ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.1284del (p.Lys429fs)

dbSNP: rs1057517613
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410913 SCV000489476 uncertain significance Colorectal cancer, susceptibility to, 12 2016-10-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003539877 SCV000946352 pathogenic not provided 2024-07-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys429Argfs*4) in the POLE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POLE are known to be pathogenic (PMID: 23230001, 25948378, 30503519). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with POLE-related conditions. ClinVar contains an entry for this variant (Variation ID: 372007). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003539877 SCV005625186 uncertain significance not provided 2024-04-30 criteria provided, single submitter clinical testing The POLE c.1284del (p.Lys429Argfs*4) variant alters the translational reading frame of the POLE mRNA and is predicted to cause the premature termination of POLE protein synthesis. However, due to limited published evidence, the association of loss-of-function variants in POLE with the cancer predisposition syndrome PPAP (polymerase proofreading-association polyposis) has not been established (PMID: 23447401 (2013)). This variant has not been reported in individuals with POLE-related conditions in the published literature. This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, we are unable to determine the clinical significance of this variant.

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