Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001346113 | SCV001540288 | uncertain significance | Polyglandular autoimmune syndrome, type 1 | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with leucine at codon 494 of the AIRE protein (p.Arg494Leu). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and leucine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. 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 leucine 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. |
Natera, |
RCV001346113 | SCV002076140 | uncertain significance | Polyglandular autoimmune syndrome, type 1 | 2020-01-11 | no assertion criteria provided | clinical testing |