Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001210452 | SCV001381940 | pathogenic | Glycogen storage disease type III | 2019-09-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 13 of the AGL gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Disruption of this splice site has been observed in several individuals with glycogen storage disease type IIIa and has been observed to segregate with disease in a family (PMID: 8702417, 26984562, 29614965). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. |