ClinVar

Description

This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 1343 of the USH2A protein (p.Asn1343His). This variant is present in population databases (rs754634823, gnomAD 0.07%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individuals with clinical features of autosomal recessive retinitis pigmentosa (PMID: 28041643; Invitae). ClinVar contains an entry for this variant (Variation ID: 438020). 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. This variant disrupts the p.Asn1343 amino acid residue in USH2A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 33926394). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.