ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.3716_3717AT[6] (p.Asp1243fs) (rs796053072)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189052 SCV000242683 pathogenic not provided 2016-09-01 criteria provided, single submitter clinical testing c.3724_3725dupAT: p.Asp1243LeufsX28 (D1243LfsX28) in exon 19 of the SCN1A gene (NM_001165963.1). The normal sequence with the bases that are duplicated in bases is TATAT{dupAT}TGAT. The c.3724_3725dupAT pathogenic variant in the SCN1A gene has been reported previously, using alternate nomenclature, as a de novo mutation in an individual with myoclonic epilepsy in infancy (Marini et al., 2007) and in another individual with intractable epilepsy in which the inheritance pattern was unknown (Wang et al., 2012). The c.3724_3725dupAT pathogenic variant causes a frameshift starting with codon Aspartic acid 1243, changes this amino acid to a Leucine residue and creates a premature Stop codon at position 28 of the new reading frame, denoted p.Asp1243LeufsX28. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The presence of c.3724_3725dupAT is consistent with a diagnosis of an SCN1A-related disorder. The variant is found in EPILEPSY panel(s).
Invitae RCV000463766 SCV000548729 pathogenic Early infantile epileptic encephalopathy 2019-06-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp1243Leufs*28) in the SCN1A gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with epilepsy (PMID: 17561957, 23195492). This variant is also known as p.I1242ins1270X in the literature. ClinVar contains an entry for this variant (Variation ID: 206910). Loss-of-function variants in SCN1A are known to be pathogenic (PMID: 17347258, 18930999). For these reasons, this variant has been classified as 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.