ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3145T>C (p.Trp1049Arg) (rs587779787)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115078 SCV000148987 uncertain significance not provided 2018-02-26 criteria provided, single submitter clinical testing This variant is denoted APC c.3145T>C at the cDNA level, p.Trp1049Arg (W1049R) at the protein level, and results in the change of a Tryptophan to an Arginine (TGG>CGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Trp1049Arg was not observed in large population cohorts (Lek 2016). This variant is located within the beta-catenin binding domain (Azzopardi 2008). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available information, it is unclear whether APC Trp1049Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000554407 SCV000647429 uncertain significance Familial adenomatous polyposis 1 2018-09-17 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with arginine at codon 1049 of the APC protein (p.Trp1049Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an APC-related disease. ClinVar contains an entry for this variant (Variation ID: 127285). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000569217 SCV000667443 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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.