Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV003228342 | SCV003924571 | uncertain significance | not provided | 2022-11-15 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV003779824 | SCV004622189 | likely pathogenic | Polyglandular autoimmune syndrome, type 1 | 2022-12-15 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 93 of the AIRE protein (p.Leu93Gln). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Leu93 amino acid residue in AIRE. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10084559). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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) performed at Invitae indicates that this missense variant is expected to disrupt AIRE protein function. This variant has not been reported in the literature in individuals affected with AIRE-related conditions. This variant is not present in population databases (gnomAD no frequency). |