Submissions for variant NM_002386.4(MC1R):c.951G>T (p.Trp317Cys)

gnomAD frequency: 0.00001  dbSNP: rs765813858

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001117581	SCV001275785	uncertain significance	Melanoma, cutaneous malignant, susceptibility to, 5	2017-04-28	criteria provided, single submitter	clinical testing	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001117581	SCV004557557	uncertain significance	Melanoma, cutaneous malignant, susceptibility to, 5	2023-10-18	criteria provided, single submitter	clinical testing	This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 317 of the MC1R protein (p.Trp317Cys). This variant is present in population databases (rs765813858, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MC1R-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.