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NM_000352.6(ABCC8):c.1501G>A (p.Glu501Lys) AND Familial hyperinsulinism

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 11, 2022
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:
RCV002509505.2

Allele description [Variation Report for NM_000352.6(ABCC8):c.1501G>A (p.Glu501Lys)]

NM_000352.6(ABCC8):c.1501G>A (p.Glu501Lys)

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.1501G>A (p.Glu501Lys)
Other names:
NM_000352.6(ABCC8):c.1501G>A; p.Glu501Lys
HGVS:
  • NC_000011.10:g.17442849C>T
  • NG_008867.1:g.39054G>A
  • NM_000352.6:c.1501G>AMANE SELECT
  • NM_001287174.3:c.1501G>A
  • NM_001351295.2:c.1501G>A
  • NM_001351296.2:c.1498G>A
  • NM_001351297.2:c.1498G>A
  • NP_000343.2:p.Glu501Lys
  • NP_001274103.1:p.Glu501Lys
  • NP_001338224.1:p.Glu501Lys
  • NP_001338225.1:p.Glu500Lys
  • NP_001338226.1:p.Glu500Lys
  • LRG_790t1:c.1501G>A
  • LRG_790t2:c.1501G>A
  • LRG_790:g.39054G>A
  • LRG_790p1:p.Glu501Lys
  • LRG_790p2:p.Glu501Lys
  • NC_000011.9:g.17464396C>T
  • NM_000352.3:c.1501G>A
  • NM_000352.4:c.1501G>A
  • NR_147094.2:n.1567G>A
Protein change:
E500K
Links:
dbSNP: rs372307320
NCBI 1000 Genomes Browser:
rs372307320
Molecular consequence:
  • NM_000352.6:c.1501G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287174.3:c.1501G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351295.2:c.1501G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351296.2:c.1498G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351297.2:c.1498G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_147094.2:n.1567G>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002819429Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Dec 11, 2022) 		germlineclinical testing

PubMed (10)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Preoperative evaluation of infants with focal or diffuse congenital hyperinsulinism by intravenous acute insulin response tests and selective pancreatic arterial calcium stimulation.

Stanley CA, Thornton PS, Ganguly A, MacMullen C, Underwood P, Bhatia P, Steinkrauss L, Wanner L, Kaye R, Ruchelli E, Suchi M, Adzick NS.

J Clin Endocrinol Metab. 2004 Jan;89(1):288-96. Erratum in: J Clin Endocrinol Metab. 2005 Jan;90(1):189.

PubMed [citation]
PMID:
14715863

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 (10)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002819429.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (10)

Description

Variant summary: ABCC8 c.1501G>A (p.Glu501Lys) results in a conservative amino acid change located in the ABC transporter type 1, transmembrane domain (IPR011527) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250814 control chromosomes. c.1501G>A has been reported in the literature in multiple individuals affected with Congenital Hyperinsulinism predominantly with a diffuse histology (example, Su_2014, Snider_2013, Gong_2016, Li_2017, Wang_2017, Stanley_2014, Ni_2019, Atapattu_2017). 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 protein function (Yan_2007). The most pronounced variant effect results in reduced cell surface expression. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 13, 2025