ClinVar Miner

Submissions for variant NM_000075.4(CDK4):c.343G>A (p.Glu115Lys)

gnomAD frequency: 0.00001  dbSNP: rs772938517
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000563705 SCV000669128 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-26 criteria provided, single submitter clinical testing The p.E115K variant (also known as c.343G>A), located in coding exon 2 of the CDK4 gene, results from a G to A substitution at nucleotide position 343. The glutamic acid at codon 115 is replaced by lysine, 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.
Invitae RCV000821497 SCV000962255 uncertain significance Familial melanoma 2023-12-31 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 115 of the CDK4 protein (p.Glu115Lys). This variant is present in population databases (rs772938517, gnomAD 0.02%). 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: 483298). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CDK4 protein function with a negative predictive value of 95%. 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.
GeneDx RCV002264959 SCV002547165 uncertain significance not provided 2023-11-15 criteria provided, single submitter clinical testing 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; This variant is associated with the following publications: (PMID: 27612425)

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