Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002510430 | SCV002819788 | likely pathogenic | Polyglandular autoimmune syndrome, type 1 | 2022-12-24 | criteria provided, single submitter | clinical testing | Variant summary: AIRE c.1267G>T (p.Glu423X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic within ClinVar (e.g. c.1295_1296insA [p.Arg433fs], c.1480_1483del [p.Arg494fs]). The variant was absent in 182240 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1267G>T in individuals affected with Autoimmune Polyglandular Syndrome Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |