Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001063153 | SCV001227988 | uncertain significance | Familial melanoma | 2024-01-17 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg288*) in the CDK4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 16 amino acid(s) of the CDK4 protein. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with CDK4-related conditions. ClinVar contains an entry for this variant (Variation ID: 857478). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Ambry Genetics | RCV002374961 | SCV002687777 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-03 | criteria provided, single submitter | clinical testing | The p.R288* variant (also known as c.862C>T), located in coding exon 7 of the CDK4 gene, results from a C to T substitution at nucleotide position 862. This changes the amino acid from an arginine to a stop codon within coding exon 7. This alteration is expected to result in premature protein truncation. However, loss of function of CDK4 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |