Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001224672 | SCV001396886 | pathogenic | Glycogen storage disease, type IV; Glycogen storage disease IV, classic hepatic | 2023-07-19 | criteria provided, single submitter | clinical testing | The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 952547). This variant has not been reported in the literature in individuals affected with GBE1-related conditions. This sequence change creates a premature translational stop signal (p.Trp596*) in the GBE1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GBE1 are known to be pathogenic (PMID: 15452297, 20058079). |
| Broad Center for Mendelian Genomics, |
RCV001828791 | SCV002097083 | uncertain significance | Glycogen storage disease, type IV | 2022-01-27 | criteria provided, single submitter | curation | The p.Trp596Ter variant in GBE1 has not been previously reported in the literature in individuals with GBE1-related disorders but has been identified in 0.001% (1/103956) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs201029706). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#: 952547) and has been interpreted as pathogenic by Invitae. This nonsense variant leads to a premature termination codon at position 596, which is predicted to lead to a truncated or absent protein. Loss of function of the GBE1 gene is an established disease mechanism in autosomal recessive GBE1-related disorders. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PVS1, PM2_supporting (Richards 2015). |
| Baylor Genetics | RCV001828791 | SCV004198702 | pathogenic | Glycogen storage disease, type IV | 2023-07-07 | criteria provided, single submitter | clinical testing |