VCV000158670.32 - ClinVar

NM_000525.4(KCNJ11):c.1009G>A (p.Val337Ile)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign/Likely benign
Benign (9); Likely benign (4)

13 out of 17 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_000525.4(KCNJ11):c.1009G>A (p.Val337Ile)

Variation ID: 158670 Accession: VCV000158670.32

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11p15.1 11: 17387083 (GRCh38) [ NCBI UCSC ] 11: 17408630 (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	Nov 23, 2014	Feb 23, 2026	Feb 4, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_000525.4:c.1009G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000516.3:p.Val337Ile	missense
NM_001166290.2:c.748G>A	NP_001159762.1:p.Val250Ile	missense
NM_001377296.1:c.748G>A	NP_001364225.1:p.Val250Ile	missense
NM_001377297.1:c.748G>A	NP_001364226.1:p.Val250Ile	missense
NC_000011.10:g.17387083C>T
NC_000011.9:g.17408630C>T
NG_012446.1:g.6577G>A

... more HGVS ... less HGVS

Protein change

V337I, V250I

Other names

Canonical SPDI

NC_000011.10:17387082:C:T

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.

0.26937 (C)

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

Trans-Omics for Precision Medicine (TOPMed) 0.72231

The Genome Aggregation Database (gnomAD), exomes 0.64091

Exome Aggregation Consortium (ExAC) 0.64484

The Genome Aggregation Database (gnomAD) 0.71351

1000 Genomes Project 0.73063

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.73202

1000 Genomes Project 30x 0.73282

The Genome Aggregation Database (gnomAD), exomes 0.63831

The Genome Aggregation Database (gnomAD) 0.70936

Links

ClinGen: CA172316 dbSNP: rs5215 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.
KCNJ11		-	-	GRCh38 GRCh37	564	586

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	Benign (6)	criteria provided, multiple submitters, no conflicts	Apr 14, 2025	RCV000146099.20
Diabetes mellitus, transient neonatal, 3	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Jul 1, 2021	RCV000262909.10
Maturity-onset diabetes of the young type 13	Likely benign (1)	criteria provided, single submitter	Apr 27, 2017	RCV000357357.8
Hyperinsulinemic hypoglycemia, familial, 2	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Jul 1, 2021	RCV000576497.10
Permanent neonatal diabetes mellitus	Benign (1)	no assertion criteria provided	Sep 16, 2020	RCV001275131.4
Diabetes mellitus, permanent neonatal 2	Benign (1)	criteria provided, single submitter	Jul 1, 2021	RCV001533219.5
not provided	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Feb 4, 2026	RCV001512206.14
Type 2 diabetes mellitus	association (1)	no assertion criteria provided	-	RCV002221500.4

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.	Expand all rows Collapse all rows 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.
Benign (Feb 08, 2013) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2007)	not specified (Autosomal unknown)	Genetic Services Laboratory, University of Chicago Accession: SCV000193316.1 First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Apr 27, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Hyperinsulinemic hypoglycemia, familial, 2	Illumina Laboratory Services, Illumina Accession: SCV000369163.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Apr 27, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Maturity-onset diabetes of the young type 13	Illumina Laboratory Services, Illumina Accession: SCV000369161.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Apr 27, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Diabetes mellitus, transient neonatal, 3	Illumina Laboratory Services, Illumina Accession: SCV000369162.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Sep 10, 2018) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV001871118.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021	Comment: show This variant is associated with the following publications: (PMID: 31118516, 30389748, 26551672, 27398621, 17257281, 22958899) (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (Jun 02, 2021) C Contributing to aggregate classification	criteria provided, single submitter (Athena Diagnostics criteria)	not specified	Athena Diagnostics Accession: SCV000677327.2 First in ClinVar: Jan 07, 2018 Last updated: Sep 19, 2021	Publications: PubMed (5) PubMed: 11872696‚ 12475776‚ 15855351‚ 17257281‚ 22958899 Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Likely benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided (Autosomal recessive inheritance)	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005221357.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024	Observation: 1 Collection method: not provided Allele origin: germline Affected status: yes Observation 1 Collection method: not provided Allele origin: germline Affected status: yes

Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	NOT SPECIFIED	PreventionGenetics, part of Exact Sciences Accession: SCV000304660.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Jul 01, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Diabetes mellitus, transient neonatal, 3	Pars Genome Lab Accession: SCV001749014.2 First in ClinVar: Jul 14, 2021 Last updated: Apr 13, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no Sex: mixed

Benign (Jul 01, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Diabetes mellitus, permanent neonatal 2	Pars Genome Lab Accession: SCV001749015.2 First in ClinVar: Jul 14, 2021 Last updated: Apr 13, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no Sex: mixed

Benign (Jul 01, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Hyperinsulinemic hypoglycemia, familial, 2	Pars Genome Lab Accession: SCV001749032.2 First in ClinVar: Jul 14, 2021 Last updated: Apr 13, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no Sex: mixed

Benign (Apr 14, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Not specified	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV007308857.1 First in ClinVar: Jan 17, 2026 Last updated: Jan 17, 2026	Comment: show BA1, BP4 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 1

Benign (Feb 04, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001719578.6 First in ClinVar: Jun 15, 2021 Last updated: Feb 23, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Sep 16, 2020) N Not contributing to aggregate classification	no assertion criteria provided	Permanent neonatal diabetes mellitus	Natera, Inc. Accession: SCV001459962.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not specified	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001741294.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

association (-) N Not contributing to aggregate classification	no assertion criteria provided	Type 2 diabetes mellitus (Autosomal dominant inheritance)	Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic Accession: SCV002498735.1 First in ClinVar: Apr 16, 2022 Last updated: Apr 16, 2022	Publications: PubMed (1) PubMed: 33853507 Comment: show Mutations can cause decreased production of insulin and secretion. This can lead to MODY which is responsive to oral sulfonylureas. (less) Observation: 1 Collection method: research Allele origin: somatic Affected status: yes Observation 1 Collection method: research Allele origin: somatic Affected status: yes

Benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not specified	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Study: VKGL Data-share Consensus Accession: SCV001951580.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Association of common genetic variants of KCNJ11 gene with the risk of type 2 diabetes mellitus.	Malekizadeh A	Nucleosides, nucleotides & nucleic acids	2021	PMID: 33853507
Genetic risk factors for type 2 diabetes: a trans-regulatory genetic architecture?	Elbein SC	American journal of human genetics	2012	PMID: 22958899
Polymorphisms of KCNJ11 (Kir6.2 gene) are associated with Type 2 diabetes and hypertension in the Korean population.	Koo BK	Diabetic medicine : a journal of the British Diabetic Association	2007	PMID: 17257281
Single nucleotide polymorphisms in K(ATP) channels: muscular impact on type 2 diabetes.	Li L	Diabetes	2005	PMID: 15855351
The common single nucleotide polymorphism E23K in K(IR)6.2 sensitizes pancreatic beta-cell ATP-sensitive potassium channels toward activation through nucleoside diphosphates.	Schwanstecher C	Diabetes	2002	PMID: 12475776
K(IR)6.2 polymorphism predisposes to type 2 diabetes by inducing overactivity of pancreatic beta-cell ATP-sensitive K(+) channels.	Schwanstecher C	Diabetes	2002	PMID: 11872696

Text-mined citations for rs5215 ...

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 Jun 27, 2026