ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.[752C>T;761C>T]

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001779452 SCV002014857 pathogenic Glycogen storage disease, type II 2022-12-05 criteria provided, single submitter clinical testing Variant summary: GAA c.[752C>T;761C>T] (p.[Ser251Leu;Ser254Leu]) variant is a complex allele and involves the alteration of multiple nucleotides. The variant allele was found at a frequency of 0.00021 in 251124 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) (0.00021 vs 0.0042), allowing no conclusion about variant significance. c.[752C>T;761C>T] has been reported in the literature in multiple individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) in homozygous and compound heterozygous state (e.g. Labrousse_2010, Chien_2011, Liao_2014, Fukuhara_2018). These data indicate that the variant is likely to be associated with disease. Multiple publications report that this complex allele results in enzyme activity of <10% in homozygous patients (Labrousse_2010, Chien_2011, Fukuhara_2018). ClinVar submitters cite the two variants separately with conflicting assessments (Variation IDs: 325781, 325782). At least one clinical diagnostic laboratory classified this complex allele as pathogenic (SCV000626639.5). Based on the evidence outlined above, the variant was 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.