Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001388432 | SCV001589426 | pathogenic | Glycogen storage disease, type II | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln803Profs*39) 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). This variant is present in population databases (rs763048948, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with Pompe disease (PMID: 22252923). ClinVar contains an entry for this variant (Variation ID: 1074956). For these reasons, this variant has been classified as Pathogenic. |
| Revvity Omics, |
RCV001785818 | SCV002021173 | pathogenic | not provided | 2023-12-26 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001388432 | SCV003928809 | pathogenic | Glycogen storage disease, type II | 2023-04-05 | criteria provided, single submitter | clinical testing | Variant summary: GAA c.2408_2426del19 (p.Gln803ProfsX39) 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 allele was found at a frequency of 1.2e-05 in 248564 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2408_2426del19 has been reported in the literature in at least one individual affected with Glycogen Storage Disease, Type 2 (Pompe Disease) (e.g., Bali_2012). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV001388432 | SCV004197905 | pathogenic | Glycogen storage disease, type II | 2022-07-09 | criteria provided, single submitter | clinical testing |