Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001243105 | SCV001416239 | likely pathogenic | Glycogen storage disease, type II | 2022-10-24 | criteria provided, single submitter | clinical testing | 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. 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on GAA function (PMID: 21484825, 22644586). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 968057). This missense change has been observed in individual(s) with glycogen storage disease and/or Pompe disease (PMID: 18425781, 21484825, 34852371). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs747373179, gnomAD 0.005%). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 585 of the GAA protein (p.Arg585Lys). This variant also falls at the last nucleotide of exon 12, which is part of the consensus splice site for this exon. |
| Baylor Genetics | RCV001243105 | SCV005058723 | likely pathogenic | Glycogen storage disease, type II | 2024-03-27 | criteria provided, single submitter | clinical testing |