ClinVar

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 350 of the DES protein (p.Arg350Gln). This variant is present in population databases (rs57965306, gnomAD 0.005%). This missense change has been observed in individual(s) with centronuclear myopathy and/or suffered a sudden unexplained death (PMID: 29382405, 29915097). ClinVar contains an entry for this variant (Variation ID: 596421). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DES protein function. This variant disrupts the p.Arg350 amino acid residue in DES. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15800015, 17439987, 20448486, 25394388, 27393313). 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.