NM_001165963.4(SCN1A):c.1184C>A (p.Ala395Asp) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 1, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002613187.3

Allele description [Variation Report for NM_001165963.4(SCN1A):c.1184C>A (p.Ala395Asp)]

NM_001165963.4(SCN1A):c.1184C>A (p.Ala395Asp)

Gene:

SCN1A:sodium voltage-gated channel alpha subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_001165963.4(SCN1A):c.1184C>A (p.Ala395Asp)

HGVS:

NC_000002.12:g.166046963G>T
NG_011906.1:g.31677C>A
NM_001165963.1:c.1184C>A
NM_001165963.4:c.1184C>AMANE SELECT
NM_001165964.3:c.1184C>A
NM_001202435.3:c.1184C>A
NM_001353948.2:c.1184C>A
NM_001353949.2:c.1184C>A
NM_001353950.2:c.1184C>A
NM_001353951.2:c.1184C>A
NM_001353952.2:c.1184C>A
NM_001353954.2:c.1184C>A
NM_001353955.2:c.1184C>A
NM_001353957.2:c.1184C>A
NM_001353958.2:c.1184C>A
NM_001353960.2:c.1184C>A
NM_001353961.2:c.-1242C>A
NM_006920.6:c.1184C>A
NP_001159435.1:p.Ala395Asp
NP_001159436.1:p.Ala395Asp
NP_001189364.1:p.Ala395Asp
NP_001340877.1:p.Ala395Asp
NP_001340878.1:p.Ala395Asp
NP_001340879.1:p.Ala395Asp
NP_001340880.1:p.Ala395Asp
NP_001340881.1:p.Ala395Asp
NP_001340883.1:p.Ala395Asp
NP_001340884.1:p.Ala395Asp
NP_001340886.1:p.Ala395Asp
NP_001340887.1:p.Ala395Asp
NP_001340889.1:p.Ala395Asp
NP_008851.3:p.Ala395Asp
NP_008851.3:p.Ala395Asp
LRG_8t1:c.1184C>A
LRG_8:g.31677C>A
LRG_8p1:p.Ala395Asp
NC_000002.11:g.166903473G>T
NM_006920.4:c.1184C>A
NR_148667.2:n.1570C>A

Protein change:

A395D

Molecular consequence:

NM_001353961.2:c.-1242C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001165963.4:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.1570C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Early infantile epileptic encephalopathy with suppression bursts (EIEE)
Synonyms:: Early infantile epileptic encephalopathy; Ohtahara syndrome; Developmental and epileptic encephalopathy
Identifiers:: MONDO: MONDO:0100062; MedGen: C0393706; Orphanet: 1934; OMIM: PS308350

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002950936	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 1, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17347258, 31765958, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002950936

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 1, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The spectrum of SCN1A-related infantile epileptic encephalopathies.

Harkin LA, McMahon JM, Iona X, Dibbens L, Pelekanos JT, Zuberi SM, Sadleir LG, Andermann E, Gill D, Farrell K, Connolly M, Stanley T, Harbord M, Andermann F, Wang J, Batish SD, Jones JG, Seltzer WK, Gardner A; Infantile Epileptic Encephalopathy Referral Consortium., Sutherland G, Berkovic SF, et al.

Brain. 2007 Mar;130(Pt 3):843-52.

PubMed [citation]

PMID:: 17347258

Mutation spectrum of the SCN1A gene in a Hungarian population with epilepsy.

Till Á, Zima J, Fekete A, Bene J, Czakó M, Szabó A, Melegh B, Hadzsiev K.

Seizure. 2020 Jan;74:8-13. doi: 10.1016/j.seizure.2019.10.019. Epub 2019 Nov 8.

PubMed [citation]

PMID:: 31765958

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002950936.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant disrupts the p.Ala395 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been observed in individuals with SCN1A-related conditions (PMID: 17347258), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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 missense change has been observed in individual(s) with SCN1A-related conditions (PMID: 31765958). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 395 of the SCN1A protein (p.Ala395Asp).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine