Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001218009 | SCV001389873 | pathogenic | Mucopolysaccharidosis type 1 | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 240 of the IDUA protein (p.His240Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with mucopolysaccharidosis type I (PMID: 11735025, 22976768, 31194252). ClinVar contains an entry for this variant (Variation ID: 947028). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on IDUA protein function. Experimental studies have shown that this missense change affects IDUA function (PMID: 11735025). This variant disrupts the p.His240 amino acid residue in IDUA. Other variant(s) that disrupt this residue have been observed in individuals with IDUA-related conditions (PMID: 24875751), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
Myriad Genetics, |
RCV001810498 | SCV002060149 | likely pathogenic | Mucopolysaccharidosis, MPS-I-H/S | 2021-11-08 | criteria provided, single submitter | clinical testing | NM_000203.3(IDUA):c.719A>G(H240R) is a missense variant classified as likely pathogenic in the context of mucopolysaccharidosis type I. H240R has been observed in cases with relevant disease (PMID: 11735025, 22976768, 31194252). Functional assessments of this variant are available in the literature (PMID: 11735025). H240R has not been observed in population frequency databases. In summary, NM_000203.3(IDUA):c.719A>G(H240R) is a missense variant that has functional support for pathogenicity and has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. |
Natera, |
RCV001218009 | SCV002075307 | pathogenic | Mucopolysaccharidosis type 1 | 2021-08-02 | no assertion criteria provided | clinical testing |