ClinVar Miner

Submissions for variant NM_000075.4(CDK4):c.580C>T (p.Pro194Ser)

gnomAD frequency: 0.00001  dbSNP: rs1264069202
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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 RCV000567795 SCV000673199 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-21 criteria provided, single submitter clinical testing The p.P194S variant (also known as c.580C>T), located in coding exon 4 of the CDK4 gene, results from a C to T substitution at nucleotide position 580. The proline at codon 194 is replaced by serine, an amino acid with similar properties. 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.
Invitae RCV000795632 SCV000935100 uncertain significance Familial melanoma 2023-10-06 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 194 of the CDK4 protein (p.Pro194Ser). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 485495). 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. 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.
PreventionGenetics, part of Exact Sciences RCV003409848 SCV004114729 uncertain significance CDK4-related condition 2023-09-19 criteria provided, single submitter clinical testing The CDK4 c.580C>T variant is predicted to result in the amino acid substitution p.Pro194Ser. This variant has been reported in an individual with head and neck cancer (Table 3, Sabir and Mahjabeen. 2012. PubMed ID: 22932448). This variant is reported in 1 of ~251,000 alleles in gnomAD (http://gnomad.broadinstitute.org/variant/12-58144491-G-A). It is reported as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/485495/). 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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