ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.1393C>T (p.Arg465Trp)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002508431 SCV002817556 uncertain significance not provided 2022-06-28 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV002571557 SCV003254422 uncertain significance Polyglandular autoimmune syndrome, type 1 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 465 of the AIRE protein (p.Arg465Trp). This variant is present in population databases (rs370070250, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with AIRE-related conditions. 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.

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