ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.205_208dup (p.Asp70fs) (rs886041124)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000324168 SCV000329054 pathogenic not provided 2016-08-22 criteria provided, single submitter clinical testing The c.205_208dupCAGG variant in the AIRE gene has been reported previously in patients of Arabic ancestry in association with autoimmune polyendocrinopathy syndrome, type 1 (APS1) (Heino et al., 1999; Faiyaz-Ul-Haque et al., 2009). The duplication causes a frameshift starting with codon Aspartic acid 70, changes this amino acid to an Alanine residue and creates a premature Stop codon at position 148 of the new reading frame, denoted p.Asp70AlafsX148. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.
Integrated Genetics/Laboratory Corporation of America RCV000586684 SCV000696651 pathogenic Polyglandular autoimmune syndrome, type 1 2016-03-07 criteria provided, single submitter clinical testing Variant summary: This c.205_208dupCAGG variant causes a frameshift, which alters the proteins amino acid sequence beginning at position 70 and leads to a premature termination codon 148 amino acids downstream. It is predicted to cause a truncated or absent AIRE protein. Loss-of-function due to mutations in this gene is an established disease mechanism in APS1. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Arg257X, p.Cys311fs). This variant has been reported in multiple APS1 families in homozygous state. However, it was absent in approximately 120132 chromosomes from ExAC. One reputable database has classified this variant as pathogenic. Taken together, this variant has been classified as a Disease Variant/Pathogenic.
OMIM RCV000586684 SCV000023638 pathogenic Polyglandular autoimmune syndrome, type 1 2009-11-01 no assertion criteria provided literature only

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