ClinVar Miner

Submissions for variant NM_201253.3(CRB1):c.3652T>A (p.Cys1218Ser)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004527131 SCV005039664 uncertain significance not specified 2024-03-20 criteria provided, single submitter clinical testing Variant summary: CRB1 c.3652T>A (p.Cys1218Ser) results in a non-conservative amino acid change located in one of the EGF-like repeat domains (IPR000742), affecting a disulfide bond (between amino acids 1218-1229; UniProt) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249062 control chromosomes (gnomAD v2.1). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3652T>A in individuals affected with Retinal Dystrophy and no experimental evidence demonstrating its impact on protein function have been reported. However, a different missense variant affecting this cysteine residue has been reported in affected individuals (HGMD) and been classified as pathogenic in ClinVar (Variation ID: 866855), suggesting this residue may be of clinical significance. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005006437 SCV005637069 likely pathogenic Pigmented paravenous retinochoroidal atrophy; Retinitis pigmentosa 12; Leber congenital amaurosis 8 2024-03-18 criteria provided, single submitter clinical testing

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