Submissions for variant NM_000202.8(IDS):c.1425G>A (p.Trp475Ter)

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Minimum conflict level: Report conflict between different conditions

Total submissions: 4

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	RCV000011241	SCV005089569	likely pathogenic	Mucopolysaccharidosis, MPS-II	2024-06-07	criteria provided, single submitter	literature only	Null variant (PVS1_Strong), Prevalence of the variant significantly increased in affected individuals compared with controls (PS4_Supporting), Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Patient’s phenotype or family history highly specific for the disease (PP4_Moderate)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000011241	SCV002133833	pathogenic	Mucopolysaccharidosis, MPS-II	2021-10-23	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp475) in the IDS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 76 amino acid(s) of the IDS protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the IDS protein in which other variant(s) (p.Leu530Phefs8) have been determined to be pathogenic (PMID: 7581397, 17284421; external communication). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 10495). This premature translational stop signal has been observed in individual(s) with Hunter syndrome (PMID: 1303211). This variant is not present in population databases (gnomAD no frequency).
Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences	RCV000011241	SCV001480461	pathogenic	Mucopolysaccharidosis, MPS-II		criteria provided, single submitter	clinical testing
OMIM	RCV000011241	SCV000031468	pathogenic	Mucopolysaccharidosis, MPS-II	1992-08-01	no assertion criteria provided	literature only

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