ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.927C>G (p.Ile309Met)

gnomAD frequency: 0.00010  dbSNP: rs74162062
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001242282 SCV001415356 uncertain significance Polyglandular autoimmune syndrome, type 1 2022-10-21 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 309 of the AIRE protein (p.Ile309Met). This variant is present in population databases (rs74162062, gnomAD 0.03%). 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: 967385). 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) has been performed at Invitae 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.
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital RCV001242282 SCV001984725 uncertain significance Polyglandular autoimmune syndrome, type 1 2021-02-15 criteria provided, single submitter clinical testing
GeneDx RCV002473239 SCV002770388 uncertain significance not provided 2023-08-28 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 36703223, CrammerJ2022[Poster])
Natera, Inc. RCV001242282 SCV002083882 uncertain significance Polyglandular autoimmune syndrome, type 1 2020-01-15 no assertion criteria provided clinical testing

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