Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000702141 | SCV000830979 | uncertain significance | Polyglandular autoimmune syndrome, type 1 | 2023-11-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 197 of the AIRE protein (p.Gly197Ala). This variant is not present in population databases (gnomAD no frequency). 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: 578977). 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 not expected to disrupt AIRE protein function with a negative 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. |
| Ambry Genetics | RCV004026582 | SCV004879813 | uncertain significance | Inborn genetic diseases | 2024-03-07 | criteria provided, single submitter | clinical testing | The c.590G>C (p.G197A) alteration is located in exon 5 (coding exon 5) of the AIRE gene. This alteration results from a G to C substitution at nucleotide position 590, causing the glycine (G) at amino acid position 197 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |