ClinVar Miner

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

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000228327 SCV000287386 uncertain significance Cutaneous malignant melanoma 5 2019-11-27 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). ClinVar contains an entry for this variant (Variation ID: 239159). 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.
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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.