NM_172107.4(KCNQ2):c.601C>T (p.Arg201Cys) AND Seizures, benign familial neonatal, 1

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: May 4, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000679892.7

Allele description [Variation Report for NM_172107.4(KCNQ2):c.601C>T (p.Arg201Cys)]

NM_172107.4(KCNQ2):c.601C>T (p.Arg201Cys)

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.601C>T (p.Arg201Cys)

Other names:

p.R201C:CGC>TGC; NM_004518.4(KCNQ2):c.601C>T(p.Arg201Cys); NM_172106.1(KCNQ2):c.601C>T(p.Arg201Cys); NM_172107.2(KCNQ2):c.601C>T(p.Arg201Cys); NM_172108.3(KCNQ2):c.601C>T(p.Arg201Cys); NM_172109.1(KCNQ2):c.601C>T(p.Arg201Cys)

HGVS:

NC_000020.11:g.63444748G>A
NG_009004.2:g.32893C>T
NM_004518.6:c.601C>T
NM_172106.3:c.601C>T
NM_172107.4:c.601C>TMANE SELECT
NM_172108.5:c.601C>T
NM_172109.3:c.601C>T
NP_004509.2:p.Arg201Cys
NP_742104.1:p.Arg201Cys
NP_742105.1:p.Arg201Cys
NP_742106.1:p.Arg201Cys
NP_742107.1:p.Arg201Cys
NC_000020.10:g.62076101G>A
NM_172107.2:c.601C>T
NM_172107.3:c.601C>T

Protein change:

R201C

Links:

dbSNP: rs796052623

NCBI 1000 Genomes Browser:

rs796052623

Molecular consequence:

NM_004518.6:c.601C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172106.3:c.601C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172107.4:c.601C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172108.5:c.601C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172109.3:c.601C>T - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Increase in peak current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0092]
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:: Seizures, benign familial neonatal, 1
Synonyms:: Benign Neonatal Epilepsy 1; KCNQ2-Related Benign Familial Neonatal Epilepsy
Identifiers:: MONDO: MONDO:0007365; MedGen: C3149074; Orphanet: 1949; OMIM: 121200

Recent activity

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KLRC4-KLRK1 KLRC4-KLRK1 readthrough [Homo sapiens]
KLRC4-KLRK1 KLRC4-KLRK1 readthrough [Homo sapiens]
Gene ID:100528032

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000807302	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 1, 2017)	de novo	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 25326635
SCV002516604	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2019)	Pathogenic (May 4, 2022)	germline	clinical testing	Citation Link,
SCV002570027	Center of Excellence for Medical Genomics, Chulalongkorn University	no assertion criteria provided	Pathogenic (Sep 8, 2002)	de novo	research

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000807302

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 1, 2017)

de novo

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002516604

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2019)

Pathogenic
(May 4, 2022)

germline

clinical testing

Citation Link,

SCV002570027

Center of Excellence for Medical Genomics, Chulalongkorn University

no assertion criteria provided

Pathogenic
(Sep 8, 2002)

de novo

research

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
not provided	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing, research

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

Molecular findings among patients referred for clinical whole-exome sequencing.

Yang Y, Muzny DM, Xia F, Niu Z, Person R, Ding Y, Ward P, Braxton A, Wang M, Buhay C, Veeraraghavan N, Hawes A, Chiang T, Leduc M, Beuten J, Zhang J, He W, Scull J, Willis A, Landsverk M, Craigen WJ, Bekheirnia MR, et al.

JAMA. 2014 Nov 12;312(18):1870-9. doi: 10.1001/jama.2014.14601.

PubMed [citation]

PMID:: 25326635
PMCID:: PMC4326249

Details of each submission

From Baylor Genetics, SCV000807302.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing (GTR000508680.4)	PubMed (2)

Description

Likely pathogenicity based on finding it once in our laboratory de novo in a 6-month-old female with motor delays, hypotonia, epilepsy (clinically thought to be early infantile myoclonic encephalopathy, onset at day 2 of life, with apneic episodes, controlled by medication but with onset of myoclous), nystagmus

#	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	(GTR000508680.4)	not provided	not provided	not provided	not provided

From Mendelics, SCV002516604.1

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

From Center of Excellence for Medical Genomics, Chulalongkorn University, SCV002570027.1

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

#	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: May 12, 2024

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