ClinVar

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 82 of the KCNJ2 protein (p.Arg82Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with catecholaminergic polymorphic ventricular tachycardia (PMID: 16818210). ClinVar contains an entry for this variant (Variation ID: 67568). 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 KCNJ2 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects KCNJ2 function (PMID: 17341397, 22589293). This variant disrupts the p.Arg82 amino acid residue in KCNJ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16217063, 22589293, 22806368, 23644778). 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.