ClinVar Miner

Submissions for variant NM_000642.3(AGL):c.3682C>T (p.Arg1228Ter) (rs113994131)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000723820 SCV000228427 pathogenic not provided 2014-06-13 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000020377 SCV000914336 likely pathogenic Glycogen storage disease type III 2018-09-12 criteria provided, single submitter clinical testing The AGL c.3682C>T (p.Arg1228Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. The p.Arg1228Ter variant has been reported in at least three studies in which it is found in a total of six individuals with glycogen storage disease type III including in one in a homozygous state, in at least three in a compound heterozygous state and in two in a heterozygous state with no second allele described (Lucchiari et al. 2002; Shen et al. 1996; Crushell et al. 2010). The p.Arg1228Ter variant was absent from 20 controls and is reported at a frequency of 0.000058 in the East Asian population of the Genome Aggregation Database but this is based on one allele in a region of good sequence coverage so the variant is presumed to be rare. Based on the clinical evidence and the potential impact of stop-gained variants, the p.Arg1228Ter variant is classified as pathogenic for glycogen storage disease type III. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000020377 SCV001406228 pathogenic Glycogen storage disease type III 2020-10-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1228*) in the AGL gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with glycogen storage disease (PMID: 8755644, 20490926). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 21216). Loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494). For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000020377 SCV000040765 pathologic Glycogen storage disease type III 2012-09-06 no assertion criteria provided curation Converted during submission to Pathogenic.

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