ClinVar Miner

Submissions for variant NM_001365536.1(SCN9A):c.1185C>G (p.Asn395Lys) (rs80356471)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000237037 SCV000293086 pathogenic not provided 2015-08-24 criteria provided, single submitter clinical testing The N395K missense variant in the SCN9A gene has been reported previously in association with erythermalgia (Zhang et al., 2007). Functional studies show that the N395 residue, which is located in the local anesthetic binding site, is critical for lidocaine binding, and N395K was associated with altered channel function and altered lidocaine binding (Sheets et al., 2007). The N395K variant was not observed in approximately 5,900 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. It is a semi-conservative amino acid substitution, which occurs at a position in the protein that is conserved across species. Additionally, a different nucleotide substitution (c.1185 C>A) resulting in the same amino acid substitution (N395K) has also been published in association with primary erythermalgia (Drenth et al., 2005). Therefore, the presence of the N395K variant is consistent with a diagnosis of an SCN9A-related disorder

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.