Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000520378 | SCV000617380 | likely pathogenic | not provided | 2017-07-19 | criteria provided, single submitter | clinical testing | The I230F variant in the IDS gene has been reported previously in an individual with a suspected clinical diagnosis of MPS II, however, confirmatory biochemical studies including glycosaminoglycans and enzyme analysis were not included (Pollard et al., 2013). The I230F variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The I230F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (Y225D, K227Q, K227E, K227M, P228A, P228T, P228Q, P228L, H229Y, H229R, H229Q, P231L, R233G) have been reported in the Human Gene Mutation Database in association with MPS II (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret I230F as a likely pathogenic variant. |