ClinVar Miner

Submissions for variant NM_000202.8(IDS):c.238C>T (p.Gln80Ter) (rs1569560527)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000781472 SCV000919529 pathogenic Mucopolysaccharidosis, MPS-II 2018-07-24 criteria provided, single submitter clinical testing Variant summary: IDS c.238C>T (p.Gln80X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 169233 control chromosomes (gnomAD). The variant, c.238C>T, has been reported in the literature in individuals affected with severe Mucopolysaccharidosis Type II (Hunter Syndrome) (Carrozzo 1996, Vafiadaki 1998, Wang 2014, Parkinson 2004). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, by determining enzyme activity from the plasma of patients (Parkinson 2004). The most pronounced variant effect results in <10% of normal activity. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000781472 SCV001211912 pathogenic Mucopolysaccharidosis, MPS-II 2019-04-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln80*) in the IDS gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with mucopolysaccharidosis II (PMID: 8829647, 21829674). This variant is also known as 362C>T in the literature. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in IDS are known to be pathogenic (PMID: 8940265, 9875019). For these reasons, this variant has been classified as Pathogenic.

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