NM_172107.4(KCNQ2):c.2278del (p.Arg760fs) AND Early infantile epileptic encephalopathy with suppression bursts

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 1, 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:: RCV000543835.7

Allele description

NM_172107.4(KCNQ2):c.2278del (p.Arg760fs)

Gene:

KCNQ2:potassium voltage-gated channel subfamily Q member 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

20q13.33

Genomic location:

Preferred name:

NM_172107.4(KCNQ2):c.2278del (p.Arg760fs)

HGVS:

NC_000020.11:g.63406986del
NG_009004.2:g.70656del
NM_004518.6:c.2194del
NM_172106.3:c.2224del
NM_172107.4:c.2278delMANE SELECT
NM_172108.5:c.2185del
NP_004509.2:p.Arg732fs
NP_742104.1:p.Arg742fs
NP_742105.1:p.Arg760fs
NP_742106.1:p.Arg729fs
NC_000020.10:g.62038338del
NC_000020.10:g.62038339del
NM_172107.2:c.2278delC

Protein change:

R729fs

Links:

dbSNP: rs1555850590

NCBI 1000 Genomes Browser:

rs1555850590

Molecular consequence:

NM_004518.6:c.2194del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172106.3:c.2224del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172107.4:c.2278del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172108.5:c.2185del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000634064	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 1, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10482260, 21937445, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000634064

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 1, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A reduced K+ current due to a novel mutation in KCNQ2 causes neonatal convulsions.

Lerche H, Biervert C, Alekov AK, Schleithoff L, Lindner M, Klinger W, Bretschneider F, Mitrovic N, Jurkat-Rott K, Bode H, Lehmann-Horn F, Steinlein OK.

Ann Neurol. 1999 Sep;46(3):305-12.

PubMed [citation]

PMID:: 10482260

A novel degradation signal derived from distal C-terminal frameshift mutations of KCNQ2 protein which cause neonatal epilepsy.

Su J, Cao X, Wang K.

J Biol Chem. 2011 Dec 16;286(50):42949-58. doi: 10.1074/jbc.M111.287268. Epub 2011 Sep 21.

PubMed [citation]

PMID:: 21937445
PMCID:: PMC3234801

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000634064.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant results in an extension of the KCNQ2 protein. Other variant(s) that result in a similarly extended protein product (p.Gly866Alafs*64) have been determined to be pathogenic (PMID: 10482260, 21937445). This suggests that these extensions are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 461416). This variant has not been reported in the literature in individuals affected with KCNQ2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the KCNQ2 gene (p.Arg760Alafs*170). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 113 amino acid(s) of the KCNQ2 protein and extend the protein by 56 additional amino acid residues. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 20, 2024

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