ClinVar Miner

Submissions for variant NM_000077.4(CDKN2A):c.198C>T (p.His66=) (rs374984975)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000570104 SCV000664592 likely benign Hereditary cancer-predisposing syndrome 2016-02-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign
Color RCV000570104 SCV000911543 likely benign Hereditary cancer-predisposing syndrome 2017-05-25 criteria provided, single submitter clinical testing
GeneDx RCV000480893 SCV000567577 uncertain significance not provided 2018-12-20 criteria provided, single submitter clinical testing This variant is denoted CDKN2A c.241C>T at the cDNA level, p.Arg81Trp (R81W) at the protein level, and results in the change of an Arginine to a Tryptophan (CGG>TGG) in exon 2 of the p14-ARF protein. Of note, this variant also results in a change to the p16 protein; however, that amino acid substitution is silent (p.His66His). This variant has been observed in at least one individual with early-onset melanoma (Stratigos 2006). CDKN2A Arg81Trp was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether CDKN2A Arg81Trp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000477469 SCV000557472 likely benign Hereditary cutaneous melanoma 2017-01-04 criteria provided, single submitter clinical testing

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