ClinVar

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro70 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10873293, 21692908, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 expected to disrupt GJB1 protein function. This variant has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 18636082, Invitae). ClinVar contains an entry for this variant (Variation ID: 637604). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 70 of the GJB1 protein (p.Pro70Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine.