Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000708305 | SCV000837415 | likely pathogenic | Glycogen storage disease, type IV; Glycogen storage disease IV, classic hepatic | 2018-12-31 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 2-16 of the GBE1 gene. The 5' boundary is likely confined to intron 1. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. This variant has not been reported in the literature in individuals with GBE1-related disease. Two missense substitutions (p.Tyr329Cys and p.Tyr329Ser) have been determined to be pathogenic (PMID: 23034915, 8613547, 25665141, 26199317, 26385640). This suggests that the tyrosine residue is critical for GBE1 protein function and that deletion of this region may also be pathogenic. 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. |