Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001323387 | SCV001514299 | uncertain significance | Polyglandular autoimmune syndrome, type 1 | 2023-08-24 | 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. ClinVar contains an entry for this variant (Variation ID: 1023358). This missense change has been observed in individual(s) with clinical features of autoimmune polyendocrinopathy syndrome (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 56 of the AIRE protein (p.Pro56Leu). |
Prevention |
RCV003983875 | SCV004800064 | uncertain significance | AIRE-related disorder | 2023-12-11 | no assertion criteria provided | clinical testing | The AIRE c.167C>T variant is predicted to result in the amino acid substitution p.Pro56Leu. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |