ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.1231G>T (p.Val411Leu) (rs1057519945)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001420964 SCV001623443 uncertain significance not specified 2021-05-17 criteria provided, single submitter clinical testing Variant summary: POLE c.1231G>T (p.Val411Leu) results in a conservative amino acid change located in the DNA-directed DNA polymerase, family B, exonuclease domain (IPR006133) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250666 control chromosomes (gnomAD). To our knowledge, no germline occurrence of c.1231G>T in individuals affected with Colorectal Cancer has been reported. However, several somatic occurrences of this variant have been reported in the literature (example: PMID: 33727829, 33569431, 32810930). In 3->5 exonuclease activity assay the variant showed reduced activity compared to wild-type (Shinbrot_2014). One ClinVar submitter (evaluation after 2014) cites the variant as likely pathogenic in somatic state. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Database of Curated Mutations (DoCM) RCV000424174 SCV000507161 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434429 SCV000507162 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441211 SCV000507163 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423521 SCV000507164 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only

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