ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.940T>G (p.Ser314Ala) (rs770403791)

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
University of Washington Department of Laboratory Medicine, University of Washington RCV000210168 SCV000266225 uncertain significance Hereditary cancer-predisposing syndrome 2015-11-20 criteria provided, single submitter clinical testing
Invitae RCV000474943 SCV000544122 likely benign Colorectal cancer, susceptibility to, 12 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000657078 SCV000568365 uncertain significance not provided 2018-06-13 criteria provided, single submitter clinical testing This variant is denoted POLE c.940T>G at the cDNA level, p.Ser314Ala (S314A) at the protein level, and results in the change of a Serine to an Alanine (TCA>GCA). This variant was observed in at least three individuals; one with a personal history of prostate and pancreatic cancer, another with an autism spectrum disorder, and the last being someone undergoing multigene hereditary cancer panel testing (Cukier 2014, Mu 2016, Shirts 2016). POLE Ser314Ala was observed at an allele frequency of 0.23% (23/10,130) in individuals of Ashkenazi Jewish ancestry in large population cohorts (Lek 2016). This variant is located in the exonuclease domain (Preston 2010). 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 POLE Ser314Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000483379 SCV000602106 uncertain significance not specified 2017-04-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV000210168 SCV000671262 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-10 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Counsyl RCV000474943 SCV000784851 uncertain significance Colorectal cancer, susceptibility to, 12 2017-01-25 criteria provided, single submitter clinical testing
Mendelics RCV000709278 SCV000838709 uncertain significance COLORECTAL CANCER 2018-07-02 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.