ClinVar Miner

Submissions for variant NM_000642.3(AGL):c.2929C>T (p.Arg977Ter) (rs531425980)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000412306 SCV000486438 likely pathogenic Glycogen storage disease type III 2016-06-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000412306 SCV000918399 pathogenic Glycogen storage disease type III 2017-09-22 criteria provided, single submitter clinical testing Variant summary: The AGL c.2929C>T (p.Arg977X) variant results in a premature termination codon, predicted to cause a truncated or absent AGL protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., c.3216_3217delGA [p.Glu1072fsX36] and c.4529dupA [p.Tyr1510X]). MutationTaster predicts a damaging outcome for this variant. This variant was found in 1/30932 control chromosomes at a frequency of 0.0000323, which does not exceed the estimated maximal expected allele frequency of a pathogenic AGL variant (0.0022822). Of note, this is a low-quality site in the gnomAD dataset, which may make interpretation of this data unreliable. The variant has been identified in several compound heterozygote patients diagnosed with GSD III, several of whom were confirmed to have no residual AGL enzyme activity (Paesold-Burda_2007, Lucchiari_2006). One clinical diagnostic laboratory has classified this variant as likely pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000412306 SCV001211777 pathogenic Glycogen storage disease type III 2020-08-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg977*) 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 to be in combination with another AGL variant in an individual affected with glycogen storage disease type III (PMID: 16705713). ClinVar contains an entry for this variant (Variation ID: 370992). Loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494). For these reasons, this variant has been classified as Pathogenic.

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