ClinVar

Description

This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 113 of the GJB2 protein (p.Ser113Arg). This variant is present in population databases (rs80338946, gnomAD 0.03%). This missense change has been observed in individual(s) with autosomal recessive non-syndromic deafness (PMID: 9529365, 12408072, 24078562). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 21385). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GJB2 protein function with a negative predictive value of 95%. Experimental studies have shown that this missense change affects GJB2 function (PMID: 12505163). 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.