Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001018114 | SCV001179301 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-11-05 | criteria provided, single submitter | clinical testing | The p.R288P variant (also known as c.863G>C), located in coding exon 7 of the CDK4 gene, results from a G to C substitution at nucleotide position 863. The arginine at codon 288 is replaced by proline, an amino acid with dissimilar properties. This amino acid position is not well 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. |
| Labcorp Genetics |
RCV001860892 | SCV002280410 | uncertain significance | Familial melanoma | 2020-12-10 | criteria provided, single submitter | clinical testing | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CDK4 protein function. This variant has not been reported in the literature in individuals with CDK4-related conditions. ClinVar contains an entry for this variant (Variation ID: 822622). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with proline at codon 288 of the CDK4 protein (p.Arg288Pro). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and proline. |