ClinVar Miner

Submissions for variant NM_000744.6(CHRNA4):c.1525G>A (p.Ala509Thr) (rs142137599)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000624743 SCV000742167 uncertain significance Inborn genetic diseases 2017-06-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected
Ambry Genetics RCV000718069 SCV000848931 uncertain significance Seizures 2017-02-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000116719 SCV000240523 uncertain significance not provided 2018-02-05 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CHRNA4 gene. The A509T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A509T variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The A509T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this amino acid substitution is not predicted to occur within the transmembrane region of the protein, where the vast majority of pathogenic missense variants have been identified in association with epilepsy (Steinlein et al., 2010). In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Genetic Services Laboratory, University of Chicago RCV000116719 SCV000150690 uncertain significance not provided 2013-10-14 criteria provided, single submitter clinical testing

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