Submissions for variant NM_000642.3(AGL):c.293+1del

dbSNP: rs777857395

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000409817	SCV000485915	likely pathogenic	Glycogen storage disease type III	2016-03-07	criteria provided, single submitter	clinical testing
Invitae	RCV000409817	SCV000827247	likely pathogenic	Glycogen storage disease type III	2023-11-17	criteria provided, single submitter	clinical testing	This sequence change affects a splice site in intron 3 of the AGL gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494). This variant is present in population databases (rs777857395, gnomAD 0.002%). Disruption of this splice site has been observed in individual(s) with glycogen storage disease with the second AGL variant being unknown (PMID: 20648714). ClinVar contains an entry for this variant (Variation ID: 370565). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000409817	SCV001338160	likely pathogenic	Glycogen storage disease type III	2020-02-14	criteria provided, single submitter	clinical testing	Variant summary: AGL c.293+1delG is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant creates a 5 donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.2e-05 in 250334 control chromosomes (gnomAD). c.293+1delG has been reported in the literature in at least one individual affected with Glycogen Storage Disease Type III (Goldstein_2010). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Mayo Clinic Laboratories, Mayo Clinic	RCV001509044	SCV001715546	likely pathogenic	not provided	2020-03-19	criteria provided, single submitter	clinical testing	PVS1, PM2
Fulgent Genetics, Fulgent Genetics	RCV000409817	SCV002775797	likely pathogenic	Glycogen storage disease type III	2021-09-20	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000409817	SCV003836086	pathogenic	Glycogen storage disease type III	2021-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000409817	SCV004049915	likely pathogenic	Glycogen storage disease type III	2023-04-11	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000409817	SCV001454496	likely pathogenic	Glycogen storage disease type III	2020-09-16	no assertion criteria provided	clinical testing