Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001386057 | SCV001586146 | pathogenic | Congenital disorder of deglycosylation | 2022-07-05 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the NGLY1 protein in which other variant(s) (p.Gln631Serfs*7) have been determined to be pathogenic (PMID: 22581936, 24651605, 25900930). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1073150). This variant has not been reported in the literature in individuals affected with NGLY1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp583*) in the NGLY1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 72 amino acid(s) of the NGLY1 protein. |