Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000429619 | SCV000523480 | likely pathogenic | not provided | 2016-02-09 | criteria provided, single submitter | clinical testing | The Q465K variant in the IDS gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Q465K variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Q465K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. 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 at the same and nearby residues (Q465P, S464R, P467L, P467R) have been reported in the Human Gene Mutation Database in association with mucopolysaccharidosis, type II (Stenson et al., 2014), supporting the functional importance of this region of the protein. The Q465K variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded. |