ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3653C>T (p.Thr1218Met) (rs377640390)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167240 SCV000218077 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000233583 SCV000282745 uncertain significance Familial adenomatous polyposis 1 2018-12-25 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 1218 of the APC protein (p.Thr1218Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs377640390, ExAC 0.005%), including at least one homozygous individual. This variant has been reported in an individual affected with colorectal cancer (PMID: 27978560). ClinVar contains an entry for this variant (Variation ID: 187505). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.
Counsyl RCV000233583 SCV000488600 uncertain significance Familial adenomatous polyposis 1 2016-05-10 criteria provided, single submitter clinical testing
GeneDx RCV000483908 SCV000567395 uncertain significance not provided 2018-04-04 criteria provided, single submitter clinical testing This variant is denoted APC c.3653C>T at the cDNA level, p.Thr1218Met (T1218M) at the protein level, and results in the change of a Threonine to a Methionine (ACG>ATG). This variant has been reported in an individual with early-onset colon cancer (Pearlman 2017). APC Thr1218Met was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether APC Thr1218Met is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000167240 SCV000681622 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-14 criteria provided, single submitter 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.