Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002027635 | SCV002307819 | uncertain significance | Familial melanoma | 2021-12-11 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with CDK4-related conditions. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 85 of the CDK4 protein (p.Arg85Trp). This variant is present in population databases (rs759017803, gnomAD 0.01%). 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. 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 | RCV004046985 | SCV005032122 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-15 | criteria provided, single submitter | clinical testing | The p.R85W variant (also known as c.253C>T), located in coding exon 2 of the CDK4 gene, results from a C to T substitution at nucleotide position 253. The arginine at codon 85 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |