Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000003471 | SCV003444329 | likely pathogenic | Polyglandular autoimmune syndrome, type 1 | 2022-06-23 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 3308). 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. Experimental studies have shown that this missense change affects AIRE function (PMID: 14974083). 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 missense change has been observed in individual(s) with autosomal recessive autoimmune polyendocrinopathy syndrome (PMID: 9398839). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 83 of the AIRE protein (p.Lys83Glu). This variant is not present in population databases (gnomAD no frequency). |
| OMIM | RCV000003471 | SCV000023629 | pathogenic | Polyglandular autoimmune syndrome, type 1 | 1997-12-01 | no assertion criteria provided | literature only |