ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.1021G>T (p.Ala341Ser) (rs137860861)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000988954 SCV000289235 likely benign Colorectal cancer, susceptibility to, 12 2019-12-23 criteria provided, single submitter clinical testing
GeneDx RCV000657097 SCV000568953 uncertain significance not provided 2018-04-06 criteria provided, single submitter clinical testing This variant is denoted POLE c.1021G>T at the cDNA level, p.Ala341Ser (A341S) at the protein level, and results in the change of an Alanine to a Serine (GCT>TCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. POLE Ala341Ser was observed at an allele frequency of 0.1% in individuals of African ancestry in large population cohorts (Lek 2016). This variant is located in the exonuclease domain and the Pol IV polymerase domain motif (Preston 2010). While protein-based in silico analysis supports that this variant does not alter protein structure/function, splicing models are inconsistent in their assessment as to whether or not the variant is damaging. 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 Ala341Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000487424 SCV000601970 uncertain significance not specified 2017-05-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV000573548 SCV000671374 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-27 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Mendelics RCV000988954 SCV001138897 uncertain significance Colorectal cancer, susceptibility to, 12 2019-05-28 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000573548 SCV000788158 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-10 no assertion criteria provided clinical testing

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