Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001203842 | SCV001375021 | uncertain significance | Familial melanoma | 2022-02-01 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 191 of the CDK4 protein (p.Tyr191Cys). 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: 935284). |
Institute for Clinical Genetics, |
RCV003238315 | SCV002010277 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002348661 | SCV002647649 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-26 | criteria provided, single submitter | clinical testing | The p.Y191C variant (also known as c.572A>G), located in coding exon 4 of the CDK4 gene, results from an A to G substitution at nucleotide position 572. The tyrosine at codon 191 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly 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. |