ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.4369A>G (p.Ile1457Val) (rs796053142)

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 RCV000189155 SCV000242787 uncertain significance not provided 2013-05-13 criteria provided, single submitter clinical testing p.Ile1457Val (ATT>GTT): c.4369 A>G in exon 24 of the SCN2A gene (NM_021007.2). The Ile1457Val missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 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 amino acid substitution is conservative as both Isoleucine and Valine are uncharged, non-polar amino acid residues. Ile1457Val alters a highly conserved position in the S6 segment of the third transmembrane domain of the SCN2A protein; however, to our knowledge, other missense mutations in this region of the protein have not been published in association with epilepsy. In addition, while some in-silico algorithms predict Ile1457Val may be damaging to the structure/function of the protein, another model predicts it may be benign. Therefore, based on the currently available information, it is unclear whether Ile1457Val is a disease-causing mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s).

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.