Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000694477 | SCV000822925 | likely pathogenic | Glycogen storage disease, type II | 2024-11-12 | criteria provided, single submitter | clinical testing | This sequence change affects codon 286 of the GAA mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the GAA protein. This variant also falls at the last nucleotide of exon 4, which is part of the consensus splice site for this exon. This variant is present in population databases (rs201056962, gnomAD 0.003%). This variant has been observed in individual(s) with late-onset Pompe disease (PMID: 35123877). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 572952). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Fulgent Genetics, |
RCV000694477 | SCV002783659 | likely pathogenic | Glycogen storage disease, type II | 2024-04-19 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000694477 | SCV002091967 | uncertain significance | Glycogen storage disease, type II | 2019-10-28 | no assertion criteria provided | clinical testing |