ClinVar Miner

Submissions for variant NM_182760.4(SUMF1):c.1046G>A (p.Arg349Gln)

gnomAD frequency: 0.00001  dbSNP: rs137852847
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 RCV000002786 SCV001576749 pathogenic Multiple sulfatase deficiency 2024-11-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 349 of the SUMF1 protein (p.Arg349Gln). This variant is present in population databases (rs137852847, gnomAD 0.0009%). This missense change has been observed in individual(s) with multiple sulfatase deficiency (PMID: 12757705). ClinVar contains an entry for this variant (Variation ID: 2667). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SUMF1 protein function with a positive predictive value of 95%. This variant disrupts the p.Arg349 amino acid residue in SUMF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12757706, 15146462, 25373814). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV002243616 SCV002513150 likely pathogenic not provided 2022-05-02 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect showing reduced activation of sulfatases ARSA, ARSC, and ARSE compared to wild type SUMF1 (Cosma et al., 2004); Identified in a patient with severe multiple sulphatase deficiency in published literature (Cosma et al., 2003); Not observed at significant frequency in large population cohorts (gnomAD); 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: 12757706, 24484558, 28452122, 31589614, 15146462, 12757705, 18157819, 29048999, 25373814)
Fulgent Genetics, Fulgent Genetics RCV000002786 SCV005664533 likely pathogenic Multiple sulfatase deficiency 2024-02-25 criteria provided, single submitter clinical testing
OMIM RCV000002786 SCV000022944 pathogenic Multiple sulfatase deficiency 2003-05-16 no assertion criteria provided literature only
Natera, Inc. RCV000002786 SCV002079159 likely pathogenic Multiple sulfatase deficiency 2020-07-23 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.