ClinVar Miner

Submissions for variant NM_000642.3(AGL):c.1405C>T (p.Arg469Ter) (rs766536350)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001420705 SCV000918398 likely pathogenic Glycogen storage disease IIIa 2021-05-08 criteria provided, single submitter clinical testing Variant summary: AGL c.1405C>T (p.Arg469X) 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 4e-06 in 251178 control chromosomes. c.1405C>T has been reported in the literature in at-least one individual affected with Glycogen Storage Disease Type IIIa and has been subsequently cited by others (example, Wang_2009, Lu_2016). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV000780820 SCV001584152 pathogenic Glycogen storage disease type III 2020-10-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg469*) in the AGL gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs766536350, ExAC 0.01%). This variant has been observed in individual(s) with glycogen storage disease (PMID: 19951465). ClinVar contains an entry for this variant (Variation ID: 633032). Loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494). For these reasons, this variant has been classified as Pathogenic.

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