NM_000352.6(ABCC8):c.3544C>T (p.Arg1182Trp) AND Familial hyperinsulinism

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 12, 2024
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:: RCV003987437.1

Allele description [Variation Report for NM_000352.6(ABCC8):c.3544C>T (p.Arg1182Trp)]

NM_000352.6(ABCC8):c.3544C>T (p.Arg1182Trp)

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.3544C>T (p.Arg1182Trp)

HGVS:

NC_000011.10:g.17404525G>A
NG_008867.1:g.77378C>T
NM_000352.6:c.3544C>TMANE SELECT
NM_001287174.3:c.3547C>T
NM_001351295.2:c.3610C>T
NM_001351296.2:c.3544C>T
NM_001351297.2:c.3541C>T
NP_000343.2:p.Arg1182Trp
NP_001274103.1:p.Arg1183Trp
NP_001338224.1:p.Arg1204Trp
NP_001338225.1:p.Arg1182Trp
NP_001338226.1:p.Arg1181Trp
LRG_790t1:c.3544C>T
LRG_790t2:c.3547C>T
LRG_790:g.77378C>T
LRG_790p1:p.Arg1182Trp
LRG_790p2:p.Arg1183Trp
NC_000011.9:g.17426072G>A
NM_000352.3:c.3544C>T
NM_000352.5:c.3544C>T
NR_147094.2:n.3693C>T

Protein change:

R1181W; ARG1182TRP

Links:

OMIM: 600509.0031; dbSNP: rs797045209

Molecular consequence:

NM_000352.6:c.3544C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001287174.3:c.3547C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351295.2:c.3610C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351296.2:c.3544C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351297.2:c.3541C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_147094.2:n.3693C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV004804523	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jan 12, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17446535, 34566892 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004804523

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jan 12, 2024)

germline

clinical testing

PubMed (2)
[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

Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood.

Flanagan SE, Patch AM, Mackay DJ, Edghill EL, Gloyn AL, Robinson D, Shield JP, Temple K, Ellard S, Hattersley AT.

Diabetes. 2007 Jul;56(7):1930-7. Epub 2007 Apr 19. Erratum in: Diabetes. 2008 Feb;57(2):523.

PubMed [citation]

PMID:: 17446535
PMCID:: PMC7611811

Molecular Genetics, Clinical Characteristics, and Treatment Outcomes of K(ATP)-Channel Neonatal Diabetes Mellitus in Vietnam National Children's Hospital.

Ngoc CTB, Dien TM, De Franco E, Ellard S, Houghton JAL, Lan NN, Thao BP, Khanh NN, Flanagan SE, Craig ME, Dung VC.

Front Endocrinol (Lausanne). 2021;12:727083. doi: 10.3389/fendo.2021.727083.

PubMed [citation]

PMID:: 34566892
PMCID:: PMC8458931

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004804523.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: ABCC8 c.3544C>T (p.Arg1182Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251376 control chromosomes. c.3544C>T, also described as p.R1183W, has been reported in the literature in multiple individuals affected with Neonatal diabetes mellitus, and in at-least three cases, this variant arose de novo (Flanagan_2007, Ngoc_2021). Parents carrying this variant were also reported to be unaffected (Flanagan_2007). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 17446535, 34566892). ClinVar contains an entry for this variant (Variation ID: 210076. Pathogenic/Likely pathogenic). Based on the evidence outlined above, the variant was 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: Jul 14, 2026

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