ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.1427C>T (p.Ser476Leu)

gnomAD frequency: 0.00001  dbSNP: rs754217318
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002038627 SCV002312784 uncertain significance Polyglandular autoimmune syndrome, type 1 2021-08-24 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 476 of the AIRE protein (p.Ser476Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs754217318, ExAC 0.006%). This variant has not been reported in the literature in individuals affected with AIRE-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). 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 RCV004976187 SCV005580154 uncertain significance Inborn genetic diseases 2024-11-09 criteria provided, single submitter clinical testing The c.1427C>T (p.S476L) alteration is located in exon 12 (coding exon 12) of the AIRE gene. This alteration results from a C to T substitution at nucleotide position 1427, causing the serine (S) at amino acid position 476 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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