ClinVar

Description

This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1136 of the USH2A protein (p.Ser1136Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Usher syndrome, retinitis pigmentosa, or cone-rod dystrophy (PMID: 22135276, 25991456, 27460420, 27957503, 28512305, 30718709). 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: 133312). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt USH2A protein function with a positive predictive value of 95%. This variant disrupts the p.Ser1136 amino acid residue in USH2A. Other variant(s) that disrupt this residue have been observed in individuals with USH2A-related conditions (internal data), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.