ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.1634C>T (p.Pro545Leu)

gnomAD frequency: 0.00002  dbSNP: rs121907942
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
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 RCV001174962 SCV001338444 pathogenic Glycogen storage disease, type II 2020-04-30 criteria provided, single submitter clinical testing Variant summary: GAA c.1634C>T (p.Pro545Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 250468 control chromosomes. c.1634C>T has been reported in the literature in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease, Vorgerd_1998, Flanagan_2009, vanCapelle_2016). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Flanagan_2009). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Revvity Omics, Revvity Omics RCV001785449 SCV002021171 pathogenic not provided 2021-10-12 criteria provided, single submitter clinical testing
Invitae RCV001174962 SCV002213638 pathogenic Glycogen storage disease, type II 2023-07-25 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 4032). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GAA function (PMID: 7881422). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This missense change has been observed in individuals with glycogen storage disease type II (PMID: 7881422, 14695532, 25526786). This variant is present in population databases (rs121907942, gnomAD 0.01%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 545 of the GAA protein (p.Pro545Leu).
Baylor Genetics RCV001174962 SCV004197837 pathogenic Glycogen storage disease, type II 2023-05-04 criteria provided, single submitter clinical testing
OMIM RCV000004247 SCV000024413 pathogenic Glycogen storage disease II, adult form 1994-12-01 no assertion criteria provided literature only
Natera, Inc. RCV001174962 SCV002092051 pathogenic Glycogen storage disease, type II 2020-12-15 no assertion criteria provided clinical testing

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.