Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000559264 | SCV000626659 | pathogenic | Glycogen storage disease type III | 2017-05-09 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494). This sequence change deletes 1 nucleotide from exon 9 of the AGL mRNA (c.1102delG), causing a frameshift at codon 368. This creates a premature translational stop signal (p.Glu368Lysfs*14) and is expected to result in an absent or disrupted protein product. |
| Stanford Center for Inherited Cardiovascular Disease, |
RCV000786274 | SCV000925029 | pathogenic | not provided | 2017-06-19 | no assertion criteria provided | provider interpretation | Given that this type of variant results in a loss-of-function of one copy of the AGL gene, and its absence in population databases, we consider this variant pathogenic and we do feel it is suitable to offer carrier testing to relatives. The AGL gene encodes the glycogen debrancher enzyme. Two loss-of-function variants causes glycogen storage disease IIIb. At this point, we have identified ONE pathogenic variant in AGL. This does NOT give a patient a diagnosis of glycogen storage disease IIIb. Typical features of GSD IIIb are ketotic hypoglycemia in infancy and early childhood, hepatomegaly, hyperlipidemia and elevated hepatic transaminases. Hypertrophic cardiomyopathy develops during childhood which ranges from mild to severe. Skeletal myopathy is a prominent feature in the 20s and 30s. The presence of a single variant in the AGL gene is unlikely to cause heart disease in our patient. The patient was found to be a carrier by chance. This variant has not been reported in the literature; however, frameshift variants in AGL are a known mechanism of loss-of-function. This variant is not listed in the Genome Aggregation Consortium Dataset (gnomAD; http://gnomad.broadinstitute.org/), which currently includes variant calls on >140,000 unrelated individuals of African, Asian, European, Latino, and Ashkenazi descent. The average coverage at that site in gnomAD is 40x. |