rs201888584

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 1302 of the TRPM1 protein (p.Cys1302Arg). This variant is present in population databases (rs201888584, gnomAD 0.04%). This missense change has been observed in individual(s) with clinical features of cone dystrophies (PMID: 22277662). ClinVar contains an entry for this variant (Variation ID: 850230). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.