ClinVar Miner

Submissions for variant NM_000038.6(APC):c.296G>A (p.Arg99Gln) (rs199842850)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000585993 SCV000209563 uncertain significance not provided 2018-01-31 criteria provided, single submitter clinical testing This variant is denoted APC c.296G>A at the cDNA level, p.Arg99Gln (R99Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGG>CAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Arg99Gln 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 Arg99Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000197478 SCV000254003 uncertain significance Familial adenomatous polyposis 1 2018-10-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 99 of the APC protein (p.Arg99Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs199842850, ExAC 0.03%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 181832). 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: "Possibly 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.
Counsyl RCV000197478 SCV000489619 uncertain significance Familial adenomatous polyposis 1 2016-11-09 criteria provided, single submitter clinical testing
Ambry Genetics RCV000491566 SCV000579871 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000491566 SCV000681568 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-17 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000585993 SCV000694023 uncertain significance not provided 2015-11-13 criteria provided, single submitter clinical testing
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000761017 SCV000890932 uncertain significance B Lymphoblastic Leukemia/Lymphoma with Hypodiploidy 2016-03-03 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.