ClinVar Miner

Submissions for variant NM_006920.6(SCN1A):c.664C>T (p.Arg222Ter) (rs121918624)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000188841 SCV000111477 pathogenic not provided 2016-05-03 criteria provided, single submitter clinical testing
Center for Bioinformatics, Peking University RCV000032604 SCV000221894 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
GeneDx RCV000188841 SCV000242471 pathogenic not provided 2018-12-19 criteria provided, single submitter clinical testing The R222X nonsense mutation in the SCN1A gene has been reported multiple times in association with SCN1A-related disorders (Claes et al., 2001). This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is found in CHILD-EPI panel(s).
NeuroMeGen,Hospital Clinico Santiago de Compostela RCV000032604 SCV000693790 likely pathogenic Severe myoclonic epilepsy in infancy 2018-01-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000032604 SCV000697774 pathogenic Severe myoclonic epilepsy in infancy 2016-05-04 criteria provided, single submitter clinical testing Variant summary: The SCN1A c.664C>T (p.Arg222X) variant results in a premature termination codon, predicted to cause a truncated or absent SCN1A protein, which is a commonly known mechanism for disease. The variant is absent in 116,872 control chromosomes and has been reported by multiple reputable clinical labs as pathogenic. The literature reports this variant in numerous SMEI patients, many of whom have confirmed de novo inheritance. Functional study proved that variant did not generate Na+current and showed significantly slower kinetics of recovery from inactivation compared to WT (Bechi_2012). Taken together, this variant has been classified as pathogenic.
Ambry Genetics RCV000720398 SCV000851275 pathogenic History of neurodevelopmental disorder 2016-10-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense),Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Fulgent Genetics,Fulgent Genetics RCV000763461 SCV000894238 pathogenic Familial hemiplegic migraine type 3; Severe myoclonic epilepsy in infancy; Generalized epilepsy with febrile seizures plus, type 2 2018-10-31 criteria provided, single submitter clinical testing
OMIM RCV000032604 SCV000056358 pathogenic Severe myoclonic epilepsy in infancy 2001-06-01 no assertion criteria provided literature only
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000032604 SCV000805025 pathogenic Severe myoclonic epilepsy in infancy 2016-12-21 no assertion criteria provided 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.