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

gnomAD frequency: 0.00001  dbSNP: rs531425980

Total submissions: 9

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	2022-11-15	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 370992). This premature translational stop signal has been observed in individual(s) with glycogen storage disease type III (PMID: 16705713). This variant is present in population databases (rs531425980, gnomAD 0.007%). 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. Loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494).
Genome-Nilou Lab	RCV000412306	SCV002055492	pathogenic	Glycogen storage disease type III	2021-07-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000412306	SCV002780857	pathogenic	Glycogen storage disease type III	2021-09-21	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000412306	SCV003816719	pathogenic	Glycogen storage disease type III	2022-10-07	criteria provided, single submitter	clinical testing
GeneDx	RCV003238758	SCV003936785	pathogenic	not provided	2023-01-03	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 26984562, 16705713, 33763395)
Baylor Genetics	RCV000412306	SCV004211146	pathogenic	Glycogen storage disease type III	2023-08-17	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000412306	SCV002094508	pathogenic	Glycogen storage disease type III	2021-09-09	no assertion criteria provided	clinical testing