ClinVar Miner

Submissions for variant NM_002386.3(MC1R):c.464T>C (p.Ile155Thr) (rs1110400)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001081128 SCV000287381 benign Cutaneous malignant melanoma 5 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000247792 SCV000308869 likely benign not specified criteria provided, single submitter clinical testing
GeneDx RCV000254880 SCV000322071 pathogenic not provided 2016-07-01 criteria provided, single submitter clinical testing The I155T variant in the MC1R gene has been reported numerous times in the both the heterozygous and homozygous states in association with MC1R-related phenotypes including red hair, changes in skin pigmentation, and an increased risk for UV exposure-related melanoma (Flanagan et al., 2000; Beaumont et al., 2007; Raimondi et al., 2008; Cust et al., 2012; Puig-Butillé et al., 2013). The NHLBI Exome Sequencing Project reports I155T was observed in 1.05% (90/8598) alleles from individuals of European American ancestry. The I155T 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 where amino acids with similar properties to Isoleucine are tolerated across species. Functional studies demonstrate that I155T reduces cell surface expression of the MC1R protein and results in loss of cAMP signaling (Beaumont et al., 2007).
Illumina Clinical Services Laboratory,Illumina RCV001081128 SCV000399957 likely benign Cutaneous malignant melanoma 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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000254880 SCV000608794 uncertain significance not provided 2018-01-01 criteria provided, single submitter clinical testing

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