ClinVar Miner

Submissions for variant NM_000203.5(IDUA):c.298A>G (p.Arg100Gly)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002952549 SCV003267331 uncertain significance Mucopolysaccharidosis type 1 2021-11-02 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 100 of the IDUA protein (p.Arg100Gly). This variant is present in population databases (rs201345740, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of mucopolysaccharidosis type I (PMID: 28728811). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Revvity Omics, Revvity RCV003130782 SCV003817635 uncertain significance not provided 2023-03-10 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003403968 SCV004106086 likely pathogenic IDUA-related disorder 2022-10-17 criteria provided, single submitter clinical testing The IDUA c.298A>G variant is predicted to result in the amino acid substitution p.Arg100Gly. This variant was reported in compound heterozygous state in an individual with severe form of Mucopolysaccharidosis I. (Zhang et al. 2022. PubMed ID: 35787971, Table 3). This variant is reported in 0.012% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-981736-A-G). This variant is predicted to disrupt the GT donor splice site and interfere with normal splicing (Alamut Visual v2.11; predicted probability of splice site loss -0.65). Variants that disrupt the consensus splice site in IDUA are expected to be pathogenic. This variant is interpreted as likely pathogenic.

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