VCV000158680.24 - ClinVar

NM_000525.4(KCNJ11):c.570C>T (p.Ala190=)

Germline

Classification

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

Benign/Likely benign
Benign (6); Likely benign (4)

10 out of 11 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.570C>T (p.Ala190=)

Variation ID: 158680 Accession: VCV000158680.24

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11p15.1 11: 17387522 (GRCh38) [ NCBI UCSC ] 11: 17409069 (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.570C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000516.3:p.Ala190=	synonymous
NM_001166290.2:c.309C>T	NP_001159762.1:p.Ala103=	synonymous
NM_001377296.1:c.309C>T	NP_001364225.1:p.Ala103=	synonymous
NM_001377297.1:c.309C>T	NP_001364226.1:p.Ala103=	synonymous
NC_000011.10:g.17387522G>A
NC_000011.9:g.17409069G>A
NG_012446.1:g.6138C>T

... more HGVS ... less HGVS

Protein change

Other names

p.Ala190=

Canonical SPDI

NC_000011.10:17387521:G:A

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.

0.22744 (A)

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

Trans-Omics for Precision Medicine (TOPMed) 0.21009

1000 Genomes Project 30x 0.21502

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.22286

1000 Genomes Project 0.22744

The Genome Aggregation Database (gnomAD) 0.22765

The Genome Aggregation Database (gnomAD) 0.23002

Links

ClinGen: CA172336 dbSNP: rs5218 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 (3)	criteria provided, multiple submitters, no conflicts	Apr 14, 2025	RCV000146111.12
Diabetes mellitus, transient neonatal, 3	Likely benign (1)	criteria provided, single submitter	Apr 27, 2017	RCV000300958.6
Maturity-onset diabetes of the young type 13	Likely benign (1)	criteria provided, single submitter	Apr 27, 2017	RCV000353536.6
Hyperinsulinemic hypoglycemia, familial, 2	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Apr 28, 2017	RCV000576830.7
Permanent neonatal diabetes mellitus	Benign (1)	no assertion criteria provided	Sep 16, 2020	RCV001275136.2
not provided	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Feb 4, 2026	RCV001520555.12

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: SCV000193328.1 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

Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	NOT SPECIFIED	PreventionGenetics, part of Exact Sciences Accession: SCV000304666.1 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 (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: SCV001729677.6 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 (Apr 28, 2017) C Contributing to aggregate classification	criteria provided, single submitter (Athena Diagnostics Criteria)	Hyperinsulinemic hypoglycemia, familial, 2	Athena Diagnostics Accession: SCV000677329.1 First in ClinVar: Jan 07, 2018 Last updated: Jan 07, 2018	Publications: PubMed (2) PubMed: 14551916‚ 18290324 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: SCV000369178.3 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)	Hyperinsulinemic hypoglycemia, familial, 2	Illumina Laboratory Services, Illumina Accession: SCV000369176.3 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: SCV000369177.3 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 17, 2018) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV001873066.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021	Comment: show This variant is associated with the following publications: (PMID: 14871556, 29396286, 17327377, 17823772, 22916062, 22512215, 28460053, 21573802, 24018988, 1731660, 17727257, 16429405, 11310586, 26740944, 15115830, 24068186, 21765448, 25725792, 17257281, 14551916, 18290324) (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

Likely benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided (Autosomal recessive inheritance)	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005221358.1 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 (Apr 14, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Not specified	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV007308858.1 First in ClinVar: Jan 17, 2026 Last updated: Jan 17, 2026	Comment: show BA1 (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 (Sep 16, 2020) N Not contributing to aggregate classification	no assertion criteria provided	Permanent neonatal diabetes mellitus	Natera, Inc. Accession: SCV001459967.1 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

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:

This variant is associated with the following publications: (PMID: 14871556, 29396286, 17327377, 17823772, 22916062, 22512215, 28460053, 21573802, 24018988, 1731660, 17727257, 16429405, 11310586, 26740944, 15115830, 24068186, 21765448, 25725792, 17257281, 14551916, 18290324)

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Alanine in HI: a silent mutation cries out!	Shah JH	Advances in experimental medicine and biology	2008	PMID: 18290324
Candidate gene association study in type 2 diabetes indicates a role for genes involved in beta-cell function as well as insulin action.	Barroso I	PLoS biology	2003	PMID: 14551916

Text-mined citations for rs5218 ...

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 Apr 13, 2026