NM_001165963.4(SCN1A):c.5245G>A (p.Gly1749Arg) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 4, 2021
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:: RCV001861426.6

Allele description [Variation Report for NM_001165963.4(SCN1A):c.5245G>A (p.Gly1749Arg)]

NM_001165963.4(SCN1A):c.5245G>A (p.Gly1749Arg)

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.5245G>A (p.Gly1749Arg)

HGVS:

NC_000002.12:g.165992030C>T
NG_011906.1:g.86610G>A
NM_001165963.4:c.5245G>AMANE SELECT
NM_001165964.3:c.5161G>A
NM_001202435.3:c.5245G>A
NM_001353948.2:c.5245G>A
NM_001353949.2:c.5212G>A
NM_001353950.2:c.5212G>A
NM_001353951.2:c.5212G>A
NM_001353952.2:c.5212G>A
NM_001353954.2:c.5209G>A
NM_001353955.2:c.5209G>A
NM_001353957.2:c.5161G>A
NM_001353958.2:c.5161G>A
NM_001353960.2:c.5158G>A
NM_001353961.2:c.2803G>A
NM_006920.6:c.5212G>A
NP_001159435.1:p.Gly1749Arg
NP_001159436.1:p.Gly1721Arg
NP_001189364.1:p.Gly1749Arg
NP_001340877.1:p.Gly1749Arg
NP_001340878.1:p.Gly1738Arg
NP_001340879.1:p.Gly1738Arg
NP_001340880.1:p.Gly1738Arg
NP_001340881.1:p.Gly1738Arg
NP_001340883.1:p.Gly1737Arg
NP_001340884.1:p.Gly1737Arg
NP_001340886.1:p.Gly1721Arg
NP_001340887.1:p.Gly1721Arg
NP_001340889.1:p.Gly1720Arg
NP_001340890.1:p.Gly935Arg
NP_008851.3:p.Gly1738Arg
LRG_8:g.86610G>A
NC_000002.11:g.166848540C>T
NM_001165963.1:c.5245G>A
NR_148667.2:n.5662G>A

Protein change:

G1720R

Links:

dbSNP: rs1057518258

NCBI 1000 Genomes Browser:

rs1057518258

Molecular consequence:

NM_001165963.4:c.5245G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.5161G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.5245G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.5245G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.5212G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.5212G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.5212G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.5212G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.5209G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.5209G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.5161G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.5161G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.5158G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353961.2:c.2803G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.5212G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.5662G>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002153458	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 4, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002153458

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 4, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002153458.3

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

Description

This variant is not present in population databases (ExAC no frequency). 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 observed in individual(s) with clinical features of SCN1A-related conditions (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 373157). This sequence change replaces glycine with arginine at codon 1749 of the SCN1A protein (p.Gly1749Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine.

#	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: Mar 5, 2024

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