rs727504182

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 928 of the TRPM1 protein (p.Arg928Trp). This variant is present in population databases (rs727504182, gnomAD 0.008%). This missense change has been observed in individuals with CSNB (PMID: 28341476, 32141364). ClinVar contains an entry for this variant (Variation ID: 167749). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg928 amino acid residue in TRPM1. Other variant(s) that disrupt this residue have been observed in individuals with TRPM1-related conditions (PMID: 24715752), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.