ClinVar Miner

Submissions for variant NM_000642.3(AGL):c.3980G>A (p.Trp1327Ter)

gnomAD frequency: 0.00006  dbSNP: rs267606640
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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000435914 SCV000331819 pathogenic not provided 2016-04-15 criteria provided, single submitter clinical testing
GeneDx RCV000435914 SCV000517381 pathogenic not provided 2021-11-02 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: 26704523, 12442284, 18924225, 23207808, 17047887, 19834502, 29374762, 22089644, 20490926, 25525159, 31661040, 31319225, 32714838, 33726816, 33782433, 31589614)
Labcorp Genetics (formerly Invitae), Labcorp RCV000333868 SCV000827885 pathogenic Glycogen storage disease type III 2024-01-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp1327*) 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). This variant is present in population databases (rs267606640, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with glycogen storage disease (PMID: 12442284, 16189622, 18924225, 19834502, 20490926, 22089644). ClinVar contains an entry for this variant (Variation ID: 1108). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000333868 SCV000916430 pathogenic Glycogen storage disease type III 2018-12-10 criteria provided, single submitter clinical testing Variant summary: AGL c.3980G>A (p.Trp1327X) 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 (eg. c.4221delA, p.Lys1407fsX8 and c.4529dupA, p.Tyr1510X). The variant allele was found at a frequency of 5.8e-05 in 276740 control chromosomes (gnomAD). c.3980G>A has been reported in the literature in multiple homozygous individuals affected with Glycogen Storage Disease Type III and indicated to be a Tunisian founder mutation (Cherif_2012). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as likely pathogenic/pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV000333868 SCV001523373 pathogenic Glycogen storage disease type III 2024-02-12 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000333868 SCV002055505 pathogenic Glycogen storage disease type III 2021-07-15 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000333868 SCV003816730 pathogenic Glycogen storage disease type III 2022-12-20 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000435914 SCV004225858 pathogenic not provided 2023-01-12 criteria provided, single submitter clinical testing PP4, PM2, PM3, PS4_moderate, PVS1
CeGaT Center for Human Genetics Tuebingen RCV000435914 SCV004699273 pathogenic not provided 2024-01-01 criteria provided, single submitter clinical testing AGL: PVS1, PM3:Strong, PM2
OMIM RCV000001167 SCV000021317 pathogenic Glycogen storage disease IIIa 2009-11-01 no assertion criteria provided literature only
Division of Human Genetics, Children's Hospital of Philadelphia RCV000333868 SCV000536862 likely pathogenic Glycogen storage disease type III 2016-09-05 no assertion criteria provided research
GenomeConnect, ClinGen RCV000333868 SCV000607271 not provided Glycogen storage disease type III no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Counsyl RCV000333868 SCV001132326 pathogenic Glycogen storage disease type III 2014-01-02 no assertion criteria provided clinical testing
Natera, Inc. RCV000333868 SCV001456554 pathogenic Glycogen storage disease type III 2020-09-16 no assertion criteria provided clinical testing

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