ClinVar

Description

The p.R82W pathogenic mutation (also known as c.244C>T), located in coding exon 1 of the KCNJ2 gene, results from a C to T substitution at nucleotide position 244. The arginine at codon 82 is replaced by tryptophan, an amino acid with dissimilar properties. This alteration has been reported in Andersen-Tawil syndrome (ATS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and long QT syndrome (LQTS) cohorts (Tester DJ et al. Heart Rhythm, 2006 Jul;3:800-5; Lieve KV et al. Genet Test Mol Biomarkers, 2013 Jul;17:553-61; Kimura H et al. Circ Cardiovasc Genet, 2012 Jun;5:344-53; Kostera-Pruszczyk A et al. Muscle Nerve, 2015 Feb;51:192-6; Rhodes T et al. Card Electrophysiol Clin, 2015 Sep;7:479-86; Krych M et al. J Cardiol, 2017 Nov;70:504-510). Functional studies indicate that this variant has a dominant negative impact on current density (Eckhardt LL et al. Heart Rhythm, 2007 Mar;4:323-9; Kimura H et al. Circ Cardiovasc Genet, 2012 Jun;5:344-53). In addition, a likely pathogenic alteration in the same codon (p.R82Q) has been described (Davies NP et al. Neurology. 2005 Oct 11;65(7):1083-9). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.