Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV000056096 | SCV002097088 | pathogenic | Glycogen storage disease, type IV | 2022-01-27 | criteria provided, single submitter | curation | The p.Trp548Ter variant in GBE1 has been reported in 1 individual, in the homozygous state, with glycogen storage disease type IV (GSD IV) (PMID: 1766224) and has been identified in 0.009% (1/11570) of East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs137852894). 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#: 2793) and has been interpreted as pathogenic by OMIM and GeneReviews. In vitro functional studies provide some evidence that the p.Trp548Ter variant may impact protein function (PMID: 1766224). However, these types of assays may not accurately represent biological function. This nonsense variant leads to a premature termination codon at position 548, 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 GSD IV. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for GSD IV. ACMG/AMP Criteria applied: PVS1_strong, PM2_supporting, PS3_moderate, PM3_supporting (Richards 2015). |
OMIM | RCV000002927 | SCV000023085 | pathogenic | Glycogen storage disease due to glycogen branching enzyme deficiency, congenital neuromuscular form | 2007-09-21 | no assertion criteria provided | literature only | |
Gene |
RCV000056096 | SCV000087168 | pathologic | Glycogen storage disease, type IV | 2009-04-02 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |