ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.1480C>T (p.Arg494Cys) (rs1465595959)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000633443 SCV000754669 uncertain significance Polyglandular autoimmune syndrome, type 1 2018-11-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 494 of the AIRE protein (p.Arg494Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with AIRE-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15". The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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