Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001345891 | SCV001540038 | likely pathogenic | Glycogen storage disease, type II | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 765 of the GAA protein (p.Gly765Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Pompe disease (PMID: 31086307; Invitae). ClinVar contains an entry for this variant (Variation ID: 1042001). 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 with a positive predictive value of 95%. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235554 | SCV003934321 | uncertain significance | not specified | 2023-05-17 | criteria provided, single submitter | clinical testing | Variant summary: GAA c.2294G>A (p.Gly765Asp) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250094 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2294G>A has been reported in the literature in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) (Kishnani_2019). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 31086307). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Baylor Genetics | RCV001345891 | SCV004195449 | likely pathogenic | Glycogen storage disease, type II | 2023-10-13 | criteria provided, single submitter | clinical testing |