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NM_000352.6(ABCC8):c.2992C>T (p.Arg998Ter)

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Interpretation:
Conflicting interpretations of pathogenicity​

Pathogenic(3);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
7 (Most recent: Nov 19, 2021)
Last evaluated:
Oct 23, 2020
Accession:
VCV000434053.9
Variation ID:
434053
Description:
single nucleotide variant
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NM_000352.6(ABCC8):c.2992C>T (p.Arg998Ter)

Allele ID
429204
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
11p15.1
Genomic location
11: 17407058 (GRCh38) GRCh38 UCSC
11: 17428605 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000011.10:g.17407058G>A
NG_008867.1:g.74845C>T
NM_000352.6:c.2992C>T MANE Select NP_000343.2:p.Arg998Ter nonsense
... more HGVS
Protein change
R998*, R999*, R1020*, R997*
Other names
-
Canonical SPDI
NC_000011.10:17407057:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
Links
ClinGen: CA5902951
dbSNP: rs769518471
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 3 criteria provided, multiple submitters, no conflicts Oct 23, 2020 RCV000517672.5
Pathogenic 2 criteria provided, single submitter Nov 25, 2015 RCV000499389.3
Uncertain significance 1 criteria provided, single submitter Mar 3, 2017 RCV000664138.2
Hereditary hyperinsulinism
Pathogenic 1 no assertion criteria provided Sep 16, 2020 RCV001277193.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
ABCC8 - - GRCh38
GRCh37
1055 1124

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Nov 25, 2015)
criteria provided, single submitter
Method: clinical testing
Hyperinsulinemic hypoglycemia, familial, 1
Allele origin: germline
Genetic Services Laboratory,University of Chicago
Accession: SCV000592991.1
Submitted: (Jul 05, 2017)
Evidence details
Uncertain significance
(Mar 03, 2017)
criteria provided, single submitter
Method: research
Monogenic diabetes
Allele origin: unknown
Personalized Diabetes Medicine Program,University of Maryland School of Medicine
Study: Personalized Diabetes Medicine Program
Accession: SCV000787590.1
Submitted: (Jan 10, 2018)
Evidence details
Comment:
ACMG Criteria:PP3 (2 predictors), BP4 (2 predictors), PVS1 (stopgain)
Pathogenic
(Sep 10, 2015)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Athena Diagnostics Inc
Accession: SCV000612206.2
Submitted: (Aug 31, 2018)
Evidence details
Publications
PubMed (6)
Pathogenic
(Oct 23, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Invitae
Accession: SCV000931645.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (6)
Comment:
This sequence change creates a premature translational stop signal (p.Arg998*) in the ABCC8 gene. It is expected to result in an absent or disrupted protein … (more)
Pathogenic
(Dec 21, 2018)
no assertion criteria provided
Method: clinical testing
Hyperinsulinemic hypoglycemia, familial, 1
Allele origin: unknown
Counsyl
Accession: SCV001132112.1
Submitted: (Aug 05, 2019)
Evidence details
Publications
PubMed (3)
Pathogenic
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Hereditary hyperinsulinism
Allele origin: germline
Natera, Inc.
Accession: SCV001464091.1
Submitted: (Dec 28, 2020)
Evidence details
Pathogenic
(Sep 04, 2019)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
PerkinElmer Genomics
Accession: SCV002018617.1
Submitted: (Nov 19, 2021)
Evidence details

Functional evidence

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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.

Citations for this variant

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Title Author Journal Year Link
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. Xiong HY Science (New York, N.Y.) 2015 PMID: 25525159
Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism. Kapoor RR European journal of endocrinology 2013 PMID: 23345197
Genotype and phenotype correlations in 417 children with congenital hyperinsulinism. Snider KE The Journal of clinical endocrinology and metabolism 2013 PMID: 23275527
Molecular and clinical analysis of Japanese patients with persistent congenital hyperinsulinism: predominance of paternally inherited monoallelic mutations in the KATP channel genes. Yorifuji T The Journal of clinical endocrinology and metabolism 2011 PMID: 20943781
ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism. Bellanné-Chantelot C Journal of medical genetics 2010 PMID: 20685672
Diagnosis and localization of focal congenital hyperinsulinism by 18F-fluorodopa PET scan. Hardy OT The Journal of pediatrics 2007 PMID: 17236890
Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism. Suchi M Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 2006 PMID: 16357843
Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes. Henwood MJ The Journal of clinical endocrinology and metabolism 2005 PMID: 15562009
Preoperative evaluation of infants with focal or diffuse congenital hyperinsulinism by intravenous acute insulin response tests and selective pancreatic arterial calcium stimulation. Stanley CA The Journal of clinical endocrinology and metabolism 2004 PMID: 14715863
Histopathology of congenital hyperinsulinism: retrospective study with genotype correlations. Suchi M Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 2003 PMID: 14692646

Text-mined citations for rs769518471...

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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 Nov 28, 2021