Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002349481 | SCV002649344 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-21 | criteria provided, single submitter | clinical testing | The p.R181* variant (also known as c.541C>T), located in coding exon 4 of the CDK4 gene, results from a C to T substitution at nucleotide position 541. This changes the amino acid from an arginine to a stop codon within coding exon 4. This alteration is expected to result in protein truncation or nonsense-mediated mRNA decay. However, loss of function of CDK4 has not been established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003585258 | SCV004320397 | uncertain significance | Familial melanoma | 2024-10-07 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg181*) in the CDK4 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in CDK4 cause disease. This variant is not present in population databases (gnomAD no frequency). 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: 1747429). 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. |