ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.1942G>A (p.Gly648Ser) (rs536906561)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169262 SCV000220552 likely pathogenic Glycogen storage disease, type II 2014-07-24 criteria provided, single submitter literature only
Invitae RCV000169262 SCV000626535 pathogenic Glycogen storage disease, type II 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 648 of the GAA protein (p.Gly648Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs536906561, ExAC 0.05%). This variant has been reported in combination with another GAA variant in individuals affected with glycogen storage disease type II (Pompe disease) (PMID: 9535769, 17643989, 26575883), including the finding of this variant on the opposite chromosome (in trans) from a pathogenic variant. This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 188902). Experimental studies have shown that this missense change causes a severe reduction in GAA enzyme activity (PMID: 9535769, 19862843). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. A different missense substitution at this codon (p.Gly648Asp) has been reported in an individual affected with Pompe disease (PMID: 23146291, 22644586). For these reasons, this variant has been classified as Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.