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NM_172107.4(KCNQ2):c.775G>A (p.Asp259Asn) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 23, 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:
RCV001217360.7

Allele description [Variation Report for NM_172107.4(KCNQ2):c.775G>A (p.Asp259Asn)]

NM_172107.4(KCNQ2):c.775G>A (p.Asp259Asn)

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.775G>A (p.Asp259Asn)
HGVS:
  • NC_000020.11:g.63442447C>T
  • NG_009004.2:g.35194G>A
  • NM_004518.6:c.775G>A
  • NM_172106.3:c.775G>A
  • NM_172107.4:c.775G>AMANE SELECT
  • NM_172108.5:c.775G>A
  • NM_172109.3:c.775G>A
  • NP_004509.2:p.Asp259Asn
  • NP_742104.1:p.Asp259Asn
  • NP_742105.1:p.Asp259Asn
  • NP_742106.1:p.Asp259Asn
  • NP_742107.1:p.Asp259Asn
  • NC_000020.10:g.62073800C>T
  • NM_172107.2:c.775G>A
  • NM_172107.3:c.775G>A
Protein change:
D259N
Links:
dbSNP: rs777257591
NCBI 1000 Genomes Browser:
rs777257591
Molecular consequence:
  • NM_004518.6:c.775G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172106.3:c.775G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172107.4:c.775G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172108.5:c.775G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172109.3:c.775G>A - 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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001389196Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Nov 23, 2022)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Clinical and genetic features of 13 Spanish patients with KCNQ2 mutations.

Hortigüela M, Fernández-Marmiesse A, Cantarín V, Gouveia S, García-Peñas JJ, Fons C, Armstrong J, Barrios D, Díaz-Flores F, Tirado P, Couce ML, Gutiérrez-Solana LG.

J Hum Genet. 2017 Feb;62(2):185-189. doi: 10.1038/jhg.2016.104. Epub 2016 Aug 18.

PubMed [citation]
PMID:
27535030

Genetic analysis of benign familial epilepsies in the first year of life in a Chinese cohort.

Zeng Q, Yang X, Zhang J, Liu A, Yang Z, Liu X, Wu Y, Wu X, Wei L, Zhang Y.

J Hum Genet. 2018 Jan;63(1):9-18. doi: 10.1038/s10038-017-0359-x. Epub 2017 Nov 13.

PubMed [citation]
PMID:
29215089
PMCID:
PMC8075886
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001389196.5

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

Description

ClinVar contains an entry for this variant (Variation ID: 692196). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Asp259 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been observed in individuals with KCNQ2-related conditions (PMID: 27535030), which suggests that this may be a clinically significant amino acid residue. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KCNQ2 protein function. This missense change has been observed in individual(s) with benign familial epilepsy (PMID: 29215089). 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 aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 259 of the KCNQ2 protein (p.Asp259Asn).

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

Last Updated: Sep 29, 2024