NM_000525.3(KCNJ11):c.36C>A (p.Tyr12Ter) AND Islet cell hyperplasia

Clinical significance:Pathogenic (Last evaluated: Apr 20, 2015)

Review status:1 star out of maximum of 4 stars

classified by single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000009208.2

Allele description [Variation Report for ]

NM_000525.3(KCNJ11):c.36C>A (p.Tyr12Ter)

Gene:
KCNJ11:potassium channel, inwardly rectifying subfamily J, member 11 [Gene - OMIM]
Variant type:
single nucleotide variant
Cytogenetic location:
11p15.1
Genomic location:
Preferred name:
NM_000525.3(KCNJ11):c.36C>A (p.Tyr12Ter)
HGVS:
  • NC_000011.10:g.17388056G>T
  • NG_012446.1:g.5604C>A
  • NM_000525.3:c.36C>A
  • NM_001166290.1:c.-16-210C>A
  • NP_000516.3:p.Tyr12Ter
  • NC_000011.9:g.17409603G>T
Protein change:
Y12*; TYR12TER
Links:
OMIM: 600937.0009; dbSNP: 104894236
NCBI 1000 Genomes Browser:
rs104894236
Molecular consequence:
  • NM_001166290.1:c.-16-210C>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000525.3:c.36C>A - nonsense - [Sequence Ontology: SO:0001587]

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/infancy
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 StatusClinical Significance
(Last evaluated)
OriginMethodConsequenceCitations
SCV000029426OMIMPathogenic
(Apr 20, 2015)
germlineliterature only

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

Citations

PubMed

A nonsense mutation in the inward rectifier potassium channel gene, Kir6.2, is associated with familial hyperinsulinism.

Nestorowicz A, Inagaki N, Gonoi T, Schoor KP, Wilson BA, Glaser B, Landau H, Stanley CA, Thornton PS, Seino S, Permutt MA.

Diabetes. 1997 Nov;46(11):1743-8.

PubMed [citation]
PMID:
9356020

Details of each submission

From OMIM, SCV000029426.2

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

Description

In a Palestinian Arab boy with hyperinsulinemic hypoglycemia (HHF2; 601820), born of first-cousin parents, Nestorowicz et al. (1997) identified homozygosity for a 39C-A transversion in the KCNJ11 gene, resulting in a tyr12-to-ter (Y12X) substitution. The mutation is predicted to produce a truncated Kir6.2 polypeptide lacking the putative K+ ion-selective pore region as well as those domains proposed to confer the gating and inward rectification properties of the molecule. In vitro studies in transfected COS-1 cells confirmed the deleterious effect of the mutation on channel activity. The authors noted that this patient was clinically indistinguishable from patients with severe hyperinsulinism caused by mutations in SUR1 (ABCC8; 600509; see HHF1, 600509).

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

Last Updated: Apr 23, 2015