ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7588C>T (p.Arg2530Trp) (rs730881265)

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
GeneDx RCV000656751 SCV000209552 uncertain significance not provided 2017-08-08 criteria provided, single submitter clinical testing This variant is denoted APC c.7588C>T at the cDNA level, p.Arg2530Trp (R2530W) at the protein level, and results in the change of an Arginine to a Tryptophan (CGG>TGG). This variant has not been reported as a germline pathogenic variant to our knowledge, but has been published as a somatic variant in gastric cancer, neuroblastoma, and at least one sporadic colorectal cancer tumor with no loss of heterozygosity (Christie 2013, Chen 2015, Padovan-Merhar 2016). APC Arg2530Trp was observed at an allele frequency of 0.009% (6/66708) in individuals of European (Non-Finnish) ancestry in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Arginine and Tryptophan differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Arg2530Trp occurs at a position that is conserved across species and is not located in a known functional domain. In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether APC Arg2530Trp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000159576 SCV000217928 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000472135 SCV000552720 uncertain significance Familial adenomatous polyposis 1 2018-12-06 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 2530 of the APC protein (p.Arg2530Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs730881265, ExAC 0.009%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 181824). 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: "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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000211935 SCV000600154 uncertain significance not specified 2017-06-13 criteria provided, single submitter clinical testing
Color RCV000159576 SCV000681879 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-17 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.