ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.1367G>A (p.Arg456His)

gnomAD frequency: 0.00005  dbSNP: rs554954634
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001246932 SCV001420324 uncertain significance Polyglandular autoimmune syndrome, type 1 2022-06-23 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 456 of the AIRE protein (p.Arg456His). This variant is present in population databases (rs554954634, gnomAD 0.01%). 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: 971203). 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) performed at Invitae indicates that this missense variant is not expected to disrupt 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.
Ambry Genetics RCV002570351 SCV003754915 uncertain significance Inborn genetic diseases 2022-08-16 criteria provided, single submitter clinical testing The c.1367G>A (p.R456H) alteration is located in exon 11 (coding exon 11) of the AIRE gene. This alteration results from a G to A substitution at nucleotide position 1367, causing the arginine (R) at amino acid position 456 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001246932 SCV002076127 uncertain significance Polyglandular autoimmune syndrome, type 1 2020-03-19 no assertion criteria provided clinical testing

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