ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.1180C>T (p.Gln394Ter)

dbSNP: rs1565975090
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000679597 SCV000806712 uncertain significance not provided 2017-01-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV001010161 SCV001170316 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-29 criteria provided, single submitter clinical testing The p.Q394* variant (also known as c.1180C>T), located in coding exon 12 of the POLE gene, results from a C to T substitution at nucleotide position 1180. This changes the amino acid from a glutamine to a stop codon within coding exon 12. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, loss of function via haploinsufficiency in POLE has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000679597 SCV002197715 pathogenic not provided 2024-08-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln394*) 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: 560839). For these reasons, this variant has been classified as Pathogenic.

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