ClinVar Miner

Submissions for variant NM_006920.6(SCN1A):c.3719T>C (p.Met1240Thr) (rs749638533)

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
Invitae RCV000474433 SCV000548785 uncertain significance Early infantile epileptic encephalopathy 2018-09-17 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 1251 of the SCN1A protein (p.Met1251Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is present in population databases (rs749638533, ExAC 0.02%) but has not been reported in the literature in individuals with a SCN1A-related disease. This variant identified in the SCN1A gene is located in the transmembrane spanning D3-S2 region of the resulting protein (PMID: 25348405, 18804930), but it is unclear how this variant impacts the function of this protein. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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.