ClinVar

Description

This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 21 of the SOD1 protein (p.Phe21Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant amyotrophic lateral sclerosis and/or SOD1-related condition (PMID: 22722621, 35260199; Invitae). This variant is also known as F20L. ClinVar contains an entry for this variant (Variation ID: 859765). 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 disrupts the p.Phe21 amino acid residue in SOD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17453632, 23280792). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.