NM_001165963.4(SCN1A):c.4934G>A (p.Arg1645Gln) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 30, 2023
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:: RCV001208285.13

Allele description [Variation Report for NM_001165963.4(SCN1A):c.4934G>A (p.Arg1645Gln)]

NM_001165963.4(SCN1A):c.4934G>A (p.Arg1645Gln)

Genes:

SCN1A:sodium voltage-gated channel alpha subunit 1 [Gene - OMIM - HGNC]
LOC102724058:uncharacterized LOC102724058 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_001165963.4(SCN1A):c.4934G>A (p.Arg1645Gln)

Other names:

p.R1645Q:CGA>CAA

HGVS:

NC_000002.12:g.165992341C>T
NG_011906.1:g.86299G>A
NM_001165963.1:c.[4934G>A]
NM_001165963.4:c.4934G>AMANE SELECT
NM_001165963.4:c.4934G>A
NM_001165964.3:c.4850G>A
NM_001202435.3:c.4934G>A
NM_001353948.2:c.4934G>A
NM_001353949.2:c.4901G>A
NM_001353950.2:c.4901G>A
NM_001353951.2:c.4901G>A
NM_001353952.2:c.4901G>A
NM_001353954.2:c.4898G>A
NM_001353955.2:c.4898G>A
NM_001353957.2:c.4850G>A
NM_001353958.2:c.4850G>A
NM_001353960.2:c.4847G>A
NM_001353961.2:c.2492G>A
NM_006920.6:c.4901G>A
NP_001159435.1:p.Arg1645Gln
NP_001159436.1:p.Arg1617Gln
NP_001189364.1:p.Arg1645Gln
NP_001340877.1:p.Arg1645Gln
NP_001340878.1:p.Arg1634Gln
NP_001340879.1:p.Arg1634Gln
NP_001340880.1:p.Arg1634Gln
NP_001340881.1:p.Arg1634Gln
NP_001340883.1:p.Arg1633Gln
NP_001340884.1:p.Arg1633Gln
NP_001340886.1:p.Arg1617Gln
NP_001340887.1:p.Arg1617Gln
NP_001340889.1:p.Arg1616Gln
NP_001340890.1:p.Arg831Gln
NP_008851.3:p.Arg1634Gln
LRG_8t1:c.4901G>A
LRG_8:g.86299G>A
NC_000002.11:g.166848851C>T
NM_001165963.1:c.4934G>A
NM_001165963.1:c.[4934G>A]
NM_006920.4:c.4901G>A
NR_148667.2:n.5351G>A

Protein change:

R1616Q

Links:

UniProtKB/Swiss-Prot: VAR_064269; dbSNP: rs121917976

NCBI 1000 Genomes Browser:

rs121917976

Molecular consequence:

NM_001165963.4:c.4934G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.4850G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.4934G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.4934G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.4901G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.4901G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.4901G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.4901G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.4898G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.4898G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.4850G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.4850G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.4847G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353961.2:c.2492G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.4901G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.5351G>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
SCV001379664	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 30, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17347258, 27864847, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001379664

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 30, 2023)

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

Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.

Parrini E, Marini C, Mei D, Galuppi A, Cellini E, Pucatti D, Chiti L, Rutigliano D, Bianchini C, Virdò S, De Vita D, Bigoni S, Barba C, Mari F, Montomoli M, Pisano T, Rosati A; Clinical Study Group., Guerrini R.

Hum Mutat. 2017 Feb;38(2):216-225. doi: 10.1002/humu.23149. Epub 2016 Dec 9.

PubMed [citation]

PMID:: 27864847

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001379664.5

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

Description

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. ClinVar contains an entry for this variant (Variation ID: 68558). This missense change has been observed in individual(s) with Dravet syndrome (PMID: 17347258, 27864847). In at least one individual the variant was observed to be de novo. This variant is present in population databases (rs121917976, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1645 of the SCN1A protein (p.Arg1645Gln).

#	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: Jun 2, 2024

ClinVar

Relating variation to medicine