Submissions for variant NM_000642.3(AGL):c.118C>T (p.Gln40Ter)

dbSNP: rs771961377

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169437	SCV000220854	likely pathogenic	Glycogen storage disease type III	2014-11-05	criteria provided, single submitter	literature only
GeneDx	RCV000579304	SCV000680764	pathogenic	not provided	2017-09-22	criteria provided, single submitter	clinical testing	The Q40X nonsense variant in the AGL gene has been reported previously in individuals with glycogen storage disease type III who were also found to harbor a second AGL gene variant (Austin et al., 2012; Li et al., 2014 ). The Q40X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we interpret this variant as pathogenic.
Invitae	RCV000169437	SCV000814986	pathogenic	Glycogen storage disease type III	2023-09-10	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: 189045). This premature translational stop signal has been observed in individuals with glycogen storage disease type III (PMID: 20648714, 23430941, 25451272). This variant is present in population databases (rs771961377, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Gln40*) 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	RCV000169437	SCV002055464	pathogenic	Glycogen storage disease type III	2021-07-15	criteria provided, single submitter	clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV000169437	SCV003932244	pathogenic	Glycogen storage disease type III	2023-01-03	criteria provided, single submitter	clinical testing	PVS1, PM2, PS3
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000169437	SCV004099594	pathogenic	Glycogen storage disease type III	2023-09-07	criteria provided, single submitter	clinical testing	Variant summary: AGL c.118C>T (p.Gln40X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, a commonly known mechanism for disease. The variant allele was found at a frequency of 8e-06 in 251268 control chromosomes (gnomAD). c.118C>T has been reported in the literature as a biallelic genotype in at least one individual affected with Glycogen Storage Disease Type III (e.g. Laforet_2019). These data indicate that the variant is likely associated with disease. The following publication has been ascertained in the context of this evaluation (PMID: 31661040). Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Division of Human Genetics, Children's Hospital of Philadelphia	RCV000169437	SCV000536806	pathogenic	Glycogen storage disease type III	2016-04-28	no assertion criteria provided	research