NM_172107.4(KCNQ2):c.740C>G (p.Ser247Trp) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 11, 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:: RCV001059860.9

Allele description [Variation Report for NM_172107.4(KCNQ2):c.740C>G (p.Ser247Trp)]

NM_172107.4(KCNQ2):c.740C>G (p.Ser247Trp)

Gene:

KCNQ2:potassium voltage-gated channel subfamily Q member 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q13.33

Genomic location:

Preferred name:

NM_172107.4(KCNQ2):c.740C>G (p.Ser247Trp)

HGVS:

NC_000020.11:g.63442482G>C
NG_009004.2:g.35159C>G
NM_004518.6:c.740C>G
NM_172106.3:c.740C>G
NM_172107.4:c.740C>GMANE SELECT
NM_172108.5:c.740C>G
NM_172109.3:c.740C>G
NP_004509.2:p.Ser247Trp
NP_742104.1:p.Ser247Trp
NP_742105.1:p.Ser247Trp
NP_742106.1:p.Ser247Trp
NP_742107.1:p.Ser247Trp
NC_000020.10:g.62073835G>C
NM_172107.2:c.740C>G
O43526:p.Ser247Trp

Protein change:

S247W; SER247TRP

Links:

UniProtKB: O43526#VAR_026991; OMIM: 602235.0008; dbSNP: rs74315392

NCBI 1000 Genomes Browser:

rs74315392

Molecular consequence:

NM_004518.6:c.740C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172106.3:c.740C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172107.4:c.740C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172108.5:c.740C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172109.3:c.740C>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001224511	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 11, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 29314763, 31199083, 12742592, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001224511

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 11, 2022)

germline

clinical testing

PubMed (4)
[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

Integrating exome sequencing into a diagnostic pathway for epileptic encephalopathy: Evidence of clinical utility and cost effectiveness.

Palmer EE, Schofield D, Shrestha R, Kandula T, Macintosh R, Lawson JA, Andrews I, Sampaio H, Johnson AM, Farrar MA, Cardamone M, Mowat D, Elakis G, Lo W, Zhu Y, Ying K, Morris P, Tao J, Dias KR, Buckley M, Dinger ME, Cowley MJ, et al.

Mol Genet Genomic Med. 2018 Mar;6(2):186-199. doi: 10.1002/mgg3.355. Epub 2018 Jan 4.

PubMed [citation]

PMID:: 29314763
PMCID:: PMC5902395

KCNQ2 mutations in childhood nonlesional epilepsy: Variable phenotypes and a novel mutation in a case series.

Lee IC, Chang TM, Liang JS, Li SY.

Mol Genet Genomic Med. 2019 Jul;7(7):e00816. doi: 10.1002/mgg3.816. Epub 2019 Jun 14.

PubMed [citation]

PMID:: 31199083
PMCID:: PMC6625149

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001224511.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This missense change has been observed in individual(s) with clinical features of KCNQ2-related conditions (PMID: 12742592; Invitae). 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 serine, which is neutral and polar, with tryptophan, which is neutral and slightly polar, at codon 247 of the KCNQ2 protein (p.Ser247Trp). ClinVar contains an entry for this variant (Variation ID: 7389). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ser247 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29314763, 31199083). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects KCNQ2 function (PMID: 12742592). 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 KCNQ2 protein function.

#	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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