Submissions for variant NM_001165963.4(SCN1A):c.2956C>T (p.Leu986Phe)

dbSNP: rs121918625

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000794577	SCV000933993	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2022-07-05	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 986 of the SCN1A protein (p.Leu986Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with severe myoclonic epilepsy of infancy (PMID: 11359211). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 12890). 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. Experimental studies have shown that this missense change affects SCN1A function (PMID: 14672992, 18804930, 23086956, 25348405). For these reasons, this variant has been classified as Pathogenic.
OMIM	RCV000032605	SCV000056359	pathogenic	Severe myoclonic epilepsy in infancy	2001-06-01	no assertion criteria provided	literature only
UniProtKB/Swiss-Prot	RCV000032605	SCV000091014	not provided	Severe myoclonic epilepsy in infancy		no assertion provided	not provided
Channelopathy-Associated Epilepsy Research Center	RCV000032605	SCV004809261	not provided	Severe myoclonic epilepsy in infancy		no assertion provided	literature only