ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.1280T>C (p.Met427Thr)

dbSNP: rs1555600212
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 RCV000665730 SCV000789896 uncertain significance Glycogen storage disease, type II 2017-03-13 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000665730 SCV005725914 likely pathogenic Glycogen storage disease, type II 2024-11-01 criteria provided, single submitter clinical testing Variant summary: GAA c.1280T>C (p.Met427Thr) results in a non-conservative amino acid change located in the Glycoside hydrolase family 31, TIM barrel domain (IPR000322) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 236646 control chromosomes. c.1280T>C has been reported in the presumed compound heterozygous state in the literature in multiple individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) (example, Ding_2015, Li_2023, Zhao_2024). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported, however all individuals cited had residual/low GAA enzyme activity <30% of control values, which could not be entirely explained by the opposite allele (example, Ding_2015, Li_2023, Zhao_2024). The following publications have been ascertained in the context of this evaluation (PMID: 26310554, 38162137, 39010129). ClinVar contains an entry for this variant (Variation ID: 550859). Based on the evidence outlined above, the variant was classified as likely 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.