ClinVar Miner

Submissions for variant NM_000075.4(CDK4):c.109G>A (p.Val37Met) (rs1060501930)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000460166 SCV000547950 uncertain significance Hereditary melanoma 2020-09-02 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 37 of the CDK4 protein (p.Val37Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CDK4-related disease. ClinVar contains an entry for this variant (Variation ID: 408336). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). 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 RCV001017293 SCV001178353 uncertain significance Hereditary cancer-predisposing syndrome 2020-08-05 criteria provided, single submitter clinical testing The p.V37M variant (also known as c.109G>A), located in coding exon 1 of the CDK4 gene, results from a G to A substitution at nucleotide position 109. The valine at codon 37 is replaced by methionine, an amino acid with highly similar properties. 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.
GeneDx RCV001555943 SCV001777437 uncertain significance not provided 2019-05-31 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 25231023)

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