745
Growth failure in early childhood v3.56 SOS2 Arina Puzriakova Phenotypes for gene: SOS2 were changed from Noonan syndrome 9 to Noonan syndrome 9, OMIM:616559
Growth failure in early childhood v3.55 SOS1 Arina Puzriakova Phenotypes for gene: SOS1 were changed from Rasopathy; Noonan syndrome; Noonan syndrome 4 to Noonan syndrome 4, OMIM:610733
Growth failure in early childhood v3.54 SLX4 Arina Puzriakova Phenotypes for gene: SLX4 were changed from 613951 Fanconi Anemia Fanconi anemia, complementation group P; Fanconi anemia, complementation group P, 613951; Fanconi Anemia to Fanconi anemia, complementation group P, OMIM:613951
Growth failure in early childhood v3.53 SHOX Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Dorsolateral bowed, short radii;Bowing and curving of radius;Radioulnar shortening
Growth failure in early childhood v3.53 SHOX Arina Puzriakova Phenotypes for gene: SHOX were changed from Langer mesomelic dysplasia, OMIM:249700 (PR); Leri-Weill dyschondrosteosis, OMIM:127300 (PD); Short stature, idiopathic familial, OMIM:300582; Dorsolateral bowed, short radii; Bowing and curving of radius; Radioulnar shortening to Langer mesomelic dysplasia, OMIM:249700 (PR); Leri-Weill dyschondrosteosis, OMIM:127300 (PD); Short stature, idiopathic familial, OMIM:300582
Growth failure in early childhood v3.52 SHOC2 Arina Puzriakova Phenotypes for gene: SHOC2 were changed from Noonan with loss of anagen hair; Noonan-like syndrome with loose anagen hair to Noonan syndrome-like with loose anagen hair 1, OMIM:607721
Growth failure in early childhood v3.51 RIT1 Arina Puzriakova Phenotypes for gene: RIT1 were changed from Rasopathy; Noonan syndrome 8; Noonan syndrome type 8 to Noonan syndrome 8, OMIM:615355
Growth failure in early childhood v3.50 RAF1 Arina Puzriakova Phenotypes for gene: RAF1 were changed from Rasopathy; Noonan syndrome; LEOPARD syndrome 2; Noonan syndrome 5; LEOPARD syndrome to LEOPARD syndrome 2, OMIM:611554; Noonan syndrome 5, OMIM:611553
Growth failure in early childhood v3.49 PTPN11 Arina Puzriakova Phenotypes for gene: PTPN11 were changed from LEOPARD syndrome 1; LEOPARD syndrome; Noonan syndrome 1; Noonan syndrome to LEOPARD syndrome 1, OMIM:151100; Noonan syndrome 1, OMIM:163950
Growth failure in early childhood v3.48 PPP1CB Arina Puzriakova Phenotypes for gene: PPP1CB were changed from Noonan syndrome-like disorder with loose anagen hair 2, 617506; Rasopathy with developmental delay, short stature and sparse slow-growing hair to Noonan syndrome-like disorder with loose anagen hair 2, OMIM:617506
Growth failure in early childhood v3.47 PLAG1 Arina Puzriakova Phenotypes for gene: PLAG1 were changed from SRS; Silver-Russell syndrome to Silver-Russell syndrome 4, OMIM:618907
Growth failure in early childhood v3.46 PIK3R1 Arina Puzriakova Phenotypes for gene: PIK3R1 were changed from SHORT syndrome, 269880; SHORT to SHORT syndrome, OMIM:269880
Growth failure in early childhood v3.45 PALB2 Arina Puzriakova Phenotypes for gene: PALB2 were changed from Fanconi anemia, complementation group N, 610832; 610832 Fanconi anemia, complementation group N to Fanconi anemia, complementation group N, OMIM:610832
Growth failure in early childhood v3.44 OBSL1 Arina Puzriakova Phenotypes for gene: OBSL1 were changed from 3M; 3-M syndrome 2, 612921 to 3-M syndrome 2, OMIM:612921
Growth failure in early childhood v3.43 NRAS Arina Puzriakova Phenotypes for gene: NRAS were changed from Noonan syndrome; CFC Syndrome; A restricted spectrum of NRAS mutations causes Noonan syndrome. (Nat Genet. 42: 27-29, 2010.); Noonan syndrome 6; Cardio-Facio-cutanenous syndrome to Noonan syndrome 6, OMIM:613224
Growth failure in early childhood v3.42 NHLRC2 Arina Puzriakova Phenotypes for gene: NHLRC2 were changed from FINCA syndrome OMIM:618278 to FINCA syndrome, OMIM:618278
Growth failure in early childhood v3.41 NBN Arina Puzriakova Phenotypes for gene: NBN were changed from Nijmegen; Nijmegen breakage syndrome, 251260 to Nijmegen breakage syndrome, OMIM:251260
Growth failure in early childhood v3.40 NBAS Arina Puzriakova Phenotypes for gene: NBAS were changed from Short stature, optic nerve atrophy, and Pelger-Huet anomaly, 614800 to Short stature, optic nerve atrophy, and Pelger-Huet anomaly, OMIM:614800
Growth failure in early childhood v3.39 MTX2 Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes (overwritten): Mandibuloacral dysplasia;lipodystrophy;arterial calcification;growth retardation
Growth failure in early childhood v3.39 MTX2 Arina Puzriakova Phenotypes for gene: MTX2 were changed from Mandibuloacral dysplasia; lipodystrophy; arterial calcification; growth retardation to Mandibuloacral dysplasia progeroid syndrome, OMIM:619127
Growth failure in early childhood v3.38 MAP2K2 Arina Puzriakova Phenotypes for gene: MAP2K2 were changed from CFC syndrome; Cardiofaciocutaneous syndrome 4; Cardiofaciocutaneous syndrome; Cardio-Facio-Cutaneous syndrome type 4; Cardiofaciocutaneous Syndrome; Cardio-Facio-Cutaneous syndrome to Cardiofaciocutaneous syndrome 4, OMIM:615280
Growth failure in early childhood v3.37 MAP2K1 Arina Puzriakova Phenotypes for gene: MAP2K1 were changed from LEOPARD syndrome; CFC syndrome; Cardiofaciocutaneous syndrome; Cardiofaciocutaneous Syndrome; Cardio-Facio-Cutaneous syndrome; Cardiofaciocutaneous syndrome 3; ?Noonan syndrome to Cardiofaciocutaneous syndrome 3, OMIM:615279
Growth failure in early childhood v3.36 LZTR1 Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes (overwritten): Noonan syndrome 10;increased nuchal translucency;Prenatal hydrops;cardiac findings
Growth failure in early childhood v3.36 LZTR1 Arina Puzriakova Phenotypes for gene: LZTR1 were changed from Noonan syndrome 10; increased nuchal translucency; Prenatal hydrops; cardiac findings to Noonan syndrome 10, OMIM:616564 (AD); Noonan syndrome 2, OMIM:605275 (AR)
Growth failure in early childhood v3.35 KRAS Arina Puzriakova Phenotypes for gene: KRAS were changed from Rasopathy; Noonan syndrome; CFC syndrome; Cardiofaciocutaneous syndrome 2; Noonan syndrome 3; Cardiofaciocutaneous Syndrome; Cardio-Facio-Cutaneous syndrome to Cardiofaciocutaneous syndrome 2, OMIM:615278; Noonan syndrome 3, OMIM:609942
Growth failure in early childhood v3.34 IGFALS Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Short stature;Delayed puberty;Very low IGF-I levels
Growth failure in early childhood v3.34 IGFALS Arina Puzriakova Phenotypes for gene: IGFALS were changed from Acid-labile subunit, deficiency of, OMIM:615961; Short stature; Delayed puberty; Very low IGF-I levels to Acid-labile subunit, deficiency of, OMIM:615961
Growth failure in early childhood v3.33 IGF2 Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes (overwritten): SRS;IUGR;Pre- and post-natal growth failure;?Growth restriction, severe, with distinctive facies, 616489;Silver-Russell phenptype
Growth failure in early childhood v3.33 IGF2 Arina Puzriakova Phenotypes for gene: IGF2 were changed from SRS; IUGR; Pre- and post-natal growth failure; ?Growth restriction, severe, with distinctive facies, 616489; Silver-Russell phenptype to Silver-Russell syndrome 3, OMIM:616489
Growth failure in early childhood v3.32 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from Insulin-Like Growth Factor I Deficiency; Growth retardation with deafness and mental retardation due to IGF1 deficiency, 608747; IGF1 to Insulin-like growth factor I deficiency, OMIM:608747
Growth failure in early childhood v3.31 HRAS Arina Puzriakova Phenotypes for gene: HRAS were changed from Costello syndrome, 218040; Costello; Costello syndrome to Costello syndrome, OMIM:218040
Growth failure in early childhood v3.30 FGFR3 Arina Puzriakova Phenotypes for gene: FGFR3 were changed from Hypochondroplasia, 146000 to Hypochondroplasia, OMIM:146000; Crouzon syndrome with acanthosis nigricans, OMIM:612247; Thanatophoric dysplasia, type I, OMIM:187600; Thanatophoric dysplasia, type II, OMIM:187601
Growth failure in early childhood v3.29 FANCL Arina Puzriakova Phenotypes for gene: FANCL were changed from Fanconi anemia; Fanconi anemia, complementation group L, 614083; 614083Fanconi anemia, complementation group L; Fanconi Anemia to Fanconi anemia, complementation group L, OMIM:614083
Growth failure in early childhood v3.28 FANCI Arina Puzriakova Phenotypes for gene: FANCI were changed from Fanconi anemia; Fanconi anemia, complementation group I, 609053; 609053 Fanconi anemia, complementation group I; Fanconi Anemia to Fanconi anemia, complementation group I, OMIM:609053
Growth failure in early childhood v3.27 FANCG Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes (overwritten): 614082 Fanconi anemia, complementation group G;pre- and postnatal growth retardation;a typical facial appearance with small head, eyes, and mouth;hypogonadism and reduced fertility;Fanconi anemia, complementation group G, 614082;Fanconi anemia complementation group G;malformations of the kidneys, heart, and skeleton (absent or abnormal thumbs and radii);cutaneous abnormalities (hyper- or hypopigmentation and cafe-au-lait spots);hearing loss;and susceptibility to cancer, predominantly acute myeloid leukemia.;Fanconi Anemia;Fanconi anemia;bone marrow failure
Growth failure in early childhood v3.27 FANCG Arina Puzriakova Phenotypes for gene: FANCG were changed from 614082 Fanconi anemia, complementation group G; pre- and postnatal growth retardation; a typical facial appearance with small head, eyes, and mouth; hypogonadism and reduced fertility; Fanconi anemia, complementation group G, 614082; Fanconi anemia complementation group G; malformations of the kidneys, heart, and skeleton (absent or abnormal thumbs and radii); cutaneous abnormalities (hyper- or hypopigmentation and cafe-au-lait spots); hearing loss; and susceptibility to cancer, predominantly acute myeloid leukemia.; Fanconi Anemia; Fanconi anemia; bone marrow failure to Fanconi anemia, complementation group G, OMIM:614082
Growth failure in early childhood v3.26 FANCF Arina Puzriakova Phenotypes for gene: FANCF were changed from Fanconi anemia; Fanconi anemia, complementation group F, 603467; 603467 Fanconi anemia, complementation group F; Fanconi Anemia to Fanconi anemia, complementation group F, OMIM:603467
Growth failure in early childhood v3.25 FANCE Arina Puzriakova Phenotypes for gene: FANCE were changed from Fanconi anemia, complementation group E, 600901; Fanconi anemia; 600901 Fanconi anemia, complementation group E; Fanconi Anemia to Fanconi anemia, complementation group E, OMIM:600901
Growth failure in early childhood v3.24 FANCD2 Arina Puzriakova Phenotypes for gene: FANCD2 were changed from Fanconi anemia; Fanconi anemia, complementation group D2, 227646; 227646 Fanconi anemia, complementation group D2; Fanconi Anemia to Fanconi anemia, complementation group D2, OMIM:227646
Growth failure in early childhood v3.23 FANCC Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes (overwritten): pre- and postnatal growth retardation;a typical facial appearance with small head, eyes, and mouth;hypogonadism and reduced fertility;malformations of the kidneys, heart, and skeleton (absent or abnormal thumbs and radii);cutaneous abnormalities (hyper- or hypopigmentation and cafe-au-lait spots);hearing loss;and susceptibility to cancer, predominantly acute myeloid leukemia.;Fanconi Anemia;Fanconi anemia, complementation group C, 227645;Fanconi anemia;bone marrow failure;227645 Fanconi anemia, complementation group C
Growth failure in early childhood v3.23 FANCC Arina Puzriakova Phenotypes for gene: FANCC were changed from pre- and postnatal growth retardation; a typical facial appearance with small head, eyes, and mouth; hypogonadism and reduced fertility; malformations of the kidneys, heart, and skeleton (absent or abnormal thumbs and radii); cutaneous abnormalities (hyper- or hypopigmentation and cafe-au-lait spots); hearing loss; and susceptibility to cancer, predominantly acute myeloid leukemia.; Fanconi Anemia; Fanconi anemia, complementation group C, 227645; Fanconi anemia; bone marrow failure; 227645 Fanconi anemia, complementation group C to Fanconi anemia, complementation group C, OMIM:227645
Growth failure in early childhood v3.22 FANCB Arina Puzriakova Phenotypes for gene: FANCB were changed from Fanconi Anemia Type B; VACTERL Association with Hydrocephalus; 300514 Fanconi anemia, complementation group B; Fanconi Anemia, X-Linked; Fanconi Anaemia; Fanconi anemia; Falcon anemia; Fanconi anemia, complementation group B, 300514 to Fanconi anemia, complementation group B, OMIM:300514
Growth failure in early childhood v3.21 FANCA Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes (overwritten): pre- and postnatal growth retardation;a typical facial appearance with small head, eyes, and mouth;hypogonadism and reduced fertility;malformations of the kidneys, heart, and skeleton (absent or abnormal thumbs and radii);Fanconi anemia, complementation group A, 227650;cutaneous abnormalities (hyper- or hypopigmentation and cafe-au-lait spots);hearing loss;and susceptibility to cancer, predominantly acute myeloid leukemia.;Fanconi Anemia;227650 Fanconi anemia complementation group A;Fanconi anemia;bone marrow failure
Growth failure in early childhood v3.21 FANCA Arina Puzriakova Phenotypes for gene: FANCA were changed from pre- and postnatal growth retardation; a typical facial appearance with small head, eyes, and mouth; hypogonadism and reduced fertility; malformations of the kidneys, heart, and skeleton (absent or abnormal thumbs and radii); Fanconi anemia, complementation group A, 227650; cutaneous abnormalities (hyper- or hypopigmentation and cafe-au-lait spots); hearing loss; and susceptibility to cancer, predominantly acute myeloid leukemia.; Fanconi Anemia; 227650 Fanconi anemia complementation group A; Fanconi anemia; bone marrow failure to Fanconi anemia, complementation group A, OMIM:227650
Growth failure in early childhood v3.20 ERCC4 Arina Puzriakova Phenotypes for gene: ERCC4 were changed from Fanconi anemia, complementation group Q, 615272; 615272 Fanconi anemia, complementation group Q to Fanconi anemia, complementation group Q, OMIM:615272
Growth failure in early childhood v3.19 CUL7 Arina Puzriakova Phenotypes for gene: CUL7 were changed from 3-M syndrome 1, 273750; 3M to 3-M syndrome 1, OMIM:273750
Growth failure in early childhood v3.18 CEP57 Arina Puzriakova Phenotypes for gene: CEP57 were changed from Mosaic variegated aneuploidy syndrome 2, 614114 to Mosaic variegated aneuploidy syndrome 2, OMIM:614114
Growth failure in early childhood v3.17 CDKN1C Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes (overwritten): SRS/BWS;Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies;Beckwith-Wiedemann syndrome, 130650
Growth failure in early childhood v3.17 CDKN1C Arina Puzriakova Phenotypes for gene: CDKN1C were changed from SRS/BWS; Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies; Beckwith-Wiedemann syndrome, 130650 to IMAGE syndrome, OMIM:614732
Growth failure in early childhood v3.16 CCDC8 Arina Puzriakova Phenotypes for gene: CCDC8 were changed from 3-M syndrome 3, 614205; 3M to 3-M syndrome 3, OMIM:614205
Growth failure in early childhood v3.15 CBL Arina Puzriakova Phenotypes for gene: CBL were changed from Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia; NOONAN SYNDROME-LIKE DISORDER WITH OR WITHOUT JUVENILE MEYLOMONOCYTIC LEUKEMIA to Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, OMIM:613563
Growth failure in early childhood v3.14 BRAF Arina Puzriakova Phenotypes for gene: BRAF were changed from LEOPARD syndrome 3; LEOPARD Syndrome; Cardiofaciocutaneous syndrome; Cardiofaciocutaneous Syndrome; Cardio-facio-cutaneous syndrome; Noonan Syndrome to Cardiofaciocutaneous syndrome, OMIM:115150; LEOPARD syndrome 3, OMIM:613707; Noonan syndrome 7, OMIM:613706
Growth failure in early childhood v3.13 ANKRD11 Arina Puzriakova Phenotypes for gene: ANKRD11 were changed from KBG; KBG syndrome, 148050 to KBG syndrome, OMIM:148050
Growth failure in early childhood v3.12 ACAN Arina Puzriakova Phenotypes for gene: ACAN were changed from Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans (AD), 165800; Spondyloepimetaphyseal dysplasia, aggrecan type (AR), 612813; short stature, accelerated bone maturation, Spondyloepiphyseal dysplasia, early onset osteoarthritis; ?Spondyloepiphyseal dysplasia, Kimberley type (AD), 608361 to Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans, OMIM:165800 (AD); ?Spondyloepiphyseal dysplasia, Kimberley type, OMIM:608361 (AD); Spondyloepimetaphyseal dysplasia, aggrecan type, OMIM:612813 (AR)
Fetal anomalies v3.146 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from RAPADILINO SYNDROME; ROTHMUND-THOMSON SYNDROME; BALLER-GEROLD SYNDROME to Baller-Gerold syndrome, OMIM:218600; RAPADILINO syndrome, OMIM:266280; Rothmund-Thomson syndrome, type 2, OMIM:268400
Non-syndromic familial congenital anorectal malformations v1.9 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Baller-Gerold syndrome 218600; Rothmund-Thomson syndrome 268400 to Baller-Gerold syndrome, OMIM:218600; Rothmund-Thomson syndrome, type 2, OMIM:268400
Cutaneous photosensitivity with a likely genetic cause v3.5 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Rothmund-Thomson syndrome, 268400 to Rothmund-Thomson syndrome, type 2, OMIM:268400
Primary immunodeficiency or monogenic inflammatory bowel disease v4.196 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Combined immunodeficiency; Rothmund-Thomson syndrome, 268400 to Rothmund-Thomson syndrome, type 2, OMIM:268400; Combined immunodeficiency
Bilateral congenital or childhood onset cataracts v4.9 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Rothmund-Thomson syndrome, 268400; RAPADILINO syndrome, 266280; Baller-Gerold syndrome, 218600; Rothmund-Thomson syndrome to Rothmund-Thomson syndrome, type 2, OMIM:268400
Pigmentary skin disorders v3.11 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Rothmund-Thompson syndrome; RTS2; RAPADILINO SYNDROME, ROTHMUND-THOMSON SYNDROME, TYPE 2 to Baller-Gerold syndrome, OMIM:218600; Rothmund-Thomson syndrome, type 2, OMIM:268400
Childhood solid tumours cancer susceptibility v1.27 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Rothmund Thomson Syndrome to Rothmund-Thomson syndrome, type 2, OMIM:268400
Sarcoma cancer susceptibility v1.25 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Rothmund-Thomson, Beller-Gerold and RAPADALINO syndromes; Osteosarcoma to Rothmund-Thomson syndrome, type 2, OMIM:268400; Osteosarcoma
Childhood solid tumours v4.16 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Rothmund Thomson Syndrome; 268400 to Rothmund-Thomson syndrome, type 2, OMIM:268400
Skeletal dysplasia v4.54 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from RAPILINO syndrome 266280; Rothmund-Thomson syndrome 268400; Baller-Gerold syndrome 218600 to Baller-Gerold syndrome, OMIM:218600; RAPADILINO syndrome, OMIM:266280; Rothmund-Thomson syndrome, type 2, OMIM:268400
Limb disorders v4.18 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Baller-Gerold syndrome 218600; RAPILINO syndrome 266280; RAPILINO syndrome, 266280; Rothmund-Thomson syndrome, 268400; Rothmund-Thomson syndrome 268400; Baller-Gerold syndrome, 218600 to Baller-Gerold syndrome, OMIM:218600; RAPADILINO syndrome, OMIM:266280; Rothmund-Thomson syndrome, type 2, OMIM:268400
Radial dysplasia v1.24 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Baller-Gerold syndrome, 218600; RAPILINO syndrome, 266280; Rothmund-Thomson syndrome, 268400 to Baller-Gerold syndrome, OMIM:218600; RAPADILINO syndrome, OMIM:266280; Rothmund-Thomson syndrome, type 2, OMIM:268400
Growth failure in early childhood v3.11 RECQL4 Arina Puzriakova Publications for gene: RECQL4 were set to PMID: 38021400
Growth failure in early childhood v3.10 RECQL4 Arina Puzriakova Tag Q1_24_promote_green tag was added to gene: RECQL4.
Tag Q1_24_NHS_review tag was added to gene: RECQL4.
Growth failure in early childhood v3.10 RECQL4 Arina Puzriakova Classified gene: RECQL4 as Amber List (moderate evidence)
Growth failure in early childhood v3.10 RECQL4 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Melissa Connolly. RECQL4 is associated with multiple phenotypes, one of which is Rothmund-Thomson syndrome which can present with short stature. Review of case reports in the literature did not clearly indicate the level of severity, although 'small size' for height and weight is often mentioned. Patients have been followed up specifically for short stature, indicating that this panel is a plausible route for referral.

