Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002581889 | SCV003487918 | uncertain significance | Polyglandular autoimmune syndrome, type 1 | 2023-11-19 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 316 of the AIRE protein (p.Arg316Trp). This variant is present in population databases (rs139874934, gnomAD 0.006%). This missense change has been observed in individual(s) with pernicious anemia (PMID: 26084028). ClinVar contains an entry for this variant (Variation ID: 2173395). 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 with a positive predictive value of 95%. 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. |