ClinVar

Description

This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 4112 of the USH2A protein (p.Gly4112Ser). This variant is present in population databases (rs147496855, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with USH2A-related conditions. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on USH2A protein function. 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.