ClinVar

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Cys179 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17620124, 17100997). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with GJB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 637144). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with arginine at codon 179 of the GJB1 protein (p.Cys179Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine.