Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001389201 | SCV001590470 | pathogenic | Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease axonal type 2V | 2023-10-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln388*) in the NAGLU gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 356 amino acid(s) of the NAGLU protein. This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 1075574). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts a region of the NAGLU protein in which other variant(s) (p.Arg626*) have been determined to be pathogenic (PMID: 8650226, 9832037, 10094189). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |