Submissions for variant NM_000202.8(IDS):c.1165C>T (p.Gln389Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003050662	SCV003445270	pathogenic	Mucopolysaccharidosis, MPS-II	2022-06-01	criteria provided, single submitter	clinical testing	This variant disrupts a region of the IDS protein in which other variant(s) (p.Gln531*) have been determined to be pathogenic (PMID: 7581397, 17091340). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This premature translational stop signal has been observed in individuals with IDS-related conditions (PMID: 7887413, 32005694, 33075783). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln389*) in the IDS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 162 amino acid(s) of the IDS protein.
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	RCV003050662	SCV005089455	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_Moderate), 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)