ClinVar Miner

Submissions for variant NM_000199.5(SGSH):c.220C>T (p.Arg74Cys)

gnomAD frequency: 0.00051  dbSNP: rs104894636
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Total submissions: 20
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins NTD LLC (GA) RCV000078354 SCV000227052 pathogenic not provided 2016-09-02 criteria provided, single submitter clinical testing
GeneDx RCV000078354 SCV000321945 pathogenic not provided 2022-03-07 criteria provided, single submitter clinical testing Published functional studies demonstrate very low sulfamidase production compared to wild-type (Perkins et al., 1999).; 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: 18407553, 24816101, 11668611, 21061399, 31236806, 28963436, 30809705, 30548430, 10601282, 18392742, 15146460, 11793481, 22976768, 26787381, 21671382, 29023963, 28844463, 9285796, 31718697, 31980526, 32036093, 34349725, 34426522, 31589614, 33726816)
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000005415 SCV000590925 pathogenic Mucopolysaccharidosis, MPS-III-A 2017-06-07 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000005415 SCV000745252 pathogenic Mucopolysaccharidosis, MPS-III-A 2015-09-21 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626628 SCV000747329 likely pathogenic Abnormal circulating carbohydrate concentration 2017-01-01 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories,Mayo Clinic RCV000005415 SCV000782576 pathogenic Mucopolysaccharidosis, MPS-III-A 2017-01-19 criteria provided, single submitter clinical testing
Invitae RCV000005415 SCV000820679 pathogenic Mucopolysaccharidosis, MPS-III-A 2021-12-18 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 74 of the SGSH protein (p.Arg74Cys). This variant is present in population databases (rs104894636, gnomAD 0.04%). This missense change has been observed in individuals with MPS type IIIA (PMID: 9285796, 9401012, 22976768, 28844463). ClinVar contains an entry for this variant (Variation ID: 5108). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects SGSH function (PMID: 10601282, 15146460). This variant disrupts the p.Arg74 amino acid residue in SGSH. Other variant(s) that disrupt this residue have been observed in individuals with SGSH-related conditions (PMID: 9401012, 15542396), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Laboratory of Diagnosis and Therapy of Lysosomal Disorders,University of Padova RCV000005415 SCV000929892 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2019-01-01 criteria provided, single submitter literature only PS3: Low/absent in vivo enzymatic activity in homozygote. PS3: Low in vitro enzymatic activity. PM2: Very low frequency in GnomAD
Myriad Women's Health, Inc. RCV000005415 SCV001194099 pathogenic Mucopolysaccharidosis, MPS-III-A 2019-12-26 criteria provided, single submitter clinical testing NM_000199.3(SGSH):c.220C>T(R74C) is classified as pathogenic in the context of mucopolysaccharidosis type IIIA. Sources cited for classification include the following: PMID 9401012, 15146460, 11182930, 18407553, 24314109, 21061399 and 11182930. Classification of NM_000199.3(SGSH):c.220C>T(R74C) is based on the following criteria: This is a well-established pathogenic variant in the literature that has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
CeGaT Center for Human Genetics Tuebingen RCV000078354 SCV001247663 pathogenic not provided 2021-12-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000005415 SCV001366179 pathogenic Mucopolysaccharidosis, MPS-III-A 2018-09-25 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PP3,PP4.
Centre for Inherited Metabolic Diseases, Karolinska University Hospital RCV000005415 SCV001548177 pathogenic Mucopolysaccharidosis, MPS-III-A 2021-03-25 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000005415 SCV002045508 pathogenic Mucopolysaccharidosis, MPS-III-A 2021-11-07 criteria provided, single submitter clinical testing
OMIM RCV000005415 SCV000025597 pathogenic Mucopolysaccharidosis, MPS-III-A 1997-01-01 no assertion criteria provided literature only
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000005415 SCV000733744 pathogenic Mucopolysaccharidosis, MPS-III-A no assertion criteria provided clinical testing
GeneReviews RCV001030813 SCV001194302 pathogenic Mucopolysaccharidosis 2019-09-04 no assertion criteria provided literature only
Natera, Inc. RCV000005415 SCV001453824 pathogenic Mucopolysaccharidosis, MPS-III-A 2020-09-16 no assertion criteria provided clinical testing
Genomics England Pilot Project,Genomics England RCV000005415 SCV001760415 pathogenic Mucopolysaccharidosis, MPS-III-A no assertion criteria provided clinical testing
PerkinElmer Genomics RCV000005415 SCV002021245 pathogenic Mucopolysaccharidosis, MPS-III-A 2019-10-09 no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000078354 SCV002037524 pathogenic not provided no assertion criteria provided clinical testing

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