ClinVar Miner

Submissions for variant NM_000202.8(IDS):c.1327C>T (p.Arg443Ter)

dbSNP: rs199422227
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000011232 SCV007095897 pathogenic Mucopolysaccharidosis, MPS-II 2025-10-08 criteria provided, single submitter clinical testing A hemizygous nonsense variant in exon 9 of the IDS gene that results in the stop codon and truncation of the protein at codon 443 was detected. The observed variant c.1327C>T (p.Arg443Ter) has not been reported in the 1000 genomes and gnomAD databases. The in silico prediction of the variant is deleterious by MutationTaster2 and DANN. The variant has previously been reported in patients with MPS II (PMID:21291454). In summary, the variant meets our criteria to be classified as pathogenic.
Laboratory of Genetics, Children's Clinical University Hospital Latvia RCV005434600 SCV006105571 pathogenic not provided 2025-02-16 criteria provided, single submitter clinical testing
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV000011232 SCV005089526 pathogenic Mucopolysaccharidosis, MPS-II 2024-06-07 criteria provided, single submitter literature only Null variant (PVS1_Strong), In vitro or in vivo functional studies supportive of a damaging effect (PS3_Moderate), 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), Cosegregation with disease in multiple affected family members (PP1_Moderate), Patient’s phenotype or family history highly specific for the disease (PP4_Moderate)
Centre of Medical Genetics, University Hospital Muenster RCV004584323 SCV002577793 pathogenic See cases 2021-12-20 criteria provided, single submitter clinical testing ACMG categories: PVS1,PM2,PP5
Genome-Nilou Lab RCV000011232 SCV002014470 pathogenic Mucopolysaccharidosis, MPS-II 2021-09-05 criteria provided, single submitter clinical testing
Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences RCV000011232 SCV001480523 pathogenic Mucopolysaccharidosis, MPS-II criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000011232 SCV000940520 pathogenic Mucopolysaccharidosis, MPS-II 2025-11-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg443*) in the IDS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 108 amino acid(s) of the IDS protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with mucopolysaccharidosis II (PMID: 1303211, 18500569, 21291454, 21829674, 27146977). ClinVar contains an entry for this variant (Variation ID: 10486). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic.
IIFP, CONICET-UNLP RCV000011232 SCV000262530 pathogenic Mucopolysaccharidosis, MPS-II 2012-12-13 criteria provided, single submitter research
Natera, Inc. RCV001831559 SCV002084457 pathogenic Mucopolysaccharidosis, MPS-III-A 2020-12-08 no assertion criteria provided clinical testing
Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital RCV000011232 SCV001482335 pathogenic Mucopolysaccharidosis, MPS-II 2019-05-31 no assertion criteria provided research
OMIM RCV000011232 SCV000031459 pathogenic Mucopolysaccharidosis, MPS-II 1993-01-01 no assertion criteria provided literature only

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