ClinVar

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg4737 amino acid residue in RYR1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16163667, 18564801, 19648156, 25960145). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects RYR1 function (PMID: 27558158). 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 RYR1 protein function. ClinVar contains an entry for this variant (Variation ID: 133060). This variant is also known as p.Arg4736Trp. This missense change has been observed in individual(s) with malignant hyperthermia (PMID: 12208234, 16163667, 26631338). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 4737 of the RYR1 protein (p.Arg4737Trp).