ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6665C>T (p.Pro2222Leu) (rs367761032)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478110 SCV000571077 uncertain significance not provided 2016-07-19 criteria provided, single submitter clinical testing This variant is denoted APC c.6665C>T at the cDNA level, p.Pro2222Leu (P2222L) at the protein level, and results in the change of a Proline to a Leucine (CCT>CTT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Pro2222Leu was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Proline and Leucine differ in some properties, this is considered a semi-conservative amino acid substitution. APC Pro2222Leu occurs at a position that is conserved across species and is located in the basic domain (Azzopardi 2008). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether APC Pro2222Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000554526 SCV000647658 uncertain significance Familial adenomatous polyposis 1 2017-04-19 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 2222 of the APC protein (p.Pro2222Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. The frequency data for this variant (rs367761032) in the population databases is unreliable, as metrics indicate poor quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with an APC-related disease. 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, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000569654 SCV000667363 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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.