U.S. flag

An official website of the United States government

NM_000525.4(KCNJ11):c.874G>A (p.Glu292Lys) AND not provided

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Nov 29, 2022
Review status:
criteria provided, conflicting classifications
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:
RCV000992254.3

Allele description [Variation Report for NM_000525.4(KCNJ11):c.874G>A (p.Glu292Lys)]

NM_000525.4(KCNJ11):c.874G>A (p.Glu292Lys)

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.874G>A (p.Glu292Lys)
HGVS:
  • NC_000011.10:g.17387218C>T
  • NG_012446.1:g.6442G>A
  • NM_000525.4:c.874G>AMANE SELECT
  • NM_001166290.2:c.613G>A
  • NM_001377296.1:c.613G>A
  • NM_001377297.1:c.613G>A
  • NP_000516.3:p.Glu292Lys
  • NP_000516.3:p.Glu292Lys
  • NP_001159762.1:p.Glu205Lys
  • NP_001364225.1:p.Glu205Lys
  • NP_001364226.1:p.Glu205Lys
  • NC_000011.9:g.17408765C>T
  • NC_000011.9:g.17408765C>T
  • NM_000525.3:c.874G>A
Protein change:
E205K
Links:
dbSNP: rs1174593640
NCBI 1000 Genomes Browser:
rs1174593640
Molecular consequence:
  • NM_000525.4:c.874G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001166290.2:c.613G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377296.1:c.613G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377297.1:c.613G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001144384Athena Diagnostics
criteria provided, single submitter

(Athena Diagnostics Criteria)
Uncertain significance
(Apr 24, 2019)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004295357Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely pathogenic
(Nov 29, 2022)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317

Clinical and histological heterogeneity of congenital hyperinsulinism due to paternally inherited heterozygous ABCC8/KCNJ11 mutations.

Arya VB, Guemes M, Nessa A, Alam S, Shah P, Gilbert C, Senniappan S, Flanagan SE, Ellard S, Hussain K.

Eur J Endocrinol. 2014 Dec;171(6):685-95. doi: 10.1530/EJE-14-0353. Epub 2014 Sep 8.

PubMed [citation]
PMID:
25201519
See all PubMed Citations (4)

Details of each submission

From Athena Diagnostics, SCV001144384.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV004295357.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 804977). This missense change has been observed in individuals with autosomal dominant familial hyperinsulinism (PMID: 25201519). This variant has been reported in individual(s) with paternally inherited focal hyperinsulinism (PMID: 23345197); however, the role of the variant in this condition is currently unclear. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 292 of the KCNJ11 protein (p.Glu292Lys).

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

Last Updated: May 7, 2024