NM_000352.6(ABCC8):c.3748C>T (p.Arg1250Ter) AND Familial hyperinsulinism

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 5, 2017
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000779675.2

Allele description [Variation Report for NM_000352.6(ABCC8):c.3748C>T (p.Arg1250Ter)]

NM_000352.6(ABCC8):c.3748C>T (p.Arg1250Ter)

Gene:

ABCC8:ATP binding cassette subfamily C member 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.1

Genomic location:

Preferred name:

NM_000352.6(ABCC8):c.3748C>T (p.Arg1250Ter)

HGVS:

NC_000011.10:g.17398344G>A
NG_008867.1:g.83559C>T
NM_000352.6:c.3748C>TMANE SELECT
NM_001287174.3:c.3751C>T
NM_001351295.2:c.3814C>T
NM_001351296.2:c.3748C>T
NM_001351297.2:c.3745C>T
NP_000343.2:p.Arg1250Ter
NP_001274103.1:p.Arg1251Ter
NP_001338224.1:p.Arg1272Ter
NP_001338225.1:p.Arg1250Ter
NP_001338226.1:p.Arg1249Ter
LRG_790t1:c.3748C>T
LRG_790t2:c.3751C>T
LRG_790:g.83559C>T
LRG_790p1:p.Arg1250Ter
LRG_790p2:p.Arg1251Ter
NC_000011.9:g.17419891G>A
NM_000352.3:c.3748C>T
NR_147094.2:n.3897C>T

Protein change:

R1249*

Links:

dbSNP: rs1057516281

NCBI 1000 Genomes Browser:

rs1057516281

Molecular consequence:

NR_147094.2:n.3897C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000352.6:c.3748C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001287174.3:c.3751C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351295.2:c.3814C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351296.2:c.3748C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351297.2:c.3745C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Familial hyperinsulinism
Synonyms:: Congenital hyperinsulinism
Identifiers:: MONDO: MONDO:0017182; MedGen: C3888018

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000916395	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Dec 5, 2017)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20943781, 23275527, 18339976, 23345197, 16429405 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000916395

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Dec 5, 2017)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular and clinical analysis of Japanese patients with persistent congenital hyperinsulinism: predominance of paternally inherited monoallelic mutations in the KATP channel genes.

Yorifuji T, Kawakita R, Nagai S, Sugimine A, Doi H, Nomura A, Masue M, Nishibori H, Yoshizawa A, Okamoto S, Doi R, Uemoto S, Nagasaka H.

J Clin Endocrinol Metab. 2011 Jan;96(1):E141-5. doi: 10.1210/jc.2010-1281. Epub 2010 Oct 13.

PubMed [citation]

PMID:: 20943781

Genotype and phenotype correlations in 417 children with congenital hyperinsulinism.

Snider KE, Becker S, Boyajian L, Shyng SL, MacMullen C, Hughes N, Ganapathy K, Bhatti T, Stanley CA, Ganguly A.

J Clin Endocrinol Metab. 2013 Feb;98(2):E355-63. doi: 10.1210/jc.2012-2169. Epub 2012 Dec 28.

PubMed [citation]

PMID:: 23275527
PMCID:: PMC3565119

See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000916395.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Variant summary: The ABCC8 c.3748C>T (p.Arg1250X) variant results in a premature termination codon, predicted to cause a truncated or absent ABCC8 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., c.4013G>A [p.Trp1338X] and c.4306C>T [p.Arg1436X]). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 246308 control chromosomes, but has been reported in numerous patients with congenital hyperinsulism as a homozygous and compound heterozygous allele (e.g., Kapoor_2013, Snider_2013). In addition, one clinical diagnostic laboratory classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 15, 2024

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