Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001378699 | SCV001576325 | pathogenic | Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease axonal type 2V | 2022-01-13 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with leucine, which is neutral and non-polar, at codon 649 of the NAGLU protein (p.Trp649Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Trp649 amino acid residue in NAGLU. Other variant(s) that disrupt this residue have been observed in individuals with NAGLU-related conditions (PMID: 11153910), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 143187). This missense change has been observed in individual(s) with mucopolysaccharidosis type III (PMID: 23661660). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. |
| Undiagnosed Diseases Program Translational Research Laboratory, |
RCV000132721 | SCV000187650 | pathogenic | Mucopolysaccharidosis, MPS-III-B | no assertion criteria provided | not provided | Converted during submission to Pathogenic. |