Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000468563 | SCV000547954 | uncertain significance | Familial melanoma | 2016-09-07 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in the germline of individuals with a CDK4-related disease. This sequence change replaces aspartic acid with histidine at codon 97 of the CDK4 protein (p.Asp97His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). |
| Ambry Genetics | RCV002436425 | SCV002750889 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-24 | criteria provided, single submitter | clinical testing | The p.D97H variant (also known as c.289G>C), located in coding exon 2 of the CDK4 gene, results from a G to C substitution at nucleotide position 289. The aspartic acid at codon 97 is replaced by histidine, an amino acid with similar properties. This amino acid position is 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. |