ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.659C>T (p.Ser220Phe)

gnomAD frequency: 0.00008  dbSNP: rs753236604
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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 RCV000816189 SCV000956684 uncertain significance Polyglandular autoimmune syndrome, type 1 2024-12-04 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 220 of the AIRE protein (p.Ser220Phe). This variant is present in population databases (rs753236604, gnomAD 0.04%). 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: 659221). Invitae Evidence 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 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.
Ambry Genetics RCV004972999 SCV005586583 uncertain significance Inborn genetic diseases 2024-09-26 criteria provided, single submitter clinical testing The c.659C>T (p.S220F) alteration is located in exon 6 (coding exon 6) of the AIRE gene. This alteration results from a C to T substitution at nucleotide position 659, causing the serine (S) at amino acid position 220 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000816189 SCV002083866 uncertain significance Polyglandular autoimmune syndrome, type 1 2020-08-14 no assertion criteria provided clinical testing

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