Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000411961 | SCV000485928 | likely pathogenic | Mucopolysaccharidosis, MPS-III-B | 2016-11-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003766125 | SCV004571375 | pathogenic | Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease axonal type 2V | 2023-02-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu336*) in the NAGLU gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 408 amino acid(s) of the NAGLU protein. 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. This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type III (PMID: 11153910). ClinVar contains an entry for this variant (Variation ID: 370575). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects NAGLU function (PMID: 11153910, 29979746). 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. |