Submissions for variant NM_001165963.4(SCN1A):c.787C>G (p.Leu263Val)

dbSNP: rs2105890052

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002568220	SCV003524820	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2023-06-04	criteria provided, single submitter	clinical testing	Experimental studies have shown that this missense change affects SCN1A function (PMID: 18621678). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Leu263 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SCN1A protein function. ClinVar contains an entry for this variant (Variation ID: 1177384). This missense change has been observed in individual(s) with familial hemiplegic migraine with or without epilepsy (PMID: 19220312). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 263 of the SCN1A protein (p.Leu263Val).
GeneReviews	RCV001533164	SCV001748983	not provided	Familial hemiplegic migraine		no assertion provided	literature only
Channelopathy-Associated Epilepsy Research Center	RCV003992532	SCV004809260	not provided	Severe myoclonic epilepsy in infancy		no assertion provided	literature only