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NM_172107.4(KCNQ2):c.587C>T (p.Ala196Val) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 27, 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:
RCV001066784.9

Allele description [Variation Report for NM_172107.4(KCNQ2):c.587C>T (p.Ala196Val)]

NM_172107.4(KCNQ2):c.587C>T (p.Ala196Val)

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.587C>T (p.Ala196Val)
HGVS:
  • NC_000020.11:g.63444762G>A
  • NG_009004.2:g.32879C>T
  • NM_004518.6:c.587C>T
  • NM_172106.3:c.587C>T
  • NM_172107.4:c.587C>TMANE SELECT
  • NM_172108.5:c.587C>T
  • NM_172109.3:c.587C>T
  • NP_004509.2:p.Ala196Val
  • NP_742104.1:p.Ala196Val
  • NP_742105.1:p.Ala196Val
  • NP_742106.1:p.Ala196Val
  • NP_742107.1:p.Ala196Val
  • NC_000020.10:g.62076115G>A
  • NM_172107.2:c.587C>T
  • NM_172107.3:c.587C>T
Protein change:
A196V
Links:
dbSNP: rs118192199
NCBI 1000 Genomes Browser:
rs118192199
Molecular consequence:
  • NM_004518.6:c.587C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172106.3:c.587C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172107.4:c.587C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172108.5:c.587C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172109.3:c.587C>T - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
  • Mild decrease in peak current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0085]
  • Normal rate of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0011]
  • Severe depolarizing shift of voltage dependence of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0026]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001231804Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 27, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Genetic testing in benign familial epilepsies of the first year of life: clinical and diagnostic significance.

Zara F, Specchio N, Striano P, Robbiano A, Gennaro E, Paravidino R, Vanni N, Beccaria F, Capovilla G, Bianchi A, Caffi L, Cardilli V, Darra F, Bernardina BD, Fusco L, Gaggero R, Giordano L, Guerrini R, Incorpora G, Mastrangelo M, Spaccini L, Laverda AM, et al.

Epilepsia. 2013 Mar;54(3):425-36. doi: 10.1111/epi.12089. Epub 2013 Jan 29.

PubMed [citation]
PMID:
23360469

Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.

Carvill GL, Heavin SB, Yendle SC, McMahon JM, O'Roak BJ, Cook J, Khan A, Dorschner MO, Weaver M, Calvert S, Malone S, Wallace G, Stanley T, Bye AM, Bleasel A, Howell KB, Kivity S, Mackay MT, Rodriguez-Casero V, Webster R, Korczyn A, Afawi Z, et al.

Nat Genet. 2013 Jul;45(7):825-30. doi: 10.1038/ng.2646. Epub 2013 May 26.

PubMed [citation]
PMID:
23708187
PMCID:
PMC3704157
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001231804.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This missense change has been observed in individual(s) with benign familial neonatal seizures and early onset epileptic encephalopathy (PMID: 17475800, 23360469, 23708187). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 196 of the KCNQ2 protein (p.Ala196Val). ClinVar contains an entry for this variant (Variation ID: 21792). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects KCNQ2 function (PMID: 17475800). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 24, 2024