ClinVar Miner

Submissions for variant NM_000642.3(AGL):c.16C>T (p.Gln6Ter) (rs113994126)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000675315 SCV000227162 pathogenic not provided 2014-06-13 criteria provided, single submitter clinical testing
Myriad Women's Health, Inc. RCV000020373 SCV001193853 likely pathogenic Glycogen storage disease type III 2019-12-09 criteria provided, single submitter clinical testing NM_000642.2(AGL):c.16C>T(Q6*) is classified as likely pathogenic in the context of glycogen storage disease type III. Sources cited for classification include the following: PMID 23430490, 20648714 and 8755644. Classification of NM_000642.2(AGL):c.16C>T(Q6*) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is observed in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.
Invitae RCV000020373 SCV001382848 pathogenic Glycogen storage disease type III 2020-08-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln6*) in the AGL gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs113994126, ExAC 0.001%). This variant has been observed in individual(s) with glycogen storage disease type III (PMID: 8755644, 23430490). 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: 1095). Loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000020373 SCV001623203 pathogenic Glycogen storage disease type III 2021-04-26 criteria provided, single submitter clinical testing Variant summary: AGL c.16C>T (p.Gln6X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the 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. The variant allele was found at a frequency of 1.6e-05 in 251440 control chromosomes. c.16C>T has been reported in the literature in individuals affected with Glycogen Storage Disease Type III and subsequently cited by others (example, Shen_1996, Sentner_2012, Perveen_2019). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic (n=2)/likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as pathogenic.
GeneDx RCV000675315 SCV001765379 pathogenic not provided 2019-12-12 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 a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 20648714, 8755644, 23430490)
OMIM RCV000001153 SCV000021303 pathogenic Glycogen storage disease IIIb 1996-07-15 no assertion criteria provided literature only
GeneReviews RCV000020373 SCV000040761 pathologic Glycogen storage disease type III 2012-09-06 no assertion criteria provided curation Converted during submission to Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic RCV000675315 SCV000800980 pathogenic not provided 2017-03-23 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.