U.S. flag

An official website of the United States government

NM_172107.4(KCNQ2):c.748G>T (p.Val250Leu) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 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:
RCV001389467.9

Allele description [Variation Report for NM_172107.4(KCNQ2):c.748G>T (p.Val250Leu)]

NM_172107.4(KCNQ2):c.748G>T (p.Val250Leu)

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.748G>T (p.Val250Leu)
HGVS:
  • NC_000020.11:g.63442474C>A
  • NG_009004.2:g.35167G>T
  • NM_004518.6:c.748G>T
  • NM_172106.3:c.748G>T
  • NM_172107.4:c.748G>TMANE SELECT
  • NM_172108.5:c.748G>T
  • NM_172109.3:c.748G>T
  • NP_004509.2:p.Val250Leu
  • NP_742104.1:p.Val250Leu
  • NP_742105.1:p.Val250Leu
  • NP_742106.1:p.Val250Leu
  • NP_742107.1:p.Val250Leu
  • NC_000020.10:g.62073827C>A
Protein change:
V250L
Links:
dbSNP: rs2081190344
NCBI 1000 Genomes Browser:
rs2081190344
Molecular consequence:
  • NM_004518.6:c.748G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172106.3:c.748G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172107.4:c.748G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172108.5:c.748G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172109.3:c.748G>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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001590854Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

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

PubMed (2)
[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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001590854.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 250 of the KCNQ2 protein (p.Val250Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with KCNQ2-related conditions (PMID: 27779742). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 872260). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts the p.Val250 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 8, 2024