ClinVar Miner

Submissions for variant NM_002386.3(MC1R):c.766C>T (p.Pro256Ser) (rs200215218)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000532822 SCV000648555 uncertain significance Cutaneous malignant melanoma 5 2019-11-26 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 256 of the MC1R protein (p.Pro256Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs200215218, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in multiple individuals affected with melanoma (PMID: 23647022, 24982914, 15998953, 19799798, 25284244), however segregation studies have not been reported. This variant has also been reported in several unaffected individuals (PMID: 19269164, 19585506, 24982914). ClinVar contains an entry for this variant (Variation ID: 470711). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Fulgent Genetics,Fulgent Genetics RCV000764098 SCV000895062 uncertain significance Tyrosinase-positive oculocutaneous albinism; Skin/hair/eye pigmentation, variation in, 2; Increased analgesia from kappa-opioid receptor agonist, female-specific; Cutaneous malignant melanoma 5 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000532822 SCV001279603 uncertain significance Cutaneous malignant melanoma 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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