ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.1345T>C (p.Cys449Arg)

gnomAD frequency: 0.00001  dbSNP: rs957681340
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000418507 SCV000512007 uncertain significance not provided 2016-09-07 criteria provided, single submitter clinical testing The C449R variant in the AIRE gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The C449R variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The C449R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret C449R as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001273733 SCV003447174 uncertain significance Polyglandular autoimmune syndrome, type 1 2022-10-27 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 377458). This variant has not been reported in the literature in individuals affected with AIRE-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 449 of the AIRE protein (p.Cys449Arg).
Natera, Inc. RCV001273733 SCV001457190 uncertain significance Polyglandular autoimmune syndrome, type 1 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.