Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001378365 | SCV001575917 | pathogenic | Mucopolysaccharidosis type 1 | 2022-02-01 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 1067173). This missense change has been observed in individual(s) with IDUA-related conditions (PMID: 19396826). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 620 of the IDUA protein (p.Val620Phe). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001378365 | SCV004037743 | likely pathogenic | Mucopolysaccharidosis type 1 | 2023-08-30 | criteria provided, single submitter | clinical testing | Variant summary: IDUA c.1858G>T (p.Val620Phe) 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 248056 control chromosomes (gnomAD). c.1858G>T has been reported in the literature in individuals affected with Mucopolysaccharidosis Type 1 (example: Vazna_2009). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (example: Vazna_2009). The following publication has been ascertained in the context of this evaluation (PMID: 19396826). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |