Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001936291 | SCV002201825 | uncertain significance | Familial melanoma | 2021-05-18 | 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. This variant is present in population databases (rs747362286, ExAC 0.02%). This sequence change replaces valine with alanine at codon 242 of the CDK4 protein (p.Val242Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. |
| Ambry Genetics | RCV003167311 | SCV003870473 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-07 | criteria provided, single submitter | clinical testing | The p.V242A variant (also known as c.725T>C), located in coding exon 6 of the CDK4 gene, results from a T to C substitution at nucleotide position 725. The valine at codon 242 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. 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. |