ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.2932G>T (p.Glu978Ter)

dbSNP: rs1555225958
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000663250 SCV000786475 likely pathogenic Colorectal cancer, susceptibility to, 12 2018-05-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003656131 SCV001385287 pathogenic not provided 2022-05-27 criteria provided, single submitter clinical testing 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: 548907). This sequence change creates a premature translational stop signal (p.Glu978*) 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). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000758173 SCV002750188 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-15 criteria provided, single submitter clinical testing The p.E978* variant (also known as c.2932G>T), located in coding exon 25 of the POLE gene, results from a G to T substitution at nucleotide position 2932. This changes the amino acid from a glutamic acid to a stop codon within coding exon 25. 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.
True Health Diagnostics RCV000758173 SCV000886709 pathogenic Hereditary cancer-predisposing syndrome 2018-08-09 no assertion criteria provided clinical testing

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