Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001378371 | SCV001575923 | likely pathogenic | Mucopolysaccharidosis, MPS-II | 2021-09-24 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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. This variant disrupts the p.Arg110 amino acid residue in IDS. Other variant(s) that disrupt this residue have been observed in individuals with IDS-related conditions (PMID: 27246110), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects IDS protein function (PMID: 30639582). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individual(s) with mucopolysaccharidosis II (PMID: 30639582; Invitae). This sequence change replaces arginine with glycine at codon 110 of the IDS protein (p.Arg110Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. |