Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000668435 | SCV000793035 | likely pathogenic | Mucopolysaccharidosis, MPS-III-B | 2017-07-27 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001248721 | SCV001422227 | pathogenic | Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease, axonal type 2V | 2019-11-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 674 of the NAGLU protein (p.Arg674Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs763299645, ExAC 0.007%). This variant has been observed in individual(s) with mucopolysaccharidosis type IIIB (PMID: 9443875, 10094189). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 553061). 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.Arg674 amino acid residue in NAGLU. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8650226, 9443875, 9950362, 20852935). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |