ClinVar

Description

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 101 of the SOD1 protein (p.Glu101Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant amyotrophic lateral sclerosis (PMID: 15258228, 20460594, 20540686, 29411640; Invitae). It has also been observed to segregate with disease in related individuals. This variant is also known as 382G>A (E100K). ClinVar contains an entry for this variant (Variation ID: 574319). 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 SOD1 protein function with a negative predictive value of 95%. Experimental studies have shown that this missense change affects SOD1 function (PMID: 19483195, 23280792, 25600987). This variant disrupts the p.Glu101 amino acid residue in SOD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19483195, 20399791, 23280792, 26362407, 28105640). 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.