ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5167T>C (p.Ser1723Pro) (rs1553520320)

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 RCV000554528 SCV000633870 likely pathogenic Early infantile epileptic encephalopathy 2017-11-19 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 1723 of the SCN1A protein (p.Ser1723Pro). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with SCN1A-related disease (Invitae). This variant identified in the SCN1A gene is located in the extracellular D4-S5/S6 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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.