Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001247939 | SCV001421392 | pathogenic | Glycogen storage disease, type IV; Glycogen storage disease IV, classic hepatic | 2023-08-04 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with GBE1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Asp24Thrfs*15) 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). ClinVar contains an entry for this variant (Variation ID: 972014). For these reasons, this variant has been classified as Pathogenic. |
| Broad Center for Mendelian Genomics, |
RCV001830027 | SCV002097124 | likely pathogenic | Glycogen storage disease, type IV | 2022-01-27 | criteria provided, single submitter | curation | The p.Asp24fs variant in GBE1 has not been previously reported in the literature in individuals with GBE1-related disorders but has been identified in 0.007% (1/15356) of African/African American chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs1407149518). 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#: 972014) and has been interpreted as pathogenic by Invitae. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 24 and leads to a premature termination codon 15 amino acids downstream. This alteration is then 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, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive GBE1-related disorders. ACMG/AMP Criteria applied: PVS1, PM2 (Richards 2015). |
| Baylor Genetics | RCV001830027 | SCV005058931 | likely pathogenic | Glycogen storage disease, type IV | 2024-01-02 | criteria provided, single submitter | clinical testing |