ClinVar Miner

Submissions for variant NM_000077.4(CDKN2A):c.176T>G (p.Val59Gly) (rs104894099)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409228 SCV000489045 likely pathogenic Melanoma-pancreatic cancer syndrome 2016-08-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV000494082 SCV000581514 likely pathogenic Hereditary cancer-predisposing syndrome 2016-09-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Deficient protein function in appropriate functional assay(s),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Invitae RCV000545232 SCV000637399 pathogenic Hereditary cutaneous melanoma 2018-12-14 criteria provided, single submitter clinical testing This sequence change replaces valine with glycine at codon 59 of the p16INK4a protein (p.Val59Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. This variant is present in population databases (rs104894099, ExAC 0.01%). This variant has been reported in several individuals and families affected with melanoma (PMID: 12700603, 9425228, 22841127, 19799798, 21893440, 15146471, 26681309, 20653773, 19571771). Haplotype analysis in families of Tunisian, Moroccan, French, and Spanish ancestry has determined that this variant resulted from a single founder event in these families (PMID: 12700603). ClinVar contains an entry for this variant (Variation ID: 9423). Experimental studies have shown that this missense change impairs CDK4 and CDK6 binding to p16INK4a, and reduces its ability to block proliferation in vitro (PMID: 12700603). For these reasons, this variant has been classified as Pathogenic.
Color RCV000494082 SCV000684515 likely pathogenic Hereditary cancer-predisposing syndrome 2018-09-02 criteria provided, single submitter clinical testing
OMIM RCV000010030 SCV000030251 risk factor Cutaneous malignant melanoma 2 2003-04-01 no assertion criteria provided literature only

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.