ClinVar Miner

Submissions for variant NM_000203.5(IDUA):c.1045G>T (p.Asp349Tyr)

dbSNP: rs368454909
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV000790541 SCV000929874 likely pathogenic Mucopolysaccharidosis type 1 2019-01-01 criteria provided, single submitter literature only PS1:Same amino acid change as a previously established pathogenic variant regardless of nucleotide change [c.1045G>A; p.(Asp349Asn)]. PM2: Absent from GnomAD. PP3:multiple lines of computational evidence supporting a deleterious effect (DANN, MutationTaster, GERP, SIFT). PP5: Reputable source recently reports variants as pathogenic
Labcorp Genetics (formerly Invitae), Labcorp RCV000790541 SCV001199924 pathogenic Mucopolysaccharidosis type 1 2023-06-15 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 349 of the IDUA protein (p.Asp349Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with mucopolysaccharidosis type I (PMID: 12203999, 12559846, 28752568, 30809705). ClinVar contains an entry for this variant (Variation ID: 638075). 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. Experimental studies have shown that this missense change affects IDUA function (PMID: 12559846). This variant disrupts the p.Asp349 amino acid residue in IDUA. Other variant(s) that disrupt this residue have been observed in individuals with IDUA-related conditions (PMID: 8680403), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005036124 SCV005667768 likely pathogenic Mucopolysaccharidosis, MPS-I-S; Hurler syndrome; Mucopolysaccharidosis, MPS-I-H/S 2024-02-06 criteria provided, single submitter clinical testing
Natera, Inc. RCV000790541 SCV002075330 pathogenic Mucopolysaccharidosis type 1 2021-10-07 no assertion criteria provided clinical testing

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