ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.655G>A (p.Gly219Ser) (rs139620961)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000291566 SCV000338370 uncertain significance not provided 2015-12-22 criteria provided, single submitter clinical testing
Invitae RCV000801112 SCV000940871 uncertain significance Polyglandular autoimmune syndrome, type 1 2018-09-12 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 219 of the AIRE protein (p.Gly219Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs139620961, ExAC 0.01%). This variant has not been reported in the literature in individuals with AIRE-related disease. ClinVar contains an entry for this variant (Variation ID: 285376). 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 serine 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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