ClinVar Miner

Submissions for variant NM_000077.5(CDKN2A):c.294C>T (p.His98=)

dbSNP: rs752685118
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000541028 SCV000637436 uncertain significance Familial melanoma 2020-09-10 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 113 of the CDKN2A (p14ARF) protein (p.Pro113Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs752685118, ExAC 0.002%). This variant has been observed in several individuals affected with primary cutaneous melanoma (PMID: 26775776, 29464027). ClinVar contains an entry for this variant (Variation ID: 463515). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Mendelics RCV000709067 SCV000838327 uncertain significance Melanoma, cutaneous malignant, susceptibility to, 2 2018-07-02 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001176321 SCV001340246 likely benign Hereditary cancer-predisposing syndrome 2018-12-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV001176321 SCV002749314 likely benign Hereditary cancer-predisposing syndrome 2020-09-25 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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