NM_000525.4(KCNJ11):c.440T>C (p.Leu147Pro) AND Hyperinsulinemic hypoglycemia, familial, 2

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 16, 2015
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:: RCV000009197.5

Allele description [Variation Report for NM_000525.4(KCNJ11):c.440T>C (p.Leu147Pro)]

NM_000525.4(KCNJ11):c.440T>C (p.Leu147Pro)

Gene:

KCNJ11:potassium inwardly rectifying channel subfamily J member 11 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.1

Genomic location:

Preferred name:

NM_000525.4(KCNJ11):c.440T>C (p.Leu147Pro)

HGVS:

NC_000011.10:g.17387652A>G
NG_012446.1:g.6008T>C
NM_000525.4:c.440T>CMANE SELECT
NM_001166290.2:c.179T>C
NM_001377296.1:c.179T>C
NM_001377297.1:c.179T>C
NP_000516.3:p.Leu147Pro
NP_000516.3:p.Leu147Pro
NP_001159762.1:p.Leu60Pro
NP_001364225.1:p.Leu60Pro
NP_001364226.1:p.Leu60Pro
NC_000011.9:g.17409199A>G
NM_000525.3:c.440T>C
p.(Leu147Pro)

Protein change:

L147P; LEU147PRO

Links:

OMIM: 600937.0001; dbSNP: rs28936678

NCBI 1000 Genomes Browser:

rs28936678

Molecular consequence:

NM_000525.4:c.440T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001166290.2:c.179T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001377296.1:c.179T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001377297.1:c.179T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Hyperinsulinemic hypoglycemia, familial, 2
Synonyms:: HYPERINSULINEMIC HYPOGLYCEMIA, PERSISTENT; HYPERINSULINISM, NEONATAL
Identifiers:: MONDO: MONDO:0011153; MedGen: C2931833; Orphanet: 276580; Orphanet: 276603; OMIM: 601820

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000029414	OMIM	no assertion criteria provided	Pathogenic (Feb 1, 1995)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000292230	Center of Genomic medicine, Geneva, University Hospital of Geneva - Final Reports_Cases2015_1	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 16, 2015)	paternal	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000029414

OMIM

no assertion criteria provided

Pathogenic
(Feb 1, 1995)

germline

literature only

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

SCV000292230

Center of Genomic medicine, Geneva, University Hospital of Geneva - Final Reports_Cases2015_1

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 16, 2015)

paternal

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	paternal	yes	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy.

Thomas PM, Cote GJ, Hallman DM, Mathew PM.

Am J Hum Genet. 1995 Feb;56(2):416-21.

PubMed [citation]

PMID:: 7847376
PMCID:: PMC1801118

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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Center of Genomic medicine, Geneva, University Hospital of Geneva - Final Reports_Cases2015_1, SCV000292230.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	paternal	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

Last Updated: Jun 10, 2023

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