NM_172107.4(KCNQ2):c.612G>C (p.Gln204His) AND Inborn genetic diseases

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 8, 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:: RCV002517871.2

Allele description [Variation Report for NM_172107.4(KCNQ2):c.612G>C (p.Gln204His)]

NM_172107.4(KCNQ2):c.612G>C (p.Gln204His)

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.612G>C (p.Gln204His)

Other names:

p.Q204H:CAG>CAC

HGVS:

NC_000020.11:g.63444737C>G
NG_009004.2:g.32904G>C
NM_004518.6:c.612G>C
NM_172106.3:c.612G>C
NM_172107.4:c.612G>CMANE SELECT
NM_172108.5:c.612G>C
NM_172109.3:c.612G>C
NP_004509.2:p.Gln204His
NP_742104.1:p.Gln204His
NP_742105.1:p.Gln204His
NP_742106.1:p.Gln204His
NP_742107.1:p.Gln204His
NC_000020.10:g.62076090C>G
NM_172106.1:c.612G>C
NM_172107.2:c.612G>C

Protein change:

Q204H

Links:

dbSNP: rs796052625

NCBI 1000 Genomes Browser:

rs796052625

Molecular consequence:

NM_004518.6:c.612G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_172106.3:c.612G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_172107.4:c.612G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_172108.5:c.612G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_172109.3:c.612G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003636158	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Aug 8, 2022)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 9836639, 10684873, 11572947, 12742592, 14534157, 17872363, 27602407, 29655203, 35104249 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003636158

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Aug 8, 2022)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

Citation Link

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

KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel.

Wang HS, Pan Z, Shi W, Brown BS, Wymore RS, Cohen IS, Dixon JE, McKinnon D.

Science. 1998 Dec 4;282(5395):1890-3.

PubMed [citation]

PMID:: 9836639

Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K(+) channels that underlie the neuronal M current.

Shapiro MS, Roche JP, Kaftan EJ, Cruzblanca H, Mackie K, Hille B.

J Neurosci. 2000 Mar 1;20(5):1710-21.

PubMed [citation]

PMID:: 10684873
PMCID:: PMC6772928

See all PubMed Citations (9)

Details of each submission

From Ambry Genetics, SCV003636158.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

The c.612G>C (p.Q204H) alteration is located in exon 4 (coding exon 4) of the KCNQ2 gene. This alteration results from a G to C substitution at nucleotide position 612, causing the glutamine (Q) at amino acid position 204 to be replaced by a histidine (H). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been detected in the heterozygous state in a parent and a child with benign neonatal familial epilepsy (Millichap, 2016), and in an individual with neonatal focal onset seizures (Lindy, 2018). This amino acid position is highly conserved in available vertebrate species. Based on internal structural analysis, Q204H is deleterious. The variant disrupts a known structural motif necessary for protein function (Shapiro, 2000; Wuttke, 2007; Dedek, 2003; Singh, 2003; Dedek, 2001; Wang, 1998). Functional assays show reduced electrophysiology in vitro (Vanoye, 2022). Based on the available evidence, this alteration is classified as likely 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: May 1, 2024

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