Total submissions: 13
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Medical Genetic Diagnosis and Therapy Center, |
RCV000011233 | SCV007101785 | pathogenic | Mucopolysaccharidosis, MPS-II | 2025-10-27 | criteria provided, single submitter | clinical testing | P: PS4+PM1+PM2+PM5+PP3. This variant has been reported in the following publication(s): [1] Zhong L, Gao X, Wang Y, et al. Clinical characteristics and genotypes of 201 patients with mucopolysaccharidosis type II in China: A retrospective, observational study[J]. Clinical Genetics, 2023, 103(6): 655-662. [2] Lin C Y, Lin H Y, Chuang C K, et al. Effect of mutated ids overexpression on ids enzyme activity and developmental phenotypes in zebrafish embryos: A valuable index for assessing critical point-mutations associated with mucopolysaccharidosis type II occurrence in humans[J]. Diagnostics, 2020, 10(10): 854. |
| Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV000011233 | SCV005089333 | 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) |
| Neuberg Centre For Genomic Medicine, |
RCV000011233 | SCV005042552 | pathogenic | Mucopolysaccharidosis, MPS-II | criteria provided, single submitter | clinical testing | The missense variant c.998C>Tp.Ser333Leu in IDS gene has been reported previously in hemizygous state in most of the individuals with mucopolysaccharidosis type II. Experimental studies have shown that this missense change affects IDS function Sukegawa-Hayasaka K, et al., 2006, Vollebregt AAM, et al., 2017. The variant is novel not in any individuals in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic multiple submissions.The amino acid Serine at position 333 is changed to a Leucine changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by SIFT. The amino acid change p.Ser333Leu in IDS is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic. | |
| Gene |
RCV000790725 | SCV002578620 | pathogenic | not provided | 2022-10-05 | criteria provided, single submitter | clinical testing | Published functional studies with S333L transfected into CHO, HEK293T, and COS-7 cells indicate a severe impairment of protein function (Sukegawa-Hayasaka et al., 2006; Vollebregt et al., 2017; Lin et al., 2019); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 16495038, 9921913, 9660053, 27246110, 1639384, 27695081, 30548430, 30639582, 9950361, 27896113, 27883178, 8830188, 28543354, 9875019, 21291454, 21829674, 33676511, 31877959, 34258227, 35144014, 17091340, 24125893) |
| Genome- |
RCV000011233 | SCV002014474 | pathogenic | Mucopolysaccharidosis, MPS-II | 2021-09-05 | criteria provided, single submitter | clinical testing | |
| Department of Medical Genetics, |
RCV000011233 | SCV001480194 | pathogenic | Mucopolysaccharidosis, MPS-II | criteria provided, single submitter | clinical testing | ||
| Labcorp Genetics |
RCV000011233 | SCV001207067 | pathogenic | Mucopolysaccharidosis, MPS-II | 2023-12-29 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 333 of the IDS protein (p.Ser333Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with mucopolysaccharidosis type II (MPS II) (PMID: 1639384, 28543354, 30639582; Invitae). ClinVar contains an entry for this variant (Variation ID: 10487). 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) performed at Invitae 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: 17091340, 28543354). For these reasons, this variant has been classified as Pathogenic. |
| IIFP, |
RCV000011233 | SCV000262529 | pathogenic | Mucopolysaccharidosis, MPS-II | 2010-04-16 | criteria provided, single submitter | research | |
| Eurofins Ntd Llc |
RCV000790725 | SCV000232028 | pathogenic | not provided | 2013-08-29 | criteria provided, single submitter | clinical testing | |
| Developmental and Behavioral Pediatrics, |
RCV000011233 | SCV002575080 | pathogenic | Mucopolysaccharidosis, MPS-II | no assertion criteria provided | provider interpretation | ||
| Division of Medical Genetics, |
RCV000011233 | SCV001573787 | affects | Mucopolysaccharidosis, MPS-II | 2014-04-07 | no assertion criteria provided | research | The change c.998C>T (p.S333L) was found to be a missense variant, where the hydroxyl-containing polar neutral amino acid Serine at 333 position was substituted by aliphatic nonpolar neutral amino acid Leucine. It was detected in a hemizygous state in one case with severe phenotype from Haryana, India. |
| Gene |
RCV000011233 | SCV000999926 | not provided | Mucopolysaccharidosis, MPS-II | no classification provided | literature only | ||
| OMIM | RCV000011233 | SCV000031460 | pathogenic | Mucopolysaccharidosis, MPS-II | 1992-07-01 | no assertion criteria provided | literature only |