ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.2456G>A (p.Arg819Gln)

gnomAD frequency: 0.00006  dbSNP: rs374687883
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000545406 SCV000626572 likely pathogenic Glycogen storage disease, type II 2024-12-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 819 of the GAA protein (p.Arg819Gln). This variant is present in population databases (rs374687883, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with GAA-related conditions. ClinVar contains an entry for this variant (Variation ID: 456403). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt GAA protein function with a positive predictive value of 95%. This variant disrupts the p.Arg819 amino acid residue in GAA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 33741225; internal data). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic RCV004791521 SCV005408543 uncertain significance not provided 2024-05-20 criteria provided, single submitter clinical testing PP3, PM2, PM5
Fulgent Genetics, Fulgent Genetics RCV000545406 SCV005653251 likely pathogenic Glycogen storage disease, type II 2024-04-16 criteria provided, single submitter clinical testing
Natera, Inc. RCV000545406 SCV002094463 uncertain significance Glycogen storage disease, type II 2019-10-28 no assertion criteria provided clinical testing

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