Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002871829 | SCV003232761 | pathogenic | Glycogen storage disease, type II | 2022-09-14 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp859*) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with GAA-related conditions. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002871829 | SCV005884008 | pathogenic | Glycogen storage disease, type II | 2024-12-11 | criteria provided, single submitter | clinical testing | Variant summary: GAA c.2577G>A (p.Trp859X) 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. The variant allele was found at a frequency of 4.2e-06 in 239268 control chromosomes. c.2577G>A has been reported in the literature in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) (example, Thuriot_2021). The following publication has been ascertained in the context of this evaluation (PMID: 34501319). ClinVar contains an entry for this variant (Variation ID: 2030537). Based on the evidence outlined above, the variant was classified as pathogenic. |