ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.251A>G (p.Tyr84Cys)

dbSNP: rs121917964
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255485 SCV000321935 pathogenic not provided 2021-05-26 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This substitution is predicted to be within the N-terminal cytoplasmic domain; This variant is associated with the following publications: (PMID: 19589774, 21248271, 32090326, 17347258, 23195492, 29933521, 31031587)
Labcorp Genetics (formerly Invitae), Labcorp RCV000695650 SCV000824162 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2021-01-11 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. This variant has been reported in individual(s) with Dravet syndrome (PMID: 17347258, 23195492, 22050978). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 68520). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 84 of the SCN1A protein (p.Tyr84Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine.
Fulgent Genetics, Fulgent Genetics RCV000763463 SCV000894240 likely pathogenic Migraine, familial hemiplegic, 3; Severe myoclonic epilepsy in infancy; Generalized epilepsy with febrile seizures plus, type 2 2018-10-31 criteria provided, single submitter clinical testing
UniProtKB/Swiss-Prot RCV000059392 SCV000090916 not provided Severe myoclonic epilepsy in infancy no assertion provided not provided

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