ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.892G>A (p.Glu298Lys)

gnomAD frequency: 0.00001  dbSNP: rs763636007
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000674603 SCV000799969 uncertain significance Polyglandular autoimmune syndrome, type 1 2018-05-15 criteria provided, single submitter clinical testing
Invitae RCV000674603 SCV001382424 uncertain significance Polyglandular autoimmune syndrome, type 1 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 298 of the AIRE protein (p.Glu298Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs763636007, ExAC 0.006%). This missense change has been observed in individual(s) with autoimmune polyendocrinopathy syndrome (PMID: 18682433, 20407228, 28911151). ClinVar contains an entry for this variant (Variation ID: 558351). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects AIRE function (PMID: 26084028). 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.
GenomeConnect - Invitae Patient Insights Network RCV001535539 SCV001749513 not provided not provided no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 06-28-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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