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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004297362Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Mar 26, 2023) 		germlineclinical testing

PubMed (3)
[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

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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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).

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

Last Updated: Sep 29, 2024