ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.4375G>T (p.Glu1459Ter)

dbSNP: rs778238908
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003771048 SCV003028701 pathogenic not provided 2024-07-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu1459*) 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: 1050781). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Dr. med. U. Finckh, Human Genetics, Eurofins MVZ RCV003234793 SCV003932795 likely pathogenic Facial dysmorphism-immunodeficiency-livedo-short stature syndrome; Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency 2023-01-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001358643 SCV001554437 pathogenic Carcinoma of colon no assertion criteria provided clinical testing The POLE p.Glu1459* variant was not identified in the literature nor was it identified in the following databases: dbSNP, ClinVar, Cosmic, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.Glu1459* variant leads to a premature stop codon at position 1459, which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the POLE gene are the type of variant expected to cause the disorder. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic.
Dr. med. U. Finckh, Human Genetics, Eurofins MVZ RCV002548528 SCV003932836 uncertain significance Colorectal cancer, susceptibility to, 12 flagged submission clinical testing

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