ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.1168A>G (p.Thr390Ala)

gnomAD frequency: 0.00006  dbSNP: rs771790456
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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 RCV000686368 SCV000813884 uncertain significance Polyglandular autoimmune syndrome, type 1 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 390 of the AIRE protein (p.Thr390Ala). This variant is present in population databases (rs771790456, gnomAD 0.003%). 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: 566533). 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 with a negative predictive value of 95%. 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 RCV003278987 SCV003954434 likely benign Inborn genetic diseases 2023-03-27 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Natera, Inc. RCV000686368 SCV002083898 uncertain significance Polyglandular autoimmune syndrome, type 1 2019-10-28 no assertion criteria provided clinical testing

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