ClinVar Miner

Submissions for variant NM_000075.4(CDK4):c.523G>A (p.Val175Ile) (rs587778186)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165893 SCV000216646 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-03 criteria provided, single submitter clinical testing The p.V175I variant (also known as c.523G>A) is located in coding exon 4 of the CDK4 gene. The valine at codon 175 is replaced by isoleucine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 4. This amino acid position is highly 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000120535 SCV000601006 uncertain significance not specified 2017-05-10 criteria provided, single submitter clinical testing
Invitae RCV000685170 SCV000812643 uncertain significance Hereditary melanoma 2020-10-21 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 175 of the CDK4 protein (p.Val175Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. 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: 133875). 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: Benign; 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.
ITMI RCV000120535 SCV000084688 not provided not specified 2013-09-19 no assertion provided reference population

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