ClinVar

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 172 of the ACTA1 protein (p.Ala172Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ACTA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1018348). 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 ACTA1 protein function. This variant disrupts the p.Ala172 amino acid residue in ACTA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12921789, 19562689, 32222963, 35081925). 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.