This, considered alongside the Green rating that has been allocated to the other Rothmund-Thomson syndrome gene (ANAPC1) as highlighted by Melissa Connolly, supports the promotion of RECQL4 to Green status at the next GMS panel update.
Growth failure in early childhood v3.10 RECQL4 Arina Puzriakova Gene: recql4 has been classified as Amber List (Moderate Evidence).
Growth failure in early childhood v3.9 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Short stature; frontal bossing; prognathism; juvenile cataracts to Rothmund-Thomson syndrome, type 2, OMIM:268400
Growth failure in early childhood v3.8 MSTO1 Arina Puzriakova Tag Q1_24_NHS_review tag was added to gene: MSTO1.
Ichthyosis and erythrokeratoderma v3.25 ABHD5 Arina Puzriakova changed review comment from: Comment on list classification: New gene added to this panel by Tom Cullup (GOSH). There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Chanarin-Dorfman, caused by biallelic variants in the ABHD5 gene, is a neutral lipid storage disorder. The phenotype is variable with multiple organ involvement; however, one of the most the most prominent of features is non-bullous congenital ichthyosiform erythroderma. As ichthyosis is a cardinal feature of this condition, a Green rating on this panel is warranted.; to: Comment on list classification: New gene added to this panel by Tom Cullup (GOSH). There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Chanarin-Dorfman, caused by biallelic variants in the ABHD5 gene, is a neutral lipid storage disorder. The phenotype is variable with multiple organ involvement; however, the most prominent feature is non-bullous congenital ichthyosiform erythroderma. As ichthyosis is a cardinal feature of this condition, a Green rating on this panel is warranted.
Ichthyosis and erythrokeratoderma v3.25 ABHD5 Arina Puzriakova Classified gene: ABHD5 as Amber List (moderate evidence)
Ichthyosis and erythrokeratoderma v3.25 ABHD5 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Tom Cullup (GOSH). There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Chanarin-Dorfman, caused by biallelic variants in the ABHD5 gene, is a neutral lipid storage disorder. The phenotype is variable with multiple organ involvement; however, one of the most the most prominent of features is non-bullous congenital ichthyosiform erythroderma. As ichthyosis is a cardinal feature of this condition, a Green rating on this panel is warranted.
Ichthyosis and erythrokeratoderma v3.25 ABHD5 Arina Puzriakova Gene: abhd5 has been classified as Amber List (Moderate Evidence).
Ichthyosis and erythrokeratoderma v3.24 ABHD5 Arina Puzriakova Tag Q1_24_promote_green tag was added to gene: ABHD5.
Tag Q1_24_NHS_review tag was added to gene: ABHD5.
Ichthyosis and erythrokeratoderma v3.24 ABHD5 Arina Puzriakova Publications for gene: ABHD5 were set to PubMed: 11590543
Intellectual disability v5.505 ABHD5 Arina Puzriakova Phenotypes for gene: ABHD5 were changed from Chanarin-Dorfman syndrome, 275630; CHANARIN-DORFMAN SYNDROME (CDS) to Chanarin-Dorfman syndrome, OMIM:275630
Palmoplantar keratodermas v3.25 ABHD5 Arina Puzriakova Phenotypes for gene: ABHD5 were changed from Neutral lipid storage disease to Chanarin-Dorfman syndrome, OMIM:275630
Ichthyosis and erythrokeratoderma v3.23 ABHD5 Arina Puzriakova Phenotypes for gene: ABHD5 were changed from Chanarin-Dorfman syndrome to Chanarin-Dorfman syndrome, OMIM:275630
Pulmonary fibrosis familial v1.7 ZCCHC8 Arina Puzriakova Publications for gene: ZCCHC8 were set to 31488579
Malformations of cortical development v4.25 COL3A1 Eleanor Williams gene: COL3A1 was added
gene: COL3A1 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: COL3A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL3A1 were set to 19455184; 25205403; 28742248; 28258187
Phenotypes for gene: COL3A1 were set to Polymicrogyria with or without vascular-type EDS, OMIM:618343; polymicrogyria with or without vascular-type Ehlers-Danlos syndrome, MONDO:0032688
Review for gene: COL3A1 was set to GREEN
Added comment: Associated with Polymicrogyria with or without vascular-type EDS in OMIM (OMIM:618343) with a autosomal recessive mode of inheritance.

Several cases reported:

PMID: 19455184 Plancke et al 2009 - report an 11 year old female with consangiuneous parents, who had vascular EDS. The phenotype also included diffuse cortical dysplasia. A homozygous nucleotide duplication (c.479dupT) in COL3A1 resulting in a premature termination codon (p.Lys161GlnfsX45) was identified. Both parents were heterozygous for this variant.

PMID: 25205403 Jørgensen et al 2015 - report 2 siblings who are compound heterozygous for COL3A1 sequence variants. One sibling died suddenly due to extensive aortic dissection at age 15. The younger sibling was cerebral cortical dysplasia with thickened frontoparietal cortices bilaterally, small gyri and findings consistent with pachy micropolygyria
Sources: Literature
Malformations of cortical development v4.25 COL3A1 Eleanor Williams gene: COL3A1 was added
gene: COL3A1 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: COL3A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL3A1 were set to 19455184; 25205403; 28742248; 28258187
Phenotypes for gene: COL3A1 were set to Polymicrogyria with or without vascular-type EDS, OMIM:618343; polymicrogyria with or without vascular-type Ehlers-Danlos syndrome, MONDO:0032688
Review for gene: COL3A1 was set to GREEN
Added comment: Associated with Polymicrogyria with or without vascular-type EDS in OMIM (OMIM:618343) with a autosomal recessive mode of inheritance.

Several cases reported:

PMID: 19455184 Plancke et al 2009 - report an 11 year old female with consangiuneous parents, who had vascular EDS. The phenotype also included diffuse cortical dysplasia. A homozygous nucleotide duplication (c.479dupT) in COL3A1 resulting in a premature termination codon (p.Lys161GlnfsX45) was identified. Both parents were heterozygous for this variant.

PMID: 25205403 Jørgensen et al 2015 - report 2 siblings who are compound heterozygous for COL3A1 sequence variants. One sibling died suddenly due to extensive aortic dissection at age 15. The younger sibling was cerebral cortical dysplasia with thickened frontoparietal cortices bilaterally, small gyri and findings consistent with pachy micropolygyria
Sources: Literature
Vascular skin disorders v1.63 STAMBP Arina Puzriakova Tag Q1_24_promote_green tag was added to gene: STAMBP.
Vascular skin disorders v1.63 STAMBP Arina Puzriakova Publications for gene: STAMBP were set to 23542699
Vascular skin disorders v1.62 STAMBP Arina Puzriakova Classified gene: STAMBP as Amber List (moderate evidence)
Vascular skin disorders v1.62 STAMBP Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Zornitza Stark (Australian Genomics). There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Multiple unrelated cases reported in the literature of biallelic variants in the STAMBP gene as the cause of microcephaly-capillary malformation syndrome (PMID: 21271646; 21548128; 21815250; 23542699; 25692795; 27531570; 29907875). Generalised capillary malformations on the skin are a cardinal feature of this condition and therefore inclusion of STAMBP on the panel is warranted.
Vascular skin disorders v1.62 STAMBP Arina Puzriakova Gene: stambp has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.504 STAMBP Arina Puzriakova Phenotypes for gene: STAMBP were changed from MICROCEPHALY CAPILLARY MALFORMATION (MIC-CAP) SYNDROME to Microcephaly-capillary malformation syndrome, OMIM:614261
Early onset or syndromic epilepsy v4.183 STAMBP Arina Puzriakova Phenotypes for gene: STAMBP were changed from Microcephaly-capillary malformation syndrome 614261 to Microcephaly-capillary malformation syndrome, OMIM:614261
Clefting v4.108 STAMBP Arina Puzriakova Phenotypes for gene: STAMBP were changed from MICROCEPHALY-CAPILLARY MALFORMATION SYNDROME; MICCAP to Microcephaly-capillary malformation syndrome, OMIM:614261
Fetal anomalies v3.145 STAMBP Arina Puzriakova Phenotypes for gene: STAMBP were changed from MICROCEPHALYÐCAPILLARY MALFORMATION (MIC-CAP) SYNDROME to Microcephaly-capillary malformation syndrome, OMIM:614261
Severe microcephaly v4.66 STAMBP Arina Puzriakova Phenotypes for gene: STAMBP were changed from Microcephaly-capillary malformation syndrome 614261 to Microcephaly-capillary malformation syndrome, OMIM:614261
Vascular skin disorders v1.61 STAMBP Arina Puzriakova Phenotypes for gene: STAMBP were changed from Microcephaly-capillary malformation syndrome, MIM# 614261 to Microcephaly-capillary malformation syndrome, OMIM:614261
Vascular skin disorders v1.60 PIK3R2 Arina Puzriakova Publications for gene: PIK3R2 were set to 22729224; 23745720; 28502725
Vascular skin disorders v1.59 PIK3R2 Arina Puzriakova commented on gene: PIK3R2
Vascular skin disorders v1.59 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME 1, OMIM:603387 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Intellectual disability v5.503 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome, 603387; MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME 1 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Early onset or syndromic epilepsy v4.182 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 603387 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Clefting v4.107 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME 1; MPPH1 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Fetal anomalies v3.144 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME 1 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Limb disorders v4.17 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 603387; Polydactyly to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Malformations of cortical development v4.24 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 603387 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Segmental overgrowth disorders - Deep sequencing v3.17 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, 603387; MPPH1; Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome, 603387; Macrocephaly and Overgrowth Syndromes; Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus syndrome 1 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Vascular skin disorders v1.58 FOXC2 Arina Puzriakova Classified gene: FOXC2 as Green List (high evidence)
Vascular skin disorders v1.58 FOXC2 Arina Puzriakova Added comment: Comment on list classification: Inclusion of FOXC2 should be reviewed by the GMS specialist team due to conflicting reviews.

Lymphedema-distichiasis syndrome caused by heterozygous variants in this gene does not seem to fit the panel scope and is more appropriate for R136 Primary lymphoedema.
Vascular skin disorders v1.58 FOXC2 Arina Puzriakova Gene: foxc2 has been classified as Green List (High Evidence).
Vascular skin disorders v1.57 FOXC2 Arina Puzriakova Tag Q1_24_demote_red tag was added to gene: FOXC2.
Tag Q1_24_expert_review tag was added to gene: FOXC2.
Vascular skin disorders v1.57 FLT4 Arina Puzriakova Classified gene: FLT4 as Green List (high evidence)
Vascular skin disorders v1.57 FLT4 Arina Puzriakova Added comment: Comment on list classification: Inclusion of FLT4 should be reviewed by the GMS specialist team due to conflicting reviews.

Primary lymphoedema caused by heterozygous variants in this gene does not fit the panel scope and is more appropriate for R136 Primary lymphoedema. Since 2002, there has only been one report of a somatic variant causing skin capillary haemangiomas (PMID:11807987). There has been no evidence of germline variants causing a similar phenotype.
Vascular skin disorders v1.57 FLT4 Arina Puzriakova Gene: flt4 has been classified as Green List (High Evidence).
Vascular skin disorders v1.56 FLT4 Arina Puzriakova Tag somatic tag was added to gene: FLT4.
Tag Q1_24_demote_red tag was added to gene: FLT4.
Tag Q1_24_expert_review tag was added to gene: FLT4.
Pulmonary fibrosis familial v1.6 ZCCHC8 Matthew Edwards reviewed gene: ZCCHC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 31488579, 38375433; Phenotypes: Pulmonary fibrosis (PF), telomere related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Growth failure in early childhood v3.8 RECQL4 Melissa Connolly changed review comment from: ANAPC1 was added to the R147.1 panel for Rothmund-Thomson syndrome but RECQL4 gene, which is a more common cause of the this disorder was not. From gene reviews this gene causes 60% of RTS cases vs. ANAPC1 causing 10%. To complete the screening for RTS in short stature patients, this gene should be added to the panel
Sources: Literature; to: ANAPC1 was added to the R147.1 panel for Rothmund-Thomson syndrome but RECQL4, which is a more common cause of the this disorder was not. From gene reviews this gene causes 60% of RTS cases vs. ANAPC1 causing 10%. To complete the screening for RTS in short stature patients, this gene should be added to the panel
Sources: Literature
Growth failure in early childhood v3.8 RECQL4 Melissa Connolly gene: RECQL4 was added
gene: RECQL4 was added to Growth failure in early childhood. Sources: Literature
Mode of inheritance for gene: RECQL4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RECQL4 were set to PMID: 38021400
Phenotypes for gene: RECQL4 were set to Short stature; frontal bossing; prognathism; juvenile cataracts
Penetrance for gene: RECQL4 were set to Complete
Review for gene: RECQL4 was set to GREEN
Added comment: ANAPC1 was added to the R147.1 panel for Rothmund-Thomson syndrome but RECQL4 gene, which is a more common cause of the this disorder was not. From gene reviews this gene causes 60% of RTS cases vs. ANAPC1 causing 10%. To complete the screening for RTS in short stature patients, this gene should be added to the panel
Sources: Literature
CAKUT v1.175 ROBO1 Arina Puzriakova Phenotypes for gene: ROBO1 were changed from unilateral kidney agenesis; bilateral kidney agenesis; vesicoureteral junction obstruction; vesicoureteral reflux; posterior urethral valve; genital malformation; increased kidney echogenicity to Neurooculorenal syndrome, OMIM:620305
CAKUT v1.174 ROBO1 Arina Puzriakova Classified gene: ROBO1 as Green List (high evidence)
CAKUT v1.174 ROBO1 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Laura Claus (UMC). Rating Green as there is enough evidence to support the gene-disease association. Included on the R27 Paediatric disorders GMS panel via inclusion on the R29 Intellectual disability panel.

Biallelic variants in the ROBO1 gene are associated with neurooculorenal syndrome (OMIM:620305). Clinical manifestations are generally highly variable and involve several organ systems which may be include a syndromic form of congenital anomalies of the kidney and urinary tract (CAKUT) (PMID: 35227688)
CAKUT v1.174 ROBO1 Arina Puzriakova Gene: robo1 has been classified as Green List (High Evidence).
Fetal anomalies v3.143 ROBO1 Arina Puzriakova Publications for gene: ROBO1 were set to 28592524; 28485101; 30712880; 29194579; 35227688
Fetal anomalies v3.143 ROBO1 Arina Puzriakova Publications for gene: ROBO1 were set to 28592524; 28485101; 30712880
Fetal anomalies v3.142 ROBO1 Arina Puzriakova Added comment: Comment on mode of inheritance: Should be updated from 'monoallelic' to 'both mono- and biallelic' at the next GMS panel update.

