ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.1433+2T>C

gnomAD frequency: 0.00001  dbSNP: rs920850257
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001956083 SCV002237809 pathogenic Progressive sclerosing poliodystrophy 2023-08-17 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 7 of the POLG gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in POLG are known to be pathogenic (PMID: 18546365). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with Alpers syndrome (PMID: 21880868). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1457847). 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.
Baylor Genetics RCV001956083 SCV004205870 likely pathogenic Progressive sclerosing poliodystrophy 2023-09-25 criteria provided, single submitter clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV004698864 SCV005200911 likely pathogenic POLG-related disorder 2024-06-26 criteria provided, single submitter clinical testing PVS1, PM2

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