VCV000211244.42 - ClinVar

NM_020822.3(KCNT1):c.3641G>A (p.Arg1214Gln)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(1); Likely benign(6)

8 out of 10 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_020822.3(KCNT1):c.3641G>A (p.Arg1214Gln)

Variation ID: 211244 Accession: VCV000211244.42

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 9q34.3 9: 135792094 (GRCh38) [ NCBI UCSC ] 9: 138683940 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Oct 5, 2015	Apr 20, 2025	Feb 2, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_020822.3:c.3641G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_065873.2:p.Arg1214Gln	missense
NM_001272003.2:c.3569G>A	NP_001258932.1:p.Arg1190Gln	missense
NC_000009.12:g.135792094G>A
NC_000009.11:g.138683940G>A
NG_033070.1:g.94910G>A

... more HGVS ... less HGVS

Protein change

R1214Q, R1190Q

Other names

Canonical SPDI

NC_000009.12:135792093:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00020 (A)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 30x 0.00016

1000 Genomes Project 0.00020

Exome Aggregation Consortium (ExAC) 0.00090

The Genome Aggregation Database (gnomAD) 0.00102

The Genome Aggregation Database (gnomAD), exomes 0.00105

The Genome Aggregation Database (gnomAD) 0.00128

Trans-Omics for Precision Medicine (TOPMed) 0.00141

The Genome Aggregation Database (gnomAD), exomes 0.00171

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00200

Links

ClinGen: CA206835 dbSNP: rs138282349 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
KCNT1		-	-	GRCh38 GRCh37	2418	2497

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Conflicting classifications of pathogenicity (3)	criteria provided, conflicting classifications	Apr 28, 2017	RCV000193382.29
Autosomal dominant nocturnal frontal lobe epilepsy 5 Developmental and epileptic encephalopathy, 14	Likely benign (1)	criteria provided, single submitter	Feb 2, 2025	RCV001080555.14
not provided	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Oct 1, 2024	RCV000471444.29
Self-limited epilepsy with centrotemporal spikes	Pathogenic (1)	no assertion criteria provided	Jan 1, 2017	RCV000656028.10
Inborn genetic diseases	Likely benign (1)	criteria provided, single submitter	Jul 27, 2021	RCV002311297.9
KCNT1-related disorder	Likely benign (1)	no assertion criteria provided	Jul 28, 2020	RCV003917754.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (May 26, 2015) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000247679.1 First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015
Likely benign (Apr 27, 2021) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000524869.5 First in ClinVar: Mar 08, 2017 Last updated: Sep 25, 2021
Likely benign (Feb 02, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Autosomal dominant nocturnal frontal lobe epilepsy 5 Developmental and epileptic encephalopathy, 14 Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000563634.9 First in ClinVar: Apr 17, 2017 Last updated: Mar 04, 2025
Likely benign (Oct 16, 2015) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000334784.5 First in ClinVar: Dec 06, 2016 Last updated: Apr 13, 2025	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=KCNT1 Number of individuals with the variant: 3 Zygosity: Single Heterozygote Sex: mixed
Likely benign (Apr 28, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not Specified Affected status: unknown Allele origin: germline	Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital Accession: SCV000864308.1 First in ClinVar: Jan 22, 2019 Last updated: Jan 22, 2019	Comment: BS1,BP4,BP6; This alteration has an allele frequency that is greater than expected for the associated disease, is predicted to be tolerated by multiple functional prediction … (more) BS1,BP4,BP6; This alteration has an allele frequency that is greater than expected for the associated disease, is predicted to be tolerated by multiple functional prediction tools, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory). (less)
Benign (Jun 17, 2019) C Contributing to aggregate classification	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Athena Diagnostics Accession: SCV001144346.1 First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020
Likely benign (Jul 27, 2021) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000846325.4 First in ClinVar: Nov 08, 2018 Last updated: May 01, 2024	Comment: This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more) This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Likely benign (Oct 01, 2024) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV004010897.15 First in ClinVar: Jul 16, 2023 Last updated: Apr 20, 2025	Comment: KCNT1: BP4, BS1 Number of individuals with the variant: 5
Pathogenic (Jan 01, 2017) N Not contributing to aggregate classification	no assertion criteria provided Method: case-control	Self-limited epilepsy with centrotemporal spikes Affected status: yes Allele origin: germline	Bioinformatics Core, Luxembourg Center for Systems Biomedicine Study: EUROEPINOMICS COGIE Accession: SCV000588304.1 First in ClinVar: Jun 01, 2018 Last updated: Jun 01, 2018	Publications: PubMed (1) PubMed: 29358611 Comment: CAADphred>15
Likely benign (Jul 28, 2020) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	KCNT1-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004728425.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Comment:

BS1,BP4,BP6; This alteration has an allele frequency that is greater than expected for the associated disease, is predicted to be tolerated by multiple functional prediction tools, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory).

Comment:

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Exome-wide analysis of mutational burden in patients with typical and atypical Rolandic epilepsy.	Bobbili DR	European journal of human genetics : EJHG	2018	PMID: 29358611
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=KCNT1	-	-	-	-

Text-mined citations for rs138282349 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated May 17, 2025

ClinVar Genomic variation as it relates to human health

NM_020822.3(KCNT1):c.3641G>A (p.Arg1214Gln)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs138282349 ...