Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000206239 | SCV000259629 | uncertain significance | Familial melanoma | 2022-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 82 of the CDK4 protein (p.Arg82Gln). This variant is present in population databases (rs3211612, gnomAD 0.01%). This missense change has been observed in individual(s) with colorectal cancer (PMID: 27978560). ClinVar contains an entry for this variant (Variation ID: 219640). 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. 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. |
| Gene |
RCV000477988 | SCV000568163 | uncertain significance | not provided | 2023-03-24 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in a patient with colorectal cancer (Pearlman et al., 2017); This variant is associated with the following publications: (PMID: 19139070, 30886832, 32579932, 27978560) |
| Ambry Genetics | RCV000573084 | SCV000669087 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-07 | criteria provided, single submitter | clinical testing | The p.R82Q variant (also known as c.245G>A), located in coding exon 2 of the CDK4 gene, results from a G to A substitution at nucleotide position 245. The arginine at codon 82 is replaced by glutamine, an amino acid with highly similar properties. This alteration was detected in 1/450 patients with colorectal cancer diagnosed under the age of 50 who were tested with a multi-gene panel, and p.R82Q was called a variant of uncertain significance by the study authors (Pearlman R et al. JAMA Oncol, 2017 Apr;3:464-471). 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. |
| Center for Genomic Medicine, |
RCV003493497 | SCV004243472 | uncertain significance | not specified | 2024-02-06 | criteria provided, single submitter | clinical testing |