ClinVar Miner

Submissions for variant NM_000642.3(AGL):c.1783C>T (p.Arg595Ter) (rs765367405)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000805441 SCV000945397 pathogenic Glycogen storage disease type III 2019-08-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg595*) in the AGL gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs765367405, ExAC 0.001%). This variant has been observed in the homozygous or compound heterozygous state in individuals affected with glycogen storage disease (PMID: 19834502, 25388549). 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 RCV000805441 SCV001426804 pathogenic Glycogen storage disease type III 2020-07-20 criteria provided, single submitter clinical testing Variant summary: AGL c.1783C>T (p.Arg595X) 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 8e-06 in 251218 control chromosomes (gnomAD). c.1783C>T has been reported in the literature in compound heterozygous or homozygous state in individuals affected with Glycogen Storage Disease Type III (Aoyama_2009, Goldstein_2010, Decostre_2017). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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