Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003764518 | SCV004569657 | likely pathogenic | Glycogen storage disease, type IV; Glycogen storage disease IV, classic hepatic | 2022-10-18 | criteria provided, single submitter | clinical testing | 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. Studies have shown that disruption of this splice site results in skipping of exon 7, but is expected to preserve the integrity of the reading-frame (PMID: 8613547). Experimental studies have shown that disruption of this splice site affects GBE1 function (PMID: 8613547). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 2776). This variant is also known as a 210-bp deletion from nucleotide 873 to 1082 due to a g-to-a substitution at the 3' end of the intron. Disruption of this splice site has been observed in individual(s) with glycogen storage disease (PMID: 8613547). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 6 of the GBE1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. |
| OMIM | RCV000002906 | SCV000023064 | pathogenic | Glycogen storage disease due to glycogen branching enzyme deficiency, congenital neuromuscular form | 1996-02-15 | no assertion criteria provided | literature only |