NM_001165963.4(SCN1A):c.485C>T (p.Thr162Ile) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 4, 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:: RCV001879864.7

Allele description [Variation Report for NM_001165963.4(SCN1A):c.485C>T (p.Thr162Ile)]

NM_001165963.4(SCN1A):c.485C>T (p.Thr162Ile)

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.485C>T (p.Thr162Ile)

HGVS:

NC_000002.12:g.166054755G>A
NG_011906.1:g.23885C>T
NM_001165963.4:c.485C>TMANE SELECT
NM_001165964.3:c.485C>T
NM_001202435.3:c.485C>T
NM_001353948.2:c.485C>T
NM_001353949.2:c.485C>T
NM_001353950.2:c.485C>T
NM_001353951.2:c.485C>T
NM_001353952.2:c.485C>T
NM_001353954.2:c.485C>T
NM_001353955.2:c.485C>T
NM_001353957.2:c.485C>T
NM_001353958.2:c.485C>T
NM_001353960.2:c.485C>T
NM_001353961.2:c.-1941C>T
NM_006920.6:c.485C>T
NP_001159435.1:p.Thr162Ile
NP_001159436.1:p.Thr162Ile
NP_001189364.1:p.Thr162Ile
NP_001340877.1:p.Thr162Ile
NP_001340878.1:p.Thr162Ile
NP_001340879.1:p.Thr162Ile
NP_001340880.1:p.Thr162Ile
NP_001340881.1:p.Thr162Ile
NP_001340883.1:p.Thr162Ile
NP_001340884.1:p.Thr162Ile
NP_001340886.1:p.Thr162Ile
NP_001340887.1:p.Thr162Ile
NP_001340889.1:p.Thr162Ile
NP_008851.3:p.Thr162Ile
LRG_8:g.23885C>T
NC_000002.11:g.166911265G>A
NC_000002.11:g.166911265G>A
NM_001165963.1:c.485C>T
NR_148667.2:n.871C>T

Protein change:

T162I

Links:

dbSNP: rs1698960532

NCBI 1000 Genomes Browser:

rs1698960532

Molecular consequence:

NM_001353961.2:c.-1941C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001165963.4:c.485C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.485C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.485C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.485C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.485C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.485C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.485C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.485C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.485C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.485C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.485C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.485C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.485C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.485C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.871C>T - 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
SCV002238269	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 4, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28202706, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002238269

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 4, 2023)

germline

clinical testing

PubMed (2)
[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

Clinical and genetic factors predicting Dravet syndrome in infants with SCN1A mutations.

Cetica V, Chiari S, Mei D, Parrini E, Grisotto L, Marini C, Pucatti D, Ferrari A, Sicca F, Specchio N, Trivisano M, Battaglia D, Contaldo I, Zamponi N, Petrelli C, Granata T, Ragona F, Avanzini G, Guerrini R.

Neurology. 2017 Mar 14;88(11):1037-1044. doi: 10.1212/WNL.0000000000003716. Epub 2017 Feb 15.

PubMed [citation]

PMID:: 28202706
PMCID:: PMC5384833

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002238269.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 162 of the SCN1A protein (p.Thr162Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Dravet syndrome (PMID: 28202706). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 975943). 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. For these reasons, this variant has been classified as Pathogenic.

#	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

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