ClinVar Miner

Submissions for variant NM_000075.4(CDK4):c.88C>T (p.His30Tyr)

dbSNP: rs750707985
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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 RCV001018479 SCV001179724 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-03 criteria provided, single submitter clinical testing The p.H30Y variant (also known as c.88C>T), located in coding exon 1 of the CDK4 gene, results from a C to T substitution at nucleotide position 88. The histidine at codon 30 is replaced by tyrosine, 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.
Invitae RCV001308785 SCV001498255 uncertain significance Familial melanoma 2024-01-21 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 30 of the CDK4 protein (p.His30Tyr). This variant is present in population databases (rs750707985, gnomAD 0.003%). 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: 822805). 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.

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