ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.2974G>A (p.Ala992Thr) (rs115193764)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001081527 SCV000289317 benign Colorectal cancer, susceptibility to, 12 2019-12-27 criteria provided, single submitter clinical testing
GeneDx RCV000236957 SCV000293175 uncertain significance not provided 2018-01-09 criteria provided, single submitter clinical testing This variant is denoted POLE c.2974G>A at the cDNA level, p.Ala992Thr (A992T) at the protein level, and results in the change of an Alanine to a Threonine (GCC>ACC). This variant has been observed in at least one individual with advanced cancer (Mandelker 2017). POLE Ala992Thr was observed at an allele frequency of 0.4% (74/18,868) in individuals of East Asian 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 Ala992Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000562428 SCV000671303 likely benign Hereditary cancer-predisposing syndrome 2015-06-24 criteria provided, single submitter clinical testing Subpopulation frequency in support of benign classification;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
PreventionGenetics,PreventionGenetics RCV000236957 SCV000806754 uncertain significance not provided 2018-01-24 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000236957 SCV001134704 benign not provided 2018-10-11 criteria provided, single submitter clinical testing

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