ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3716G>A (p.Arg1239Lys)

dbSNP: rs754067085
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000776254 SCV000911507 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV000776254 SCV001182510 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-27 criteria provided, single submitter clinical testing The p.R1239K variant (also known as c.3716G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 3716. The arginine at codon 1239 is replaced by lysine, an amino acid with highly 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 RCV003653259 SCV002194100 uncertain significance Familial adenomatous polyposis 1 2023-11-21 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 1239 of the APC protein (p.Arg1239Lys). This variant is present in population databases (rs754067085, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 559947). 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.
GeneDx RCV002462012 SCV002757625 uncertain significance not provided 2022-11-22 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Identified as a candidate variant in at least one individual with congenital heart disease (Zhou et al., 2021); This variant is associated with the following publications: (PMID: 35141295)
Baylor Genetics RCV002544686 SCV004205349 uncertain significance Familial adenomatous polyposis 1 2023-06-14 criteria provided, single submitter clinical testing
3DMed Clinical Laboratory Inc RCV000677743 SCV000803899 uncertain significance Colon cancer 2017-04-12 no assertion criteria provided clinical testing
3DMed Clinical Laboratory Inc RCV000677744 SCV000803900 uncertain significance Neoplasm of the liver 2017-04-12 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.