ClinVar Miner

Submissions for variant NM_000203.5(IDUA):c.903C>G (p.Asp301Glu)

dbSNP: rs759390416
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001975007 SCV002241985 pathogenic Mucopolysaccharidosis type 1 2020-12-10 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 301 of the IDUA protein (p.Asp301Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with mucopolysaccharidosis type I (PMID: 31194252, 31298590, 31236806). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt IDUA protein function. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001975007 SCV005422169 pathogenic Mucopolysaccharidosis type 1 2024-10-23 criteria provided, single submitter clinical testing Variant summary: IDUA c.903C>G (p.Asp301Glu) results in a conservative amino acid change located in the Glycosyl hydrolases family 39, N-terminal catalytic domain (IPR049166) of the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 186460 control chromosomes (gnomAD). c.903C>G has been reported in the literature in multiple individuals affected with Mucopolysaccharidosis Type 1 (examples: Clarke_2019, Kamranjam_2019, Shafaat_2019, Taghikhani_2019). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 31194252, 31298590, 31236806, 31386236). ClinVar contains an entry for this variant (Variation ID: 1458511). Based on the evidence outlined above, the variant was classified as pathogenic.

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