Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001975783 | SCV002252635 | likely pathogenic | Retinitis pigmentosa 12; Leber congenital amaurosis 8 | 2021-10-25 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Glu1403 amino acid residue in CRB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24715753). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individual(s) with macular dystrophy (PMID: 32901921). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 1403 of the CRB1 protein (p.Glu1403Asp). |