Submissions for variant NM_000202.8(IDS):c.1589dup (p.Leu530fs)

dbSNP: rs2124648266

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001946683	SCV002232154	pathogenic	Mucopolysaccharidosis, MPS-II	2021-07-24	criteria provided, single submitter	clinical testing	This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type II (PMID: 17284421; external communication). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu530Phefs*8) in the IDS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 21 amino acid(s) of the IDS protein. This variant is also known as c.1587~1588insT . 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.Gln531*) have been determined to be pathogenic (PMID: 7581397). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing.
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	RCV001946683	SCV005089639	pathogenic	Mucopolysaccharidosis, MPS-II	2024-06-07	criteria provided, single submitter	literature only	Null variant (PVS1_Strong), Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Patient’s phenotype or family history highly specific for the disease (PP4_Strong)