Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001062519 | SCV001227326 | pathogenic | Glycogen storage disease type III | 2024-06-23 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln719*) in the AGL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with glycogen storage disease (PMID: 20648714). ClinVar contains an entry for this variant (Variation ID: 856946). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001062519 | SCV002766090 | likely pathogenic | Glycogen storage disease type III | 2022-11-18 | criteria provided, single submitter | clinical testing | Variant summary: AGL c.2155C>T (p.Gln719X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250058 control chromosomes (gnomAD). c.2155C>T has been reported in the literature in individuals affected with Glycogen Storage Disease (example: Hijazi_2021 and Sadeh_2021). These data indicate that the variant may be associated with disease. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Genome- |
RCV001062519 | SCV004049992 | likely pathogenic | Glycogen storage disease type III | 2023-04-11 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV001062519 | SCV004216191 | pathogenic | Glycogen storage disease type III | 2023-09-25 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV001062519 | SCV005086585 | pathogenic | Glycogen storage disease type III | 2024-09-21 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with glycogen storage disease IIIa (MIM#232400) and glycogen storage disease IIIb (MIM#232400). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been classified as pathogenic or likely pathogenic by several clinical laboratories in ClinVar, and has been observed with another NMD-predicted variant in at least one individual with glycogen storage disease in the literature (PMIDs: 34820282, 23062577). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |