NM_001040142.2(SCN2A):c.4712T>C (p.Ile1571Thr) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 3, 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:: RCV002545228.5

Allele description [Variation Report for NM_001040142.2(SCN2A):c.4712T>C (p.Ile1571Thr)]

NM_001040142.2(SCN2A):c.4712T>C (p.Ile1571Thr)

Gene:

SCN2A:sodium voltage-gated channel alpha subunit 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_001040142.2(SCN2A):c.4712T>C (p.Ile1571Thr)

HGVS:

NC_000002.12:g.165386906T>C
NG_008143.1:g.152505T>C
NM_001040142.2:c.4712T>CMANE SELECT
NM_001040143.2:c.4712T>C
NM_001371246.1:c.4712T>C
NM_001371247.1:c.4712T>C
NM_021007.3:c.4712T>C
NP_001035232.1:p.Ile1571Thr
NP_001035233.1:p.Ile1571Thr
NP_001358175.1:p.Ile1571Thr
NP_001358176.1:p.Ile1571Thr
NP_066287.2:p.Ile1571Thr
NC_000002.11:g.166243416T>C
NM_001040142.1:c.4712T>C

Protein change:

I1571T

Links:

dbSNP: rs2105398463

Molecular consequence:

NM_001040142.2:c.4712T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001040143.2:c.4712T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001371246.1:c.4712T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001371247.1:c.4712T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_021007.3:c.4712T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Seizures, benign familial infantile, 3 (BFIS3)
Synonyms:: CONVULSIONS, BENIGN FAMILIAL INFANTILE, 3; Familial neonatal seizures
Identifiers:: MONDO: MONDO:0011904; MedGen: C1843140; Orphanet: 140927; Orphanet: 306; OMIM: 607745

Name:: Developmental and epileptic encephalopathy, 11 (DEE11)
Synonyms:: Early infantile epileptic encephalopathy 11
Identifiers:: MONDO: MONDO:0013388; MedGen: C3150987; Orphanet: 1934; OMIM: 613721

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003459839	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 3, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 30185235, 30776697, 32400968, 32613771, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003459839

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 3, 2022)

germline

clinical testing

PubMed (5)
[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

Novel and de novo mutations in pediatric refractory epilepsy.

Liu J, Tong L, Song S, Niu Y, Li J, Wu X, Zhang J, Zai CC, Luo F, Wu J, Li H, Wong AHC, Sun R, Liu F, Li B.

Mol Brain. 2018 Sep 5;11(1):48. doi: 10.1186/s13041-018-0392-5. Erratum in: Mol Brain. 2018 Oct 16;11(1):59. doi: 10.1186/s13041-018-0399-y..

PubMed [citation]

PMID:: 30185235
PMCID:: PMC6125990

Gene mutational analysis in a cohort of Chinese children with unexplained epilepsy: Identification of a new KCND3 phenotype and novel genes causing Dravet syndrome.

Wang J, Wen Y, Zhang Q, Yu S, Chen Y, Wu X, Zhang Y, Bao X.

Seizure. 2019 Mar;66:26-30. doi: 10.1016/j.seizure.2019.01.025. Epub 2019 Jan 28.

PubMed [citation]

PMID:: 30776697

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003459839.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects SCN2A function (PMID: 32400968). 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 SCN2A protein function. ClinVar contains an entry for this variant (Variation ID: 1342682). This missense change has been observed in individual(s) with SCN2A-related conditions (PMID: 30185235, 30776697, 32400968, 32613771). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1571 of the SCN2A protein (p.Ile1571Thr).

#	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: Feb 23, 2026

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