ClinVar Miner

Submissions for variant NM_002386.3(MC1R):c.67C>T (p.Gln23Ter) (rs201533137)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000578946 SCV000680654 likely pathogenic not provided 2018-11-13 criteria provided, single submitter clinical testing The Q23X variant in the MC1R gene has been reported previously in two redhead Jamaican individuals who harbored a second MC1R variant (McKenzie et al., 2003). The Q23X variant has also been observed in one patient from a cohort of individuals at risk for pancreatic cancer (Smith er al., 2016); however, additional clinical details and family history were not provided. This variant is predicted to cause loss of normal protein function through protein truncation. The Q23X variant is observed in 119/23452 (0.5%) alleles from individuals of African background in large population cohorts (Lek et al., 2016). We interpret Q23X as a likely pathogenic variant.
Invitae RCV000228327 SCV000287386 uncertain significance Cutaneous malignant melanoma 5 2016-07-01 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the last exon of the MC1R mRNA at codon 23 (p.Gln23*). While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated MC1R protein. This variant is present in population databases (rs201533137, ExAC 0.6%). This variant has been reported to co-occur with other MC1R variants in individuals with red hair (PMID: 12839583). Pigmentation of the hair and skin is correlated with ultraviolet sensitivity and skin cancer. Other loss of function missense variants in MC1R have been correlated with lighter skin pigmentation (PMID: 11030758) and possibly increased melanoma risk, although no definitive disease association has been concluded (PMID: 18366057, 21128237). In summary, this is a truncating variant in a gene in which other loss of function variants have a suggested association with increased melanoma risk. However, the relative disease risk of this variant has not been assessed. Therefore, it has been classified as a Variant of Uncertain Significance.

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