Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003876612 | SCV004679046 | uncertain significance | Polyglandular autoimmune syndrome, type 1 | 2023-02-10 | 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. This variant has not been reported in the literature in individuals affected with AIRE-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 80 of the AIRE protein (p.Val80Met). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004701858 | SCV005203811 | uncertain significance | not specified | 2024-07-02 | criteria provided, single submitter | clinical testing | Variant summary: AIRE c.238G>A (p.Val80Met) results in a conservative amino acid change located in the HSR domain (IPR004865) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 250996 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.238G>A in individuals affected with Autoimmune Polyglandular Syndrome Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 3016461). Based on the evidence outlined above, the variant was classified as uncertain significance. |