ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7235A>G (p.Lys2412Arg)

dbSNP: rs869312785
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER _CC_NCGL, University of Washington RCV000211508 SCV000212181 uncertain significance Familial adenomatous polyposis 1 2015-03-11 criteria provided, single submitter research
University of Washington Department of Laboratory Medicine, University of Washington RCV000210156 SCV000266145 uncertain significance Colorectal cancer, susceptibility to 2015-11-20 criteria provided, single submitter clinical testing
Invitae RCV003743641 SCV002270973 uncertain significance Familial adenomatous polyposis 1 2024-01-27 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 2412 of the APC protein (p.Lys2412Arg). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with colon cancer (PMID: 26845104). ClinVar contains an entry for this variant (Variation ID: 224554). 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 APC 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 RCV003165517 SCV003855138 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-27 criteria provided, single submitter clinical testing The p.K2412R variant (also known as c.7235A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 7235. The lysine at codon 2412 is replaced by arginine, an amino acid with highly similar properties. This variant was detected in a patient with a personal history of colon cancer and less than 5 lifetime cumulative polyps (Shirts BH et al. Genet Med, 2016 Oct;18:974-81). 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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