Biallelic variants in the ROBO1 gene are associated with neurooculorenal syndrome (OMIM:620305). Clinical manifestations are generally highly variable and involve several organ systems. However, some cases do present in utero with renal agenesis and structural brain abnormalities (PMID: 29194579; 35227688) indicating that the phenotype is relevant to this panel.
Fetal anomalies v3.142 ROBO1 Arina Puzriakova Mode of inheritance for gene: ROBO1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v3.141 ROBO1 Arina Puzriakova Phenotypes for gene: ROBO1 were changed from tetralogy of Fallot and septal defects to Tetralogy of Fallot and septal defects; Neurooculorenal syndrome, OMIM:620305
Fetal anomalies v3.140 ROBO1 Arina Puzriakova Tag Q1_24_MOI tag was added to gene: ROBO1.
Intellectual disability v5.502 ROBO1 Arina Puzriakova Tag watchlist_moi tag was added to gene: ROBO1.
Albinism or congenital nystagmus v3.5 ROBO1 Arina Puzriakova Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (?Nystagmus 8, congenital, autosomal recessive, OMIM:257400). OMIM have only listed the publications already considered (PMID: 35348658) and therefore there is no new evidence to warrant further review.
Albinism or congenital nystagmus v3.5 ROBO1 Arina Puzriakova Phenotypes for gene: ROBO1 were changed from nystagmus, congenital, autosomal recessive, MONDO:0009762 to ?Nystagmus 8, congenital, autosomal recessive, OMIM:257400
Pituitary hormone deficiency v3.11 ROBO1 Arina Puzriakova Tag watchlist tag was added to gene: ROBO1.
Pituitary hormone deficiency v3.11 ROBO1 Arina Puzriakova Publications for gene: ROBO1 were set to 28402530
Pituitary hormone deficiency v3.10 ROBO1 Arina Puzriakova changed review comment from: Comment on phenotypes: This gene is now associated with relevant phenotype in OMIM (Pituitary hormone deficiency, combined or isolated, 8, OMIM:620303). OMIM have listed the all of the publications (PMID: 28402530; 31448886; 33270637) already previously considered by the GMS expert group and therefore no new evidence to support promotion from amber to green.; to: Comment on phenotypes: This gene is now associated with relevant phenotype in OMIM (Pituitary hormone deficiency, combined or isolated, 8, OMIM:620303). OMIM have listed the all of the publications (PMID: 28402530; 31448886; 33270637) already previously considered by the GMS expert group and therefore there is no new evidence to support promotion from amber to green.
Pituitary hormone deficiency v3.10 ROBO1 Arina Puzriakova changed review comment from: Comment on phenotypes: This gene is now associated with relevant phenotype in OMIM (Pituitary hormone deficiency, combined or isolated, 8, OMIM:620303); to: Comment on phenotypes: This gene is now associated with relevant phenotype in OMIM (Pituitary hormone deficiency, combined or isolated, 8, OMIM:620303). OMIM have listed the all of the publications (PMID: 28402530; 31448886; 33270637) already previously considered by the GMS expert group and therefore no new evidence to support promotion from amber to green.
Pituitary hormone deficiency v3.10 ROBO1 Arina Puzriakova Added comment: Comment on phenotypes: This gene is now associated with relevant phenotype in OMIM (Pituitary hormone deficiency, combined or isolated, 8, OMIM:620303)
Pituitary hormone deficiency v3.10 ROBO1 Arina Puzriakova Phenotypes for gene: ROBO1 were changed from pituitary stalk interruption syndrome, MONDO:0019828 to Pituitary hormone deficiency, combined or isolated, 8, OMIM:620303
Intellectual disability v5.502 CLEC16A Sarah Leigh edited their review of gene: CLEC16A: Added comment: Heterozygous CLEC16A variants have been identified as a genetic risk factor for several autoimmune disorders and for Parkinson disease (PMID: 37175930). PMID: 36538041 reports the neurological effect of homozygous terminating CLEC16A variants in two families. In family 1, the first child died at 5 months, he had progressive microcephaly, failure to thrive and cranial CT showed brain atrophy, dilatation of both central and peripheral liquor spaces, hypoplasia of the corpus callosum (no genetic testing was done), the third pregnancy was terminated (17 weeks of gestation) after prenatal ultrasound showed ventriculomegaly, agenesis of corpus callosum (no genetic testing was done), the fourth pregnancy was also terminated (22 weeks of gestation) as the prenatal ultrasound showed agenesis of corpus callosum. This fetus was homozygous for NM_001243403.1(CLEC16A):c.2062 + 5G > A, RT-PRC showed that this variant resulted in the deletion of exon 19 and a frame shift. Both parents and an unaffected sibling were heterozygous for this variant. In family 2, a single affected child was homozygous for NM_001243403.1(CLEC16A):c.-4_12del, p.Met1fs*. This child had progressive microcephaly, failure to thrive, severe global developmental delay, global brain atrophy and died at 6 years. There is no genetic data from the parents or unaffected siblings in Family 2. PMID: 37175930, also presents zebrafish experiments, where mutagenesis of
clec16a by CRISPR–Cas9 resulted in accumulated acidic/phagolysosome compartments, in neurons
and microglia, and dysregulated mitophagy. This was rescued by wild type CLEC16A, but not by the C-terminal truncated variant. The authors conclude that dysregulation of CLEC16A-mediated endosomal sorting is associated with neurodegeneration.; Changed rating: GREEN; Changed publications to: 36538041; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.502 CLEC16A Sarah Leigh Classified gene: CLEC16A as Amber List (moderate evidence)
Intellectual disability v5.502 CLEC16A Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be green on this panel.
Intellectual disability v5.502 CLEC16A Sarah Leigh Gene: clec16a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.501 CLEC16A Sarah Leigh Publications for gene: CLEC16A were set to 36538041
Intellectual disability v5.500 CLEC16A Sarah Leigh Publications for gene: CLEC16A were set to PMID: 36538041
Intellectual disability v5.500 CLEC16A Sarah Leigh Classified gene: CLEC16A as Amber List (moderate evidence)
Intellectual disability v5.500 CLEC16A Sarah Leigh Gene: clec16a has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v4.23 FHL1 Sarah Leigh reviewed gene: FHL1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.499 ZFHX3 Sarah Leigh edited their review of gene: ZFHX3: Added comment: Personal communication from Nour Elkhateeb (Clinical Fellow in Genomics, Genomics England): we have data about 12 individuals with nonsense/frameshift/exon deletions in ZFHX3. Five of the variants are located in exon 9/10 or exon 9, which has been shown to harbour the highest density of pathogenic variants (PMID: 38412861). Eleven of these cases presented with developmental delay / intellectual disability and a range of other features, including dysmorphology, seizures and failure to thrive.; Changed publications to: 38412861
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.32 SMCHD1 Sarah Leigh Tag Q1_24_promote_green tag was added to gene: SMCHD1.
Tag Q1_24_MOI tag was added to gene: SMCHD1.
Tag Q1_24_NHS_review tag was added to gene: SMCHD1.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.32 SMCHD1 Sarah Leigh Phenotypes for gene: SMCHD1 were changed from Fascioscapulohumeral muscular dystrophy 2, digenic 158901; fascioscapulohumeral muscular dystrophy to Fascioscapulohumeral muscular dystrophy 2, digenic, OMIM:158901; facioscapulohumeral muscular dystrophy 2, MONDO:0008031
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.31 SMCHD1 Sarah Leigh Publications for gene: SMCHD1 were set to
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.30 SMCHD1 Sarah Leigh Deleted their comment
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.30 SMCHD1 Sarah Leigh changed review comment from: In line with Ian Berry's (Leeds Genetics Laboratory) review, the mode of inheritance for SMCHD1 should be updated to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown. At least 10 SMCHD1 variants in unrelated cases have been associated with Fascioscapulohumeral muscular dystrophy 2, digenic (OMIM:158901)(PMID: 23143600; 24075187;31600781).; to: In line with the recommendations from Ian Berry (Leeds Genetics Laboratory), it is recommended that the mode of inheritance for this gene should be changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown. At least 10 SMCHD1 variants in unrelated cases have been associated with Fascioscapulohumeral muscular dystrophy 2, digenic (OMIM:158901)(PMID: 23143600; 24075187;31600781).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.30 SMCHD1 Sarah Leigh edited their review of gene: SMCHD1: Added comment: In line with Ian Berry's (Leeds Genetics Laboratory) review, the mode of inheritance for SMCHD1 should be updated to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown. At least 10 SMCHD1 variants in unrelated cases have been associated with Fascioscapulohumeral muscular dystrophy 2, digenic (OMIM:158901)(PMID: 23143600; 24075187;31600781).; Changed publications to: 23143600, 24075187, 31600781
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.30 SMCHD1 Sarah Leigh edited their review of gene: SMCHD1: Added comment: In line with the recommendations from Ian Berry (Leeds Genetics Laboratory), it is recommended that the mode of inheritance for this gene should be changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown. At least five SMCHD1 variants in unrelated cases have been associated with Fascioscapulohumeral muscular dystrophy 2, digenic, (OMIM:158901)(PMID: ).; Changed rating: GREEN; Changed publications to: 23143600; Changed phenotypes to: Fascioscapulohumeral muscular dystrophy 2, digenic, OMIM:158901, facioscapulohumeral muscular dystrophy 2, MONDO:0008031; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy or pain disorder v3.83 SPG7 Sarah Leigh Tag Q1_24_promote_green tag was added to gene: SPG7.
Tag Q1_24_NHS_review tag was added to gene: SPG7.
Hereditary neuropathy or pain disorder v3.83 SPG7 Sarah Leigh edited their review of gene: SPG7: Added comment: SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive (OMIM:607259) and have a definitive association with the same condition on the Eye panel at Gen2Phen. Various phenotypic features are apparent in cases of OMIM:607259. Peripheral neuropathy has been reported in at least three cases (PMID: 35096021, in the review on this panel by Williams Kirsty), and optical neuropathy has been reported in many more cases (as mentioned in PMID:35243150).; Changed rating: GREEN; Changed publications to: 30098094, 35637455, 35096021, 35243150, 22964162
Ataxia and cerebellar anomalies - narrow panel v4.58 ZFHX3 Dmitrijs Rots reviewed gene: ZFHX3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v4.58 ZFHX3 Sarah Leigh reviewed gene: ZFHX3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.499 ZFHX3 Sarah Leigh Tag Q1_24_promote_green tag was added to gene: ZFHX3.
Tag Q1_24_NHS_review tag was added to gene: ZFHX3.
Intellectual disability v5.499 ZFHX3 Sarah Leigh reviewed gene: ZFHX3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v4.58 ZFHX3 Sarah Leigh Tag STR tag was added to gene: ZFHX3.
Ataxia and cerebellar anomalies - narrow panel v4.58 ZFHX3 Sarah Leigh Phenotypes for gene: ZFHX3 were changed from syndromic intellectual disability to Spinocerebellar ataxia 4, OMIM:600223; spinocerebellar ataxia type 4, MONDO:0010847
Ataxia and cerebellar anomalies - narrow panel v4.57 ZFHX3 Sarah Leigh Entity copied from Intellectual disability - microarray and sequencing v5.499
Ataxia and cerebellar anomalies - narrow panel v4.57 ZFHX3 Sarah Leigh gene: ZFHX3 was added
gene: ZFHX3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: ZFHX3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZFHX3 were set to 38412861; 38035881; 37292950
Phenotypes for gene: ZFHX3 were set to syndromic intellectual disability
Intellectual disability v5.499 ZFHX3 Sarah Leigh Classified gene: ZFHX3 as Amber List (moderate evidence)
Intellectual disability v5.499 ZFHX3 Sarah Leigh Gene: zfhx3 has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder - nuclear genes v3.103 ATP5E Sarah Leigh Tag new-gene-name was removed from gene: ATP5E.
Tag Q4_23_promote_green was removed from gene: ATP5E.
Tag Q4_23_NHS_review was removed from gene: ATP5E.
Tag watchlist tag was added to gene: ATP5E.
Tag Q1_24_promote_green tag was added to gene: ATP5E.
Tag Q1_24_NHS_review tag was added to gene: ATP5E.
Possible mitochondrial disorder - nuclear genes v3.103 ATP5E Sarah Leigh changed review comment from: PMID: 34954817 reports two further cases of OMIM: 614053 who are both homozygous for ATP5E (new gene name: ATP5F1E) variant c.35A>G, p.Tyr12Cys (rs387906929), previously reported in PubMed: 20566710. Personal communication with the lead author of PMID: 34954817, confirmed that none of these cases were related to one another and so represent independent occurrences of this variant.; to: PMID: 34954817 reports two further cases of OMIM: 614053 who are both homozygous for ATP5E (new gene name: ATP5F1E) variant c.35A>G, p.Tyr12Cys (rs387906929), previously reported in PubMed: 20566710. Personal communication with the lead author of PMID: 34954817, confirmed that none of these cases were related to one another and so represent independent occurrences of this variant. In addition, PMID: 34954817 reports significantly reduced ATPase amounts associated with the ATP5F1E variants.
Intellectual disability v5.498 ZFHX3 Sarah Leigh gene: ZFHX3 was added
gene: ZFHX3 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: ZFHX3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZFHX3 were set to 38412861; 38035881; 37292950
Phenotypes for gene: ZFHX3 were set to syndromic intellectual disability
Hereditary neuropathy or pain disorder v3.83 XK Alexander Rossor commented on gene: XK: Should be included in R78 as now inlcudes many other complex phenotype genes that can present with neuropathy
Hereditary neuropathy or pain disorder v3.83 TYMP Alexander Rossor edited their review of gene: TYMP: Added comment: Can present with neuropathy and should be included in R78 panel; Changed publications to: 21933806
Hereditary neuropathy or pain disorder v3.83 SURF1 Alexander Rossor edited their review of gene: SURF1: Added comment: Should be included as R78 now includes complex phenotype genes; Changed publications to: 27475922, 12026244, 24027061
Hereditary neuropathy or pain disorder v3.83 SPTBN4 Alexander Rossor commented on gene: SPTBN4
Hereditary neuropathy or pain disorder v3.83 SLC25A19 Alexander Rossor edited their review of gene: SLC25A19: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed phenotypes to: Acute encephalopathic episodes and paralysis following febrile illness with almost complete recovery. Absent sensory-motor action potential during illness. Bilateral striatal necrosis on MRI. Additional chronic progressive axonal neuropathy
Hereditary neuropathy or pain disorder v3.83 SCARB2 Alexander Rossor edited their review of gene: SCARB2: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 21670406, 19597094
Hereditary neuropathy or pain disorder v3.83 SACS Alexander Rossor edited their review of gene: SACS: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 30460542
Hereditary neuropathy or pain disorder v3.83 POLR3A Alexander Rossor commented on gene: POLR3A: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 PNPLA6 Alexander Rossor commented on gene: PNPLA6: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 PMM2 Alexander Rossor edited their review of gene: PMM2: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed phenotypes to: Neonatal onset, leukodystrophy, abnormal serum glycoproteins, mental retardation, hypotonia, ataxia, retinitis pigmentosa, seizures, slowly progressive neuropathy with SNCV, severe infections, hepatic insufficiency and cardiomyopathy.
Hereditary neuropathy or pain disorder v3.83 PLP1 Alexander Rossor edited their review of gene: PLP1: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 12601703
Hereditary neuropathy or pain disorder v3.83 PEX7 Alexander Rossor edited their review of gene: PEX7: Added comment: Should be included in R78 as can present with neuropathy and other complex disease are now include in R78; Changed publications to: 11493716
Hereditary neuropathy or pain disorder v3.83 PEX10 Alexander Rossor edited their review of gene: PEX10: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 27230853, 20695019
Hereditary neuropathy or pain disorder v3.83 PDYN Alexander Rossor commented on gene: PDYN: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 NAGA Alexander Rossor commented on gene: NAGA: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 MTTP Alexander Rossor commented on gene: MTTP: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 MMACHC Alexander Rossor edited their review of gene: MMACHC: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed phenotypes to: Onset infancy to adulthood, thrombotic thrombocytopenia with encephalopathy, myelopathy, renal and pulmonary complications (can be life threatening), retinitis pigmentosa, axonal motor neuropathy. Treated with high dose vitamin B12.
Hereditary neuropathy or pain disorder v3.83 LYST Alexander Rossor commented on gene: LYST: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 IARS2 Alexander Rossor edited their review of gene: IARS2: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 25130867, 28328135, 30041933, 30419932
Hereditary neuropathy or pain disorder v3.83 GBA2 Alexander Rossor commented on gene: GBA2: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 BCKDHB Alexander Rossor edited their review of gene: BCKDHB: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 18855118, 11180212; Changed phenotypes to: Maple Syrup Urine Disease, Metabolic encephalopathy, elevated branched chain amino acids in urine, acute axonal neuropathy
Hereditary neuropathy or pain disorder v3.83 B4GALNT1 Alexander Rossor commented on gene: B4GALNT1: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 APOA1 Alexander Rossor commented on gene: APOA1: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 AP1S1 Alexander Rossor Deleted their comment
Hereditary neuropathy or pain disorder v3.83 AP1S1 Alexander Rossor commented on gene: AP1S1: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 AGXT Alexander Rossor edited their review of gene: AGXT: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 4701948, 25363903
Hereditary neuropathy or pain disorder v3.83 AGTPBP1 Alexander Rossor commented on gene: AGTPBP1: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 ABHD12 Alexander Rossor edited their review of gene: ABHD12: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 29571850, 20797687
Hereditary neuropathy or pain disorder v3.83 GAN Alexander Rossor commented on gene: GAN: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 FXN Alexander Rossor edited their review of gene: FXN: Added comment: FA can present with a sensory neuropathy and should be included in the R78 panel. A missense may prompt testing for an expansion in the other allele.; Changed publications to: 20339857
Hereditary neuropathy or pain disorder v3.83 GALC Alexander Rossor edited their review of gene: GALC: Added comment: Can present with peripheral neuropathy and should be included in R78 panel; Changed publications to: 26840509; Changed phenotypes to: Krabbe. Spastic paraplegia, developmental delay, optic atrophy, adult onset has spastic paraplegia and sensory-motor axonal neuropathy with slow or normal conduction velocities, MRI shows leukodystrophy
Intellectual disability v5.497 SOX9 Tracy Lester reviewed gene: SOX9: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Skeletal dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic neuropathy v4.24 SNF8 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are two unrelated cases reported with optic atrophy and hence this gene should be rated amber with Current evidence.; to: Comment on list classification: There are two unrelated cases reported with optic atrophy and hence this gene should be rated amber with current evidence.
Optic neuropathy v4.24 SNF8 Achchuthan Shanmugasundram Classified gene: SNF8 as Amber List (moderate evidence)
Optic neuropathy v4.24 SNF8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases reported with optic atrophy and hence this gene should be rated amber with Current evidence.
Optic neuropathy v4.24 SNF8 Achchuthan Shanmugasundram Gene: snf8 has been classified as Amber List (Moderate Evidence).
Optic neuropathy v4.23 SNF8 Achchuthan Shanmugasundram gene: SNF8 was added
gene: SNF8 was added to Optic neuropathy. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to neurodevelopmental disorder, MONDO:0700092; optic atrophy, MONDO:0003608
Review for gene: SNF8 was set to AMBER
Added comment: PMID:38423010 reported nine individuals from six families presenting with a spectrum of neurodevelopmental/ neurodegenerative features caused by biallelic variants in SNF8.

