ClinVar Miner

Submissions for variant NM_000075.4(CDK4):c.347C>T (p.Thr116Met) (rs1060501931)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000459093 SCV000547953 uncertain significance Hereditary melanoma 2020-10-08 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 116 of the CDK4 protein (p.Thr116Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine 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: 408339). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV000565797 SCV000669094 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-03 criteria provided, single submitter clinical testing The p.T116M variant (also known as c.347C>T), located in coding exon 2 of the CDK4 gene, results from a C to T substitution at nucleotide position 347. The threonine at codon 116 is replaced by methionine, 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.

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