NM_000525.4(KCNJ11):c.617G>A (p.Arg206His) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 8, 2023
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:: RCV002564187.5

Allele description [Variation Report for NM_000525.4(KCNJ11):c.617G>A (p.Arg206His)]

NM_000525.4(KCNJ11):c.617G>A (p.Arg206His)

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.617G>A (p.Arg206His)

HGVS:

NC_000011.10:g.17387475C>T
NG_012446.1:g.6185G>A
NM_000525.4:c.617G>AMANE SELECT
NM_001166290.2:c.356G>A
NM_001377296.1:c.356G>A
NM_001377297.1:c.356G>A
NP_000516.3:p.Arg206His
NP_001159762.1:p.Arg119His
NP_001364225.1:p.Arg119His
NP_001364226.1:p.Arg119His
NC_000011.9:g.17409022C>T
NM_000525.3:c.617G>A

Protein change:

R119H

Links:

dbSNP: rs1554901747

NCBI 1000 Genomes Browser:

rs1554901747

Molecular consequence:

NM_000525.4:c.617G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001166290.2:c.356G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377296.1:c.356G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377297.1:c.356G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002951259	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 8, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 31291970, 32027066, 31464105, 25555642, 27908292, 30026763, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002951259

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 8, 2023)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

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

Next-generation sequencing identifies monogenic diabetes in 16% of patients with late adolescence/adult-onset diabetes selected on a clinical basis: a cross-sectional analysis.

Donath X, Saint-Martin C, Dubois-Laforgue D, Rajasingham R, Mifsud F, Ciangura C, Timsit J, Bellanné-Chantelot C; Monogenic Diabetes Study Group of the Société Francophone du Diabète.

BMC Med. 2019 Jul 11;17(1):132. doi: 10.1186/s12916-019-1363-0.

PubMed [citation]

PMID:: 31291970
PMCID:: PMC6621990

Update of variants identified in the pancreatic β-cell K(ATP) channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes.

De Franco E, Saint-Martin C, Brusgaard K, Knight Johnson AE, Aguilar-Bryan L, Bowman P, Arnoux JB, Larsen AR, Sanyoura M, Greeley SAW, Calzada-León R, Harman B, Houghton JAL, Nishimura-Meguro E, Laver TW, Ellard S, Del Gaudio D, Christesen HT, Bellanné-Chantelot C, Flanagan SE.

Hum Mutat. 2020 May;41(5):884-905. doi: 10.1002/humu.23995. Epub 2020 Feb 17. Review.

PubMed [citation]

PMID:: 32027066
PMCID:: PMC7187370

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002951259.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 206 of the KCNJ11 protein (p.Arg206His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant familial hyperinsulinism and/or later‚Äêonset diabetes (PMID: 31291970, 31464105, 32027066). ClinVar contains an entry for this variant (Variation ID: 1162197). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNJ11 protein function. Experimental studies have shown that this missense change affects KCNJ11 function (PMID: 31464105). This variant disrupts the p.Arg206 amino acid residue in KCNJ11. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25555642, 27908292, 30026763). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as 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: Feb 16, 2025

ClinVar

Relating variation to medicine