ClinVar Miner

Submissions for variant NM_002863.5(PYGL):c.1729C>T (p.Gln577Ter)

gnomAD frequency: 0.00010  dbSNP: rs149096315
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000779139 SCV000915644 uncertain significance Glycogen storage disease, type VI 2017-09-19 criteria provided, single submitter clinical testing The PYGL c.1729C>T (p.Gln577Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. The variant has been reported in one study in which it is identified in a compound heterozygous state in a sibling pair who presented initially with hepatomegaly at the age of eight months and 13 months, respectively (Roscher et al. 2014). One sister showed septum wall and left ventricular posterior wall thickening during follow-up three years after diagnosis (Roscher et al. 2014). Control data are unavailable for this variant which is reported at a frequency of 0.000126 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the potential impact of stop-gained variants and limited evidence, the p.Gln577Ter variant is classified as a variant of uncertain significance but suspicious for pathogenicity for glycogen storage disease type VI. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Labcorp Genetics (formerly Invitae), Labcorp RCV000779139 SCV000943489 pathogenic Glycogen storage disease, type VI 2023-11-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln577*) in the PYGL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PYGL are known to be pathogenic (PMID: 9536091, 21646031). This variant is present in population databases (rs149096315, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with glycogen storage disease type VI (PMID: 25266922). ClinVar contains an entry for this variant (Variation ID: 632216). 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.
GeneDx RCV001585707 SCV001818320 likely pathogenic not provided 2022-03-18 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25266922)

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