ClinVar Miner

Submissions for variant NM_000075.4(CDK4):c.599T>C (p.Val200Ala)

dbSNP: rs1060501929
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000465037 SCV000547948 uncertain significance Familial melanoma 2024-06-24 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 200 of the CDK4 protein (p.Val200Ala). 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: 408335). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 RCV001024773 SCV001186852 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-25 criteria provided, single submitter clinical testing The p.V200A variant (also known as c.599T>C), located in coding exon 4 of the CDK4 gene, results from a T to C substitution at nucleotide position 599. The valine at codon 200 is replaced by alanine, an amino acid with similar properties. This amino acid position is not 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.
GeneDx RCV003168799 SCV003914870 uncertain significance not provided 2022-10-06 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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