ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.4551+2_4551+3delTG (rs1251654299)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000508279 SCV000602050 uncertain significance not specified 2017-03-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV000570392 SCV000671668 uncertain significance Hereditary cancer-predisposing syndrome 2017-02-27 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000650737 SCV000772586 uncertain significance Colorectal cancer, susceptibility to, 12 2019-11-03 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 35 of the POLE gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with colorectal cancer (PMID: 28975465). ClinVar contains an entry for this variant (Variation ID: 439274). Missense variants that disrupt the 3'-5' exonuclease (proof-reading) activity of the POLE protein, while not abolishing its polymerase enzyme activity, are associated with an increased risk for colonic adenomatous polyps and colon cancer (PMID: 23263490, 23447401). Loss-of-function variants, which result in an absent or severely disrupted POLE protein, are therefore unlikely to be associated with disease. Without further clinical and genetic evidence, however, this variant has been classified as a Variant of Uncertain Significance.

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