ClinVar Miner

Submissions for variant NC_000012.11:g.(?_133222176)_133226475del

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001362859 SCV001558907 uncertain significance Colorectal cancer, susceptibility to, 12 2020-08-07 criteria provided, single submitter clinical testing This variant is a complex sequence change that deletes the genomic region encompassing exons 30-32 and inserts another 47 nucleotides at the intron 29-exon 30 boundary (c.3583_4150-1613delins47) of the POLE gene. It is expected to result in a frameshift (p.Val1195Trpfs*951) and disrupt the last 1092 amino acids of the POLE protein. This variant has not been reported in the literature in individuals with POLE-related disease. ClinVar contains an entry for this variant (Variation ID: 861109). Missense variants that disrupt the 3'-5' exonuclease (proof-reading) activity of the POLE protein are associated with an increased risk for colonic adenomatous polyps and colon cancer (PMID: 23263490, 23447401). However, loss-of-function variants that result in an absent or severely disrupted POLE protein, and missense variants outside the exonuclease domain, are unlikely to be associated with polyposis or colon cancer. Without further clinical and genetic evidence, this variant has been classified as a Variant of Uncertain Significance.

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