The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy with leukoencephalopathy and early death in three of those cases. Two individuals died too young to develop epilepsy. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous. Three of the patients (from two families) with the milder phenotype also have optic atrophy.

Functional studies using fibroblasts derived from patients and zebrafish model showed loss of function as the disease mechanism.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Early onset or syndromic epilepsy v4.181 SNF8 Achchuthan Shanmugasundram Classified gene: SNF8 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.181 SNF8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are only two unrelated patients reported with seizures and hence this gene should be rated amber with current evidence.
Early onset or syndromic epilepsy v4.181 SNF8 Achchuthan Shanmugasundram Gene: snf8 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.180 SNF8 Achchuthan Shanmugasundram gene: SNF8 was added
gene: SNF8 was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027
Review for gene: SNF8 was set to AMBER
Added comment: PMID:38423010 reported nine individuals from six families presenting with a spectrum of neurodevelopmental/ neurodegenerative features caused by biallelic variants in SNF8.

The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy with leukoencephalopathy and early death in three of those cases. Two individuals died too young to develop epilepsy. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.

Functional studies using fibroblasts derived from patients and zebrafish model showed loss of function as the disease mechanism.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Likely inborn error of metabolism - targeted testing not possible v4.134 G6PC Arina Puzriakova Phenotypes for gene: G6PC were changed from Glycogen Storage Disease Type I; Glycogen Storage Disorders- Liver; Glycogen Storage Disease; Glycogen Storage Disease Ia; Glycogen storage disease Ia, 232200; Glycogen storage disease type 1a, von Gierke (Glycogen storage disorders); Glycogen storage disease Ia; fasting intolerance with enlarged liver, renal tubular disease to Glycogen storage disease Ia, OMIM:232200
Mitochondrial disorders v4.167 G6PC Arina Puzriakova Phenotypes for gene: G6PC were changed from Glycogen storage disease Ia to Glycogen storage disease Ia, OMIM:232200
Possible mitochondrial disorder - nuclear genes v3.103 G6PC Arina Puzriakova Phenotypes for gene: G6PC were changed from Glycogen storage disease Ia, 232200 to Glycogen storage disease Ia, OMIM:232200
Undiagnosed metabolic disorders v1.615 G6PC Arina Puzriakova Phenotypes for gene: G6PC were changed from Glycogen storage disease type 1a, von Gierke (Glycogen storage disorders); fasting intolerance with enlarged liver, renal tubular disease; Glycogen storage disease Ia, 232200; Glycogen Storage Disease Type I; Glycogen Storage Disorders- Liver; Glycogen Storage Disease; Glycogen Storage Disease Ia to Glycogen storage disease Ia, OMIM:232200
Glycogen storage disease v2.4 G6PC Arina Puzriakova Phenotypes for gene: G6PC were changed from Glycogen storage disease Ia 232200 to Glycogen storage disease Ia, OMIM:232200
Ketotic hypoglycaemia v1.9 G6PC Arina Puzriakova Phenotypes for gene: G6PC were changed from fasting intolerance with enlarged liver, renal tubular disease; Glycogen storage disease Ia, 232200; Glycogen Storage Disease Type I; Glycogen Storage Disorders- Liver; Glycogen Storage Disease; Glycogen Storage Disease Ia to Glycogen storage disease Ia, OMIM:232200
Mitochondrial disorder with complex V deficiency v2.16 ATPAF1 Arina Puzriakova Classified gene: ATPAF1 as Red List (low evidence)
Mitochondrial disorder with complex V deficiency v2.16 ATPAF1 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Mitochondrial disorder with complex V deficiency v2.16 ATPAF1 Arina Puzriakova Gene: atpaf1 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.102 ATPAF1 Arina Puzriakova Classified gene: ATPAF1 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.102 ATPAF1 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Possible mitochondrial disorder - nuclear genes v3.102 ATPAF1 Arina Puzriakova Gene: atpaf1 has been classified as Red List (Low Evidence).
Mitochondrial disorder with complex IV deficiency v3.19 COA4 Arina Puzriakova Classified gene: COA4 as Red List (low evidence)
Mitochondrial disorder with complex IV deficiency v3.19 COA4 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Mitochondrial disorder with complex IV deficiency v3.19 COA4 Arina Puzriakova Gene: coa4 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.101 COA4 Arina Puzriakova Classified gene: COA4 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.101 COA4 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Possible mitochondrial disorder - nuclear genes v3.101 COA4 Arina Puzriakova Gene: coa4 has been classified as Red List (Low Evidence).
Mitochondrial disorder with complex IV deficiency v3.18 COX17 Arina Puzriakova Classified gene: COX17 as Red List (low evidence)
Mitochondrial disorder with complex IV deficiency v3.18 COX17 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Mitochondrial disorder with complex IV deficiency v3.18 COX17 Arina Puzriakova Gene: cox17 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.100 COX17 Arina Puzriakova Classified gene: COX17 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.100 COX17 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Possible mitochondrial disorder - nuclear genes v3.100 COX17 Arina Puzriakova Gene: cox17 has been classified as Red List (Low Evidence).
Mitochondrial disorder with complex IV deficiency v3.17 COX18 Arina Puzriakova Classified gene: COX18 as Red List (low evidence)
Mitochondrial disorder with complex IV deficiency v3.17 COX18 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Mitochondrial disorder with complex IV deficiency v3.17 COX18 Arina Puzriakova Gene: cox18 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.99 COX18 Arina Puzriakova Classified gene: COX18 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.99 COX18 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Possible mitochondrial disorder - nuclear genes v3.99 COX18 Arina Puzriakova Gene: cox18 has been classified as Red List (Low Evidence).
Mitochondrial disorder with complex IV deficiency v3.16 COX19 Arina Puzriakova Classified gene: COX19 as Red List (low evidence)
Mitochondrial disorder with complex IV deficiency v3.16 COX19 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Mitochondrial disorder with complex IV deficiency v3.16 COX19 Arina Puzriakova Gene: cox19 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.98 COX19 Arina Puzriakova Classified gene: COX19 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.98 COX19 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Possible mitochondrial disorder - nuclear genes v3.98 COX19 Arina Puzriakova Gene: cox19 has been classified as Red List (Low Evidence).
Mitochondrial disorder with complex IV deficiency v3.15 COX6B2 Arina Puzriakova Classified gene: COX6B2 as Red List (low evidence)
Mitochondrial disorder with complex IV deficiency v3.15 COX6B2 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Mitochondrial disorder with complex IV deficiency v3.15 COX6B2 Arina Puzriakova Gene: cox6b2 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.97 COX6B2 Arina Puzriakova Classified gene: COX6B2 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.97 COX6B2 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Possible mitochondrial disorder - nuclear genes v3.97 COX6B2 Arina Puzriakova Gene: cox6b2 has been classified as Red List (Low Evidence).
Mitochondrial disorder with complex I deficiency v3.8 NDUFAF7 Arina Puzriakova Classified gene: NDUFAF7 as Red List (low evidence)
Mitochondrial disorder with complex I deficiency v3.8 NDUFAF7 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Mitochondrial disorder with complex I deficiency v3.8 NDUFAF7 Arina Puzriakova Gene: ndufaf7 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.96 NDUFAF7 Arina Puzriakova Classified gene: NDUFAF7 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.96 NDUFAF7 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Possible mitochondrial disorder - nuclear genes v3.96 NDUFAF7 Arina Puzriakova Gene: ndufaf7 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.95 SDHAF3 Arina Puzriakova Classified gene: SDHAF3 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.95 SDHAF3 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Possible mitochondrial disorder - nuclear genes v3.95 SDHAF3 Arina Puzriakova Gene: sdhaf3 has been classified as Red List (Low Evidence).
Mitochondrial disorder with complex II deficiency v2.10 SDHAF3 Arina Puzriakova Classified gene: SDHAF3 as Red List (low evidence)
Mitochondrial disorder with complex II deficiency v2.10 SDHAF3 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Mitochondrial disorder with complex II deficiency v2.10 SDHAF3 Arina Puzriakova Gene: sdhaf3 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.94 SDHAF4 Arina Puzriakova Classified gene: SDHAF4 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.94 SDHAF4 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Possible mitochondrial disorder - nuclear genes v3.94 SDHAF4 Arina Puzriakova Gene: sdhaf4 has been classified as Red List (Low Evidence).
Mitochondrial disorder with complex II deficiency v2.9 SDHAF4 Arina Puzriakova Classified gene: SDHAF4 as Red List (low evidence)
Mitochondrial disorder with complex II deficiency v2.9 SDHAF4 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Mitochondrial disorder with complex II deficiency v2.9 SDHAF4 Arina Puzriakova Gene: sdhaf4 has been classified as Red List (Low Evidence).
Mitochondrial disorder with complex V deficiency v2.15 ATP5J2 Arina Puzriakova Classified gene: ATP5J2 as Red List (low evidence)
Mitochondrial disorder with complex V deficiency v2.15 ATP5J2 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with a human disease.
Mitochondrial disorder with complex V deficiency v2.15 ATP5J2 Arina Puzriakova Gene: atp5j2 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.93 ATP5J2 Arina Puzriakova Classified gene: ATP5J2 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.93 ATP5J2 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with a human disease.
Possible mitochondrial disorder - nuclear genes v3.93 ATP5J2 Arina Puzriakova Gene: atp5j2 has been classified as Red List (Low Evidence).
Mitochondrial disorders v4.166 ATP5J2 Arina Puzriakova Classified gene: ATP5J2 as Red List (low evidence)
Mitochondrial disorders v4.166 ATP5J2 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with a human disease.
Mitochondrial disorders v4.166 ATP5J2 Arina Puzriakova Gene: atp5j2 has been classified as Red List (Low Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.133 CYCS Arina Puzriakova Phenotypes for gene: CYCS were changed from Thrombocytopenia 4, 612004 to Thrombocytopenia 4, OMIM:612004
Possible mitochondrial disorder - nuclear genes v3.92 CYCS Arina Puzriakova Phenotypes for gene: CYCS were changed from Thrombocytopenia 4, 612004 to Thrombocytopenia 4, OMIM:612004
Possible mitochondrial disorder - nuclear genes v3.91 CYCS Arina Puzriakova Publications for gene: CYCS were set to
Cytopenia - NOT Fanconi anaemia v3.27 CYCS Arina Puzriakova Phenotypes for gene: CYCS were changed from Thrombocytopenia 4, 612004; Thrombocytopenia to Thrombocytopenia 4, OMIM:612004
Bleeding and platelet disorders v3.8 CYCS Arina Puzriakova Phenotypes for gene: CYCS were changed from 612004 Thrombocytopenia 4 to Thrombocytopenia 4, OMIM:612004
Cytopenias and congenital anaemias v1.118 CYCS Arina Puzriakova Phenotypes for gene: CYCS were changed from Thrombocytopenia 4, 612004 to Thrombocytopenia 4, OMIM:612004
Inherited bleeding disorders v1.176 CYCS Arina Puzriakova Phenotypes for gene: CYCS were changed from Thrombocytopenia 4 to Thrombocytopenia 4, OMIM:612004
Mitochondrial disorders v4.165 CYCS Arina Puzriakova Phenotypes for gene: CYCS were changed from Thrombocytopenia 4, 612004 to Thrombocytopenia 4, OMIM:612004
Possible mitochondrial disorder - nuclear genes v3.90 CYCS Arina Puzriakova Classified gene: CYCS as Amber List (moderate evidence)
Possible mitochondrial disorder - nuclear genes v3.90 CYCS Arina Puzriakova Added comment: Comment on list classification: There are sufficient unrelated cases to support a gene-disease association and given that in vitro studies of patient variants have shown functional defects in the mitochondrial respiratory chain, this gene can be promoted to Green status at the next GMS panel update.
Possible mitochondrial disorder - nuclear genes v3.90 CYCS Arina Puzriakova Gene: cycs has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder - nuclear genes v3.89 CYCS Arina Puzriakova Tag Q1_24_promote_green tag was added to gene: CYCS.
Possible mitochondrial disorder - nuclear genes v3.89 CYCS Arina Puzriakova commented on gene: CYCS
Mitochondrial disorders v4.164 CYCS Arina Puzriakova Tag Q1_24_promote_green tag was added to gene: CYCS.
Mitochondrial disorders v4.164 CYCS Arina Puzriakova Classified gene: CYCS as Amber List (moderate evidence)
Mitochondrial disorders v4.164 CYCS Arina Puzriakova Added comment: Comment on list classification: There are sufficient unrelated cases to support a gene-disease association and given that in vitro studies of patient variants have shown functional defects in the mitochondrial respiratory chain, this gene can be promoted to Green status at the next GMS panel update.
Mitochondrial disorders v4.164 CYCS Arina Puzriakova Gene: cycs has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.163 SPATA5 Arina Puzriakova Tag Q1_24_promote_green tag was added to gene: SPATA5.
Mitochondrial disorders v4.163 SPATA5 Arina Puzriakova Publications for gene: SPATA5 were set to 27246907; 29343804; 26299366; 28293831
Mitochondrial disorders v4.162 SPATA5 Arina Puzriakova Classified gene: SPATA5 as Amber List (moderate evidence)
Mitochondrial disorders v4.162 SPATA5 Arina Puzriakova Added comment: Comment on list classification: There are sufficient cases to promote this gene to Green at the next GMS panel update. Patients display a phenotype that resembles a mitochondrial disorder and functional studies on patient-derived cells have demonstrated an impact on mitochondrial function, further supporting inclusion of SPATA5 on this panel.
Mitochondrial disorders v4.162 SPATA5 Arina Puzriakova Gene: spata5 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.161 SPATA5 Arina Puzriakova Phenotypes for gene: SPATA5 were changed from Epilepsy, hearing loss, and mental retardation syndrome 616577 to Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities, OMIM:616577
Intellectual disability v5.497 SPATA5 Arina Puzriakova Phenotypes for gene: SPATA5 were changed from Epilepsy, hearing loss, and mental retardation syndrome, 616577 to Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities, OMIM:616577
Early onset or syndromic epilepsy v4.179 SPATA5 Arina Puzriakova Phenotypes for gene: SPATA5 were changed from Epilepsy, hearing loss, and mental retardation syndrome 616577 to Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities, OMIM:616577
Monogenic hearing loss v4.26 SPATA5 Arina Puzriakova Phenotypes for gene: SPATA5 were changed from Epilepsy, hearing loss, and mental retardation syndrome 616577 to Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities, OMIM:616577
Fetal anomalies v3.140 SPATA5 Arina Puzriakova Phenotypes for gene: SPATA5 were changed from EPILEPSY, HEARING LOSS, AND MENTAL RETARDATION SYNDROME to Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities, OMIM:616577
Childhood onset dystonia, chorea or related movement disorder v3.74 PRNP Arina Puzriakova changed review comment from: Comment on list classification: Given that the age of onset associated with the multiple phenotypes related to this gene, inclusion on this panel should be reviewed by the GMS specialist group.; to: Comment on list classification: Given that the age of onset associated with the multiple phenotypes related to this gene is almost always in adulthood and poses risk of incidental findings, inclusion of PRNP on this panel should be reviewed by the GMS specialist group.
Childhood onset dystonia, chorea or related movement disorder v3.74 PRNP Arina Puzriakova Classified gene: PRNP as Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v3.74 PRNP Arina Puzriakova Added comment: Comment on list classification: Given that the age of onset associated with the multiple phenotypes related to this gene, inclusion on this panel should be reviewed by the GMS specialist group.
Childhood onset dystonia, chorea or related movement disorder v3.74 PRNP Arina Puzriakova Gene: prnp has been classified as Green List (High Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.73 PRNP Arina Puzriakova Phenotypes for gene: PRNP were changed from Creutzfeldt-Jakob disease 123400; Huntington disease-like 1 603218; Cerebral amyloid angiopathy, PRNP-related 137440; Gerstmann-Straussler disease 137440 to Cerebral amyloid angiopathy, PRNP-related, OMIM:137440; Huntington disease-like 1, OMIM:603218; Gerstmann-Straussler disease, OMIM:137440; Creutzfeldt-Jakob disease, OMIM:123400
Childhood onset dystonia, chorea or related movement disorder v3.72 PRNP Arina Puzriakova Publications for gene: PRNP were set to
Childhood onset dystonia, chorea or related movement disorder v3.71 PRNP Arina Puzriakova Tag Q1_24_demote_red tag was added to gene: PRNP.
Tag Q1_24_expert_review tag was added to gene: PRNP.
Childhood onset dystonia, chorea or related movement disorder v3.71 PRNP Arina Puzriakova reviewed gene: PRNP: Rating: ; Mode of pathogenicity: None; Publications: 16831973; Phenotypes: ; Mode of inheritance: None
Sarcoma susceptibility v1.81 TP53 Arina Puzriakova Phenotypes for gene: TP53 were changed from Li-Fraumeni syndrome, OMIM:151623; Sarcoma, MONDO:0005089 to Li-Fraumeni syndrome, OMIM:151623; Solitary Fibrous Tumour; Sarcoma, MONDO:0005089
Sarcoma susceptibility v1.80 TP53 Arina Puzriakova Publications for gene: TP53 were set to 27050224; 28338660
Sarcoma susceptibility v1.79 TERT Arina Puzriakova Publications for gene: TERT were set to PMID: 31529158
Sarcoma susceptibility v1.78 TERT Arina Puzriakova Classified gene: TERT as Red List (low evidence)
Sarcoma susceptibility v1.78 TERT Arina Puzriakova Added comment: Comment on list classification: Although there is evidence to support that TERT promoter variants affect prognosis, they are not the driving alteration in SFT. Furthermore, this cancer panel is intended for germline susceptibility findings rather than somatic variants as described in the case of TERT.

