ClinVar Miner

Submissions for variant NM_000744.7(CHRNA4):c.718C>T (p.Arg240Trp)

gnomAD frequency: 0.00001  dbSNP: rs757030850
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484246 SCV000571640 uncertain significance not provided 2016-09-15 criteria provided, single submitter clinical testing The R240W variant in the CHRNA4 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R240W variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R240W 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. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R240W as a variant of uncertain significance.
Invitae RCV002525902 SCV003470712 uncertain significance Autosomal dominant nocturnal frontal lobe epilepsy 2023-07-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 240 of the CHRNA4 protein (p.Arg240Trp). This variant is present in population databases (rs757030850, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CHRNA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 422228). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CHRNA4 protein function. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.