ClinVar Miner

Submissions for variant NM_002863.5(PYGL):c.772+1G>A

gnomAD frequency: 0.00003  dbSNP: rs776545903
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000797589 SCV000937153 likely pathogenic Glycogen storage disease, type VI 2019-02-28 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 6 of the PYGL gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs776545903, ExAC 0.01%). This variant has not been reported in the literature in individuals with PYGL-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PYGL are known to be pathogenic (PMID: 9536091, 21646031). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx RCV003332253 SCV004040359 pathogenic not provided 2023-03-29 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele 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: 33763395, 32892177)

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