NM_172107.4(KCNQ2):c.443C>A (p.Ala148Glu) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 27, 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:: RCV001879339.7

Allele description [Variation Report for NM_172107.4(KCNQ2):c.443C>A (p.Ala148Glu)]

NM_172107.4(KCNQ2):c.443C>A (p.Ala148Glu)

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.443C>A (p.Ala148Glu)

HGVS:

NC_000020.11:g.63445309G>T
NG_009004.2:g.32332C>A
NM_001382235.1:c.443C>A
NM_004518.6:c.443C>A
NM_172106.3:c.443C>A
NM_172107.4:c.443C>AMANE SELECT
NM_172108.5:c.443C>A
NM_172109.3:c.443C>A
NP_001369164.1:p.Ala148Glu
NP_004509.2:p.Ala148Glu
NP_742104.1:p.Ala148Glu
NP_742105.1:p.Ala148Glu
NP_742106.1:p.Ala148Glu
NP_742107.1:p.Ala148Glu
NC_000020.10:g.62076662G>T

Protein change:

A148E

Links:

dbSNP: rs2145779347

NCBI 1000 Genomes Browser:

rs2145779347

Molecular consequence:

NM_001382235.1:c.443C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004518.6:c.443C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172106.3:c.443C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172107.4:c.443C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172108.5:c.443C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172109.3:c.443C>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002141453	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 27, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002141453

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 27, 2022)

germline

clinical testing

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

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

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, SCV002141453.3

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

Description

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. 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) performed at Invitae indicates that this missense variant is expected to disrupt KCNQ2 protein function. 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 replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 148 of the KCNQ2 protein (p.Ala148Glu).

#	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: Sep 29, 2024

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