ClinVar Miner

Submissions for variant NM_000642.3(AGL):c.18_19del (p.Gln6fs) (rs113994127)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000723819 SCV000227163 pathogenic not provided 2014-06-13 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000175637 SCV000346051 likely pathogenic Glycogen storage disease type III 2017-04-27 criteria provided, single submitter clinical testing The AGL c.18_19delGA (p.Gln6HisfsTer20) variant, also referred to as c.17_18delAG, results in a frameshift, and is predicted to result in premature termination of the protein. The p.Gln6HisfsTer20 variant has been reported in at least three studies in which it is found in a total of 17 patients with glycogen storage disease type III, including in one in a homozygous state, in three in a compound heterozygous state, and in 13 in a heterozygous state where a second variant was not identified (Shen et al. 1996; Goldstein et al. 2010; Hobson-Webb et al. 2010). The p.Gln6HisfsTer20 variant was absent from 20 controls, but is reported at a frequency of 0.00009 in the European (non-Finnish) population of the Exome Aggregation Consortium. Based on the evidence and the potential impact of frameshift variants, the p.Gln6HisfsTer20 variant is classified as likely pathogenic for glycogen storage disease type III. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000001155 SCV000697529 pathogenic Glycogen storage disease IIIb 2017-03-30 criteria provided, single submitter clinical testing Variant summary: The AGL c.18_19delGA (p.Gln6Hisfs) 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.Glu1072fs). This variant is absent from 121356 control chromosomes (ExAC dataset). This variant has been reported homozygously and in compound heterozygosity in patients with clinically and biochemically confirmed dx of GSD IIIb (Goldstein_GeneticsMed_2010). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as "likely pathogenic/pathogenic". Taken together, this variant is classified as pathogenic.
Invitae RCV000175637 SCV000939193 pathogenic Glycogen storage disease type III 2020-10-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln6Hisfs*20) in the AGL gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs113994127, ExAC 0.009%). This variant has been observed as homozygous or in combination with another AGL variant in several individuals affected with glycogen storage disease III (PMID: 8755644, 20648714, 20490926). ClinVar contains an entry for this variant (Variation ID: 195097). Loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494). For these reasons, this variant has been classified as Pathogenic.
Myriad Women's Health, Inc. RCV000175637 SCV001194065 likely pathogenic Glycogen storage disease type III 2019-12-04 criteria provided, single submitter clinical testing NM_000642.2(AGL):c.18_19delGA(Q6Hfs*20) is classified as likely pathogenic in the context of glycogen storage disease type III. Sources cited for classification include the following: PMID 20648714 and 8755644. Classification of NM_000642.2(AGL):c.18_19delGA(Q6Hfs*20) 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 reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV000175637 SCV001448994 pathogenic Glycogen storage disease type III 2017-09-18 criteria provided, single submitter clinical testing
OMIM RCV000001155 SCV000021305 pathogenic Glycogen storage disease IIIb 1996-07-15 no assertion criteria provided literature only
GeneReviews RCV000175637 SCV000040762 pathologic Glycogen storage disease type III 2012-09-06 no assertion criteria provided curation Converted during submission to Pathogenic.
Natera, Inc. RCV000175637 SCV001454492 pathogenic Glycogen storage disease type III 2020-09-16 no assertion criteria provided clinical testing

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