ClinVar Miner

Submissions for variant NM_000075.4(CDK4):c.310C>A (p.Leu104Met) (rs759535768)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000575523 SCV000669116 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-13 criteria provided, single submitter clinical testing The p.L104M variant (also known as c.310C>A), located in coding exon 2 of the CDK4 gene, results from a C to A substitution at nucleotide position 310. The leucine at codon 104 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.
Invitae RCV000697682 SCV000826307 uncertain significance Hereditary melanoma 2020-09-03 criteria provided, single submitter clinical testing This sequence change replaces leucine with methionine at codon 104 of the CDK4 protein (p.Leu104Met). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and methionine. This variant is present in population databases (rs759535768, ExAC 0.001%). This variant has not been reported in the literature in individuals with CDK4-related disease. ClinVar contains an entry for this variant (Variation ID: 483291). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or 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.

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