Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002620738 | SCV003510989 | uncertain significance | Polyglandular autoimmune syndrome, type 1 | 2022-02-10 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 109 of the AIRE protein (p.Pro109Ala). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with AIRE-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Clinical Genomics Laboratory, |
RCV002620738 | SCV005047095 | uncertain significance | Polyglandular autoimmune syndrome, type 1 | 2024-05-08 | criteria provided, single submitter | clinical testing | The AIRE c.325C>G (p.Pro109Ala) variant, to our knowledge, has not been reported in the medical literature and is only observed on 1/245,860 alleles in the general population (gnomAD v.2.1.1), indicating it is not a common variant. Computational predictors suggest that the variant does not impact AIRE function. This variant has been reported in the ClinVar database as a germline variant of uncertain significance in polyglandular autoimmune syndrome, type 1 by one submitter (ClinVar ID: 2191709). Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time. |