ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.796C>T (p.Arg266Ter)

gnomAD frequency: 0.00001  dbSNP: rs767666219
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000662418 SCV000784854 uncertain significance Colorectal cancer, susceptibility to, 12 2017-01-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV001027015 SCV001189503 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-26 criteria provided, single submitter clinical testing The p.R266* variant (also known as c.796C>T), located in coding exon 8 of the POLE gene, results from a C to T substitution at nucleotide position 796. This changes the amino acid from an arginine to a stop codon within coding exon 8. 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 RCV003656649 SCV001517950 pathogenic not provided 2023-07-12 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 548720). This variant has not been reported in the literature in individuals affected with POLE-related conditions. This variant is present in population databases (rs767666219, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Arg266*) 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).

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