VCV000370722.8 - ClinVar

NM_000352.6(ABCC8):c.4021C>T (p.Gln1341Ter)

Germline

Classification

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

Conflicting classifications of pathogenicity
Pathogenic(3); Uncertain significance(2)

5 out of 6 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_000352.6(ABCC8):c.4021C>T (p.Gln1341Ter)

Variation ID: 370722 Accession: VCV000370722.8

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11p15.1 11: 17397014 (GRCh38) [ NCBI UCSC ] 11: 17418561 (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	Jan 6, 2017	Jun 29, 2025	Mar 25, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000352.6:c.4021C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000343.2:p.Gln1341Ter	nonsense
NM_000352.5:c.4021C>T
NM_001287174.3:c.4024C>T	NP_001274103.1:p.Gln1342Ter	nonsense
NM_001351295.2:c.4087C>T	NP_001338224.1:p.Gln1363Ter	nonsense
NM_001351296.2:c.4021C>T	NP_001338225.1:p.Gln1341Ter	nonsense
NM_001351297.2:c.4018C>T	NP_001338226.1:p.Gln1340Ter	nonsense
NR_147094.2:n.4316C>T		non-coding transcript variant
NC_000011.10:g.17397014G>A
NC_000011.9:g.17418561G>A
NG_008867.1:g.84889C>T
LRG_790:g.84889C>T
LRG_790t1:c.4021C>T	LRG_790p1:p.Gln1341Ter
LRG_790t2:c.4024C>T	LRG_790p2:p.Gln1342Ter

... more HGVS ... less HGVS

Protein change

Q1341*, Q1342*, Q1340*, Q1363*

Other names

Canonical SPDI

NC_000011.10:17397013: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.

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

The Genome Aggregation Database (gnomAD), exomes 0.00000

Links

ClinGen: CA16041439 dbSNP: rs1057516718 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.
ABCC8		Gene associated with autosomal recessive phenotype	No evidence available	GRCh38 GRCh37	2732	2883

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.
Hyperinsulinemic hypoglycemia, familial, 1	Pathogenic (2)	criteria provided, single submitter	Mar 25, 2024	RCV000411306.6
Transitory neonatal diabetes mellitus	Uncertain significance (1)	criteria provided, single submitter	-	RCV002244850.2
Maturity onset diabetes mellitus in young	Uncertain significance (1)	criteria provided, single submitter	-	RCV002244849.2
Type 2 diabetes mellitus	Pathogenic (1)	criteria provided, single submitter	Aug 23, 2023	RCV003470332.1
not provided	Pathogenic (1)	criteria provided, single submitter	Aug 19, 2023	RCV003558361.3

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.
Uncertain significance (-) C Contributing to aggregate classification	criteria provided, single submitter (K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1)	Maturity onset diabetes mellitus in young (Somatic mutation)	Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic Accession: SCV002513509.1 First in ClinVar: May 21, 2022 Last updated: May 21, 2022	Publications: PubMed (8) PubMed: 16885549‚ 21989597‚ 27538677‚ 18981553‚ 32027066‚ 16613899‚ 18025408‚ 32792356 Comment: show Mutations in ABCC8 gene are associated with both neonatal diabetes mellitus as well as MODY. Patients with this mutation may have a better response to sulfonylureas. However, no sufficient evidence is found to ascertain the role of this particular variant (rs1057516718) in MODY yet. (less) Observation: 1 Collection method: research Allele origin: somatic Affected status: unknown Observation 1 Collection method: research Allele origin: somatic Affected status: unknown

Uncertain significance (-) C Contributing to aggregate classification	criteria provided, single submitter (K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1)	Transitory neonatal diabetes mellitus (Somatic mutation)	Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic Accession: SCV002513510.1 First in ClinVar: May 21, 2022 Last updated: May 21, 2022	Publications: PubMed (8) PubMed: 16885549‚ 21989597‚ 27538677‚ 18981553‚ 32027066‚ 16613899‚ 18025408‚ 32792356 Comment: show Mutations in ABCC8 gene are associated with both neonatal diabetes mellitus as well as MODY. Patients with this mutation may have a better response to sulfonylureas. However, no sufficient evidence is found to ascertain the role of this particular variant (rs1057516718) in neonatal diabetes yet. (less) Observation: 1 Collection method: research Allele origin: somatic Affected status: unknown Observation 1 Collection method: research Allele origin: somatic Affected status: unknown

