ClinVar Miner

Submissions for variant NM_000202.8(IDS):c.1478G>A (p.Arg493His)

gnomAD frequency: 0.00002  dbSNP: rs782347729
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001243617 SCV001416785 uncertain significance Mucopolysaccharidosis, MPS-II 2022-08-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 493 of the IDS protein (p.Arg493His). This variant is present in population databases (rs782347729, gnomAD 0.02%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with abnormal newborn screening results (PMID: 29801497). ClinVar contains an entry for this variant (Variation ID: 968479). 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"). This variant disrupts the p.Arg493 amino acid residue in IDS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22976778, 24515576, 31877959). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002393637 SCV002699545 uncertain significance Inborn genetic diseases 2018-12-29 criteria provided, single submitter clinical testing The p.R493H variant (also known as c.1478G>A), located in coding exon 9 of the IDS gene, results from a G to A substitution at nucleotide position 1478. The arginine at codon 493 is replaced by histidine, an amino acid with highly similar properties. Another alteration affecting the same amino acid, p.R493P (c.1478G>C), has been reported in a mucopolysaccharidosis cohort (Pollard LM et al. J. Inherit. Metab. Dis., 2013 Mar;36:179-87). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Laboratory of Medical Genetics, University of Torino RCV001243617 SCV002760127 likely pathogenic Mucopolysaccharidosis, MPS-II 2022-11-29 criteria provided, single submitter research
Natera, Inc. RCV001829038 SCV002084455 uncertain significance Mucopolysaccharidosis, MPS-III-A 2020-04-08 no assertion criteria provided clinical testing

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