ClinVar Miner

Submissions for variant NM_000075.4(CDK4):c.209A>G (p.Asn70Ser)

dbSNP: rs1595110952
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000804030 SCV000943921 uncertain significance Familial melanoma 2023-12-04 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 70 of the CDK4 protein (p.Asn70Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 26976419). ClinVar contains an entry for this variant (Variation ID: 649162). 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 with a positive 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 RCV002422751 SCV002724517 uncertain significance Hereditary cancer-predisposing syndrome 2021-06-23 criteria provided, single submitter clinical testing The p.N70S variant (also known as c.209A>G), located in coding exon 1 of the CDK4 gene, results from an A to G substitution at nucleotide position 209. The asparagine at codon 70 is replaced by serine, an amino acid with highly similar properties. This alteration has been reported in a cohort of 488 patients with stages I to III breast cancer who were tested with a 25-gene panel test (Tung N et al. J Clin Oncol, 2016 May;34:1460-8). 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.

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