NM_000352.6(ABCC8):c.76T>A (p.Cys26Ser) AND Familial hyperinsulinism

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 3, 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:: RCV001844417.5

Allele description [Variation Report for NM_000352.6(ABCC8):c.76T>A (p.Cys26Ser)]

NM_000352.6(ABCC8):c.76T>A (p.Cys26Ser)

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.76T>A (p.Cys26Ser)

Other names:

NM_000352.6(ABCC8):c.76T>A; p.Cys26Ser

HGVS:

NC_000011.10:g.17476701A>T
NG_008867.1:g.5202T>A
NM_000352.6:c.76T>AMANE SELECT
NM_001287174.3:c.76T>A
NM_001351295.2:c.76T>A
NM_001351296.2:c.76T>A
NM_001351297.2:c.76T>A
NP_000343.2:p.Cys26Ser
NP_001274103.1:p.Cys26Ser
NP_001338224.1:p.Cys26Ser
NP_001338225.1:p.Cys26Ser
NP_001338226.1:p.Cys26Ser
LRG_790t1:c.76T>A
LRG_790t2:c.76T>A
LRG_790:g.5202T>A
LRG_790p1:p.Cys26Ser
LRG_790p2:p.Cys26Ser
NC_000011.9:g.17498248A>T
NC_000011.9:g.17498248A>T
NM_000352.4:c.76T>A
NR_147094.2:n.145T>A

Protein change:

C26S

Links:

dbSNP: rs1462559571

Molecular consequence:

NM_000352.6:c.76T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001287174.3:c.76T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351295.2:c.76T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351296.2:c.76T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351297.2:c.76T>A - missense variant - [Sequence Ontology: SO:0001583]
NR_147094.2:n.145T>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
SCV002103457	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Jun 3, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21199866, 22311976 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002103457

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Jun 3, 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

Conserved intramolecular disulfide bond is critical to trafficking and fate of ATP-binding cassette (ABC) transporters ABCB6 and sulfonylurea receptor 1 (SUR1)/ABCC8.

Fukuda Y, Aguilar-Bryan L, Vaxillaire M, Dechaume A, Wang Y, Dean M, Moitra K, Bryan J, Schuetz JD.

J Biol Chem. 2011 Mar 11;286(10):8481-8492. doi: 10.1074/jbc.M110.174516. Epub 2011 Jan 3.

PubMed [citation]

PMID:: 21199866
PMCID:: PMC3048732

Role of Derlin-1 protein in proteostasis regulation of ATP-sensitive potassium channels.

Wang F, Olson EM, Shyng SL.

J Biol Chem. 2012 Mar 23;287(13):10482-10493. doi: 10.1074/jbc.M111.312223. Epub 2012 Feb 6.

PubMed [citation]

PMID:: 22311976
PMCID:: PMC3322999

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002103457.2

#	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.76T>A (p.Cys26Ser) 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 allele was found at a frequency of 4.1e-06 in 244362 control chromosomes. c.76T>A has been reported in the literature in at least one individual affected with hyperinsulinemic hypoglycemia (Fukuda_2011). These data do not allow any conclusion about variant significance. At least two publications report experimental evidence evaluating an impact on protein function and showed that C26S led to instability and ER retention (Fukuda_2011, Wang_2012). The following publications have been ascertained in the context of this evaluation (PMID: 21199866, 22311976). ClinVar contains an entry for this variant (Variation ID: 1338491). Based on the evidence outlined above, the variant was classified as likely 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: Mar 14, 2026

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