ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.857C>G (p.Pro286Arg)

dbSNP: rs1057519943
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
Labcorp Genetics (formerly Invitae), Labcorp RCV003766182 SCV000653485 uncertain significance not provided 2017-01-12 criteria provided, single submitter clinical testing In summary, this variant is a rare missense change that is not present in the population and has been shown to affect protein function. Although this variant has been found as a frequent somatic event in tumors, it has not been observed in the germline of affected individuals. In the absence of genetic and/or additional evidence, this variant has been classified as Variant of Uncertain Significance. This variant is located within the evolutionarily conserved exonuclease domain of the POLE protein (PMID: 23447401, 24525744). Experimental studies have shown that the P301R yeast mutant, corresponding to the p.Pro286Arg change, severely affects the fidelity rather than the proofreading function of the POLE protein, causing a strong mutator phenotype in a yeast model system (PMID: 24525744). In addition, this variant showed a reduced 3'-5' exonuclease activity compared to the wild-type protein (PMID: 25228659). This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in the germline of individuals with a POLE-related disease, however, it has been reported as a frequent somatic change in endometrial and colorectal cancers (PMID: 23263490, 23447401, 25224212, 24525744). This sequence change replaces proline with arginine at codon 286 of the POLE protein (p.Pro286Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine.
Oxford Haemato-Oncology Service, Oxford University Hospitals NHS Foundation Trust RCV000626454 SCV000734844 drug response Programmed death ligand-1 (PD-L1) blocking antibody response 2017-11-27 no assertion criteria provided clinical testing
Gynecological Pathology Laboratory, Kaohsiung Medical University Chung-Ho Memorial Hospital RCV002480276 SCV002769683 established risk allele Endometrioid adenocarcinoma 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.