Therefore, assigning a Red rating to the TERT gene on this panel.
Sarcoma susceptibility v1.78 TERT Arina Puzriakova Gene: tert has been classified as Red List (Low Evidence).
Sarcoma susceptibility v1.77 TERT Arina Puzriakova Tag promoter tag was added to gene: TERT.
Tag somatic tag was added to gene: TERT.
Sarcoma susceptibility v1.77 TERT Arina Puzriakova reviewed gene: TERT: Rating: ; Mode of pathogenicity: None; Publications: 24726063, 27562490, 29985536, 31529158, 31321477, 38392213, 38357190; Phenotypes: Solitary Fibrous Tumours; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v5.496 SNF8 Achchuthan Shanmugasundram Classified gene: SNF8 as Amber List (moderate evidence)
Intellectual disability v5.496 SNF8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three unrelated cases with intellectual disability and hence this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.496 SNF8 Achchuthan Shanmugasundram Gene: snf8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.495 SNF8 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: SNF8.
Intellectual disability v5.495 SNF8 Achchuthan Shanmugasundram changed review comment from: PMID:38423010 reported nine individuals from six families presenting with a spectrum of neurodevelopmental/ neurodegenerative features caused by biallelic variants in SNF8. The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy with leukoencephalopathy and early death in three of those cases. Two individuals died too young to develop epilepsy. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous. Functional studies using fibroblasts derived from patients and zebrafish model showed loss of function as the disease mechanism.
Sources: Literature; to: PMID:38423010 reported nine individuals from six families presenting with a spectrum of neurodevelopmental/ neurodegenerative features caused by biallelic variants in SNF8.

The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy with leukoencephalopathy and early death in three of those cases. Two individuals died too young to develop epilepsy. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.

Functional studies using fibroblasts derived from patients and zebrafish model showed loss of function as the disease mechanism.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.495 SNF8 Achchuthan Shanmugasundram gene: SNF8 was added
gene: SNF8 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: SNF8 was set to GREEN
Added comment: PMID:38423010 reported nine individuals from six families presenting with a spectrum of neurodevelopmental/ neurodegenerative features caused by biallelic variants in SNF8. The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy with leukoencephalopathy and early death in three of those cases. Two individuals died too young to develop epilepsy. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous. Functional studies using fibroblasts derived from patients and zebrafish model showed loss of function as the disease mechanism.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.195 EZR Arina Puzriakova Classified gene: EZR as Red List (low evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.195 EZR Arina Puzriakova Added comment: Comment on list classification: New gene added by Boaz Palterer. Not yet associated with any phenotype in OMIM or G2P. Rating Red as only a single case has been reported to date (PMID: 37301410). Patient had B-cell deficiency with progressive hypogammaglobulinemia. Additional cases required prior to promoting this gene.

A homozygous variant in EZR was also found in two siblings with a profound intellectual disability (PMID: 25504542) but no immunological manifestations were reported.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.195 EZR Arina Puzriakova Gene: ezr has been classified as Red List (Low Evidence).
Vascular skin disorders v1.56 CCBE1 Arina Puzriakova commented on gene: CCBE1
Vascular skin disorders v1.56 CCBE1 Arina Puzriakova Tag Q1_24_demote_red tag was added to gene: CCBE1.
Tag Q1_24_expert_review tag was added to gene: CCBE1.
Intellectual disability v5.494 CCBE1 Arina Puzriakova Phenotypes for gene: CCBE1 were changed from Hennekam lymphangiectasia-lymphedema syndrome, 235510; HENNEKAM LYMPHANGIECTASIA-LYMPHEDEMA SYNDROME (HLLS) to Hennekam lymphangiectasia-lymphedema syndrome 1, OMIM:235510
Primary lymphoedema v3.10 CCBE1 Arina Puzriakova Phenotypes for gene: CCBE1 were changed from Hennekam lymphangiectasia-lymphedema syndrome, 235510; Hennekam Lymphangiectasia-Lymphedema Syndrome to Hennekam lymphangiectasia-lymphedema syndrome 1, OMIM:235510
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.179 CCBE1 Arina Puzriakova Phenotypes for gene: CCBE1 were changed from Hennekam-lymphangiectasia-lymphedema syndrome 1 235510 to Hennekam lymphangiectasia-lymphedema syndrome 1, OMIM:235510
Fetal anomalies v3.139 CCBE1 Arina Puzriakova Phenotypes for gene: CCBE1 were changed from HENNEKAM LYMPHANGIECTASIA-LYMPHEDEMA SYNDROME to Hennekam lymphangiectasia-lymphedema syndrome 1, OMIM:235510
Primary immunodeficiency or monogenic inflammatory bowel disease v4.194 CCBE1 Arina Puzriakova Phenotypes for gene: CCBE1 were changed from Hennekam lymphangiectasia-lymphedema syndrome 1, 235510; Lymphangiectasia and lymphedema with facial abnormalities and other dysmorphic features; Combined immunodeficiencies with associated or syndromic features to Hennekam lymphangiectasia-lymphedema syndrome 1, OMIM:235510; Lymphangiectasia and lymphedema with facial abnormalities and other dysmorphic features; Combined immunodeficiencies with associated or syndromic features
Fetal hydrops v1.64 CCBE1 Arina Puzriakova Phenotypes for gene: CCBE1 were changed from Hennekam lymphangiectasia-lymphedema syndrome 1, 235510; generalised lymphatic dysplasia; fetal hydrops to Hennekam lymphangiectasia-lymphedema syndrome 1, OMIM:235510; generalised lymphatic dysplasia; fetal hydrops
Vascular skin disorders v1.56 ALAS2 Arina Puzriakova Classified gene: ALAS2 as Green List (high evidence)
Vascular skin disorders v1.56 ALAS2 Arina Puzriakova Added comment: Comment on list classification: Inclusion of ALAS2 was reassessed in light of the Red review by Zornitza Stark (Australian Genomics).

Gain-of-function variants in the ALAS2 gene cause erythropoietic protoporphyria which is associated with acute phototoxic skin reactions following sunlight exposure. Although the origin of cutaneous manifestations is not directly vascular, this panel may provide a differential diagnosis. The FECH gene which also causes erythropoietic protoporphyria is also included on the panel.

Additionally, previous discussions with the clinical specialist team indicated that this gene should be on the panel and therefore maintaining the current Green rating.
Vascular skin disorders v1.56 ALAS2 Arina Puzriakova Gene: alas2 has been classified as Green List (High Evidence).
Mitochondrial disorders v4.160 ALAS2 Arina Puzriakova Phenotypes for gene: ALAS2 were changed from Anemia, sideroblastic, 1 300751; Protoporphyria, erythropoietic, X-linked 300752 to Anemia, sideroblastic, 1, OMIM:300751; Protoporphyria, erythropoietic, X-linked, OMIM:300752
Likely inborn error of metabolism - targeted testing not possible v4.132 ALAS2 Arina Puzriakova Phenotypes for gene: ALAS2 were changed from Erythropoietic protoporphyria, mild variant; X-linked sideroblastic anaemia (XLSA) (Porphyrias with acute painful photosensitivity); X-linked dominant protoporphyria (Porphyrias with acute painful photosensitivity) to Anemia, sideroblastic, 1, OMIM:300751; Protoporphyria, erythropoietic, X-linked, OMIM:300752
Undiagnosed metabolic disorders v1.614 ALAS2 Arina Puzriakova Phenotypes for gene: ALAS2 were changed from X-linked dominant protoporphyria (Porphyrias with acute painful photosensitivity); X-linked sideroblastic anaemia (XLSA) (Porphyrias with acute painful photosensitivity); Erythropoietic protoporphyria, mild variant to Anemia, sideroblastic, 1, OMIM:300751; Protoporphyria, erythropoietic, X-linked, OMIM:300752
Iron metabolism disorders - NOT common HFE mutations v2.5 ALAS2 Arina Puzriakova Phenotypes for gene: ALAS2 were changed from Protoporphyria, erythropoietic, X-linked OMIM:300752; Anemia, sideroblastic, 1 OMIM:300751; X-linked erythropoietic protoporphyria MONDO:0010420; X-linked sideroblastic anemia 1 MONDO:0020721 to Anemia, sideroblastic, 1, OMIM:300751
Rare anaemia v3.8 ALAS2 Arina Puzriakova Phenotypes for gene: ALAS2 were changed from Anemia, sideroblastic, 1, 300751; Anemia, sideroblastic, 1 300751; 300751 Sideroblastic anaemia 1; 300751 Anemia, sideroblastic, 1 to Anemia, sideroblastic, 1, OMIM:300751
Cytopenias and congenital anaemias v1.117 ALAS2 Arina Puzriakova Phenotypes for gene: ALAS2 were changed from Anemia, sideroblastic, 1 300751 to Anemia, sideroblastic, 1, OMIM:300751
Cutaneous photosensitivity with a likely genetic cause v3.4 ALAS2 Arina Puzriakova Phenotypes for gene: ALAS2 were changed from Protoporphyria, erythropoietic, X-linked, 300752; Anemia, sideroblastic, X-linked, 300751 to Protoporphyria, erythropoietic, X-linked, OMIM:300752
Non-acute porphyrias v1.24 ALAS2 Arina Puzriakova Phenotypes for gene: ALAS2 were changed from Protoporphyria, erythropoietic, X-linked OMIM:300752; X-linked erythropoietic protoporphyria MONDO:0010420; Anemia, sideroblastic, X-linked OMIM:300751; X-linked sideroblastic anemia 1 MONDO:0020721 to Protoporphyria, erythropoietic, X-linked, OMIM:300752
Erythropoietic protoporphyria, mild variant v1.3 ALAS2 Arina Puzriakova Phenotypes for gene: ALAS2 were changed from Anemia, sideroblastic, X-linked, 300751; Protoporphyria, erythropoietic, X-linked, 300752 to Protoporphyria, erythropoietic, X-linked, OMIM:300752
Vascular skin disorders v1.55 ADAMTS13 Arina Puzriakova changed review comment from: Comment on list classification: Inclusion of ADAMTS13 was reassessed in light of the Red review by Zornitza Stark (Australian Genomics).

ADAMTS13 deficiency causes thrombotic thrombocytopenic purpura which is predominantly characterised by haematological abnormalities. These defects can results in secondary dermatological features such as purpura, petechiae and vasculitis, indicating that this panel may be applicable in some cases and represents a differential diagnosis.

Additionally, previous discussions with the clinical specialist team indicated that this gene should be on the panel and therefore maintaining the current Green rating.; to: Comment on list classification: Inclusion of ADAMTS13 was reassessed in light of the Red review by Zornitza Stark (Australian Genomics).

ADAMTS13 deficiency causes thrombotic thrombocytopenic purpura which is predominantly characterised by haematological abnormalities. These defects can results in secondary dermatological features such as purpura and petechiae, indicating that this panel may be applicable in some cases and represents a differential diagnosis.

Additionally, previous discussions with the clinical specialist team indicated that this gene should be on the panel and therefore maintaining the current Green rating.
Vascular skin disorders v1.55 ADAMTS13 Arina Puzriakova changed review comment from: Comment on list classification: Inclusion of ADAMTS13 was reassessed in light of the Red review by Zornitza Stark (Australian Genomics).

ADAMTS13 deficiency causes thrombotic thrombocytopenic purpura which is predominantly characterised by haematological abnormalities. These defects can results in secondary dermatological features such as purpura, petechiae and vasculitis, indicating that this panel may be applicable in some cases and represents a differential diagnosis.

Previous discussions with the clinical specialist team indicated that this gene should be on the panel and therefore maintaining the current Green rating.; to: Comment on list classification: Inclusion of ADAMTS13 was reassessed in light of the Red review by Zornitza Stark (Australian Genomics).

ADAMTS13 deficiency causes thrombotic thrombocytopenic purpura which is predominantly characterised by haematological abnormalities. These defects can results in secondary dermatological features such as purpura, petechiae and vasculitis, indicating that this panel may be applicable in some cases and represents a differential diagnosis.

Additionally, previous discussions with the clinical specialist team indicated that this gene should be on the panel and therefore maintaining the current Green rating.
Vascular skin disorders v1.55 ADAMTS13 Arina Puzriakova changed review comment from: Comment on list classification: Inclusion of ADAMTS13 was reassessed in light of the Red review by Zornitza Stark (Australian Genomics).

ADAMTS13 deficiency causes thrombotic thrombocytopenic purpura which is predominantly characterised by haematological abnormalities. These defects can results in secondary dermatological features such as purpura, petechiae and vasculitis, indicates that this panel may be applicable in some cases and represents a differential diagnosis.

Previous discussions with the clinical specialist team indicated that this gene should be on the panel and therefore maintaining the current Green rating.; to: Comment on list classification: Inclusion of ADAMTS13 was reassessed in light of the Red review by Zornitza Stark (Australian Genomics).

ADAMTS13 deficiency causes thrombotic thrombocytopenic purpura which is predominantly characterised by haematological abnormalities. These defects can results in secondary dermatological features such as purpura, petechiae and vasculitis, indicating that this panel may be applicable in some cases and represents a differential diagnosis.

Previous discussions with the clinical specialist team indicated that this gene should be on the panel and therefore maintaining the current Green rating.
Vascular skin disorders v1.55 ADAMTS13 Arina Puzriakova Classified gene: ADAMTS13 as Green List (high evidence)
Vascular skin disorders v1.55 ADAMTS13 Arina Puzriakova Added comment: Comment on list classification: Inclusion of ADAMTS13 was reassessed in light of the Red review by Zornitza Stark (Australian Genomics).

ADAMTS13 deficiency causes thrombotic thrombocytopenic purpura which is predominantly characterised by haematological abnormalities. These defects can results in secondary dermatological features such as purpura, petechiae and vasculitis, indicates that this panel may be applicable in some cases and represents a differential diagnosis.

Previous discussions with the clinical specialist team indicated that this gene should be on the panel and therefore maintaining the current Green rating.
Vascular skin disorders v1.55 ADAMTS13 Arina Puzriakova Gene: adamts13 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v3.26 TUBA4A Achchuthan Shanmugasundram Phenotypes for gene: TUBA4A were changed from Thrombocytopenia to autosomal dominant macrothrombocytopenia, MONDO:0015372
Cytopenia - NOT Fanconi anaemia v3.25 TUBA4A Achchuthan Shanmugasundram Classified gene: TUBA4A as Red List (low evidence)
Cytopenia - NOT Fanconi anaemia v3.25 TUBA4A Achchuthan Shanmugasundram Gene: tuba4a has been classified as Red List (Low Evidence).
Cytopenia - NOT Fanconi anaemia v3.24 TUBA4A Achchuthan Shanmugasundram reviewed gene: TUBA4A: Rating: RED; Mode of pathogenicity: None; Publications: 30760556; Phenotypes: autosomal dominant macrothrombocytopenia, MONDO:0015372; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.193 PTCRA Boaz Palterer gene: PTCRA was added
gene: PTCRA was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: PTCRA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTCRA were set to 38422122
Phenotypes for gene: PTCRA were set to Autoimmunity; elevated TCRgamma/delta T cells; lymphopenia; low TREC
Penetrance for gene: PTCRA were set to Incomplete
Review for gene: PTCRA was set to GREEN
Added comment: Materna et al. identified 10 subjects from 7 kindreds with biallelic LOF PTCRA variants, moreover, the authors identified common hypomorphic alleles significantly associated with autoimmunity. Extensive in vivo, in vitro, and mouse functional validation and epidemiologic data.
Sources: Literature
Retinal disorders v4.81 SLC37A3 Siying Lin reviewed gene: SLC37A3: Rating: GREEN; Mode of pathogenicity: Other; Publications: 35486108; Phenotypes: Retinitis pigmentosa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.25 RIPOR2 Dmitrijs Rots reviewed gene: RIPOR2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32631815; Phenotypes: Adult-onset hearing loss; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Neurological segmental overgrowth v2.9 MAX James Poulter gene: MAX was added
gene: MAX was added to Neurological segmental overgrowth. Sources: Literature
Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAX were set to PMID:38141607
Phenotypes for gene: MAX were set to Macrocephaly; Polydactyly; delayed ophthalmic development; autism
Penetrance for gene: MAX were set to Complete
Review for gene: MAX was set to GREEN
Added comment: Recurrent de novo variant (p.Arg60Gln) identified in 3 unrelated individuals. Pathogenicity supported by functional analysis.
Sources: Literature
Intellectual disability v5.493 DYNC2H1 Arina Puzriakova commented on gene: DYNC2H1: - PMID: 22589734 (2012) - A 29 Mb deletion encompassing DYNC2H1 was found in one patient with syndromic hirschsprung disease which included moderate mental retardation, mild hydrocephalus, microcephaly, cardiomyopathy and congenital hypotonia. Other candidate genes in this region include CNTN5 and CARD17. Skeletal findings that are typical for DYNC2H1 are not reported.

