ClinVar Miner

Submissions for variant NM_000199.5(SGSH):c.571G>A (p.Gly191Arg)

gnomAD frequency: 0.00001  dbSNP: rs753666460
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413143 SCV000491271 pathogenic not provided 2023-01-28 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect, including inactive or significantly reduced enzymatic activity (Muschol et al., 2004); 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: 24816101, 21061399, 19099774, 25807448, 15146460, 29023963, 34813777, 31069529, 34047372, 34991944)
Labcorp Genetics (formerly Invitae), Labcorp RCV000672002 SCV002281415 pathogenic Mucopolysaccharidosis, MPS-III-A 2024-03-07 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 191 of the SGSH protein (p.Gly191Arg). This variant is present in population databases (rs753666460, gnomAD 0.01%). This missense change has been observed in individuals with mucopolysaccharidosis type III (PMID: 15146460, 21061399, 23084433, 34813777). ClinVar contains an entry for this variant (Variation ID: 372781). 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 SGSH protein function. Experimental studies have shown that this missense change affects SGSH function (PMID: 15146460). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000672002 SCV002813988 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2022-05-03 criteria provided, single submitter clinical testing
Intergen, Intergen Genetics and Rare Diseases Diagnosis Center RCV000672002 SCV004015112 pathogenic Mucopolysaccharidosis, MPS-III-A 2023-07-21 criteria provided, single submitter clinical testing
Baylor Genetics RCV000672002 SCV004201088 pathogenic Mucopolysaccharidosis, MPS-III-A 2024-01-03 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV000672002 SCV005382435 pathogenic Mucopolysaccharidosis, MPS-III-A 2023-05-20 criteria provided, single submitter clinical testing The missense c.571G>A (p.Gly191Arg) variant in the SGSH gene has been observed in individuals with mucopolysaccharidosis type III. Experimental studies have shown that this missense change affects SGSH function (Muschol, Nicole et al.,2004). This variant is reported with the allele frequency (0.001%) in the gnomAD Exomes. It is submitted to ClinVar as Likely Pathogenic/ Pathogenic. The amino acid Glycine at position 191 is changed to a Arginine changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid Glycine in SGSH is predicted as conserved by GERP++ and PhyloP across 100 vertebrates Multiple lines of computational evidence (Polyphen - Damaging, SIFT – Damaging and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000672002 SCV000797053 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2018-01-15 no assertion criteria provided clinical testing
Natera, Inc. RCV000672002 SCV002095135 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2020-12-28 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.