Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001925653 | SCV002180391 | uncertain significance | Polyglandular autoimmune syndrome, type 1 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 264 of the AIRE protein (p.Ala264Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs746154390, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with AIRE-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |