Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001295061 | SCV001483970 | likely pathogenic | Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease axonal type 2V | 2024-11-18 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 153 of the NAGLU protein (p.Glu153Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NAGLU-related conditions. ClinVar contains an entry for this variant (Variation ID: 999108). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt NAGLU protein function with a positive predictive value of 95%. This variant disrupts the p.Glu153 amino acid residue in NAGLU. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9443878, 11793481, 29979746, 31236806). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |