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

dbSNP: rs199422227

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
IIFP, CONICET-UNLP	RCV000011232	SCV000262530	pathogenic	Mucopolysaccharidosis, MPS-II	2012-12-13	criteria provided, single submitter	research
Labcorp Genetics (formerly Invitae), Labcorp	RCV000011232	SCV000940520	pathogenic	Mucopolysaccharidosis, MPS-II	2023-06-29	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 10486). This premature translational stop signal has been observed in individuals with mucopolysaccharidosis II (PMID: 1303211, 18500569, 21291454, 21829674, 27146977). This variant is not present in population databases (gnomAD no frequency). 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.
Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences	RCV000011232	SCV001480523	pathogenic	Mucopolysaccharidosis, MPS-II		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000011232	SCV002014470	pathogenic	Mucopolysaccharidosis, MPS-II	2021-09-05	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University Hospital Muenster	RCV004584323	SCV002577793	pathogenic	See cases	2021-12-20	criteria provided, single submitter	clinical testing	ACMG categories: PVS1,PM2,PP5
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)
OMIM	RCV000011232	SCV000031459	pathogenic	Mucopolysaccharidosis, MPS-II	1993-01-01	no assertion criteria provided	literature only
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
Natera, Inc.	RCV001831559	SCV002084457	pathogenic	Mucopolysaccharidosis, MPS-III-A	2020-12-08	no assertion criteria provided	clinical testing