ClinVar Miner

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

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
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
Color RCV000494082 SCV000684515 likely pathogenic Hereditary cancer-predisposing syndrome 2018-09-02 criteria provided, single submitter clinical testing
Counsyl RCV000409228 SCV000489045 likely pathogenic Melanoma-pancreatic cancer syndrome 2016-08-10 criteria provided, single submitter clinical testing
Invitae RCV000545232 SCV000637399 pathogenic Hereditary cutaneous melanoma 2018-04-08 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.
OMIM RCV000010030 SCV000030251 risk factor Cutaneous malignant melanoma 2 2003-04-01 no assertion criteria provided literature only

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