ClinVar

Description

This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 22 of the GJA8 protein (p.Gly22Cys). 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.Gly22 amino acid residue in GJA8. Other variant(s) that disrupt this residue have been observed in individuals with GJA8-related conditions (PMID: 31618082, 34722561), which suggests that this may be a clinically significant amino acid residue. 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 GJA8 protein function. This missense change has been observed in individual(s) with clinical features of autosomal dominant GJA8-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency).