Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clinical Biomedical Laboratory, |
RCV003066392 | SCV007538936 | likely pathogenic | Mucopolysaccharidosis, MPS-II | 2026-03-10 | criteria provided, single submitter | clinical testing | This variant is absent from the Genome Aggregation Database, v2.1.1.Computational tools: (REVEL 0.98) suggest that the amino acid is conserved and that the change is detrimental to protein function. This specific variant has been published in individuals with attenuated mucopolysaccharidosis II (PMID 21291454), which is in accordance with the phenotype of the proband. Based on the ACMG variant interpretation guidelines, the available evidence supports classification of this variant as likely pathogenic. |
| Gene |
RCV004700920 | SCV005201689 | pathogenic | not provided | 2023-12-20 | criteria provided, single submitter | clinical testing | 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: 9660053, 21204210, 33960103, 12572848, 27695081, 21291454, 33676511, 24550654, 27883178, 24125893, 17391447) |
| Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV003066392 | SCV005089343 | likely pathogenic | Mucopolysaccharidosis, MPS-II | 2024-06-07 | criteria provided, single submitter | literature only | Prevalence of the variant significantly increased in affected individuals compared with controls (PS4_Supporting), 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), Missense change at the same amino acid residue as a pathogenic variant (PM5_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) |
| Labcorp Genetics |
RCV003066392 | SCV003445913 | pathogenic | Mucopolysaccharidosis, MPS-II | 2025-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 335 of the IDS protein (p.His335Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with mucopolysaccharidosis type II (PMID: 9660053, 12572848, 21291454, 33676511). ClinVar contains an entry for this variant (Variation ID: 2138748). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic. |