NM_172107.4(KCNQ2):c.850T>C (p.Tyr284His) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 26, 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:: RCV003588801.2

Allele description [Variation Report for NM_172107.4(KCNQ2):c.850T>C (p.Tyr284His)]

NM_172107.4(KCNQ2):c.850T>C (p.Tyr284His)

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.850T>C (p.Tyr284His)

HGVS:

NC_000020.11:g.63439675A>G
NG_009004.2:g.37966T>C
NM_001382235.1:c.850T>C
NM_004518.6:c.850T>C
NM_172106.3:c.850T>C
NM_172107.4:c.850T>CMANE SELECT
NM_172108.5:c.850T>C
NM_172109.3:c.850T>C
NP_001369164.1:p.Tyr284His
NP_004509.2:p.Tyr284His
NP_742104.1:p.Tyr284His
NP_742105.1:p.Tyr284His
NP_742106.1:p.Tyr284His
NP_742107.1:p.Tyr284His
NC_000020.10:g.62071028A>G

Protein change:

Y284H

Molecular consequence:

NM_001382235.1:c.850T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004518.6:c.850T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_172106.3:c.850T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_172107.4:c.850T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_172108.5:c.850T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_172109.3:c.850T>C - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Severe decrease in peak current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0087]
Severe hyperpolarizing shift of voltage dependence of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0031]
Severe slowing of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0015]

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
SCV004297362	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 26, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27779742, 29588952, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004297362

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 26, 2023)

germline

clinical testing

PubMed (3)
[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

Gene mutation analysis of 175 Chinese patients with early-onset epileptic encephalopathy.

Zhang Q, Li J, Zhao Y, Bao X, Wei L, Wang J.

Clin Genet. 2017 May;91(5):717-724. doi: 10.1111/cge.12901. Epub 2017 Feb 16.

PubMed [citation]

PMID:: 27779742

Gene panel analysis for nonsyndromic cryptogenic neonatal/infantile epileptic encephalopathy.

Fung CW, Kwong AK, Wong VC.

Epilepsia Open. 2017 Jun;2(2):236-243. doi: 10.1002/epi4.12055.

PubMed [citation]

PMID:: 29588952
PMCID:: PMC5719849

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004297362.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

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 KCNQ2 protein function. ClinVar contains an entry for this variant (Variation ID: 1709240). This missense change has been observed in individual(s) with developmental and epileptic encephalopathy (PMID: 27779742, 29588952). 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 tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 284 of the KCNQ2 protein (p.Tyr284His).

#	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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