NM_172107.4(KCNQ2):c.431G>A (p.Arg144Gln) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Oct 23, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000187853.30

Allele description [Variation Report for NM_172107.4(KCNQ2):c.431G>A (p.Arg144Gln)]

NM_172107.4(KCNQ2):c.431G>A (p.Arg144Gln)

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.431G>A (p.Arg144Gln)

Other names:

p.R144Q:CGG>CAG; KCNQ2

HGVS:

NC_000020.11:g.63445321C>T
NG_009004.2:g.32320G>A
NM_004518.6:c.431G>A
NM_172106.3:c.431G>A
NM_172107.4:c.431G>AMANE SELECT
NM_172108.5:c.431G>A
NM_172109.3:c.431G>A
NP_004509.2:p.Arg144Gln
NP_742104.1:p.Arg144Gln
NP_742105.1:p.Arg144Gln
NP_742106.1:p.Arg144Gln
NP_742107.1:p.Arg144Gln
NC_000020.10:g.62076674C>T
NM_004518.5:c.431G>A
NM_172107.2:c.431G>A
NM_172107.3:c.431G>A

Protein change:

R144Q

Links:

dbSNP: rs796052618

NCBI 1000 Genomes Browser:

rs796052618

Molecular consequence:

NM_004518.6:c.431G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172106.3:c.431G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172107.4:c.431G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172108.5:c.431G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172109.3:c.431G>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Moderate decrease in peak current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0086]
Severe hyperpolarizing shift of voltage dependence of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0031]
Severe slowing of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0015]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000241453	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Oct 23, 2020)	germline	clinical testing	Citation Link,
SCV001249243	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Apr 1, 2019)	germline	clinical testing	Citation Link,
SCV001448113	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 23, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001760741	Laboratoire Génétique Moléculaire, CHRU TOURS	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 16, 2020)	de novo	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	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000241453.10

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

Description

Not observed in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32860008, 28628100, 23934111, 25740509, 29186148, 30440138, 29655203, 30174244)

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

From CeGaT Center for Human Genetics Tuebingen, SCV001249243.26

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

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

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001448113.1

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

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

From Laboratoire Génétique Moléculaire, CHRU TOURS, SCV001760741.1

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

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

Last Updated: Oct 26, 2024

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