Comment on publications: PMID: 22589734 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v5.493 DYNC2H1 Arina Puzriakova Publications for gene: DYNC2H1 were set to
Neurological ciliopathies v3.18 EXOC3L2 Sarah Leigh Tag Q1_24_promote_green tag was added to gene: EXOC3L2.
Neurological ciliopathies v3.18 EXOC3L2 Sarah Leigh Classified gene: EXOC3L2 as Amber List (moderate evidence)
Neurological ciliopathies v3.18 EXOC3L2 Sarah Leigh Added comment: Comment on list classification: There is sufficient evidence for this gene to be green on this panel.
Neurological ciliopathies v3.18 EXOC3L2 Sarah Leigh Gene: exoc3l2 has been classified as Amber List (Moderate Evidence).
Neurological ciliopathies v3.17 EXOC3L2 Sarah Leigh Publications for gene: EXOC3L2 were set to 28749478; 27894351; 30327448
Neurological ciliopathies v3.16 EXOC3L2 Sarah Leigh reviewed gene: EXOC3L2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Neurological ciliopathies v3.16 EXOC3L2 Sarah Leigh Publications for gene: EXOC3L2 were set to 28749478; 27894351
Early onset or syndromic epilepsy v4.178 PCLO Sarah Leigh Classified gene: PCLO as Red List (low evidence)
Early onset or syndromic epilepsy v4.178 PCLO Sarah Leigh Added comment: Comment on list classification: There is not enough evidence for this gene to be Amber on this panel.
Early onset or syndromic epilepsy v4.178 PCLO Sarah Leigh Gene: pclo has been classified as Red List (Low Evidence).
Leber hereditary optic neuropathy v2.9 DNAJC30 Arina Puzriakova Tag curated_removed tag was added to gene: DNAJC30.
Early onset or syndromic epilepsy v4.177 ZNFX1 Sarah Leigh Entity copied from Intellectual disability - microarray and sequencing v5.492
Early onset or syndromic epilepsy v4.177 ZNFX1 Sarah Leigh gene: ZNFX1 was added
gene: ZNFX1 was added to Early onset or syndromic epilepsy. Sources: Literature,Expert Review Amber
Q1_24_promote_green, Q1_24_NHS_review tags were added to gene: ZNFX1.
Mode of inheritance for gene: ZNFX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNFX1 were set to 33876776; 33872655
Phenotypes for gene: ZNFX1 were set to Immunodeficiency 91 and hyperinflammation, OMIM:619644; immunodeficiency 91 and hyperinflammation, MONDO:0030491
Intellectual disability v5.492 ZNFX1 Sarah Leigh Tag Q1_24_promote_green tag was added to gene: ZNFX1.
Tag Q1_24_NHS_review tag was added to gene: ZNFX1.
Intellectual disability v5.492 ZNFX1 Sarah Leigh Classified gene: ZNFX1 as Amber List (moderate evidence)
Intellectual disability v5.492 ZNFX1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be green on this panel.
Intellectual disability v5.492 ZNFX1 Sarah Leigh Gene: znfx1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.491 ZNFX1 Sarah Leigh edited their review of gene: ZNFX1: Added comment: ZNFX1 variants are associated with Immunodeficiency 91 and hyperinflammation (OMIM:619644). Neurological involvement has been observed in at least 11 patients with OMIM:619644 (PMID:33876776;33872655). Of these, four had seizures, three had developmental regression, and one had developmental delay. The incidence of neurological involvement could be higher, but the mortality of affected children is high; in PMID:33872655 11/15 cases were deceased, with seven of these not surviving to 3 months of age.; Changed rating: GREEN
Intellectual disability v5.491 ZNFX1 Sarah Leigh gene: ZNFX1 was added
gene: ZNFX1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: ZNFX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNFX1 were set to 33876776; 33872655
Phenotypes for gene: ZNFX1 were set to Immunodeficiency 91 and hyperinflammation, OMIM:619644; immunodeficiency 91 and hyperinflammation, MONDO:0030491
Review for gene: ZNFX1 was set to AMBER
Added comment: Sources: Literature
Intellectual disability v5.490 SRPX2 Arina Puzriakova Phenotypes for gene: SRPX2 were changed from Rolandic epilepsy, mental retardation, and speech dyspraxia, 300643 -3; ROLANDIC EPILEPSY WITH SPEECH DYSPRAXIA AND MENTAL RETARDATION X-LINKED (RESDX) to ?Rolandic epilepsy, impaired intellectual development, and speech dyspraxia, OMIM:300643
Early onset or syndromic epilepsy v4.176 SRPX2 Arina Puzriakova Phenotypes for gene: SRPX2 were changed from ?Rolandic epilepsy, mental retardation, and speech dyspraxia 300643 to ?Rolandic epilepsy, impaired intellectual development, and speech dyspraxia, OMIM:300643
Intellectual disability v5.489 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from Gene2Phenotype confirmed gene with ID HPO to Schimke immunoosseous dysplasia, OMIM:242900
Intellectual disability v5.488 SMARCAL1 Arina Puzriakova Publications for gene: SMARCAL1 were set to
Intellectual disability v5.487 SMARCAL1 Arina Puzriakova edited their review of gene: SMARCAL1: Changed phenotypes to: Schimke immunoosseous dysplasia, OMIM:242900
Intellectual disability v5.487 SMARCAL1 Arina Puzriakova reviewed gene: SMARCAL1: Rating: ; Mode of pathogenicity: None; Publications: 28796785, 20301550; Phenotypes: ; Mode of inheritance: None
Primary immunodeficiency or monogenic inflammatory bowel disease v4.193 SMARCAL1 Arina Puzriakova Added comment: Comment on phenotypes: Previous (overwritten) phenotypes: Schimke disease;Short stature, spondiloepiphyseal dysplasia, intrauterine growth retardation, nephropathy, bacterial, viral, fungal infections, may present as SCID, bone marrow failure;Combined immunodeficiencies with associated or syndromic features
Primary immunodeficiency or monogenic inflammatory bowel disease v4.193 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from Schimke immunoosseous dysplasia 242900; Schimke disease; Short stature, spondiloepiphyseal dysplasia, intrauterine growth retardation, nephropathy, bacterial, viral, fungal infections, may present as SCID, bone marrow failure; Combined immunodeficiencies with associated or syndromic features to Schimke immunoosseous dysplasia, OMIM:242900
Proteinuric renal disease v4.7 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from Schimke immunoosseous dysplasia #242900 to Schimke immunoosseous dysplasia, OMIM:242900
Fetal anomalies v3.138 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from SCHIMKE IMMUNOOSSEOUS DYSPLASIA to Schimke immunoosseous dysplasia, OMIM:242900
Unexplained young onset end-stage renal disease v3.39 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from Schimke immunoosseous dysplasia 242900 to Schimke immunoosseous dysplasia, OMIM:242900
Cytopenia - NOT Fanconi anaemia v3.24 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from Schimke immunoosseous dysplasia, 242900 to Schimke immunoosseous dysplasia, OMIM:242900
Skeletal dysplasia v4.53 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from Schimke immunoosseous dysplasia 242900; Schimke immunoosseous dysplasia 242900 to Schimke immunoosseous dysplasia, OMIM:242900
Unexplained kidney failure in young people v1.118 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from Schimke immunoosseous dysplasia 242900 to Schimke immunoosseous dysplasia, OMIM:242900
Cerebral vascular malformations v3.11 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from Schimke immunoosseous dysplasia 242900 to Schimke immunoosseous dysplasia, OMIM:242900
Intellectual disability v5.487 ZFX Sarah Leigh changed review comment from: A single ZFX variant has been associated with a neurodevelopmental disorder, that has a Rett syndrome-like phenotype disorder, in a 14 year old male. The ZFX variant was allelic with another X-linked variant in SHROOM4. These variants were inherited from the mother, who had random X inactivation pattern (PMID: 26740508).
PMID: 38325380 reports 11 ZFX variants in 18 subjects from 16 unrelated families (14 males and 4 females) with an X-linked neurodevelopmental disorder with recurrent facial gestalt. Seven variants were truncating and the remaining were missense variants within the Zinc finger array. In the pedigree of family 6 (figure 3, PMID: 38325380), it was apparent that there were female carriers of the ZFX variant (GRCh38 chrX: 24229396A>G, c.2438A>G, p.Tyr774Cys) with hyperparathyroidism and two affected males and one affected female, with the neurodevelopmental disorder. It appeared that skewed X-inactivation in the female carriers was responsible for the different phenotypic features. The association between ZFX variants and a novel neurodevelopmental disorder, was further supported by functional studies showing altered transcriptional activity in missense variants and altered behavior in a zebrafish loss-of-function model.; to: To date, germline variants in ZFX have not been associated with a phenotype in OMIM or Gen2Phen.
A single ZFX variant has been associated with a neurodevelopmental disorder, that has a Rett syndrome-like phenotype disorder, in a 14 year old male. The ZFX variant was allelic with another X-linked variant in SHROOM4. These variants were inherited from the mother, who had random X inactivation pattern (PMID: 26740508).
PMID: 38325380 reports 11 ZFX variants in 18 subjects from 16 unrelated families (14 males and 4 females) with an X-linked neurodevelopmental disorder with recurrent facial gestalt. Seven variants were truncating and the remaining were missense variants within the Zinc finger array. In the pedigree of family 6 (figure 3, PMID: 38325380), it was apparent that there were female carriers of the ZFX variant (GRCh38 chrX: 24229396A>G, c.2438A>G, p.Tyr774Cys) with hyperparathyroidism and two affected males and one affected female, with the neurodevelopmental disorder. It appeared that skewed X-inactivation in the female carriers was responsible for the different phenotypic features. The association between ZFX variants and a novel neurodevelopmental disorder, was further supported by functional studies showing altered transcriptional activity in missense variants and altered behavior in a zebrafish loss-of-function model.
Intellectual disability v5.487 ZFX Sarah Leigh Phenotypes for gene: ZFX were changed from to X-linked neurodevelopmental disorder with recurrent facial gestalt
Intellectual disability v5.486 ZFX Sarah Leigh Publications for gene: ZFX were set to 26350204; 26740508
Intellectual disability v5.486 ZFX Sarah Leigh Classified gene: ZFX as Amber List (moderate evidence)
Intellectual disability v5.486 ZFX Sarah Leigh Added comment: Comment on list classification: There is sufficient evidence for this gene to be green on this panel.
Intellectual disability v5.486 ZFX Sarah Leigh Gene: zfx has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.485 ZFX Sarah Leigh Tag Q1_24_promote_green tag was added to gene: ZFX.
Tag Q1_24_NHS_review tag was added to gene: ZFX.
Intellectual disability v5.485 ZFX Sarah Leigh reviewed gene: ZFX: Rating: GREEN; Mode of pathogenicity: None; Publications: 38325380; Phenotypes: X-linked neurodevelopmental disorder with recurrent facial gestalt; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Leber hereditary optic neuropathy v2.9 DNAJC30 Sarah Leigh commented on gene: DNAJC30: DNAJC30 has been demoted to Grey on this panel, because in the October 2022 test directory, the single gene test for DNAJC30 was removed from the Leber hereditary optic neuropathy (R42) clinical indication and was moved to the Optic neuropathy (R41) panel (this change was visible in the April 2023 data release of PanelApp).
Intellectual disability v5.485 AFF2 Arina Puzriakova Phenotypes for gene: AFF2 were changed from Mental retardation, X-linked, FRAXE type, 309548; FRAXE Syndrome; FRAGILE X-E MENTAL RETARDATION SYNDROME (FRAXE) to Intellectual developmental disorder, X-linked 109, OMIM:309548; Fragile XE syndrome (FRAXE)
Intellectual disability v5.484 PPP2R2B Arina Puzriakova Publications for gene: PPP2R2B were set to
Intellectual disability v5.483 PPP2R2B Arina Puzriakova edited their review of gene: PPP2R2B: Added comment: - PMID: 25356899 (2014) - missense variant (c.413G>C, p.Arg138Pro) in the PPP2R2B gene identified in a 7-year-old boy with moderate ID, intractable seizures and autistic features. Otherwise limited information provided.

Comment on publications: PMID: 25356899 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques; Changed publications to: 25356899; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.483 NXF5 Arina Puzriakova Classified gene: NXF5 as Red List (low evidence)
Intellectual disability v5.483 NXF5 Arina Puzriakova Added comment: Comment on list classification: Maintaining Red rating as evidence linking this gene to ID is not definitive since patient variants have involved multiple genes and no cases of SNVs in the NXF5 gene have been reported.
Intellectual disability v5.483 NXF5 Arina Puzriakova Gene: nxf5 has been classified as Red List (Low Evidence).
Intellectual disability v5.482 NXF5 Arina Puzriakova Added comment: Comment on publications: PMID: 23675524 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v5.482 NXF5 Arina Puzriakova Publications for gene: NXF5 were set to 11566096; 26350204; 23675524; 22030050; 20096387
Intellectual disability v5.481 NXF5 Arina Puzriakova Publications for gene: NXF5 were set to 11566096; 26350204; 23675524; 22030050
Intellectual disability v5.480 NXF5 Arina Puzriakova reviewed gene: NXF5: Rating: ; Mode of pathogenicity: None; Publications: 11566096, 20096387, 22030050, 23675524; Phenotypes: ; Mode of inheritance: None
Cytopenia - NOT Fanconi anaemia v3.23 TUBA8 Achchuthan Shanmugasundram edited their review of gene: TUBA8: Changed publications to: 34704371
Cytopenia - NOT Fanconi anaemia v3.23 TUBA8 Achchuthan Shanmugasundram commented on gene: TUBA8: Six unrelated individuals were identified with TUBA8 missense variants in a large cohort of blood donors with mild thrombocytopenia and these individuals were generally asymptomatic and one had menorrhagia. There is also some functional data available.
Cytopenia - NOT Fanconi anaemia v3.23 TUBA8 Achchuthan Shanmugasundram Classified gene: TUBA8 as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v3.23 TUBA8 Achchuthan Shanmugasundram Gene: tuba8 has been classified as Amber List (Moderate Evidence).
Cytopenia - NOT Fanconi anaemia v3.22 TUBA8 Achchuthan Shanmugasundram Phenotypes for gene: TUBA8 were changed from Macrothrombocytopenia, isolated, 2, autosomal dominant to Macrothrombocytopenia, isolated, 2, autosomal dominant, OMIM:619840
Cytopenia - NOT Fanconi anaemia v3.21 TUBA8 Achchuthan Shanmugasundram reviewed gene: TUBA8: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Macrothrombocytopenia, isolated, 2, autosomal dominant, OMIM:619840; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v3.137 NHEJ1 Arina Puzriakova Phenotypes for gene: NHEJ1 were changed from Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation 611291 to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, OMIM:611291
Severe microcephaly v4.65 NHEJ1 Arina Puzriakova Phenotypes for gene: NHEJ1 were changed from Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation 611291 to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, OMIM:611291
Primary immunodeficiency or monogenic inflammatory bowel disease v4.192 NHEJ1 Arina Puzriakova Added comment: Comment on phenotypes: Previous (overwritten) phenotypes: Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation;Severe combined immunodeficiency with microcephaly, growth retardation and sensitivity to ionizing radiation, 611291;T-B- SCID;T-B+ SCID;Combined immunodeficiency;Cernunnos/XLF deficiency;Nl NK, radiation sensitive, microcephaly;Immunodeficiencies affecting cellular and humoral immunity
Primary immunodeficiency or monogenic inflammatory bowel disease v4.192 NHEJ1 Arina Puzriakova Phenotypes for gene: NHEJ1 were changed from Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation; Severe combined immunodeficiency with microcephaly, growth retardation and sensitivity to ionizing radiation, 611291; T-B- SCID; T-B+ SCID; Combined immunodeficiency; Cernunnos/XLF deficiency; Nl NK, radiation sensitive, microcephaly; Immunodeficiencies affecting cellular and humoral immunity to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, OMIM:611291
Intellectual disability v5.480 NHEJ1 Arina Puzriakova Phenotypes for gene: NHEJ1 were changed from Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, OMIM:611291
Intellectual disability v5.479 KIRREL3 Arina Puzriakova Added comment: Comment on publications: New publication added - PMID:25902260. This paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques

Provides review of cases in literature and functional studies demonstrating brain expressed proteins that interact with the KIRREL3 using yeast two-hybrid screening supporting a link to neurological and cognitive disorders. They also show KIRREL3 localisation to the Golgi complex and synaptic secretary vesicles.
Intellectual disability v5.479 KIRREL3 Arina Puzriakova Publications for gene: KIRREL3 were set to 22965935; 19012874; 29271092; 37605258; 33853164
Monogenic diabetes v2.57 SMPD4 Achchuthan Shanmugasundram Classified gene: SMPD4 as Amber List (moderate evidence)
Monogenic diabetes v2.57 SMPD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there are five individuals from three unrelated families with biallelic loss-of-function SMPD4 variants. They developed insulin-dependent diabetes, besides presenting with a severe neurodevelopmental disorder and microcephaly. In addition, review of past reports showed 27% of patients had insulin-dependent diabetes.

