ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.740G>A (p.Arg247His)

gnomAD frequency: 0.00004  dbSNP: rs763487370
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001923373 SCV002180519 uncertain significance Polyglandular autoimmune syndrome, type 1 2024-01-26 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 247 of the AIRE protein (p.Arg247His). This variant is present in population databases (rs763487370, gnomAD 0.05%), including at least one homozygous and/or hemizygous individual. 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: 1412681). 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. 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.

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