Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000824633 | SCV000965538 | uncertain significance | Polyglandular autoimmune syndrome, type 1 | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 316 of the AIRE protein (p.Arg316Gln). This variant is present in population databases (rs202027254, gnomAD 0.01%). 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: 666191). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| Neuberg Centre For Genomic Medicine, |
RCV000824633 | SCV004047011 | uncertain significance | Polyglandular autoimmune syndrome, type 1 | criteria provided, single submitter | clinical testing | The missense variant c.947G>A (p.Arg316Gln) in AIRE (NM_000383.4) gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Arg316Gln variant is reported with the allele frequency (0.004490%) in the gnomad and novel in 1000 genome database. This variant has been reported to ClinVar database as Variant of Uncertain Significance (VUS). The amino acid Arg at position 316 is changed to a Gln changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Arg316Gln in AIRE is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. In the absence of another reportable variant the molecular diagnosis is not confirmed. | |
| Natera, |
RCV000824633 | SCV001457180 | uncertain significance | Polyglandular autoimmune syndrome, type 1 | 2020-09-16 | no assertion criteria provided | clinical testing |