Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001061201 | SCV001225934 | pathogenic | Polyglandular autoimmune syndrome, type 1 | 2023-10-09 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 326 of the AIRE protein (p.Pro326Leu). This variant is present in population databases (rs179363885, gnomAD 0.003%). This missense change has been observed in individual(s) with autosomal recessive AIRE-related conditions (PMID: 11275943, 28911151, 29666621). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 68232). 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. Experimental studies have shown that this missense change affects AIRE function (PMID: 26084028). For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV001061201 | SCV002810303 | likely pathogenic | Polyglandular autoimmune syndrome, type 1 | 2022-03-21 | criteria provided, single submitter | clinical testing | |
| Uni |
RCV000059066 | SCV000090587 | not provided | not provided | no assertion provided | not provided |