ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5179T>C (p.Cys1727Arg) (rs758815860)

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
Invitae RCV000234200 SCV000282774 uncertain significance Familial adenomatous polyposis 1 2018-07-05 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 1727 of the APC protein (p.Cys1727Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is present in population databases (rs758815860, ExAC 0.002%). This variant has been reported in an individual who underwent testing for familial adenomatous polyposis (PMID: 23159591). ClinVar contains an entry for this variant (Variation ID: 236615). 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.
GeneDx RCV000478622 SCV000567794 uncertain significance not provided 2017-11-21 criteria provided, single submitter clinical testing This variant is denoted APC c.5179T>C at the cDNA level, p.Cys1727Arg (C1727R) at the protein level, and results in the change of a Cysteine to an Arginine (TGC>CGC). This variant has been reported in at least one individual undergoing clinical evaluation for Familial Adenomatous Polyposis (Kerr 2013). APC Cys1727Arg was not observed at a significant allele frequency in large population cohorts (Lek 2016). Since Cysteine and Arginine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Cys1727Arg is located in the SAMP repeats/axin binding domain and the beta-catenin down-regulating domain (Azzopardi 2008). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Based on currently available evidence, it is unclear whether APC Cys1727Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000566764 SCV000667271 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000566764 SCV000681712 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-07 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000478622 SCV000887532 uncertain significance not provided 2017-10-25 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.