Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000638952 | SCV000760509 | uncertain significance | Familial melanoma | 2021-10-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 96 of the CDKN2A (p14ARF) protein (p.Arg96Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CDKN2A (p14ARF)-related conditions. ClinVar contains an entry for this variant (Variation ID: 532271). 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. 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, |
RCV001190957 | SCV001358625 | likely benign | Hereditary cancer-predisposing syndrome | 2019-04-23 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001190957 | SCV002737892 | likely benign | Hereditary cancer-predisposing syndrome | 2021-04-11 | 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. |