Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001057510 | SCV001222008 | likely pathogenic | Mucopolysaccharidosis, MPS-II | 2020-07-30 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with glycine at codon 334 of the IDS protein (p.Asp334Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with mucopolysaccharidosis type II (PMID: 8830188, 30639582). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Asp334 amino acid residue in IDS. Other variants that disrupt this residue have been observed in individuals with IDS-related conditions (PMID: 24125893, 9660053), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Department of Medical Genetics, |
RCV001057510 | SCV001480483 | likely pathogenic | Mucopolysaccharidosis, MPS-II | criteria provided, single submitter | clinical testing |