Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001024207 | SCV001186181 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-09-12 | criteria provided, single submitter | clinical testing | The p.E184K variant (also known as c.550G>A), located in coding exon 4 of the CDK4 gene, results from a G to A substitution at nucleotide position 550. The glutamic acid at codon 184 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001364389 | SCV001560535 | uncertain significance | Familial melanoma | 2022-03-13 | 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. 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 expected to disrupt CDK4 protein function. ClinVar contains an entry for this variant (Variation ID: 825795). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 184 of the CDK4 protein (p.Glu184Lys). |
| Prevention |
RCV003413811 | SCV004116915 | uncertain significance | CDK4-related condition | 2022-10-05 | criteria provided, single submitter | clinical testing | The CDK4 c.550G>A variant is predicted to result in the amino acid substitution p.Glu184Lys. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/825795/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |