ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: 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 2021-08-03 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 variant was identified in a cohort of 681 ancestrally diverse, healthy subjects (Bodian DL et al. PLoS One, 2014 Apr;9:e94554). 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 Familial melanoma 2023-08-02 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 133875). This variant has not been reported in the literature in individuals affected with CDK4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 175 of the CDK4 protein (p.Val175Ile).
ITMI RCV000120535 SCV000084688 not provided not specified 2013-09-19 no assertion provided reference population

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