Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000672356 | SCV000797454 | likely pathogenic | Hurler syndrome | 2018-01-26 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001378363 | SCV001575915 | pathogenic | Mucopolysaccharidosis type 1 | 2024-01-26 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 179 of the IDUA protein (p.Thr179Arg). 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: 21480867). ClinVar contains an entry for this variant (Variation ID: 556358). 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 with a positive predictive value of 95%. This variant disrupts the p.Thr179 amino acid residue in IDUA. Other variant(s) that disrupt this residue have been observed in individuals with IDUA-related conditions (PMID: 28752568), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001378363 | SCV003928844 | pathogenic | Mucopolysaccharidosis type 1 | 2023-04-25 | criteria provided, single submitter | clinical testing | Variant summary: IDUA c.536C>G (p.Thr179Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250946 control chromosomes (gnomAD). c.536C>G has been reported in the literature as a biallelic genotype in multiple individuals affected with Mucopolysaccharidosis Type 1 (e.g. Wang_2012, Hu_2018, Fang_2022). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 34813777, 29095814, 21480867). Three ClinVar submitters have assessed the variant since 2014: two classified the variant as likely pathogenic, and one as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Natera, |
RCV001378363 | SCV002075294 | likely pathogenic | Mucopolysaccharidosis type 1 | 2020-04-10 | no assertion criteria provided | clinical testing |