This gene can therefore be promoted to green rating in the next GMS review.
Monogenic diabetes v2.57 SMPD4 Achchuthan Shanmugasundram Gene: smpd4 has been classified as Amber List (Moderate Evidence).
Monogenic diabetes v2.56 SMPD4 Achchuthan Shanmugasundram Phenotypes for gene: SMPD4 were changed from NDD, microcephaly and diabetes to Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies, OMIM:618622; type 1 diabetes mellitus, MONDO:0005147
Monogenic diabetes v2.55 SMPD4 Achchuthan Shanmugasundram Publications for gene: SMPD4 were set to PMID: 36732302
Monogenic diabetes v2.54 SMPD4 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: SMPD4.
Monogenic diabetes v2.54 SMPD4 Achchuthan Shanmugasundram edited their review of gene: SMPD4: Changed publications to: 36732302
Monogenic diabetes v2.54 SMPD4 Achchuthan Shanmugasundram reviewed gene: SMPD4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies, OMIM:618622, type 1 diabetes mellitus, MONDO:0005147; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.478 KIF26B Arina Puzriakova Phenotypes for gene: KIF26B were changed from to Progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis
Intellectual disability v5.477 INTS1 Arina Puzriakova Phenotypes for gene: INTS1 were changed from Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies, 618571; Hypotonia; Global developmental delay; Cataract; Abnormality of the skeletal system to Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies, OMIM:618571
Intellectual disability v5.476 INTS1 Arina Puzriakova Publications for gene: INTS1 were set to 28542170; 30622326; 17544522
Optic neuropathy v4.22 INTS8 Arina Puzriakova Phenotypes for gene: INTS8 were changed from Optic atrophy to ?Neurodevelopmental disorder with cerebellar hypoplasia and spasticity, OMIM:618572
Intellectual disability v5.475 INTS8 Arina Puzriakova Phenotypes for gene: INTS8 were changed from to ?Neurodevelopmental disorder with cerebellar hypoplasia and spasticity, OMIM:618572
Hereditary neuropathy or pain disorder v3.83 SPG7 Williams Kirsty reviewed gene: SPG7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: sensory neuropathy, motor neuropathy, lower-limb neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.474 EFNB1 Arina Puzriakova Classified gene: EFNB1 as Amber List (moderate evidence)
Intellectual disability v5.474 EFNB1 Arina Puzriakova Added comment: Comment on list classification: Upgrading from Red to Amber as a literature search did reveal evidence to suggest that some individuals may develop intellectual deficits. However, in most affected cases this was a mild presentation and there are more prominent and recognisable features observed in the general group of EFNB1-related cases which are more likely to inform diagnostic testing (e.g. craniosynostosis and clefting).
Intellectual disability v5.474 EFNB1 Arina Puzriakova Gene: efnb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.473 EFNB1 Arina Puzriakova Added comment: Comment on publications: PMID: 25679214 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v5.473 EFNB1 Arina Puzriakova Publications for gene: EFNB1 were set to 23335590
Intellectual disability v5.472 EFNB1 Arina Puzriakova reviewed gene: EFNB1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23335590, 25679214, 27650623, 31088393, 24520368; Phenotypes: Craniofrontonasal dysplasia, OMIM:304110; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early onset or syndromic epilepsy v4.175 SLC5A6 Sarah Leigh Publications for gene: SLC5A6 were set to 27904971; 31392107; 31754459; 23104561; 29669219
Early onset or syndromic epilepsy v4.174 SLC5A6 Sarah Leigh Classified gene: SLC5A6 as Red List (low evidence)
Early onset or syndromic epilepsy v4.174 SLC5A6 Sarah Leigh Gene: slc5a6 has been classified as Red List (Low Evidence).
Early onset or syndromic epilepsy v4.173 SLC5A6 Sarah Leigh edited their review of gene: SLC5A6: Added comment: There is insufficient evidence of epilepsy associated with SLC5A6 variants (PMID: 35013551; 38036278; 38012394; 37391029; 31754459) for this gene to be rated as Amber on the Early onset or syndromic epilepsy, therefore it have been demoted to Red.; Changed rating: RED
Early onset or syndromic epilepsy v4.173 SLC5A6 Sarah Leigh Tag watchlist was removed from gene: SLC5A6.
Tag for-review was removed from gene: SLC5A6.
Tag to_be_confirmed_NHSE was removed from gene: SLC5A6.
Severe microcephaly v4.64 AKT3 Sarah Leigh reviewed gene: AKT3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Severe microcephaly v4.64 AKT3 Sarah Leigh Classified gene: AKT3 as Amber List (moderate evidence)
Severe microcephaly v4.64 AKT3 Sarah Leigh Gene: akt3 has been classified as Amber List (Moderate Evidence).
Optic neuropathy v4.21 DNAJC30 Sarah Leigh Tag gene-checked was removed from gene: DNAJC30.
Leber hereditary optic neuropathy v2.9 DNAJC30 Sarah Leigh Publications for gene: DNAJC30 were set to 33465056; 35091433
Early onset or syndromic epilepsy v4.173 ANK2 Achchuthan Shanmugasundram Classified gene: ANK2 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.173 ANK2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Early onset or syndromic epilepsy v4.173 ANK2 Achchuthan Shanmugasundram Gene: ank2 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.172 ANK2 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: ANK2.
Early onset or syndromic epilepsy v4.172 ANK2 Achchuthan Shanmugasundram changed review comment from: PMID:37195288 reported 12 individuals with heterozygous de novo LoF variants in ANK2, of which seven patients had early-onset epilepsy, with an onset of epilepsy before the age of 2 years. 4 patients had neonatal onset epilepsy. 1 patient had bilateral tonic-clinic seizures at 3 years of age. Another patient had focal epilepsy with focal motor seizures.
Sources: Literature; to: PMID:37195288 reported 12 individuals with heterozygous de novo LoF variants in ANK2 and with a complex neurodevelopmental disorder comprising intellectual disability, autism spectrum disorder and early-onset epilepsy. Seven of 12 patients had early-onset epilepsy, with an onset of epilepsy before the age of 2 years. 4 patients had neonatal onset epilepsy. 1 patient had bilateral tonic-clinic seizures at 3 years of age. Another patient had focal epilepsy with focal motor seizures.
Sources: Literature
Early onset or syndromic epilepsy v4.172 ANK2 Achchuthan Shanmugasundram gene: ANK2 was added
gene: ANK2 was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: ANK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANK2 were set to 37195288
Phenotypes for gene: ANK2 were set to neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027
Review for gene: ANK2 was set to GREEN
Added comment: PMID:37195288 reported 12 individuals with heterozygous de novo LoF variants in ANK2, of which seven patients had early-onset epilepsy, with an onset of epilepsy before the age of 2 years. 4 patients had neonatal onset epilepsy. 1 patient had bilateral tonic-clinic seizures at 3 years of age. Another patient had focal epilepsy with focal motor seizures.
Sources: Literature
Retinal disorders v4.81 MT-TL1 Achchuthan Shanmugasundram Classified gene: MT-TL1 as Amber List (moderate evidence)
Retinal disorders v4.81 MT-TL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Retinal disorders v4.81 MT-TL1 Achchuthan Shanmugasundram Gene: mt-tl1 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.80 MT-TL1 Achchuthan Shanmugasundram Phenotypes for gene: MT-TL1 were changed from Retinitis pigmentosa to Retinal dystrophy, HP:0000556; Macular dystrophy, HP:0007754
Retinal disorders v4.79 MT-TL1 Achchuthan Shanmugasundram Publications for gene: MT-TL1 were set to
Retinal disorders v4.78 MT-TL1 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: MT-TL1.
Tag Q1_24_NHS_review tag was added to gene: MT-TL1.
Retinal disorders v4.78 MT-TL1 Achchuthan Shanmugasundram reviewed gene: MT-TL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18332310, 23806424; Phenotypes: Retinal dystrophy, HP:0000556, Macular dystrophy, HP:0007754; Mode of inheritance: MITOCHONDRIAL
Retinal disorders v4.78 TTC21B Achchuthan Shanmugasundram Classified gene: TTC21B as Amber List (moderate evidence)
Retinal disorders v4.78 TTC21B Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Siying Lin, an additional case has been seen with the inherited retinal disease service at Moorfields Eye Hospital and was reported with a homozygous variant in 100k genome project.

As there are three cases reported with retinal dystrophy, this gene can be promoted to green rating in the next GMS review.
Retinal disorders v4.78 TTC21B Achchuthan Shanmugasundram Gene: ttc21b has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.77 TTC21B Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: TTC21B.
Tag Q1_24_NHS_review tag was added to gene: TTC21B.
Retinal disorders v4.77 TTC21B Achchuthan Shanmugasundram edited their review of gene: TTC21B: Changed rating: GREEN
Retinal disorders v4.77 JAG1 Achchuthan Shanmugasundram Classified gene: JAG1 as Amber List (moderate evidence)
Retinal disorders v4.77 JAG1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Retinal disorders v4.77 JAG1 Achchuthan Shanmugasundram Gene: jag1 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.76 JAG1 Achchuthan Shanmugasundram Phenotypes for gene: JAG1 were changed from Alagille syndrome 1, OMIM:118450 to Alagille syndrome 1, OMIM:118450; exudative vitreoretinopathy, MONDO:0019516
Retinal disorders v4.75 JAG1 Achchuthan Shanmugasundram Publications for gene: JAG1 were set to
Retinal disorders v4.74 JAG1 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: JAG1.
Tag Q1_24_NHS_review tag was added to gene: JAG1.
Retinal disorders v4.74 JAG1 Achchuthan Shanmugasundram reviewed gene: JAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31273345, 34185059; Phenotypes: Alagille syndrome 1, OMIM:118450, exudative vitreoretinopathy, MONDO:0019516; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb disorders v4.16 EFNB1 Arina Puzriakova Phenotypes for gene: EFNB1 were changed from Craniofrontonasal syndrome, 304110 to Craniofrontonasal dysplasia, OMIM:304110
Skeletal dysplasia v4.52 EFNB1 Arina Puzriakova Phenotypes for gene: EFNB1 were changed from Craniofrontonasal dysplasia 304110 to Craniofrontonasal dysplasia, OMIM:304110
Fetal anomalies v3.136 EFNB1 Arina Puzriakova Phenotypes for gene: EFNB1 were changed from CRANIOFRONTONASAL SYNDROME to Craniofrontonasal dysplasia, OMIM:304110
Clefting v4.106 EFNB1 Arina Puzriakova Phenotypes for gene: EFNB1 were changed from CRANIOFRONTONASAL SYNDROME; CFNS to Craniofrontonasal dysplasia, OMIM:304110
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.178 EFNB1 Arina Puzriakova Phenotypes for gene: EFNB1 were changed from 304110; Craniofrontonasal syndrome 304110 to Craniofrontonasal dysplasia, OMIM:304110
Intellectual disability v5.472 EFNB1 Arina Puzriakova Phenotypes for gene: EFNB1 were changed from Gene2Phenotype confirmed gene with ID HPO to Craniofrontonasal dysplasia, OMIM:304110
Intellectual disability v5.471 EFNB1 Arina Puzriakova Publications for gene: EFNB1 were set to
Intellectual disability v5.470 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Short-rib thoracic dysplasia 3 with or without polydactyly, 613091 to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Skeletal ciliopathies v3.21 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Short-rib thoracic dysplasia 3 with or without polydactyly; Thoracic and Cranioectodermal Dysplasia (Skeletal Ciliopathy) 15 Gene Panel; Jeune syndrome; Short-rib thoracic dysplasia 3 with or without polydactyly, 613091 to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Renal ciliopathies v3.4 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Short-rib thoracic dysplasia 3 with or without polydactyly; Thoracic and Cranioectodermal Dysplasia (Skeletal Ciliopathy) 15 Gene Panel; Jeune syndrome; Short-rib thoracic dysplasia 3 with or without polydactyly, 613091 to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Rare multisystem ciliopathy disorders v1.169 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Short-rib thoracic dysplasia 3 with or without polydactyly, 613091; Thoracic and Cranioectodermal Dysplasia (Skeletal Ciliopathy) 15 Gene Panel; Jeune syndrome; Short-rib thoracic dysplasia 3 with or without polydactyly to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Clefting v4.105 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from SHORT-RIB THORACIC DYSPLASIA 3 WITH OR WITHOUT POLYDACTYLY; SRTD3 to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Unexplained young onset end-stage renal disease v3.38 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Thoracic and Cranioectodermal Dysplasia (Skeletal Ciliopathy) 15 Gene Panel; Short-rib thoracic dysplasia 3 with or without polydactyly, 613091; Short-rib thoracic dysplasia 3 with or without polydactyly; Jeune syndrome to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Skeletal dysplasia v4.51 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Short rib polydactyly syndrome (SRPS) type 3 with or without polydactyly, 613091; Short rib polydactyly syndrome (SRPS) type 1/3 (Saldino-Noonan/Verma-Naumoff); Asphyxiating thoracic dystrophy 3, 613091Short rib-polydactyly syndrome, type III, 263510Short rib-polydactyly syndrome, type IIB, 615087 to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Primary ciliary disorders v1.41 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from ciliopathies to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Ductal plate malformation v1.28 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Short-rib thoracic dysplasia 3 with or without polydactyly (613091) to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Limb disorders v4.15 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Short-rib thoracic dysplasia 3 with or without polydactyly 613091; Polydactyly to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Thoracic dystrophies v1.19 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Asphyxiating thoracic dystrophy 3, 613091Short rib-polydactyly syndrome, type III, 263510Short rib-polydactyly syndrome, type IIB, 615087 to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Intellectual disability v5.469 KCNA1 Achchuthan Shanmugasundram Phenotypes for gene: KCNA1 were changed from Episodic ataxia/myokymia syndrome, OMIM:160120 to Episodic ataxia/myokymia syndrome, OMIM:160120
Intellectual disability v5.469 KCNA1 Achchuthan Shanmugasundram Phenotypes for gene: KCNA1 were changed from Episodic ataxia/myokymia syndrome, 160120 to Episodic ataxia/myokymia syndrome, OMIM:160120
Intellectual disability v5.468 KCNA1 Achchuthan Shanmugasundram Publications for gene: KCNA1 were set to 27730449; 30055040; 34778950
Intellectual disability v5.468 KCNA1 Achchuthan Shanmugasundram Publications for gene: KCNA1 were set to 27730449
Intellectual disability v5.467 KCNA1 Achchuthan Shanmugasundram Mode of inheritance for gene: KCNA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.466 KCNA1 Achchuthan Shanmugasundram Classified gene: KCNA1 as Amber List (moderate evidence)
Intellectual disability v5.466 KCNA1 Achchuthan Shanmugasundram Gene: kcna1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.465 KCNA1 Achchuthan Shanmugasundram reviewed gene: KCNA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30055040, 34778950; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v4.171 KCNA1 Achchuthan Shanmugasundram changed review comment from: PMID:30055040 reported the identification of three heterozygous de novo variants (p.Pro403Ser, p.Pro405Leu, and p.Pro405Ser) in the pore region found in four patients from three families with severe developmental and epileptic encephalopathy (DEE). PMID:34778950 reported the comparison of these variants with a de novo variant in the voltage sensor (p.Ala261Ter) that was identified in two patients with mild, carbamazepine-responsive, focal epilepsy.

PMID:32316562 reported from the analyses of 47 deleterious KCNA1 variants that were identified from previous literature and genetic archives that epilepsy or seizure-related variants tend to cluster in the S1,S2,S5,S6 transmembrane domains and in the pore domain.

PMID:31586945 reported the identification of a homozygous KCNA1 variant (p.Val368Leu) in a patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy. This variant involves a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG).

Monoallelic variants in this gene have only been associated with episodic ataxia/ myokymia syndrome (MIM #160120) in OMIM, but not with epilepsy/ epileptic encephalopathy, and biallelic variants are not reported with any phenotypes in OMIM. Both monoallelic and biallelic variants have been associated with KCNA1-related epileptic encephalopathy in Gene2Phenotype (with 'limited' rating in the DD panel for both MOIs).; to: PMID:30055040 reported the identification of three heterozygous de novo variants (p.Pro403Ser, p.Pro405Leu, and p.Pro405Ser) in the pore region found in four patients from three families with severe developmental and epileptic encephalopathy (DEE). PMID:34778950 reported the comparison of the three variants from PMID:30055040 with a de novo variant in the voltage sensor (p.Ala261Ter) that was identified in two patients with mild, carbamazepine-responsive, focal epilepsy.

PMID:32316562 reported from the analyses of 47 deleterious KCNA1 variants that were identified from previous literature and genetic archives that epilepsy or seizure-related variants tend to cluster in the S1,S2,S5,S6 transmembrane domains and in the pore domain.

PMID:31586945 reported the identification of a homozygous KCNA1 variant (p.Val368Leu) in a patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy. This variant involves a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG).

Monoallelic variants in this gene have only been associated with episodic ataxia/ myokymia syndrome (MIM #160120) in OMIM, but not with epilepsy/ epileptic encephalopathy, and biallelic variants are not reported with any phenotypes in OMIM. Both monoallelic and biallelic variants have been associated with KCNA1-related epileptic encephalopathy in Gene2Phenotype (with 'limited' rating in the DD panel for both MOIs).
Early onset or syndromic epilepsy v4.171 KCNA1 Achchuthan Shanmugasundram changed review comment from: PMID:32316562 reported from the analyses of 47 deleterious KCNA1 variants that were identified from previous literature and genetic archives that epilepsy or seizure-related variants tend to cluster in the S1,S2,S5,S6 transmembrane domains and in the pore domain.

PMID:34778950 reported the identification of three heterozygous de novo variants (p.Pro403Ser, p.Pro405Leu, and p.Pro405Ser) in the pore region found in four patients from three families with severe developmental and epileptic encephalopathy (DEE) and a de novo variant in the voltage sensor (p.Ala261Ter) identified in two patients with mild, carbamazepine-responsive, focal epilepsy.

PMID:31586945 reported the identification of a homozygous KCNA1 variant (p.Val368Leu) in a patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy. This variant involves a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG).

Monoallelic variants in this gene have only been associated with episodic ataxia/ myokymia syndrome (MIM #160120) in OMIM, but not with epilepsy/ epileptic encephalopathy, and biallelic variants are not reported with any phenotypes in OMIM. Both monoallelic and biallelic variants have been associated with KCNA1-related epileptic encephalopathy in Gene2Phenotype (with 'limited' rating in the DD panel for both MOIs).; to: PMID:30055040 reported the identification of three heterozygous de novo variants (p.Pro403Ser, p.Pro405Leu, and p.Pro405Ser) in the pore region found in four patients from three families with severe developmental and epileptic encephalopathy (DEE). PMID:34778950 reported the comparison of these variants with a de novo variant in the voltage sensor (p.Ala261Ter) that was identified in two patients with mild, carbamazepine-responsive, focal epilepsy.

PMID:32316562 reported from the analyses of 47 deleterious KCNA1 variants that were identified from previous literature and genetic archives that epilepsy or seizure-related variants tend to cluster in the S1,S2,S5,S6 transmembrane domains and in the pore domain.

PMID:31586945 reported the identification of a homozygous KCNA1 variant (p.Val368Leu) in a patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy. This variant involves a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG).

Monoallelic variants in this gene have only been associated with episodic ataxia/ myokymia syndrome (MIM #160120) in OMIM, but not with epilepsy/ epileptic encephalopathy, and biallelic variants are not reported with any phenotypes in OMIM. Both monoallelic and biallelic variants have been associated with KCNA1-related epileptic encephalopathy in Gene2Phenotype (with 'limited' rating in the DD panel for both MOIs).
Early onset or syndromic epilepsy v4.171 KCNA1 Achchuthan Shanmugasundram Classified gene: KCNA1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.171 KCNA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of monoallelic KCNA1 variants with epilepsy/ epileptic encephalopathy and hence this gene can be promoted to green rating in the next GMS review.
Early onset or syndromic epilepsy v4.171 KCNA1 Achchuthan Shanmugasundram Gene: kcna1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.170 KCNA1 Achchuthan Shanmugasundram Publications for gene: KCNA1 were set to 29056246; 11026449; 9581771; 24578548; 31586945; 32316562; 34778950
Early onset or syndromic epilepsy v4.169 KCNA1 Achchuthan Shanmugasundram edited their review of gene: KCNA1: Changed publications to: 30055040, 31586945, 32316562, 34778950
Early onset or syndromic epilepsy v4.169 KCNA1 Achchuthan Shanmugasundram changed review comment from: PMID:32316562 reported from the analyses of 47 deleterious KCNA1 variants that were identified from previous literature and genetic archives that epilepsy or seizure-related variants tend to cluster in the S1,S2,S5,S6 transmembrane domains and in the pore domain.

PMID:34778950 reported the identification of three heterozygous de novo variants (p.Pro403Ser, p.Pro405Leu, and p.Pro405Ser) in the pore region found in four patients with severe developmental and epileptic encephalopathy (DEE) and a de novo variant in the voltage sensor (p.Ala261Ter) identified in two patients with mild, carbamazepine-responsive, focal epilepsy.

PMID:31586945 reported the identification of a homozygous KCNA1 variant (p.Val368Leu) in a patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy. This variant involves a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG).

