ClinVar Miner

Submissions for variant NM_000203.5(IDUA):c.1227dup (p.Thr410fs)

dbSNP: rs1715179164
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001194418 SCV001363956 pathogenic Mucopolysaccharidosis type 1 2019-08-29 criteria provided, single submitter clinical testing Variant summary: IDUA c.1227dupG (p.Thr410AspfsX99) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 87618 control chromosomes (gnomAD). c.1227dupG has been reported in the literature in two compound heterozygote individuals affected with Mucopolysaccharidosis Type 1 (Wang_2012). The two patients had indicated IDUA activities of less than <10%. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001194418 SCV001585394 pathogenic Mucopolysaccharidosis type 1 2020-06-07 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in IDUA are known to be pathogenic (PMID: 11735025, 21480867). This variant has been observed in individual(s) with mucopolysaccharidosis type I (MPS I) (PMID: 21480867). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change creates a premature translational stop signal (p.Thr410Aspfs*99) in the IDUA gene. It is expected to result in an absent or disrupted protein product.
Clinical Genetics Laboratory, Skane University Hospital Lund RCV004697063 SCV005198460 likely pathogenic not provided 2022-05-27 criteria provided, single submitter clinical testing

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