Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001765415 | SCV001998088 | uncertain significance | not provided | 2019-10-09 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect |
Labcorp Genetics |
RCV001882889 | SCV002172153 | uncertain significance | Mucopolysaccharidosis type 1 | 2021-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with arginine at codon 500 of the IDUA protein (p.Gln500Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with IDUA-related conditions. 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. 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004699458 | SCV005205384 | uncertain significance | not specified | 2024-06-03 | criteria provided, single submitter | clinical testing | Variant summary: IDUA c.1499A>G (p.Gln500Arg) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. c.1499A>G has been reported in the literature in one individual affected with Mucopolysaccharidosis Type 1 (Xiao_2022). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 35848209). ClinVar contains an entry for this variant (Variation ID: 1309246). Based on the evidence outlined above, the variant was classified as uncertain significance. |