ClinVar Miner

Submissions for variant NM_000075.4(CDK4):c.881A>G (p.Tyr294Cys)

dbSNP: rs1565805206
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001043717 SCV001207476 uncertain significance Familial melanoma 2023-10-16 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 294 of the CDK4 protein (p.Tyr294Cys). 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: 841483). 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 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001800943 SCV002046623 uncertain significance not provided 2021-02-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV002372780 SCV002684256 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-12 criteria provided, single submitter clinical testing The p.Y294C variant (also known as c.881A>G), located in coding exon 7 of the CDK4 gene, results from an A to G substitution at nucleotide position 881. The tyrosine at codon 294 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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