Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001223303 | SCV001395445 | uncertain significance | Familial melanoma | 2023-07-18 | 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. ClinVar contains an entry for this variant (Variation ID: 951400). This variant has not been reported in the literature in individuals affected with CDK4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 19 of the CDK4 protein (p.Thr19Ala). |
| Ambry Genetics | RCV002348747 | SCV002651398 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-03 | criteria provided, single submitter | clinical testing | The p.T19A variant (also known as c.55A>G), located in coding exon 1 of the CDK4 gene, results from an A to G substitution at nucleotide position 55. The threonine at codon 19 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. 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. |