Monoallelic variants in this gene have only been associated with episodic ataxia/ myokymia syndrome (MIM #160120) in OMIM, but not with epilepsy/ epileptic encephalopathy, and biallelic variants are not reported with any phenotypes in OMIM. Both monoallelic and biallelic variants have been associated with KCNA1-related epileptic encephalopathy in Gene2Phenotype (with 'limited' rating in the DD panel for both MOIs).; to: PMID:32316562 reported from the analyses of 47 deleterious KCNA1 variants that were identified from previous literature and genetic archives that epilepsy or seizure-related variants tend to cluster in the S1,S2,S5,S6 transmembrane domains and in the pore domain.

PMID:34778950 reported the identification of three heterozygous de novo variants (p.Pro403Ser, p.Pro405Leu, and p.Pro405Ser) in the pore region found in four patients from three families with severe developmental and epileptic encephalopathy (DEE) and a de novo variant in the voltage sensor (p.Ala261Ter) identified in two patients with mild, carbamazepine-responsive, focal epilepsy.

PMID:31586945 reported the identification of a homozygous KCNA1 variant (p.Val368Leu) in a patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy. This variant involves a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG).

Monoallelic variants in this gene have only been associated with episodic ataxia/ myokymia syndrome (MIM #160120) in OMIM, but not with epilepsy/ epileptic encephalopathy, and biallelic variants are not reported with any phenotypes in OMIM. Both monoallelic and biallelic variants have been associated with KCNA1-related epileptic encephalopathy in Gene2Phenotype (with 'limited' rating in the DD panel for both MOIs).
Early onset or syndromic epilepsy v4.169 KCNA1 Achchuthan Shanmugasundram Phenotypes for gene: KCNA1 were changed from Episodic ataxia/myokymia syndrome 160120 to Episodic ataxia/ myokymia syndrome, OMIM:160120; epilepsy, MONDO:0005027
Early onset or syndromic epilepsy v4.168 KCNA1 Achchuthan Shanmugasundram Publications for gene: KCNA1 were set to 29056246; 11026449; 9581771; 24578548
Early onset or syndromic epilepsy v4.167 KCNA1 Achchuthan Shanmugasundram Mode of inheritance for gene: KCNA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v4.166 KCNA1 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: KCNA1.
Tag Q1_24_NHS_review tag was added to gene: KCNA1.
Early onset or syndromic epilepsy v4.166 KCNA1 Achchuthan Shanmugasundram reviewed gene: KCNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31586945, 32316562, 34778950; Phenotypes: epilepsy, MONDO:0005027; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
DDG2P v3.79 TAF4 Achchuthan Shanmugasundram Tag curated_removed was removed from gene: TAF4.
DDG2P v3.79 PBX1 Achchuthan Shanmugasundram Tag curated_removed was removed from gene: PBX1.
Retinal disorders v4.74 SAMD7 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: SAMD7.
Tag Q1_24_NHS_review tag was added to gene: SAMD7.
Retinal disorders v4.74 SAMD7 Achchuthan Shanmugasundram changed review comment from: Comment on phenotypes: As the evidence for this gene-disease association has been very recent, biallelic variants in SMAD7 has not yet been associated with retinal phenotypes either in OMIM or in Gene2Phenotype.; to: Comment on phenotypes: As the evidence for this gene-disease association has been very recent, biallelic variants in SAMD7 have not yet been associated with retinal phenotypes either in OMIM or in Gene2Phenotype.
Retinal disorders v4.74 SAMD7 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Siying Lin, there are six unrelated families identified with biallelic SMAD7 variants. Of these patients from four families had macular dystrophy with cone dysfunction, while patients from two families had macular dystrophy without cone dysfunction. Hence, this gene should be promoted to green rating in the next GMS review.; to: Comment on list classification: As reviewed by Siying Lin, there are six unrelated families identified with biallelic SAMD7 variants. Of these, patients from four families had macular dystrophy with cone dysfunction, while patients from two other families had macular dystrophy without cone dysfunction. Hence, this gene should be promoted to green rating in the next GMS review.
Retinal disorders v4.74 SAMD7 Achchuthan Shanmugasundram Classified gene: SAMD7 as Amber List (moderate evidence)
Retinal disorders v4.74 SAMD7 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Siying Lin, there are six unrelated families identified with biallelic SMAD7 variants. Of these patients from four families had macular dystrophy with cone dysfunction, while patients from two families had macular dystrophy without cone dysfunction. Hence, this gene should be promoted to green rating in the next GMS review.
Retinal disorders v4.74 SAMD7 Achchuthan Shanmugasundram Gene: samd7 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.73 SAMD7 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: As the evidence for this gene-disease association has been very recent, biallelic variants in SMAD7 has not yet been associated with retinal phenotypes either in OMIM or in Gene2Phenotype.
Retinal disorders v4.73 SAMD7 Achchuthan Shanmugasundram Phenotypes for gene: SAMD7 were changed from Macular dystrophy; cone dystrophy to macular dystrophy, retinal, MONDO:0031166; Congenital stationary cone dysfunction, HP:0030637
Retinal disorders v4.72 SAMD7 Achchuthan Shanmugasundram Publications for gene: SAMD7 were set to PMID: 38272031
Retinal disorders v4.71 SAMD7 Achchuthan Shanmugasundram reviewed gene: SAMD7: Rating: GREEN; Mode of pathogenicity: None; Publications: 38272031; Phenotypes: macular dystrophy, retinal, MONDO:0031166, Congenital stationary cone dysfunction, HP:0030637; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.465 CTNND2 Arina Puzriakova commented on gene: CTNND2
Intellectual disability v5.465 CTNND2 Arina Puzriakova Phenotypes for gene: CTNND2 were changed from to CTNND2-related neurodevelopmental disorder
Intellectual disability v5.464 CTNND2 Arina Puzriakova Mode of inheritance for gene: CTNND2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v5.463 CLIC2 Arina Puzriakova Tag disputed tag was added to gene: CLIC2.
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2C Sarah Leigh Tag Q1_22_NHS_review tag was added to gene: RNASEH2C.
Tag Q1_24_promote_green tag was added to gene: RNASEH2C.
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2C Sarah Leigh Deleted their comment
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2C Sarah Leigh Deleted their comment
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2C Sarah Leigh Deleted their comment
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2C Sarah Leigh Deleted their comment
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2C Sarah Leigh Deleted their comment
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2B Sarah Leigh Tag Q1_24_promote_green tag was added to gene: RNASEH2B.
Tag Q1_24_NHS_review tag was added to gene: RNASEH2B.
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2B Sarah Leigh Deleted their comment
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2B Sarah Leigh Deleted their comment
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2B Sarah Leigh Deleted their comment
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2B Sarah Leigh Deleted their comment
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2B Sarah Leigh Deleted their comment
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2A Sarah Leigh Deleted their comment
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2A Sarah Leigh Deleted their comment
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2A Sarah Leigh Deleted their comment
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2A Sarah Leigh Deleted their comment
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2A Sarah Leigh Deleted their comment
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2A Sarah Leigh Tag Q1_24_promote_green tag was added to gene: RNASEH2A.
Tag Q1_24_NHS_review tag was added to gene: RNASEH2A.
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2C Sarah Leigh edited their review of gene: RNASEH2C: Added comment: Saikat Santra (Birmingham Children's Hospital)(23 Jan 2024), has suggested that this gene should be green on this panel - R98.; Changed rating: GREEN
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2B Sarah Leigh edited their review of gene: RNASEH2B: Added comment: Saikat Santra (Birmingham Children's Hospital)(23 Jan 2024), has suggested that this gene should be green on this panel - R98.; Changed rating: GREEN
Likely inborn error of metabolism - targeted testing not possible v4.131 RNASEH2A Sarah Leigh edited their review of gene: RNASEH2A: Added comment: Saikat Santra (Birmingham Children's Hospital)(23 Jan 2024), has suggested that this gene should be green on this panel - R98.; Changed rating: GREEN
Palmoplantar keratodermas v3.24 PEX7 Sarah Leigh Tag Q1_24_demote_red tag was added to gene: PEX7.
Palmoplantar keratodermas v3.24 PEX7 Sarah Leigh reviewed gene: PEX7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Palmoplantar keratodermas v3.24 MVK Sarah Leigh reviewed gene: MVK: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Palmoplantar keratodermas v3.24 MVK Sarah Leigh Tag Q1_24_demote_red tag was added to gene: MVK.
Tag Q1_24_expert_review tag was added to gene: MVK.
Palmoplantar keratodermas v3.24 CLDN1 Sarah Leigh Tag Q1_24_demote_red tag was added to gene: CLDN1.
Tag Q1_24_expert_review tag was added to gene: CLDN1.
Palmoplantar keratodermas v3.24 CLDN1 Sarah Leigh reviewed gene: CLDN1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Palmoplantar keratodermas v3.24 CASP14 Sarah Leigh edited their review of gene: CASP14: Changed rating: RED
Palmoplantar keratodermas v3.24 CASP14 Sarah Leigh reviewed gene: CASP14: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Palmoplantar keratodermas v3.24 CASP14 Sarah Leigh Tag Q1_24_demote_red tag was added to gene: CASP14.
Tag Q1_24_expert_review tag was added to gene: CASP14.
Intellectual disability v5.463 CLIC2 Arina Puzriakova Phenotypes for gene: CLIC2 were changed from Intellectual developmental disorder, X-linked syndromic 32 , OMIM:300886 to Intellectual developmental disorder, X-linked syndromic 32, OMIM:300886
Hydrocephalus v4.4 CLIC2 Arina Puzriakova Phenotypes for gene: CLIC2 were changed from ?Mental retardation, X-linked, syndromic 32, OMIM:300886 to Intellectual developmental disorder, X-linked syndromic 32, OMIM:300886
Intellectual disability v5.462 CLIC2 Arina Puzriakova Phenotypes for gene: CLIC2 were changed from Mental retardation, X-linked, syndromic 32, 300886 to Intellectual developmental disorder, X-linked syndromic 32 , OMIM:300886
Intellectual disability v5.461 ARHGEF6 Arina Puzriakova changed review comment from: PMID: 22511880 (2012) - a variant in the ARHGEF6 gene (p.I444N) was identified in a male patient with autism. However, this individual harboured variants in other genes (UBE3B) that were likely to explain their phenotype so conclusions about the consequence of the ARHGEF6 variant cannot be made in this case.

Comment on publications: PMID: 22511880 (2012) was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques; to: PMID: 22511880 (2012) - a variant in the ARHGEF6 gene (p.I444N) was identified in a male patient with autism. However, this individual harboured variants in other genes (UBE3B) that were likely to explain their phenotype so conclusions about the consequence of the ARHGEF6 variant cannot be made in this case.

Comment on publications: PMIDs: 22511880 (2012) and 26177020 (2015) were identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v5.461 ARHGEF6 Arina Puzriakova Publications for gene: ARHGEF6 were set to 21989057; 20861843; 17304053; 11017088; 26177020; 22511880
Intellectual disability v5.461 ARHGEF6 Arina Puzriakova Publications for gene: ARHGEF6 were set to 21989057; 20861843; 17304053; 11017088; 26177020
Intellectual disability v5.460 ARHGEF6 Arina Puzriakova commented on gene: ARHGEF6: PMID: 22511880 (2012) - a variant in the ARHGEF6 gene (p.I444N) was identified in a male patient with autism. However, this individual harboured variants in other genes (UBE3B) that were likely to explain their phenotype so conclusions about the consequence of the ARHGEF6 variant cannot be made in this case.

Comment on publications: PMID: 22511880 (2012) was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v5.460 ARHGEF6 Arina Puzriakova Publications for gene: ARHGEF6 were set to 21989057; 20861843; 17304053; 11017088
Intellectual disability v5.459 ARHGEF6 Arina Puzriakova Phenotypes for gene: ARHGEF6 were changed from Mental retardation, X-linked 46, 300436; Mental Retardation, X-linked; MENTAL RETARDATION X-LINKED TYPE 46 to Intellectual developmental disorder, X-linked 46, OMIM:300436
Severe microcephaly v4.63 CAMSAP1 Achchuthan Shanmugasundram changed review comment from: Seven children from five unrelated families were identified with either homozygous or compound heterozygous CAMSAP1 variants and were reported with a severe neurodevelopmental disorder apparent from infancy. Clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, lissencephaly, agenesis or severe hypogenesis of the corpus callosum, severe or profound global developmental delay, cortical visual impairment, and seizures.

This gene has been associated with relevant phenotypes in both OMIM (MIM #620316) and in Gene2Phenotype (with 'moderate' rating in the DD panel).
Sources: Literature; to: Seven children from five unrelated families were identified with either homozygous or compound heterozygous CAMSAP1 variants and were reported with a severe neurodevelopmental disorder apparent from infancy. Clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, lissencephaly, agenesis or severe hypogenesis of the corpus callosum, severe or profound global developmental delay, cortical visual impairment, and seizures. Microcephaly was severe in five children from four families.

This gene has been associated with relevant phenotypes in both OMIM (MIM #620316) and in Gene2Phenotype (with 'moderate' rating in the DD panel).
Sources: Literature
Severe microcephaly v4.63 CAMSAP1 Achchuthan Shanmugasundram Classified gene: CAMSAP1 as Amber List (moderate evidence)
Severe microcephaly v4.63 CAMSAP1 Achchuthan Shanmugasundram Gene: camsap1 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v4.62 CAMSAP1 Achchuthan Shanmugasundram Classified gene: CAMSAP1 as Red List (low evidence)
Severe microcephaly v4.62 CAMSAP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Severe microcephaly v4.62 CAMSAP1 Achchuthan Shanmugasundram Gene: camsap1 has been classified as Red List (Low Evidence).
Severe microcephaly v4.61 CAMSAP1 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: CAMSAP1.
Early onset or syndromic epilepsy v4.166 CAMSAP1 Achchuthan Shanmugasundram Classified gene: CAMSAP1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.166 CAMSAP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Early onset or syndromic epilepsy v4.166 CAMSAP1 Achchuthan Shanmugasundram Gene: camsap1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.165 CAMSAP1 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: CAMSAP1.
Intellectual disability v5.458 CAMSAP1 Achchuthan Shanmugasundram Classified gene: CAMSAP1 as Amber List (moderate evidence)
Intellectual disability v5.458 CAMSAP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.458 CAMSAP1 Achchuthan Shanmugasundram Gene: camsap1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.457 CAMSAP1 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: CAMSAP1.
Severe microcephaly v4.61 CAMSAP1 Achchuthan Shanmugasundram gene: CAMSAP1 was added
gene: CAMSAP1 was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: CAMSAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAMSAP1 were set to 36283405
Phenotypes for gene: CAMSAP1 were set to Cortical dysplasia, complex, with other brain malformations 12, OMIM:620316
Review for gene: CAMSAP1 was set to GREEN
Added comment: Seven children from five unrelated families were identified with either homozygous or compound heterozygous CAMSAP1 variants and were reported with a severe neurodevelopmental disorder apparent from infancy. Clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, lissencephaly, agenesis or severe hypogenesis of the corpus callosum, severe or profound global developmental delay, cortical visual impairment, and seizures.

This gene has been associated with relevant phenotypes in both OMIM (MIM #620316) and in Gene2Phenotype (with 'moderate' rating in the DD panel).
Sources: Literature
Early onset or syndromic epilepsy v4.165 CAMSAP1 Achchuthan Shanmugasundram gene: CAMSAP1 was added
gene: CAMSAP1 was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: CAMSAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAMSAP1 were set to 36283405
Phenotypes for gene: CAMSAP1 were set to Cortical dysplasia, complex, with other brain malformations 12, OMIM:620316
Review for gene: CAMSAP1 was set to GREEN
Added comment: Seven children from five unrelated families were identified with either homozygous or compound heterozygous CAMSAP1 variants and were reported with a severe neurodevelopmental disorder apparent from infancy. Clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, lissencephaly, agenesis or severe hypogenesis of the corpus callosum, severe or profound global developmental delay, cortical visual impairment, and seizures.

This gene has been associated with relevant phenotypes in both OMIM (MIM #620316) and in Gene2Phenotype (with 'moderate' rating in the DD panel).
Sources: Literature
Intellectual disability v5.457 CAMSAP1 Achchuthan Shanmugasundram gene: CAMSAP1 was added
gene: CAMSAP1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: CAMSAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAMSAP1 were set to 36283405
Phenotypes for gene: CAMSAP1 were set to Cortical dysplasia, complex, with other brain malformations 12, OMIM:620316
Review for gene: CAMSAP1 was set to GREEN
Added comment: Seven children from five unrelated families were identified with either homozygous or compound heterozygous CAMSAP1 variants and were reported with a severe neurodevelopmental disorder apparent from infancy. Clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, lissencephaly, agenesis or severe hypogenesis of the corpus callosum, severe or profound global developmental delay, cortical visual impairment, and seizures.

This gene has been associated with relevant phenotypes in both OMIM (MIM #620316) and in Gene2Phenotype (with 'moderate' rating in the DD panel).
Sources: Literature
Severe microcephaly v4.60 ZNF335 Achchuthan Shanmugasundram Tag Q1_24_MOI tag was added to gene: ZNF335.
Tag Q1_24_expert_review tag was added to gene: ZNF335.
Severe microcephaly v4.60 ZNF335 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: Other than the one case that was reported by Chicago lab with ZNF335 heterozygous variant (c.2515_2518dupGCCA/ p.Thr840Serfs) and with microcephaly, encephalopathy and developmental delay, all other cases reported in the literature and ClinVar had biallelic variants in ZNF335. Hence, the MOI should be updated to "BIALLELIC, autosomal or pseudoautosomal" in the next GMS review.
Severe microcephaly v4.60 ZNF335 Achchuthan Shanmugasundram Mode of inheritance for gene: ZNF335 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Severe microcephaly v4.59 ZNF335 Achchuthan Shanmugasundram edited their review of gene: ZNF335: Changed rating: GREEN
Severe microcephaly v4.59 ZNF335 Achchuthan Shanmugasundram reviewed gene: ZNF335: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.456 BAZ2B Achchuthan Shanmugasundram Classified gene: BAZ2B as Amber List (moderate evidence)
Intellectual disability v5.456 BAZ2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.456 BAZ2B Achchuthan Shanmugasundram Gene: baz2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.455 BAZ2B Achchuthan Shanmugasundram Phenotypes for gene: BAZ2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071