Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001069440 | SCV001234604 | pathogenic | Glycogen storage disease, type IV; Glycogen storage disease IV, classic hepatic | 2019-02-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in GBE1 are known to be pathogenic (PMID: 9851430, 15452297, 20058079, 23034915). This variant has not been reported in the literature in individuals with GBE1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gly416Valfs*12) in the GBE1 gene. It is expected to result in an absent or disrupted protein product. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002271617 | SCV002556005 | likely pathogenic | Glycogen storage disease, type IV | 2022-06-02 | criteria provided, single submitter | clinical testing | Variant summary: GBE1 c.1245_1258del14 (p.Gly416ValfsX12) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 243330 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1245_1258del14 in individuals affected with Glycogen Storage Disease, Type IV and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |