Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV001820447 | SCV002071346 | uncertain significance | not specified | 2019-10-28 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002542624 | SCV003272601 | uncertain significance | Polyglandular autoimmune syndrome, type 1 | 2025-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 265 of the AIRE protein (p.Ala265Thr). This variant is present in population databases (rs140835367, gnomAD 0.05%). 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: 1337433). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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 | RCV004040986 | SCV004879832 | uncertain significance | Inborn genetic diseases | 2023-10-05 | criteria provided, single submitter | clinical testing | The c.793G>A (p.A265T) alteration is located in exon 6 (coding exon 6) of the AIRE gene. This alteration results from a G to A substitution at nucleotide position 793, causing the alanine (A) at amino acid position 265 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV003968580 | SCV004779665 | uncertain significance | AIRE-related disorder | 2024-01-30 | no assertion criteria provided | clinical testing | The AIRE c.793G>A variant is predicted to result in the amino acid substitution p.Ala265Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.046% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |