ClinVar Miner

Submissions for variant NM_000744.7(CHRNA4):c.622G>A (p.Glu208Lys) (rs771249249)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186930 SCV000240501 uncertain significance not provided 2012-12-31 criteria provided, single submitter clinical testing p.Glu208Lys (GAG>AAG): c.622 G>A in exon 5 of the CHRNA4 gene (NM_000744.5)The Glu208Lys missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Glu208Lys in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The amino acid substitution is non-conservative, as a negatively charged Glutamic acid residue is replaced by a positively charged Lysine residue. This substitution alters a highly conserved position, and multiple in silico algorithms predict it may be damaging to protein structure/function. However, it does not occur within the transmembrane region of the protein, where pathogenic missense mutations have been identified in association with epilepsy (Steinlein et al., 2010).Therefore, based on the currently available information, it is unclear whether Glu208Lys is a disease-causing mutation or a rare benign variant. The variant is found in ADULT-EPI panel(s).
Ambry Genetics RCV000720257 SCV000851134 uncertain significance Seizures 2016-07-28 criteria provided, single submitter clinical testing Insufficient evidence

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