ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.3749C>T (p.Thr1250Met) (rs140731963)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188927 SCV000242557 uncertain significance not provided 2018-04-23 criteria provided, single submitter clinical testing T1250M was previously identified in a patient with genetic (generalized) epilepsy with febrile seizures plus (GEFS+) and was not detected in 200 control individuals; however, additional family members were not available to determine whether the missense change segregated with the phenotype in the family (Orrico et al., 2009). T1250M was subsequently published in a patient reported to have Dravet syndrome, but that individual also had a disease-causing splice site variant in SCN1A (Catarino et al., 2011). The T1250M variant was not observed with any significance frequencing in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. It is a non-conservative missense substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size, and/or other properties. It alters a position in the linker region between the transmembrane segments S1 and S2 of the third homologous domain of the protein, and other missense variants have been reported in this region of the protein (SCN1A Variant Database). However, it alters a position in the protein that is not conserved across species, and in silico analysis is inconsistent with regard to the effect this variant may have on the protein structure/function. Therefore, based on the currently available information, it is unclear whether T1250M is a pathogenic variant or a benign variant.
Invitae RCV000188927 SCV000559689 likely benign not provided 2019-02-03 criteria provided, single submitter clinical testing
Mendelics RCV000986886 SCV001136035 uncertain significance Severe myoclonic epilepsy in infancy 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV001413415 SCV001615528 likely benign Early infantile epileptic encephalopathy with suppression bursts 2020-11-27 criteria provided, single submitter clinical testing

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.