ClinVar Miner

Submissions for variant NM_015937.6(PIGT):c.494-2A>G

gnomAD frequency: 0.00006  dbSNP: rs200790673
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000707576 SCV000836677 pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 3 2024-10-24 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 3 of the PIGT 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 PIGT are known to be pathogenic (PMID: 24906948, 25943031). This variant is present in population databases (rs200790673, gnomAD 0.01%). Disruption of this splice site has been observed in individual(s) with congenital disorder of glycosylation (PMID: 30813157, 30976099). 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: 583283). 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.
Mendelics RCV000707576 SCV001141240 pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 3 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001092541 SCV001249086 pathogenic not provided 2021-09-01 criteria provided, single submitter clinical testing
GeneDx RCV001092541 SCV001778606 pathogenic not provided 2022-06-07 criteria provided, single submitter clinical testing Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25943031, 30813157, 30976099, 29310717, 24906948, 32725661)
Revvity Omics, Revvity RCV001092541 SCV002018804 pathogenic not provided 2021-10-28 criteria provided, single submitter clinical testing
OMIM RCV000707576 SCV003926532 pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 3 2023-05-26 no assertion criteria provided literature only

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