Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000342526 | SCV000407255 | uncertain significance | Glycogen storage disease, type II | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000418379 | SCV000517067 | likely benign | not specified | 2015-05-22 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Invitae | RCV000342526 | SCV000626538 | uncertain significance | Glycogen storage disease, type II | 2022-07-27 | 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 66 of the GAA protein (p.Arg66Gln). This variant is present in population databases (rs200202628, gnomAD 0.02%). 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: 325775). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GAA protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Center for Advanced Laboratory Medicine, |
RCV000852725 | SCV000995440 | likely benign | Cardiomyopathy | 2019-01-24 | criteria provided, single submitter | clinical testing | |
Broad Institute Rare Disease Group, |
RCV000342526 | SCV001422668 | uncertain significance | Glycogen storage disease, type II | 2020-01-22 | criteria provided, single submitter | curation | The p.Arg66Gln variant in GAA has not been previously reported in the literature in individuals with Glycogen Storage Disease II but has been reported as a VUS by Invitae and Illumina and a likely benign variant by GeneDx in ClinVar (Variation ID: 325775). This variant has been identified in 0.020% (4/19680) of East Asian chromosomes, 0.014% (5/35104) of Latino chromosomes, and 0.002% (2/125336) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs200202628). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. The Arginine (Arg) at position 66 is not highly conserved in mammals and evolutionary distant species, and 33 species (including Gibbon, Baboon, Rhesus, Prairie Vole, and Chinchilla) carry an Glutamine (Gln), raising the possibility that this change at this position may be tolerated. In summary, the clinical significance of the p.Arg66Gln variant is uncertain. ACMG/AMP Criteria applied: PM2, BP4 (Richards 2015). |
Genome- |
RCV000342526 | SCV001810174 | uncertain significance | Glycogen storage disease, type II | 2021-07-22 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV003129832 | SCV003816220 | uncertain significance | not provided | 2022-03-29 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000342526 | SCV001463468 | uncertain significance | Glycogen storage disease, type II | 2020-01-24 | no assertion criteria provided | clinical testing |