Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000341295 | SCV000331011 | likely pathogenic | not provided | 2016-06-01 | criteria provided, single submitter | clinical testing | |
Centogene AG - |
RCV001250255 | SCV001424460 | pathogenic | Mucopolysaccharidosistype IIIB | criteria provided, single submitter | clinical testing | ||
Invitae | RCV003765584 | SCV004585883 | pathogenic | Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease axonal type 2V | 2023-02-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 234 of the NAGLU protein (p.Arg234Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of mucopolysaccharidosis type IIIB (PMID: 33083013). ClinVar contains an entry for this variant (Variation ID: 280994). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NAGLU protein function. This variant disrupts the p.Arg234 amino acid residue in NAGLU. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9832037, 11286389, 18218046, 30070758). 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. |