ClinVar Miner

Submissions for variant NM_002386.4(MC1R):c.895G>A (p.Ala299Thr)

gnomAD frequency: 0.00016  dbSNP: rs370472871
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000704517 SCV000833469 uncertain significance Melanoma, cutaneous malignant, susceptibility to, 5 2023-08-01 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with melanoma (PMID: 24982914). 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. 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 not expected to disrupt MC1R protein function. ClinVar contains an entry for this variant (Variation ID: 580855). This variant is present in population databases (rs370472871, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 299 of the MC1R protein (p.Ala299Thr).
Illumina Laboratory Services, Illumina RCV000704517 SCV001274189 uncertain significance Melanoma, cutaneous malignant, susceptibility to, 5 2017-04-27 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.
CeGaT Center for Human Genetics Tuebingen RCV003420258 SCV004143629 likely benign not provided 2022-12-01 criteria provided, single submitter clinical testing MC1R: BP4

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