Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003064681 | SCV003444479 | pathogenic | Congenital adrenal hypoplasia, X-linked; 46,XY sex reversal 2 | 2022-06-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the NR0B1 protein in which other variant(s) (p.Ile439Glnfs*5) have been observed in individuals with NR0B1-related conditions (PMID: 22761912). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This premature translational stop signal has been observed in individuals with X-linked adrenal hypoplasia (PMID: 7609262, 26500747). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser431Ilefs*6) in the NR0B1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 40 amino acid(s) of the NR0B1 protein. |