ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7808A>G (p.Glu2603Gly) (rs587779807)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115123 SCV000149032 uncertain significance not provided 2017-12-18 criteria provided, single submitter clinical testing This variant is denoted APC c.7808A>G at the cDNA level, p.Glu2603Gly (E2603G) at the protein level, and results in the change of a Glutamic Acid to a Glycine (GAA>GGA). This variant has been reported in at least one individual with a Lynch syndrome-associated tumor and/or colon polyps (Yurgelun 2015). APC Glu2603Gly was not observed at a significant allele frequency in large population cohorts (Lek 2016). Since Glutamic Acid and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Glu2603Gly is located within the EB1 binding domain (Azzopardi 2008). In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Based on currently available information, it is unclear whether APC Glu2603Gly is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000568789 SCV000667260 uncertain significance Hereditary cancer-predisposing syndrome 2016-12-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Counsyl RCV000663283 SCV000786524 uncertain significance Familial adenomatous polyposis 1 2018-05-18 criteria provided, single submitter clinical testing
Invitae RCV000663283 SCV000813889 uncertain significance Familial adenomatous polyposis 1 2018-05-12 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 2603 of the APC protein (p.Glu2603Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with suspected Lynch syndrome (PMID: 25980754). ClinVar contains an entry for this variant (Variation ID: 127321). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; 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.

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.