ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.2818A>G (p.Met940Val) (rs148382941)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235528 SCV000293857 uncertain significance not provided 2018-08-02 criteria provided, single submitter clinical testing This variant is denoted POLE c.2818A>G at the cDNA level, p.Met940Val (M940V) at the protein level, and results in the change of a Methionine to a Valine (ATG>GTG). This variant has been observed in a pediatric patient with neuroblastoma and in at least one individual with an unspecified advanced cancer undergoing multi-gene panel testing (Zhang 2015, Mandelker 2017). POLE Met940Val was observed at an allele frequency of 0.13% (13/9,850) in individuals of Ashkenazi Jewish ancestry in large population cohorts (Lek 2016). This variant is located in the polymerase 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 Met940Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV001083194 SCV000544038 likely benign Colorectal cancer, susceptibility to, 12 2019-12-31 criteria provided, single submitter clinical testing

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