Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003523377 | SCV004297418 | pathogenic | Polyglandular autoimmune syndrome, type 1 | 2023-04-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the AIRE protein in which other variant(s) (p.Pro539Leu) have been determined to be pathogenic (PMID: 11836330, 15811934, 17289071, 17675238). 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 individual(s) with autoimmune polyendocrinopathy syndrome (PMID: 24158785). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala500Profs*21) in the AIRE gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 46 amino acid(s) of the AIRE protein. |