ClinVar Miner

Submissions for variant NM_002386.3(MC1R):c.451C>T (p.Arg151Cys) (rs1805007)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000242808 SCV000308868 benign not specified criteria provided, single submitter clinical testing
GeneDx RCV000255991 SCV000321867 pathogenic not provided 2016-10-12 criteria provided, single submitter clinical testing The R151C variant in the MC1R gene has been reported previously in association with red hair, fair skin, increased risk for melanoma, increased risk of photoaging and congenital melanocytic nevi (Puig-Butille et al., 2013; Elfakir et al., 2010; Kinsler et al., 2012). Functional characterization of the R151C variant show a dominant negative effect on expression, which results in a decrease in the receptor's ability to elevate intracellular cAMP levels and a complete loss of receptor function at the cell surface (Beaumont et al., 2007; Sanchez-Laorden et al., 2009). The R151C variant is a non-conservative amino acid substitution of a positively-charged Arginine with a neutral Cysteine at a residue that is conserved across species. The R151C variant was observed with a frequency of 7.6%, 655/8600 alleles, and 1.7%, 75/4396 alleles, in individuals of European and African American ancestries, respectively, in the NHLBI Exome Sequencing Project. In addition, the R151C variant was observed with a frequency of 3% among the various ethnic groups studied in the 1000 Genomes Project. We interpret R151C in the MC1R gene as a pathogenic variant.
Illumina Clinical Services Laboratory,Illumina RCV000472249 SCV000399954 benign Cutaneous malignant melanoma 5 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae RCV000472249 SCV000556936 benign Cutaneous malignant melanoma 5 2019-12-31 criteria provided, single submitter clinical testing
OMIM RCV000015385 SCV000035646 association Skin/hair/eye pigmentation 2, red hair/fair skin 2015-05-01 no assertion criteria provided literature only
OMIM RCV000015386 SCV000035647 affects Increased analgesia from kappa-opioid receptor agonist, female-specific 2015-05-01 no assertion criteria provided literature only
OMIM RCV000015387 SCV000035648 risk factor OCULOCUTANEOUS ALBINISM, TYPE II, MODIFIER OF 2015-05-01 no assertion criteria provided literature only

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