Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000779138 | SCV000915643 | uncertain significance | Glycogen storage disease, type VI | 2018-10-19 | criteria provided, single submitter | clinical testing | The PYGL c.2467C>T (p.Gln823Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. The variant has been reported in one individual affected with glycogen storage disease in a compound heterozygous state with a missense variant (Wang et al. 2012). Control data are unavailable for this variant, which is reported at a frequency of 0.00081 in the East Asian population of the Exome Aggregation Consortium. Based on the potential impact of stop-gained variants and limited evidence, the p.Gln823Ter variant is classified as a variant of unknown 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. |
Invitae | RCV000779138 | SCV000953926 | pathogenic | Glycogen storage disease, type VI | 2023-03-23 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 632215). This premature translational stop signal has been observed in individual(s) with glycogen storage disease (PMID: 22899091; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs756205397, gnomAD 0.09%). This sequence change creates a premature translational stop signal (p.Gln823*) in the PYGL gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 25 amino acid(s) of the PYGL protein. |