ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.1337G>A (p.Arg446Gln) (rs151273553)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000205876 SCV000262196 likely benign Colorectal cancer, susceptibility to, 12 2019-12-30 criteria provided, single submitter clinical testing
GeneDx RCV000657099 SCV000322490 uncertain significance not provided 2018-09-17 criteria provided, single submitter clinical testing This variant is denoted POLE c.1337G>A at the cDNA level, p.Arg446Gln (R446Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGG>CAG). This variant has been observed in an individual with adenomatous polyposis, one with a microsatellite stable endometrial cancer, and a third individual with malignant melanoma (Church 2013, Spier 2014, Aoude 2015). POLE Arg446Gln was observed at an allele frequency of 0.05% (64/126,514) in individuals of European (Non-Finnish) ancestry in large population cohorts (Lek 2016). POLE Arg446Gln is located within the exonuclease domain (Preston 2010). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether POLE Arg446Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000205876 SCV000488770 uncertain significance Colorectal cancer, susceptibility to, 12 2016-08-12 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000255280 SCV000601975 uncertain significance not specified 2017-03-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000569920 SCV000671276 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-19 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
PreventionGenetics,PreventionGenetics RCV000657099 SCV000806715 uncertain significance not provided 2017-09-01 criteria provided, single submitter clinical testing
Mendelics RCV000709276 SCV000838707 uncertain significance COLORECTAL CANCER 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000657099 SCV000888493 uncertain significance not provided 2017-10-12 criteria provided, single submitter clinical testing

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