Total submissions: 10
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000790676 | SCV005201690 | pathogenic | not provided | 2023-06-08 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate reduced IDS enzyme activity (Chang et al., 2005; Charoenwattanasatien et al., 2012); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 7814022, 22990955, 15614569, 35144014, 32036093, 27695081, 33676511, 30639582, 34813777, 26762690, 31877959) |
| Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV000177014 | SCV005088943 | 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_Strong), Prevalence of the variant significantly increased in affected individuals compared with controls (PS4_Strong), Located in a mutational hot spot and/or critical functional domain (PM1_Moderate), 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_Strong) |
| Revvity Omics, |
RCV000177014 | SCV003825279 | pathogenic | Mucopolysaccharidosis, MPS-II | 2022-06-30 | criteria provided, single submitter | clinical testing | |
| Foundation for Research in Genetics and Endocrinology, |
RCV000177014 | SCV002583505 | pathogenic | Mucopolysaccharidosis, MPS-II | 2022-09-01 | criteria provided, single submitter | clinical testing | The hemizygous status for variant c.262C>T(p.Arg88Cys) in exon 3 of IDS gene. The variant has not been repoted in the 1000 genome gnomAD databases. The in silico prediction is damaging by DANN, LRT, SIFT and MutationTaster. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000177014 | SCV002103402 | pathogenic | Mucopolysaccharidosis, MPS-II | 2022-02-23 | criteria provided, single submitter | clinical testing | Variant summary: IDS c.262C>T (p.Arg88Cys) results in a non-conservative amino acid change located in the Sulfatase, N-terminal domain (IPR000917) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 114316 control chromosomes (gnomAD). c.262C>T has been reported in the literature in multiple individuals affected with Mucopolysaccharidosis Type II (Hunter Syndrome) (e.g. Parkinson_2004, Chang_2005, Froissart_2007, Charoenwattanasatien_2012, Dvorakova_2017). These data indicate that the variant is very likely to be associated with disease. Experimental evidence demonstrated the variant confers very little residual IDS activity (Chang_2005, Charoenwattanasatien_2012). Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Kasturba Medical College, |
RCV000177014 | SCV002053817 | pathogenic | Mucopolysaccharidosis, MPS-II | criteria provided, single submitter | clinical testing | ||
| Genome- |
RCV000177014 | SCV002014482 | pathogenic | Mucopolysaccharidosis, MPS-II | 2021-09-05 | criteria provided, single submitter | clinical testing | |
| Department of Medical Genetics, |
RCV000177014 | SCV001480189 | pathogenic | Mucopolysaccharidosis, MPS-II | criteria provided, single submitter | clinical testing | ||
| Labcorp Genetics |
RCV000177014 | SCV000628121 | pathogenic | Mucopolysaccharidosis, MPS-II | 2025-12-26 | 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 88 of the IDS protein (p.Arg88Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with mucopolysaccharidosis type II (PMID: 7814022, 8940265, 9950361, 15614569, 17063374, 22990955, 24125893, 26762690). ClinVar contains an entry for this variant (Variation ID: 92618). 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 IDS protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects IDS function (PMID: 15614569, 22990955). This variant disrupts the p.Arg88 amino acid residue in IDS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9660053, 9921913, 10215411, 10838181, 24515576). 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. |
| Eurofins Ntd Llc |
RCV000790676 | SCV000228818 | pathogenic | not provided | 2013-01-09 | criteria provided, single submitter | clinical testing |