Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002040111 | SCV002116462 | uncertain significance | Familial melanoma | 2022-04-19 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 138 of the CDKN2A (p16INK4a) protein (p.Arg138Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CDKN2A (p16INK4a)-related conditions. 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. Experimental studies have shown that this missense change does not substantially affect CDKN2A (p16INK4a) function (PMID: 28120917). 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. |
| Ambry Genetics | RCV002331355 | SCV002627361 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-07 | criteria provided, single submitter | clinical testing | The p.R138K variant (also known as c.413G>A), located in coding exon 2 of the CDKN2A gene, results from a G to A substitution at nucleotide position 413. The arginine at codon 138 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |