ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.280C>T (p.Arg94Cys)

gnomAD frequency: 0.00001  dbSNP: rs118204441
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000806517 SCV000946521 pathogenic Mucopolysaccharidosis, MPS-IV-A 2023-04-09 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg94 amino acid residue in GALNS. Other variant(s) that disrupt this residue have been observed in individuals with GALNS-related conditions (PMID: 7795586, 9298823, 10814710, 23876334, 29731656), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects GALNS function (PMID: 7795586, 10814710). 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 expected to disrupt GALNS protein function. ClinVar contains an entry for this variant (Variation ID: 651205). This missense change has been observed in individuals with mucopolysaccharidosis type IVa (PMID: 10814710, 23876334, 29731656). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 94 of the GALNS protein (p.Arg94Cys).
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV000806517 SCV001547646 likely pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-02-01 criteria provided, single submitter research In vitro and vivo functional studies supportive of a damaging effect on the gene product (low to null enzymatic activity in homozygotes; low to null in vitro enzymatic activity; PS3_moderate); the prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_strong); very low frequency in gnomAD v2.1.1 (PM2_moderate); multiple lines of computational evidence support a deleterious effect on the gene (PP3_supporting)
Revvity Omics, Revvity RCV000806517 SCV002024159 pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-09-16 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000806517 SCV002045034 likely pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-11-07 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000806517 SCV002803365 likely pathogenic Mucopolysaccharidosis, MPS-IV-A 2024-05-07 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.