ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.4730A>C (p.Glu1577Ala) (rs5744948)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001079676 SCV000289401 likely benign Colorectal cancer, susceptibility to, 12 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000657111 SCV000293810 uncertain significance not provided 2018-01-25 criteria provided, single submitter clinical testing This variant is denoted POLE c.4730A>C at the cDNA level, p.Glu1577Ala (E1577A) at the protein level, and results in the change of a Glutamic Acid to an Alanine (GAG>GCG). In one yeast-based functional assay this variant, defined as E1582A in yeast, demonstrated colony growth and spontaneous mutation rates comparable to wild-type; however, this assay did not include a known pathogenic variant to serve as a positive control (Daee 2010). POLE Glu1577Ala was observed at an allele frequency of 0.2% (48/24,012) in individuals of African ancestry in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In-silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether POLE Glu1577Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000236705 SCV000602056 benign not specified 2017-03-29 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000657111 SCV000806790 uncertain significance not provided 2017-08-11 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000679006 SCV000805302 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-27 no assertion criteria provided clinical testing

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