ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.2236T>C (p.Trp746Arg)

dbSNP: rs1479740763
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins NTD LLC (GA) RCV000726989 SCV000704721 likely pathogenic not provided 2017-01-13 criteria provided, single submitter clinical testing
Counsyl RCV000598534 SCV000800152 uncertain significance Glycogen storage disease, type II 2018-05-23 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000598534 SCV001554637 likely pathogenic Glycogen storage disease, type II 2021-03-22 criteria provided, single submitter clinical testing Variant summary: GAA c.2236T>C (p.Trp746Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250780 control chromosomes. c.2236T>C has been reported in the literature in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic until more clinical and experimental data are available.
GeneDx RCV000726989 SCV001793120 pathogenic not provided 2020-06-09 criteria provided, single submitter clinical testing Published functional studies in HEK293 cells demonstrate a significant decrease or loss of enzyme activity compared to controls (Nino et al., 2013); Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31086307, 32064362, 21637107, 29122469, 23430493, 31342611, 30564623)
Genome-Nilou Lab RCV000598534 SCV001810183 likely pathogenic Glycogen storage disease, type II 2021-07-22 criteria provided, single submitter clinical testing
Invitae RCV000598534 SCV002235074 pathogenic Glycogen storage disease, type II 2021-09-01 criteria provided, single submitter clinical testing
PerkinElmer Genomics RCV000726989 SCV002023794 pathogenic not provided 2020-04-05 no assertion criteria provided clinical testing

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