ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs1060501931
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000459093 SCV000547953 uncertain significance Familial melanoma 2023-12-15 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 116 of the CDK4 protein (p.Thr116Met). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 408339). 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.
Ambry Genetics RCV000565797 SCV000669094 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-08 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.
PreventionGenetics, part of Exact Sciences RCV003401473 SCV004120761 uncertain significance CDK4-related condition 2022-08-24 criteria provided, single submitter clinical testing The CDK4 c.347C>T variant is predicted to result in the amino acid substitution p.Thr116Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.013% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-58144997-G-A), and it is documented as a variant of uncertain significance in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/408339/evidence/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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