Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001041100 | SCV001204696 | likely pathogenic | Mucopolysaccharidosis, MPS-II | 2019-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with arginine at codon 347 of the IDS protein (p.Lys347Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. 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: 27883178). 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.Lys347 amino acid residue in IDS. Other variant(s) that disrupt this residue have been observed in individuals with IDS-related conditions (PMID: 11731225, 9266380, 8940265, 9222763, 15614569), 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. |