ClinVar Miner

Submissions for variant NM_000077.5(CDKN2A):c.158T>C (p.Met53Thr)

dbSNP: rs2131096665
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002000364 SCV002260055 uncertain significance Familial melanoma 2022-10-27 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 1480737). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 53 of the CDKN2A (p16INK4a) protein (p.Met53Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with melanoma (PMID: 12417717, 21462282). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects CDKN2A (p16INK4a) function (PMID: 8573142, 12417717, 21462282). This variant disrupts the p.Met53 amino acid residue in CDKN2A (p16INK4a). Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8595405, 9328469, 9699728, 16307646, 16905682, 17171691). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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