ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.1548G>A (p.Trp516Ter) (rs140826989)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169414 SCV000220819 likely pathogenic Glycogen storage disease, type II 2014-10-20 criteria provided, single submitter literature only
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723388 SCV000224780 pathogenic not provided 2018-06-08 criteria provided, single submitter clinical testing
GeneDx RCV000723388 SCV000890165 pathogenic not provided 2018-11-09 criteria provided, single submitter clinical testing The W516X variant has been reported in multiple unrelated patients with glycogen storage disease type II (GSDII) (Hermans et al. 2004; van et al. 2015; Elder et al. 2013; Bergsma et al. 2015; de Vries JM et al. 2010). The W516X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The W516X variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we interpret this variant as pathogenic.
Invitae RCV000169414 SCV000964272 pathogenic Glycogen storage disease, type II 2018-11-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp516*) in the GAA gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with low alpha-glucosidase enzyme activity, a finding that is highly specific for Pompe disease (PMID: 25243733, 22676651). This variant has been observed in many individuals affected with Pompe disease (PMID: 14695532, 29181627, 29122469, 24715333). ClinVar contains an entry for this variant (Variation ID: 189025). Loss-of-function variants in GAA are known to be pathogenic (PMID: 18425781, 22252923). For these reasons, this variant has been classified as Pathogenic.

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