ClinVar

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Cys7 amino acid residue in SOD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21073275, 21329474, 21603025). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects SOD1 function (PMID: 23280792). 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. This variant is also known as p.Cys6Gly. This missense change has been observed in individual(s) with amyotrophic lateral sclerosis (PMID: 10624810). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 7 of the SOD1 protein (p.Cys7Gly).