ClinVar Miner

Submissions for variant NM_000642.3(AGL):c.664+3A>G (rs370792293)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169374 SCV000220754 likely pathogenic Glycogen storage disease type III 2014-09-30 criteria provided, single submitter literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000585987 SCV000697535 pathogenic Glycogen storage disease IIIa 2017-04-21 criteria provided, single submitter clinical testing Variant summary: The AGL c.664+3A>G variant is an intronic change that involves a conserved nucleotide. 3/5 splice prediction tools predict an impact on normal splicing, which was confirmed by Lucchiar_2002. The cDNA analysis revealed found an in-frame deletion of exon 6 caused by the variant of interest, and, as confirmation, all homozygous patients showed no enzymatic residual activity. This variant was found in 2/120192 control chromosomes at a frequency of 0.0000166, which does not exceed the estimated maximal expected allele frequency of a pathogenic AGL variant (0.0022822). The variant was identified in multiple GSD III patients homozygously or in compound heterozygosity. Lastly, a clinical diagnostic laboratory classifies the variant as "likely pathogenic." Taking together, the variant of interest has been classified as "pathogenic."
Invitae RCV000169374 SCV001382430 pathogenic Glycogen storage disease type III 2019-09-28 criteria provided, single submitter clinical testing This sequence change falls in intron 5 of the AGL gene. It does not directly change the encoded amino acid sequence of the AGL protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs370792293, ExAC 0.003%). This variant has been observed in several individuals affected with glycogen storage disease type III (PMID: 16705713, 12442284, 21691223). This variant is also known as IVS6 +3 A>G in the literature. ClinVar contains an entry for this variant (Variation ID: 188994). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 12442284). For these reasons, this variant has been classified as Pathogenic.
Division of Human Genetics,Children's Hospital of Philadelphia RCV000169374 SCV000536700 likely pathogenic Glycogen storage disease type III 2014-10-31 no assertion criteria provided research
Natera, Inc. RCV000169374 SCV001454498 pathogenic Glycogen storage disease type III 2020-09-16 no assertion criteria provided clinical testing

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