ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.4237G>A (p.Glu1413Lys) (rs372901803)

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 RCV001079665 SCV000289371 likely benign Colorectal cancer, susceptibility to, 12 2019-12-30 criteria provided, single submitter clinical testing
GeneDx RCV000487363 SCV000569654 likely benign not specified 2017-10-27 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
PreventionGenetics,PreventionGenetics RCV000679632 SCV000806776 uncertain significance not provided 2017-01-10 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000487363 SCV000920078 likely benign not specified 2018-12-14 criteria provided, single submitter clinical testing Variant summary: POLE c.4237G>A (p.Glu1413Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00031 in 277202 control chromosomes (gnomAD). The observed variant frequency is approximately 21.59 fold of the estimated maximal expected allele frequency for a pathogenic variant in POLE causing Colorectal Cancer phenotype (1.4e-05), strongly suggesting that the variant is benign. c.4237G>A has been reported in the literature in individual(s) affected with advanced cancer without strong evidence for causality; the variant was classified by the authors of the study as uncertain significance (Mandelker_2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign (2x) and once as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000679632 SCV001134724 benign not provided 2019-07-08 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.