NM_172107.4(KCNQ2):c.910TTC[1] (p.Phe305del) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 3, 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:: RCV001381685.7

Allele description [Variation Report for NM_172107.4(KCNQ2):c.910TTC[1] (p.Phe305del)]

NM_172107.4(KCNQ2):c.910TTC[1] (p.Phe305del)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

20q13.33

Genomic location:

Preferred name:

NM_172107.4(KCNQ2):c.910TTC[1] (p.Phe305del)

Other names:

F304delF

HGVS:

NC_000020.11:g.63439611AAG[1]
NG_009004.2:g.38026TTC[1]
NM_001382235.1:c.910TTC[1]
NM_004518.6:c.910TTC[1]
NM_172106.3:c.910TTC[1]
NM_172107.4:c.910TTC[1]MANE SELECT
NM_172107.4:c.913_915delTTC
NM_172108.5:c.910TTC[1]
NM_172109.3:c.910TTC[1]
NP_001369164.1:p.Phe305del
NP_004509.2:p.Phe305del
NP_742104.1:p.Phe305del
NP_742105.1:p.Phe305del
NP_742106.1:p.Phe305del
NP_742107.1:p.Phe305del
NC_000020.10:g.62070963_62070965del
NC_000020.10:g.62070963_62070965delGAA
NC_000020.10:g.62070964AAG[1]
NC_000020.10:g.62070967_62070969delAAG
NC_000020.10:g.62070967_62070969delAAG
NM_172107.2:c.913_915delTTC
NM_172107.3:c.913_915delTTC
NM_172107.4:c.913_915delMANE SELECT
NM_172107.4:c.913_915delTTCMANE SELECT
NM_172109.2:c.913_915del

Protein change:

F305del

Links:

dbSNP: rs118192212

NCBI 1000 Genomes Browser:

rs118192212

Molecular consequence:

NM_001382235.1:c.910TTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_004518.6:c.910TTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_172106.3:c.910TTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_172107.4:c.910TTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_172108.5:c.910TTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_172109.3:c.910TTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Functional consequence:

Mild slowing of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0013]
Normal voltage dependence of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0032]
Severe decrease in peak current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0087]

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
SCV001580178	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 3, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 25473036, 18640800, 27602407, 28728838, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001580178

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 3, 2023)

germline

clinical testing

PubMed (5)
[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

Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders.

Soden SE, Saunders CJ, Willig LK, Farrow EG, Smith LD, Petrikin JE, LePichon JB, Miller NA, Thiffault I, Dinwiddie DL, Twist G, Noll A, Heese BA, Zellmer L, Atherton AM, Abdelmoity AT, Safina N, Nyp SS, Zuccarelli B, Larson IA, Modrcin A, Herd S, et al.

Sci Transl Med. 2014 Dec 3;6(265):265ra168. doi: 10.1126/scitranslmed.3010076.

PubMed [citation]

PMID:: 25473036
PMCID:: PMC4286868

A de novo KCNQ2 mutation detected in non-familial benign neonatal convulsions.

Ishii A, Fukuma G, Uehara A, Miyajima T, Makita Y, Hamachi A, Yasukochi M, Inoue T, Yasumoto S, Okada M, Kaneko S, Mitsudome A, Hirose S.

Brain Dev. 2009 Jan;31(1):27-33. doi: 10.1016/j.braindev.2008.05.010. Epub 2008 Jul 21.

PubMed [citation]

PMID:: 18640800

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001580178.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Phe305 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25473036; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this variant affects KCNQ2 function (PMID: 18640800). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 211236). This variant is also known as c.910-2delTTC. This variant has been observed in individual(s) with KCNQ2-related conditions (PMID: 18640800, 27602407, 28728838). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This variant, c.913_915del, results in the deletion of 1 amino acid(s) of the KCNQ2 protein (p.Phe305del), but otherwise preserves the integrity of the reading frame.

#	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: Nov 24, 2024

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