Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174788 | SCV001338122 | pathogenic | Glycogen storage disease, type II | 2020-01-31 | criteria provided, single submitter | clinical testing | Variant summary: GAA c.2219_2220delTG (p.Val740GlyfsX55) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250916 control chromosomes. c.2219_2220delTG has been reported in the literature in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) to include at-least one study reporting the clinical characteristics and genotypes of patients enrolled in a clinical trial for recombinant human GAA, namely, alglucodisase alfa (NCT01526785) (example, Montalvo_2006, Remiche_2014, Reuser_2019, Kishnani_2019). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Fulgent Genetics, |
RCV001174788 | SCV002813254 | pathogenic | Glycogen storage disease, type II | 2021-09-24 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001174788 | SCV004296885 | pathogenic | Glycogen storage disease, type II | 2023-02-14 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with glycogen storage disease type II (PMID: 16917947). This sequence change creates a premature translational stop signal (p.Val740Glyfs*55) in the GAA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GAA are known to be pathogenic (PMID: 18425781, 22252923). |
| Natera, |
RCV001174788 | SCV002092113 | pathogenic | Glycogen storage disease, type II | 2020-10-21 | no assertion criteria provided | clinical testing |