ClinVar Miner

Submissions for variant NM_000203.5(IDUA):c.878_889dup (p.Thr293_Tyr296dup)

dbSNP: rs779762183
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665114 SCV000789180 likely pathogenic Hurler syndrome 2017-01-20 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000794373 SCV000933778 pathogenic Mucopolysaccharidosis type 1 2023-11-22 criteria provided, single submitter clinical testing This variant, c.878_889dup, results in the insertion of 4 amino acid(s) of the IDUA protein (p.Thr293_Tyr296dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with mucopolysaccharidosis (MPS) type I (PMID: 9787109, 12203999, 21394825, 23786846; Invitae). ClinVar contains an entry for this variant (Variation ID: 550382). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects IDUA function (PMID: 11735025). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000794373 SCV003844265 pathogenic Mucopolysaccharidosis type 1 2023-02-04 criteria provided, single submitter clinical testing Variant summary: IDUA c.878_889dup12 (p.Thr293_Tyr296dup) results in an in-frame duplication that is predicted to duplicate 4 amino acids into the encoded protein. The variant allele was found at a frequency of 6.6e-06 in 150926 control chromosomes (gnomAD v3.1.2). c.878_889dup12 has been reported in the literature as a biallelic genotype in multiple individuals affected with Mucopolysaccharidosis Type 1 (e.g. Bunge_1995, Bertola_2011, Chistiakov_2014, Ghosh_2017). These data indicate that the variant is very likely to be associated with disease. Residual IDUA activity was 0.9% in cells from a compound heterozygous individual that carried a null variant in trans, indicating this variant also results in loss of function (Oussoren_2013). Three ClinVar submitters have assessed the variant since 2014: one classified the variant as likely pathogenic, and two as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Natera, Inc. RCV000794373 SCV002075318 pathogenic Mucopolysaccharidosis type 1 2020-08-14 no assertion criteria provided clinical testing

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