Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001367740 | SCV001564103 | uncertain significance | Polyglandular autoimmune syndrome, type 1 | 2022-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 57 of the AIRE protein (p.Gln57Glu). This variant is present in population databases (rs200955183, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with AIRE-related conditions. ClinVar contains an entry for this variant (Variation ID: 1058583). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on AIRE protein function. 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. |
| Ambry Genetics | RCV003169873 | SCV003870898 | uncertain significance | Inborn genetic diseases | 2023-03-02 | criteria provided, single submitter | clinical testing | The c.169C>G (p.Q57E) alteration is located in exon 2 (coding exon 2) of the AIRE gene. This alteration results from a C to G substitution at nucleotide position 169, causing the glutamine (Q) at amino acid position 57 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Natera, |
RCV001367740 | SCV002083845 | uncertain significance | Polyglandular autoimmune syndrome, type 1 | 2020-03-02 | no assertion criteria provided | clinical testing | |
| Prevention |
RCV004754742 | SCV005345800 | uncertain significance | AIRE-related disorder | 2024-04-12 | no assertion criteria provided | clinical testing | The AIRE c.169C>G variant is predicted to result in the amino acid substitution p.Gln57Glu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.076% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |