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NM_172107.3(KCNQ2):c.868G>A (p.Gly290Ser) AND Early infantile epileptic encephalopathy

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 6, 2016
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:
RCV000466204.1

Allele description

NM_172107.3(KCNQ2):c.868G>A (p.Gly290Ser)

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_172107.3(KCNQ2):c.868G>A (p.Gly290Ser)
HGVS:
  • NC_000020.11:g.63439657C>T
  • NG_009004.2:g.37984G>A
  • NM_172107.3:c.868G>A
  • NP_742105.1:p.Gly290Ser
  • NC_000020.10:g.62071010C>T
  • NM_172107.2:c.868G>A
Protein change:
G290S
Links:
dbSNP: rs1057516098
NCBI 1000 Genomes Browser:
rs1057516098
Molecular consequence:
  • NM_172107.3:c.868G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Early infantile epileptic encephalopathy (EIEE)
Synonyms:
Ohtahara syndrome
Identifiers:
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
SCV000543199Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 6, 2016) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000543199.2

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

Description

This sequence change replaces glycine with serine at codon 290 of the KCNQ2 protein (p.Gly290Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been shown to arise de novo in several individuals affected with early onset epileptic encephalopathy (PMID: 23692823, 23621294). A different missense substitution at this codon (p.Gly290Asp) has been determined to be pathogenic (PMID: 22275249, 24318194). This suggests that the glycine residue is critical for KCNQ2 protein function and that other missense substitutions at this position may also be pathogenic. This variant occurs in the pore-forming Segment 5 and Segment 6 region of KCNQ2. 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 disruptive, but these predictions have not been confirmed by published functional studies. 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: Sep 1, 2018