Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000817898 | SCV000958483 | likely pathogenic | Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease, axonal type 2V | 2018-10-29 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the NAGLU gene (p.Trp649*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 95 amino acids of the NAGLU protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NAGLU-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the C-terminus of the NAGLU protein. Other variant(s) that disrupt this region (p.Arg674Cys, p.Arg674His, p.Trp675*, p.Gln706*) have been observed in affected individuals (PMID: 9443875). This suggests that this may be a clinically significant region of the protein. 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. |