NM_000352.6(ABCC8):c.3641G>A (p.Arg1214Gln) AND Familial hyperinsulinism

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 2, 2018
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:: RCV000779674.5

Allele description [Variation Report for NM_000352.6(ABCC8):c.3641G>A (p.Arg1214Gln)]

NM_000352.6(ABCC8):c.3641G>A (p.Arg1214Gln)

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.3641G>A (p.Arg1214Gln)

Other names:

p.Arg1214Gln; NM_000352.6(ABCC8):c.3641G>A

HGVS:

NC_000011.10:g.17402670C>T
NG_008867.1:g.79233G>A
NM_000352.6:c.3641G>AMANE SELECT
NM_001287174.3:c.3644G>A
NM_001351295.2:c.3707G>A
NM_001351296.2:c.3641G>A
NM_001351297.2:c.3638G>A
NP_000343.2:p.Arg1214Gln
NP_001274103.1:p.Arg1215Gln
NP_001338224.1:p.Arg1236Gln
NP_001338225.1:p.Arg1214Gln
NP_001338226.1:p.Arg1213Gln
LRG_790t1:c.3641G>A
LRG_790t2:c.3644G>A
LRG_790:g.79233G>A
LRG_790p1:p.Arg1214Gln
LRG_790p2:p.Arg1215Gln
NC_000011.9:g.17424217C>T
NM_000352.3:c.3641G>A
NM_000352.5:c.3641G>A
NR_147094.2:n.3790G>A

Protein change:

R1213Q

Links:

dbSNP: rs367850779

NCBI 1000 Genomes Browser:

rs367850779

Molecular consequence:

NM_000352.6:c.3641G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001287174.3:c.3644G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351295.2:c.3707G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351296.2:c.3641G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351297.2:c.3638G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_147094.2:n.3790G>A - 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
SCV000916394	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Nov 2, 2018)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 14692646, 17575084, 16416420, 20685672, 9618169, 14715863, 10685980, 9648840 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000916394

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Nov 2, 2018)

germline

clinical testing

PubMed (8)
[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

Histopathology of congenital hyperinsulinism: retrospective study with genotype correlations.

Suchi M, MacMullen C, Thornton PS, Ganguly A, Stanley CA, Ruchelli ED.

Pediatr Dev Pathol. 2003 Jul-Aug;6(4):322-33.

PubMed [citation]

PMID:: 14692646

Congenital hyperinsulinism associated ABCC8 mutations that cause defective trafficking of ATP-sensitive K+ channels: identification and rescue.

Yan FF, Lin YW, MacMullen C, Ganguly A, Stanley CA, Shyng SL.

Diabetes. 2007 Sep;56(9):2339-48. Epub 2007 Jun 15.

PubMed [citation]

PMID:: 17575084
PMCID:: PMC2225993

See all PubMed Citations (8)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000916394.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

Variant summary: ABCC8 c.3641G>A (p.Arg1214Gln) results in a conservative amino acid change located in the ABC transporter type 1, transmembrane domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 246460 control chromosomes. c.3641G>A has been reported in the literature in multiple individuals affected with Neonatal Diabetes Mellitus, both as a homozygous and compound heterozygous allele. These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on ATP-sensitive potassium channel activity, which showed the variant results in <30% of normal activity (Shyng_1998). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. 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: Jan 13, 2025

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