ClinVar

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 90 of the SOD1 protein (p.Ala90Val). This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individual(s) with autosomal dominant amyotrophic lateral sclerosis (PMID: 13129803, 31086828). It has also been observed to segregate with disease in related individuals. This variant is also known as A89V. ClinVar contains an entry for this variant (Variation ID: 1191297). 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 expected to disrupt SOD1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects SOD1 function (PMID: 23280792). This variant disrupts the p.Ala90 amino acid residue in SOD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14506936, 23280792; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.