ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.1214C>T (p.Pro405Leu)

gnomAD frequency: 0.00001  dbSNP: rs769719554
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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 RCV001218809 SCV001390713 uncertain significance Polyglandular autoimmune syndrome, type 1 2022-07-28 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 405 of the AIRE protein (p.Pro405Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 947687). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
PreventionGenetics, part of Exact Sciences RCV003425999 SCV004118484 uncertain significance AIRE-related disorder 2023-08-01 criteria provided, single submitter clinical testing The AIRE c.1214C>T variant is predicted to result in the amino acid substitution p.Pro405Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00096% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/21-45712994-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV001218809 SCV002076113 uncertain significance Polyglandular autoimmune syndrome, type 1 2020-03-07 no assertion criteria provided clinical testing

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