ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.664C>T (p.Arg222Trp)

gnomAD frequency: 0.00002  dbSNP: rs146963745
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000814925 SCV000955363 uncertain significance Mucopolysaccharidosis, MPS-IV-A 2022-09-23 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 222 of the GALNS protein (p.Arg222Trp). This variant is present in population databases (rs146963745, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with GALNS-related conditions. ClinVar contains an entry for this variant (Variation ID: 658160). 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) performed at Invitae indicates that this missense variant is not expected to disrupt GALNS protein function. 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.
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV000814925 SCV001547764 uncertain significance Mucopolysaccharidosis, MPS-IV-A 2021-02-01 criteria provided, single submitter research Very low frequency in gnomAD v2.1.1 (PM2_moderate); multiple lines of computational evidence suggest no impact on gene or gene product (BP4_supporting)
Genome-Nilou Lab RCV000814925 SCV002044991 uncertain significance Mucopolysaccharidosis, MPS-IV-A 2021-11-07 criteria provided, single submitter 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.