Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000820155 | SCV000960854 | uncertain significance | Familial melanoma | 2022-02-28 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: 662499). 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 arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 181 of the CDK4 protein (p.Arg181Gly). |
Ambry Genetics | RCV002345890 | SCV002651578 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-12 | criteria provided, single submitter | clinical testing | The p.R181G variant (also known as c.541C>G), located in coding exon 4 of the CDK4 gene, results from a C to G substitution at nucleotide position 541. The arginine at codon 181 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |