ClinVar Miner

Submissions for variant NM_015665.6(AAAS):c.1300C>T (p.Arg434Ter) (rs751369041)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000778368 SCV000914586 uncertain significance Glucocorticoid deficiency with achalasia 2017-10-03 criteria provided, single submitter clinical testing The AAAS c.1300C>T (p.Arg434Ter) variant is a stop gained variant predicted to result in premature termination of the protein. The variant has been reported in a homozygous state in one family with triple A syndrome (Krumbholz et al. 2006). Control data are unavailable for this variant, which is reported at a frequency of 0.000097 in the South Asian population of the Genome Aggregation Database. Functional studies conducted in transiently transfected HeLa cells indicate that the variant impairs protein localization, as the Arg434Ter protein was found in the cytoplasm rather than the nuclear pore like the wildtype protein (Krumbholz et al. 2006). Based on the potential impact of stop-gained variants and the limited supporting evidence from the literature, the p.Arg434Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for achalasia-addisonianism-alacrima syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

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