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NM_172107.4(KCNQ2):c.2281G>A (p.Ala761Thr) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 17, 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:
RCV002528214.4

Allele description [Variation Report for NM_172107.4(KCNQ2):c.2281G>A (p.Ala761Thr)]

NM_172107.4(KCNQ2):c.2281G>A (p.Ala761Thr)

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.2281G>A (p.Ala761Thr)
HGVS:
  • NC_000020.11:g.63406982C>T
  • NG_009004.2:g.70659G>A
  • NM_004518.6:c.2197G>A
  • NM_172106.3:c.2227G>A
  • NM_172107.4:c.2281G>AMANE SELECT
  • NM_172108.5:c.2188G>A
  • NP_004509.2:p.Ala733Thr
  • NP_742104.1:p.Ala743Thr
  • NP_742105.1:p.Ala761Thr
  • NP_742106.1:p.Ala730Thr
  • NC_000020.10:g.62038335C>T
  • NM_172107.2:c.2281G>A
Protein change:
A730T
Links:
dbSNP: rs587780366
NCBI 1000 Genomes Browser:
rs587780366
Molecular consequence:
  • NM_004518.6:c.2197G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172106.3:c.2227G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172107.4:c.2281G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172108.5:c.2188G>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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003031016Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 17, 2023) 		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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003031016.2

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 761 of the KCNQ2 protein (p.Ala761Thr). This variant is present in population databases (rs587780366, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with KCNQ2-related conditions. ClinVar contains an entry for this variant (Variation ID: 129334). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.

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

Last Updated: Oct 20, 2024