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NM_172107.4(KCNQ2):c.431G>A (p.Arg144Gln) AND KCNQ2-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 6, 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:
RCV004528968.1

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]

Condition(s)

Name:
KCNQ2-related disorder
Synonyms:
KCNQ2-Related Disorders; KCNQ2-related condition
Identifiers:
MedGen: CN169299

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004109351PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Sep 6, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 PreventionGenetics, part of Exact Sciences, SCV004109351.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The KCNQ2 c.431G>A variant is predicted to result in the amino acid substitution p.Arg144Gln. This variant has been documented as de novo in multiple individuals with KCNQ2 related disorders, and functional studies support its pathogenicity (Table S12, Allen et al. 2013. PubMed ID: 23934111; Table S4, Geisheker et al. 2017. PubMed ID: 28628100; Table S2, Zhu et al. 2017. PubMed ID: 29186148; Table S4, Lindy et al. 2018. PubMed ID: 29655203; Yuskaitis et al. 2018. PubMed ID: 30174244). At PreventionGenetics, we have observed this variant to have occurred de novo in an individual with neurodevelopmental features and seizures. This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 26, 2024