Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001212878 | SCV001384480 | uncertain significance | Familial melanoma | 2021-10-26 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with CDK4-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35"). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with glutamic acid at codon 257 of the CDK4 protein (p.Val257Glu). The valine residue is moderately conserved and there is a moderate physicochemical difference between valine and glutamic acid. |
| Ambry Genetics | RCV002402630 | SCV002674841 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-20 | criteria provided, single submitter | clinical testing | The p.V257E variant (also known as c.770T>A), located in coding exon 6 of the CDK4 gene, results from a T to A substitution at nucleotide position 770. The valine at codon 257 is replaced by glutamic acid, 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. |