ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4714A>T (p.Ile1572Phe) (rs750107668)

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 RCV000573193 SCV000667624 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-07 criteria provided, single submitter clinical testing Insufficient evidence
Color RCV000573193 SCV000681680 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-02 criteria provided, single submitter clinical testing
Invitae RCV000806673 SCV000946686 uncertain significance Familial adenomatous polyposis 1 2019-09-10 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with phenylalanine at codon 1572 of the APC protein (p.Ile1572Phe). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and phenylalanine. This variant is present in population databases (rs750107668, ExAC 0.01%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 482393). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or 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.
Integrated Genetics/Laboratory Corporation of America RCV001194205 SCV001363553 uncertain significance not specified 2019-06-17 criteria provided, single submitter clinical testing Variant summary: APC c.4714A>T (p.Ile1572Phe) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250770 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.4714A>T in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000761119 SCV000891035 uncertain significance Papillary renal cell carcinoma 2016-12-07 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.