Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000706009 | SCV000835036 | uncertain significance | Familial melanoma | 2025-01-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 124 of the CDKN2A (p16INK4a) protein (p.Arg124Gly). This variant is present in population databases (rs34170727, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CDKN2A (p16INK4a)-related conditions. ClinVar contains an entry for this variant (Variation ID: 582036). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Color Diagnostics, |
RCV000771468 | SCV000903909 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000771468 | SCV001182489 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-10-28 | criteria provided, single submitter | clinical testing | The p.R124G variant (also known as c.370C>G), located in coding exon 2 of the CDKN2A gene, results from a C to G substitution at nucleotide position 370. The arginine at codon 124 is replaced by glycine, an amino acid with dissimilar properties. Of note, this alteration is also known as c.413C>G in the p14(ARF) isoform. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Gene |
RCV004773119 | SCV005382928 | uncertain significance | not provided | 2024-01-17 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |