Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002889363 | SCV003233075 | uncertain significance | Mucopolysaccharidosis, MPS-II | 2022-08-25 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with IDS-related conditions. This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 403 of the IDS protein (p.Leu403Val). This variant is not present in population databases (gnomAD no frequency). 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 IDS protein function. This variant disrupts the p.Leu403 amino acid residue in IDS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8940265, 9660053, 18500569). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |