Submissions for variant NM_001165963.4(SCN1A):c.332_333insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNCCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCTGCCCTGTACATTTT (p.Leu111delinsPhePhePhePhePhePhePheXaaXaaXaaXaaLeuValIleArgProProArgProProLysValLeuGlyLeuGlnAlaTer)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002837753	SCV003208062	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2022-06-14	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in SCN1A are known to be pathogenic (PMID: 17347258, 18930999). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 2 of the SCN1A gene (c.332_333ins?), causing a frameshift at codon 111 (p.Leu111fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product.