ClinVar

Description

ClinVar contains an entry for this variant (Variation ID: 519476). 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. Experimental studies have shown that this missense change affects KCNJ2 function (PMID: 32499698). This variant disrupts the p.Met307 amino acid residue in KCNJ2. Other variant(s) that disrupt this residue have been observed in individuals with KCNJ2-related conditions (PMID: 17211524, 31567646), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. This missense change has been observed in individual(s) with clinical features of Andersen-Tawil syndrome (PMID: 25847018, 31068157, 31483760, 31567646, 32499698; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 307 of the KCNJ2 protein (p.Met307Val).