Pathogenic (Aug 23, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Type 2 diabetes mellitus	Baylor Genetics Accession: SCV004196201.1 First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Pathogenic (Mar 25, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Hyperinsulinemic hypoglycemia, familial, 1	Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre Accession: SCV004806087.1 First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Aug 19, 2023) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004295379.2 First in ClinVar: Feb 14, 2024 Last updated: Mar 04, 2025	Publications: PubMed (3) PubMed: 20685672‚ 23345197‚ 24401662 Comment: show For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Gln1341*) in the ABCC8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCC8 are known to be pathogenic (PMID: 20685672, 23345197). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autosomal recessive diffuse or focal hyperinsulinism (PMID: 23345197, 24401662). This variant is also known as c.4024C>T (p.Gln1342X). ClinVar contains an entry for this variant (Variation ID: 370722). (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 pathogenic (Mar 30, 2016) N Not contributing to aggregate classification	no assertion criteria provided	Hyperinsulinemic hypoglycemia, familial, 1	Counsyl Accession: SCV000486108.3 First in ClinVar: Jan 06, 2017 Last updated: Jun 29, 2025	Publications: PubMed (2) PubMed: 23345197‚ 24401662 Comment: show This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. (less) Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Comment:

Mutations in ABCC8 gene are associated with both neonatal diabetes mellitus as well as MODY. Patients with this mutation may have a better response to sulfonylureas. However, no sufficient evidence is found to ascertain the role of this particular variant (rs1057516718) in MODY yet.

Comment:

For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Gln1341*) in the ABCC8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCC8 are known to be pathogenic (PMID: 20685672, 23345197). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autosomal recessive diffuse or focal hyperinsulinism (PMID: 23345197, 24401662). This variant is also known as c.4024C>T (p.Gln1342X). ClinVar contains an entry for this variant (Variation ID: 370722).

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Molecular and clinical characteristics of monogenic diabetes mellitus in southern Chinese children with onset before 3 years of age.	Lin Y	BMJ open diabetes research & care	2020	PMID: 32792356
Update of variants identified in the pancreatic β-cell K(ATP) channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes.	De Franco E	Human mutation	2020	PMID: 32027066
ABCC8-Related Maturity-Onset Diabetes of the Young (MODY12): Clinical Features and Treatment Perspective.	Ovsyannikova AK	Diabetes therapy : research, treatment and education of diabetes and related disorders	2016	PMID: 27538677
Clinical and genetic evaluation of patients with KATP channel mutations from the German registry for congenital hyperinsulinism.	Mohnike K	Hormone research in paediatrics	2014	PMID: 24401662
Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism.	Kapoor RR	European journal of endocrinology	2013	PMID: 23345197
Heterozygous ABCC8 mutations are a cause of MODY.	Bowman P	Diabetologia	2012	PMID: 21989597
ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism.	Bellanné-Chantelot C	Journal of medical genetics	2010	PMID: 20685672
Permanent neonatal diabetes mellitus due to a C96Y heterozygous mutation in the insulin gene. A case report.	Ahamed A	JOP : Journal of the pancreas	2008	PMID: 18981553
Effective treatment with oral sulfonylureas in patients with diabetes due to sulfonylurea receptor 1 (SUR1) mutations.	Rafiq M	Diabetes care	2008	PMID: 18025408
Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.	Babenko AP	The New England journal of medicine	2006	PMID: 16885549
A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes.	Proks P	Human molecular genetics	2006	PMID: 16613899
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Text-mined citations for rs1057516718 ...

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Record last updated Oct 12, 2025

ClinVar Genomic variation as it relates to human health

NM_000352.6(ABCC8):c.4021C>T (p.Gln1341Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Citations for germline classification of this variant

Text-mined citations for rs1057516718 ...