Total submissions: 16
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Natera, |
RCV006638601 | SCV007532053 | pathogenic | Mucopolysaccharidosis, MPS-III-A | 2024-06-21 | criteria provided, single submitter | clinical testing | The c.1402C>T variant in IDS is a missense variant predicted to cause substitution of arginine to tryptophan at amino acid 468. This variant is rare in the general population with a frequency below the threshold expected for the associated phenotype(s). This variant has been observed in affected individual(s) with monoallelic occurrence (heterozygous/hemizygous) (PMID: 28077157, 30639582, 8554071, 35144014, 29966168, 33960103). Functional studies show that this variant may disrupt protein function (PMID: 31877959, 15614569). A different variant at the same position has been determined to be Pathogenic or Likely Pathogenic. Computational prediction algorithms indicate this variant is likely to affect gene or protein function. Given the available evidence, this variant is classified as Pathogenic. |
| Gene |
RCV000723439 | SCV005421303 | pathogenic | not provided | 2024-06-05 | criteria provided, single submitter | clinical testing | Expression studies found that this variant is associated with 0%-0.6% of wild-type IDS activity levels (PMID: 15614569); 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: 1284597, 27351199, 34813777, 35144014, 12048688, 29966168, 28077157, 15614569, 33676511, 30639582) |
| Juno Genomics, |
RCV000180471 | SCV005418818 | pathogenic | Mucopolysaccharidosis, MPS-II | criteria provided, single submitter | clinical testing | Absent from controls (or at extremely low frequency if recessive) in Genome Aggregation Database, Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium.;Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc).;Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before.;Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.;The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls. | |
| Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV000180471 | SCV005089553 | 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), Absent from controls (or at low frequency) in gnomAD database (PM2_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) |
| Foundation for Research in Genetics and Endocrinology, |
RCV000180471 | SCV004232630 | pathogenic | Mucopolysaccharidosis, MPS-II | 2024-01-25 | criteria provided, single submitter | clinical testing | A hemizygous missense variation in exon 9 of the IDS gene that results in the amino acid substitution of Tryptophan for Arginine at codon 468 was detected. The observed variant c.1402C>T (p.Arg468Trp) has not been reported in the 1000 genomes and gnomAD databases. The in silico prediction of the variant is damaging by PolyPhen-2 (HumDiv), SIFT, FATHMM, DANN, MetaLR and MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as a pathogenic. |
| Kasturba Medical College, |
RCV000180471 | SCV002507185 | likely pathogenic | Mucopolysaccharidosis, MPS-II | 2022-05-09 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV000180471 | SCV002014468 | pathogenic | Mucopolysaccharidosis, MPS-II | 2021-09-05 | criteria provided, single submitter | clinical testing | |
| Department of Medical Genetics, |
RCV000180471 | SCV001480197 | pathogenic | Mucopolysaccharidosis, MPS-II | criteria provided, single submitter | clinical testing | ||
| Labcorp Genetics |
RCV000180471 | SCV001376052 | pathogenic | Mucopolysaccharidosis, MPS-II | 2025-06-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 468 of the IDS protein (p.Arg468Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with mucopolysaccharidosis type II (PMID: 1284597, 15614569, 28077157, 30639582). ClinVar contains an entry for this variant (Variation ID: 10497). 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 95%. Experimental studies have shown that this missense change affects IDS function (PMID: 1284597, 15614569). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000180471 | SCV000695962 | pathogenic | Mucopolysaccharidosis, MPS-II | 2017-06-26 | criteria provided, single submitter | clinical testing | Variant summary: The IDS c.1402C>T (p.Arg468Trp) variant involves the alteration of a non-conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant is absent in 159432 control chromosomes. This variant has been reported in multiple affected individuals mostly presented with severe form of the disease. Functional studies showed variant with <5% of WTs enzyme activity. Variant affecting the same codon R468Q has also been reported in multiple affected males presenting with Mucopolysaccharidosis type II (Hunter syndrome), suggesting the functional importance of this residue. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. |
| IIFP, |
RCV000180471 | SCV000262540 | pathogenic | Mucopolysaccharidosis, MPS-II | 2014-06-10 | criteria provided, single submitter | research | |
| Eurofins Ntd Llc |
RCV000723439 | SCV000232921 | pathogenic | not provided | 2014-07-28 | criteria provided, single submitter | clinical testing | |
| Division of Medical Genetics, |
RCV000180471 | SCV001573783 | affects | Mucopolysaccharidosis, MPS-II | 2014-04-05 | no assertion criteria provided | research | The change c.1402C>T (p.R468W) was found to be a missense variant, where the basic polar positive amino acid Arginine at 468 position is substituted by aromatic nonpolar neutral amino acid Tryptophan. It was detected in a hemizygous state in three patients from two families. All three with attenuated phenotypes from UP (2 sibs) Jharkhand (single patient) India. |
| Counsyl | RCV000180471 | SCV001132228 | pathogenic | Mucopolysaccharidosis, MPS-II | 2017-06-26 | no assertion criteria provided | clinical testing | This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. |
| Gene |
RCV000180471 | SCV000999928 | not provided | Mucopolysaccharidosis, MPS-II | no classification provided | literature only | ||
| OMIM | RCV000011243 | SCV000031470 | pathogenic | Mucopolysaccharidosis, type II, mild form | 1992-12-01 | no assertion criteria provided | literature only |