ClinVar

Description

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 169 of the RHO protein (p.Ala169Thr). This variant is present in population databases (rs377687329, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with RHO-related conditions. ClinVar contains an entry for this variant (Variation ID: 1015789). 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 not expected to disrupt RHO protein function with a negative predictive value of 80%. This variant disrupts the p.Ala169 amino acid residue in RHO. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23288993). 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.