NM_000525.3(KCNJ11):c.440T>C (p.Leu147Pro) AND Islet cell hyperplasia

Clinical significance:Pathogenic (Last evaluated: Mar 16, 2015)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000009197.4

Allele description [Variation Report for NM_000525.3(KCNJ11):c.440T>C (p.Leu147Pro)]

NM_000525.3(KCNJ11):c.440T>C (p.Leu147Pro)

Gene:
KCNJ11:potassium voltage-gated channel subfamily J member 11 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11p15.1
Genomic location:
Preferred name:
NM_000525.3(KCNJ11):c.440T>C (p.Leu147Pro)
HGVS:
  • NC_000011.10:g.17387652A>G
  • NG_012446.1:g.6008T>C
  • NM_000525.3:c.440T>C
  • NP_000516.3:p.Leu147Pro
  • NC_000011.9:g.17409199A>G
  • p.(Leu147Pro)
Protein change:
L147P; LEU147PRO
Links:
OMIM: 600937.0001; dbSNP: 28936678
NCBI 1000 Genomes Browser:
rs28936678
Molecular consequence:
  • NM_000525.3:c.440T>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

Condition(s)

Name:
Islet cell hyperplasia (HHF2)
Synonyms:
HYPERINSULINEMIC HYPOGLYCEMIA DUE TO FOCAL ADENOMATOUS HYPERPLASIA; HYPERINSULINEMIC HYPOGLYCEMIA, PERSISTENT; HYPERINSULINISM, CONGENITAL; See all synonyms [MedGen]
Identifiers:
MedGen: C0027773; Orphanet: 276580; Orphanet: 276603; OMIM: 601820
Age of onset:
Neonatal
Prevalence:
Familial hyperinsulinism has been reported in virtually all major ethnic groups. Prevalence has been estimated at 1:50,000 in the European population, whereas consanguineous populations of central Finland and Saudi Arabia have disease prevalence of approximately 1:2,500. The apparent increased prevalence among Ashkenazi Jews has not been rigorously studied.

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000029414OMIMno assertion criteria providedPathogenic
(Nov 1, 1996)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000292230Genome Clinic of Geneva,University Hospital of Genevacriteria provided, single submitter
(ACMG Guidelines, 2015)
Pathogenic
(Mar 16, 2015)
paternalclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedpaternalyes2not providednot providednot providednot providedclinical testing

Citations

PubMed

Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy.

Thomas P, Ye Y, Lightner E.

Hum Mol Genet. 1996 Nov;5(11):1809-12.

PubMed [citation]
PMID:
8923010

Details of each submission

From OMIM, SCV000029414.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a male infant with profound hypoglycemia (HHF2; 601820), born of consanguineous Iranian parents, Thomas et al. (1996) identified homozygosity for a 649T-C mutation in the KCNJ11 gene, resulting in a leu147-to-pro (L147P) substitution predicted to cause disruption of the M2 alpha-helical transmembrane domain of the protein. His parents were heterozygous for the mutation.

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

From Genome Clinic of Geneva,University Hospital of Geneva, SCV000292230.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (1)

Description

This recessive mutation in the KCNJ11 gene was found in a case of congenital hyperinsulinemic hypoglycemia. The combination of this mutation with a second recessive mutation (c.154C>T) in the same gene explains the phenotype of this newborn patient.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1paternalyesnot providednot providednot provided2not providednot providednot provided

Last Updated: Jul 8, 2016