Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center of Genomic medicine, |
RCV000501317 | SCV000598137 | pathogenic | Adult polyglucosan body disease | 2016-11-15 | criteria provided, single submitter | clinical testing | This heterozygous variant in the GBE1 gene (autosomal recessive transmission), inherited from the mother, was present in a female patient who also harbours a second variant in the same codon of same gene inherited by the father (compound heterozygosity). |
| Broad Center for Mendelian Genomics, |
RCV001826408 | SCV002097114 | uncertain significance | Glycogen storage disease, type IV | 2022-01-27 | criteria provided, single submitter | curation | The p.Arg262Cys variant in GBE1 has been reported in 1 individual, in the compound heterozygous state, with glycogen storage disease type IV (GSD IV) (PMID: 16528737) and has been identified in 0.003% (3/103974) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs137852893). 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#: 2791) and has been interpreted as pathogenic by OMIM and Center of Genomic medicine (Geneva, University Hospital of Geneva). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. The phenotype of an individual compound heterozygous for this variant is highly specific for GSD IV based on strict biochemical investigations consistent with disease (PMID: 16528737). In summary, the clinical significance of the p.Arg262Cys variant is uncertain. ACMG/AMP Criteria applied: PP3, PM2_supporting, PP4 (Richards 2015). |
| Invitae | RCV002512687 | SCV003525253 | uncertain significance | Glycogen storage disease, type IV; Glycogen storage disease IV, classic hepatic | 2022-08-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 262 of the GBE1 protein (p.Arg262Cys). This variant is present in population databases (rs137852893, gnomAD 0.003%). This missense change has been observed in individual(s) with glycogen storage disease (PMID: 16528737). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 2791). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Baylor Genetics | RCV001826408 | SCV004198681 | likely pathogenic | Glycogen storage disease, type IV | 2023-09-13 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000002925 | SCV000023083 | pathogenic | Glycogen storage disease due to glycogen branching enzyme deficiency, congenital neuromuscular form | 2006-04-15 | no assertion criteria provided | literature only |