ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.502C>T (p.Arg168Trp)

gnomAD frequency: 0.00004  dbSNP: rs777473001
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
Labcorp Genetics (formerly Invitae), Labcorp RCV001044499 SCV001208300 uncertain significance Glycogen storage disease, type II 2024-07-15 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 168 of the GAA protein (p.Arg168Trp). This variant is present in population databases (rs777473001, gnomAD 0.004%). This missense change has been observed in individual(s) with Pompe disease (PMID: 30155607). ClinVar contains an entry for this variant (Variation ID: 842132). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GAA protein function. This variant disrupts the p.Arg168 amino acid residue in GAA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21488292, 24169249, 25526786, 31076647). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001759959 SCV001998265 uncertain significance not provided 2020-05-20 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30155607)
Genome-Nilou Lab RCV001044499 SCV002027216 uncertain significance Glycogen storage disease, type II 2021-09-05 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001044499 SCV002789176 uncertain significance Glycogen storage disease, type II 2021-12-10 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001759959 SCV003828439 uncertain significance not provided 2021-03-04 criteria provided, single submitter clinical testing
Natera, Inc. RCV001044499 SCV002091926 uncertain significance Glycogen storage disease, type II 2020-12-14 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.