ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.2171C>T (p.Ala724Val) (rs61734163)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000233305 SCV000289291 likely benign Colorectal cancer, susceptibility to, 12 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000657086 SCV000293515 uncertain significance not provided 2018-11-19 criteria provided, single submitter clinical testing This variant is denoted POLE c.2171C>T at the cDNA level, p.Ala724Val (A724V) at the protein level, and results in the change of an Alanine to a Valine (GCG>GTG). This variant has been reported in at least one individual with breast cancer (Dominguez-Valentin 2018). POLE Ala724Val was observed at an allele frequency of 0.06% (68/114,056) in individuals of European ancestry in large population cohorts (Lek 2016). POLE Ala724Val is located in the polymerase domain (Preston 2010). While protein-based in silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function, multiple splicing models predict that this variant may create a cryptic splice donor site and lead to abnormal splicing. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. Based on currently available evidence, it is unclear whether POLE Ala724Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000575275 SCV000671257 uncertain significance Hereditary cancer-predisposing syndrome 2015-06-19 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;In silico models in agreement (benign)
Mendelics RCV000709268 SCV000838699 uncertain significance COLORECTAL CANCER 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000657086 SCV000888509 uncertain significance not provided 2019-05-07 criteria provided, single submitter clinical testing

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