ClinVar Miner

Submissions for variant NM_002386.3(MC1R):c.880G>C (p.Asp294His) (rs1805009)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001080639 SCV000287390 benign Cutaneous malignant melanoma 5 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000243405 SCV000308874 likely benign not specified criteria provided, single submitter clinical testing
GeneDx RCV000347221 SCV000329659 pathogenic not provided 2016-12-05 criteria provided, single submitter clinical testing The D294H 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; Kinsler et al., 2012; Ibarrola-Villava et al., 2014). Functional characterization of the D294H variant showed decreased ability to stimulate cAMP production, and altered cell surface expression (Schioth et al., 1999; Sanchez-Laorden et al., 2009). The D294H variant is a non-conservative amino acid substitution which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. The D294H variant was observed with a frequency of 2.1%, 176/8496 alleles, and 0.7%, 29/4228 alleles, in individuals of European and African American ancestries, respectively, in the NHLBI Exome Sequencing Project. We interpret D294H in the MC1R gene as a pathogenic variant.
Illumina Clinical Services Laboratory,Illumina RCV001080639 SCV000399975 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.
OMIM RCV000015377 SCV000035638 association Skin/hair/eye pigmentation 2, red hair/fair skin 1995-11-01 no assertion criteria provided literature only
Yale Center for Mendelian Genomics,Yale University RCV000662303 SCV000784631 likely pathogenic Tyrosinase-positive oculocutaneous albinism 2015-09-22 no assertion criteria provided literature only
University of Washington Center for Mendelian Genomics, University of Washington RCV000851264 SCV000993520 likely pathogenic Skin and Hair Hypopigmentation 2015-09-22 no assertion criteria provided research

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