ClinVar

Description

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 CACNA1S protein function. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg1242 amino acid residue in CACNA1S. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24240197, 29048924). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 851436). This missense change has been observed in individual(s) with autosomal dominant myopathy (Invitae). In at least one individual the variant was observed to be de novo. This variant is present in population databases (rs750637537, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 1242 of the CACNA1S protein (p.Arg1242Lys).