Total submissions: 17
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000020379 | SCV000220759 | likely pathogenic | Glycogen storage disease type III | 2014-09-30 | criteria provided, single submitter | literature only | |
Eurofins Ntd Llc |
RCV000675344 | SCV000229533 | pathogenic | not provided | 2014-06-13 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000020379 | SCV000626749 | pathogenic | Glycogen storage disease type III | 2024-01-20 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 31 of the AGL gene. It does not directly change the encoded amino acid sequence of the AGL protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs369973784, gnomAD 0.02%). This variant has been observed in individuals with glycogen storage disease type III (GSDIII) (PMID: 9490286, 10655153, 11924557, 20648714, 22089644, 23430490, 25827695). It has also been observed to segregate with disease in related individuals. This variant is also known as IVS32-12A>G. ClinVar contains an entry for this variant (Variation ID: 1099). Studies have shown that this variant results in 11 nucleotide insertion and introduces a premature termination codon (PMID: 9490286). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV000020379 | SCV001162837 | pathogenic | Glycogen storage disease type III | 2024-03-14 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000020379 | SCV001362038 | pathogenic | Glycogen storage disease type III | 2019-10-31 | criteria provided, single submitter | clinical testing | Variant summary: AGL c.4260-12A>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Two predict the variant abolishes a canonical 3 acceptor site. Three predict the variant creates a cryptic 3 acceptor site. At least two publication reports this variant created a new 3' splice site and resulted in insertion of an 11-bp intron sequence between exon 32 and exon 33 in the patients debrancher mRNA. The predicted mutant enzyme was truncated by 112 amino acids as a result of premature termination (p.Phe1420Hisfs*16) (Okubo_1998, Shaiu_2000). The variant allele was found at a frequency of 5.8e-05 in 243346 control chromosomes (gnomAD). c.4260-12A>G has been reported in the literature in multiple individuals in compound heterozygous or homozygous states affected with Glycogen Storage Disease Type III (Okubo_1998, Shaiu_2000, Lu_2016, Sentner_2012). These data indicate that the variant is very likely to be associated with disease. At least two publication reports this variant had an impact on protein function and debrancher activity in a liver specimen was reduced to less than 30% of the control value (Okubo_1998, Shaiu_2000). Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Genome- |
RCV000020379 | SCV001623484 | likely pathogenic | Glycogen storage disease type III | 2021-05-18 | criteria provided, single submitter | clinical testing | |
Genetics and Molecular Pathology, |
RCV000020379 | SCV002556779 | pathogenic | Glycogen storage disease type III | 2021-07-12 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000020379 | SCV002778005 | pathogenic | Glycogen storage disease type III | 2022-01-07 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003407251 | SCV004109165 | pathogenic | AGL-related disorder | 2023-02-10 | criteria provided, single submitter | clinical testing | The AGL c.4260-12A>G variant is predicted to interfere with splicing. This variant has been reported, homozygous, in four families with multiple affected individuals with glycogen storage disease type 3 (GSD III). Haplotype analysis showed that this variant is a founder mutation in Saudia Arabia and cDNA sequence analysis showed that it leads to a truncated protein (Basit et al. 2014. PubMed ID: 25827695). It’s also been reported in the homozygous and compound heterozygous state in multiple unrelated patients, including one patient who showed excessive accumulation of glycogen in the liver (Okubo et al. 1998. PubMed ID: 9490286, Hijazi et al. 2021. PubMed ID: 34820282, Table S1 - Fang et al. 2021. PubMed ID: 33763395). This variant is reported in 0.016% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-100381954-A-G). This variant is interpreted as pathogenic. |
Gene |
RCV000675344 | SCV004168970 | likely pathogenic | not provided | 2023-04-06 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect (Okubo et al., 1998); In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 9490286, 33763395, 31589614, 34820282, 25827695) |
Revvity Omics, |
RCV000020379 | SCV004235534 | pathogenic | Glycogen storage disease type III | 2023-06-21 | criteria provided, single submitter | clinical testing | |
Center for Genomic Medicine, |
RCV000020379 | SCV004805787 | pathogenic | Glycogen storage disease type III | 2024-03-29 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000001157 | SCV000021307 | pathogenic | Glycogen storage disease IIIb | 2000-01-01 | no assertion criteria provided | literature only | |
OMIM | RCV000001158 | SCV000021308 | pathogenic | Glycogen storage disease IIIa | 2000-01-01 | no assertion criteria provided | literature only | |
Gene |
RCV000020379 | SCV000055699 | not provided | Glycogen storage disease type III | no assertion provided | literature only | Associated with milder phenotype | |
Mayo Clinic Laboratories, |
RCV000675344 | SCV000801010 | pathogenic | not provided | 2018-01-09 | no assertion criteria provided | clinical testing | |
Natera, |
RCV000020379 | SCV002094577 | pathogenic | Glycogen storage disease type III | 2020-07-20 | no assertion criteria provided | clinical testing |