ClinVar Miner

Submissions for variant NM_000202.8(IDS):c.1403G>A (p.Arg468Gln)

gnomAD frequency: 0.00001  dbSNP: rs113993946
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000790797 SCV000232923 pathogenic not provided 2013-09-25 criteria provided, single submitter clinical testing
IIFP, CONICET-UNLP RCV000180473 SCV000262515 pathogenic Mucopolysaccharidosis, MPS-II 2007-08-02 criteria provided, single submitter research
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV000180473 SCV000929887 pathogenic Mucopolysaccharidosis, MPS-II 2024-06-07 criteria provided, single submitter literature only In vitro or in vivo functional studies supportive of a damaging effect (PS3_Moderate), Prevalence of the variant significantly increased in affected individuals compared with controls (PS4_Strong), Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Cosegregation with disease in multiple affected family members (PP1_Moderate), Missense variant in a gene with a low rate of benign missense variation (PP2_Supporting), Multiple lines of computational evidence support a deleterious effect (PP3_Supporting), Patient’s phenotype or family history highly specific for the disease (PP4_Moderate)
Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences RCV000180473 SCV001480198 pathogenic Mucopolysaccharidosis, MPS-II criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000180473 SCV002014467 pathogenic Mucopolysaccharidosis, MPS-II 2021-09-05 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000180473 SCV003825334 pathogenic Mucopolysaccharidosis, MPS-II 2022-10-13 criteria provided, single submitter clinical testing
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000180473 SCV003915848 pathogenic Mucopolysaccharidosis, MPS-II 2023-03-22 criteria provided, single submitter clinical testing A hemizygous variation in exon 9 of the IDS gene detected. The observed variant c.1403G>A has not been reported in the 1000 genomes databases. The in silico prediction is damaging by SIFT, PROVEAN, Polyphen2 and MutationTaster. In summary, the variant meets our criteria to be classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000180473 SCV004299009 pathogenic Mucopolysaccharidosis, MPS-II 2023-07-25 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg468 amino acid residue in IDS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1284597, 15614569, 28077157, 30639582). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects IDS function (PMID: 18500569). 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 IDS protein function. ClinVar contains an entry for this variant (Variation ID: 10498). This missense change has been observed in individuals with mucopolysaccharidosis II (PMID: 7581397, 9266380, 9875019). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 468 of the IDS protein (p.Arg468Gln).
OMIM RCV000011244 SCV000031471 pathogenic Mucopolysaccharidosis type 2, severe form 1997-01-01 no assertion criteria provided literature only
GeneReviews RCV000180473 SCV000999927 not provided Mucopolysaccharidosis, MPS-II no assertion provided literature only

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