ClinVar Miner

Submissions for variant NM_000642.3(AGL):c.853C>T (p.Arg285Ter) (rs755747010)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000664775 SCV000788787 pathogenic Glycogen storage disease type III 2017-01-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000664775 SCV000916428 pathogenic Glycogen storage disease type III 2018-10-19 criteria provided, single submitter clinical testing Variant summary: AGL c.853C>T (p.Arg285X) 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. The variant allele was found at a frequency of 8.1e-06 in 245734 control chromosomes (gnomAD and publication). c.853C>T has been reported in the literature in multiple individuals affected with Glycogen Storage Disease Type III (Ko_2014, Lu_2016, Lucchiari_2006, Ogimoto_2007). These data indicate that the variant is very likely to be associated with disease. A functional study, Lucchiari_2006, found the variant to cause the "presence of two transcripts (Fig. 1), one correctly processed (860 bp PCR amplicon) producing a truncated protein and a second transcript excluding exon 8 (112 bp), which yields a delete and out-of-frame mRNA." A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000664775 SCV000950127 pathogenic Glycogen storage disease type III 2020-02-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg285*) in the AGL gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs755747010, ExAC 0.009%). This variant has been observed in individuals with glycogen storage disease type III (PMID: 18785866, 16705713, 17895567). 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: 550128). Loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494). For these reasons, this variant has been classified as Pathogenic.
Natera, Inc. RCV000664775 SCV001454500 pathogenic Glycogen storage disease type III 2020-09-16 no assertion criteria provided clinical testing

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