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NM_172107.4(KCNQ2):c.767G>T (p.Gly256Val) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 19, 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:
RCV001216111.9

Allele description [Variation Report for NM_172107.4(KCNQ2):c.767G>T (p.Gly256Val)]

NM_172107.4(KCNQ2):c.767G>T (p.Gly256Val)

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.767G>T (p.Gly256Val)
HGVS:
  • NC_000020.11:g.63442455C>A
  • NG_009004.2:g.35186G>T
  • NM_001382235.1:c.767G>T
  • NM_004518.6:c.767G>T
  • NM_172106.3:c.767G>T
  • NM_172107.4:c.767G>TMANE SELECT
  • NM_172108.5:c.767G>T
  • NM_172109.3:c.767G>T
  • NP_001369164.1:p.Gly256Val
  • NP_004509.2:p.Gly256Val
  • NP_742104.1:p.Gly256Val
  • NP_742105.1:p.Gly256Val
  • NP_742106.1:p.Gly256Val
  • NP_742107.1:p.Gly256Val
  • NC_000020.10:g.62073808C>A
  • NM_172107.2:c.767G>T
Protein change:
G256V
Links:
dbSNP: rs1371722284
NCBI 1000 Genomes Browser:
rs1371722284
Molecular consequence:
  • NM_001382235.1:c.767G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004518.6:c.767G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172106.3:c.767G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172107.4:c.767G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172108.5:c.767G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172109.3:c.767G>T - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001387888Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Mar 19, 2022) 		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

KCNQ2 encephalopathy: Features, mutational hot spots, and ezogabine treatment of 11 patients.

Millichap JJ, Park KL, Tsuchida T, Ben-Zeev B, Carmant L, Flamini R, Joshi N, Levisohn PM, Marsh E, Nangia S, Narayanan V, Ortiz-Gonzalez XR, Patterson MC, Pearl PL, Porter B, Ramsey K, McGinnis EL, Taglialatela M, Tracy M, Tran B, Venkatesan C, Weckhuysen S, et al.

Neurol Genet. 2016 Oct;2(5):e96. doi: 10.1212/NXG.0000000000000096.

PubMed [citation]
PMID:
27602407
PMCID:
PMC4995058

Gene Panel Testing in Epileptic Encephalopathies and Familial Epilepsies.

Møller RS, Larsen LH, Johannesen KM, Talvik I, Talvik T, Vaher U, Miranda MJ, Farooq M, Nielsen JE, Svendsen LL, Kjelgaard DB, Linnet KM, Hao Q, Uldall P, Frangu M, Tommerup N, Baig SM, Abdullah U, Born AP, Gellert P, Nikanorova M, Olofsson K, et al.

Mol Syndromol. 2016 Sep;7(4):210-219. Epub 2016 Aug 20.

PubMed [citation]
PMID:
27781031
PMCID:
PMC5073625
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001387888.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly256 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been observed in individuals with KCNQ2-related conditions (PMID: 27602407, 27781031), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 945463). This missense change has been observed in individual(s) with clinical features of KCNQ2-related disease (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 glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 256 of the KCNQ2 protein (p.Gly256Val).

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

Last Updated: Sep 29, 2024