ClinVar Miner

Submissions for variant NM_000642.3(AGL):c.4456del (p.Ser1486fs) (rs113994134)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000723822 SCV000229651 pathogenic not provided 2014-06-13 criteria provided, single submitter clinical testing
Invitae RCV000177731 SCV000626759 pathogenic Glycogen storage disease type III 2017-08-24 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 33 of the AGL mRNA (c.4456delT), causing a frameshift at codon 1486. This creates a premature translational stop signal in the last exon of the AGL mRNA (p.Ser1486Profs*18). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 47 amino acids of the AGL protein. This variant has been reported in individuals affected with glycogen storage disease III (PMID:  27065010, 25602008 9412782, 25388549, 27460348). This variant is also known as c.4455delT n the literature. For these reasons, this variant has been classified as Pathogenic.
Myriad Women's Health, Inc. RCV000177731 SCV001194233 pathogenic Glycogen storage disease type III 2019-12-20 criteria provided, single submitter clinical testing NM_000642.2(AGL):c.4456delT(S1486Pfs*18) is classified as pathogenic in the context of glycogen storage disease type III. Sources cited for classification include the following: PMID 9412782 and 25602008. Classification of NM_000642.2(AGL):c.4456delT(S1486Pfs*18) is based on the following criteria: The variant causes a premature termination codon that is not expected to be targeted by nonsense-mediated mRNA decay; however, literature evidence strongly supports pathogenicity. Please note: this variant was assessed in the context of healthy population screening.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000723822 SCV001248397 pathogenic not provided 2018-11-01 criteria provided, single submitter clinical testing
GeneDx RCV000723822 SCV001804369 pathogenic not provided 2020-11-25 criteria provided, single submitter clinical testing Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 47 amino acids are lost and replaced with 17 incorrect amino acids (Stenson et al., 2014);; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 31661040, 28888851, 25388549, 25602008, 27460348, 9412782)
OMIM RCV000001156 SCV000021306 pathogenic Glycogen storage disease IIIa 1997-09-01 no assertion criteria provided literature only
GeneReviews RCV000177731 SCV000040768 pathologic Glycogen storage disease type III 2012-09-06 no assertion criteria provided curation Converted during submission to Pathogenic.
Natera, Inc. RCV000177731 SCV001460667 pathogenic Glycogen storage disease type III 2020-09-16 no assertion criteria provided clinical testing

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