Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Medical Genetics and Genomics, |
RCV001261939 | SCV001438060 | likely pathogenic | Glycogen storage disease, type II | 2020-10-15 | criteria provided, single submitter | clinical testing | The variant c.1001G>A is likely pathogenic based on phenotype of the patient & ACMG guidelines |
Invitae | RCV001261939 | SCV004653601 | pathogenic | Glycogen storage disease, type II | 2023-09-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly334 amino acid residue in GAA. Other variant(s) that disrupt this residue have been observed in individuals with GAA-related conditions (PMID: 21687968), which suggests that this may be a clinically significant amino acid residue. 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 expected to disrupt GAA protein function. ClinVar contains an entry for this variant (Variation ID: 982365). This missense change has been observed in individual(s) with Pompe disease (PMID: 33741225). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 334 of the GAA protein (p.Gly334Asp). |