NM_000525.4(KCNJ11):c.761C>T (p.Pro254Leu) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 22, 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:: RCV002512937.3

Allele description [Variation Report for NM_000525.4(KCNJ11):c.761C>T (p.Pro254Leu)]

NM_000525.4(KCNJ11):c.761C>T (p.Pro254Leu)

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.761C>T (p.Pro254Leu)

HGVS:

NC_000011.10:g.17387331G>A
NG_012446.1:g.6329C>T
NM_000525.4:c.761C>TMANE SELECT
NM_001166290.2:c.500C>T
NM_001377296.1:c.500C>T
NM_001377297.1:c.500C>T
NP_000516.3:p.Pro254Leu
NP_001159762.1:p.Pro167Leu
NP_001364225.1:p.Pro167Leu
NP_001364226.1:p.Pro167Leu
NC_000011.9:g.17408878G>A
NC_000011.9:g.17408878G>A

Protein change:

P167L; PRO254LEU

Links:

OMIM: 600937.0011; dbSNP: rs104894237

NCBI 1000 Genomes Browser:

rs104894237

Molecular consequence:

NM_000525.4:c.761C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001166290.2:c.500C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001377296.1:c.500C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001377297.1:c.500C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
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
SCV003439573	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 22, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27188453, 15579781, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003439573

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 22, 2023)

germline

clinical testing

PubMed (3)
[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

Clinical and genetic characterization of congenital hyperinsulinism in Spain.

Martínez R, Fernández-Ramos C, Vela A, Velayos T, Aguayo A, Urrutia I, Rica I, Castaño L; Spanish Congenital Hyperinsulinism Group..

Eur J Endocrinol. 2016 Jun;174(6):717-26. doi: 10.1530/EJE-16-0027.

PubMed [citation]

PMID:: 27188453

Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence for additional locus heterogeneity.

Tornovsky S, Crane A, Cosgrove KE, Hussain K, Lavie J, Heyman M, Nesher Y, Kuchinski N, Ben-Shushan E, Shatz O, Nahari E, Potikha T, Zangen D, Tenenbaum-Rakover Y, de Vries L, Argente J, Gracia R, Landau H, Eliakim A, Lindley K, Dunne MJ, Aguilar-Bryan L, et al.

J Clin Endocrinol Metab. 2004 Dec;89(12):6224-34.

PubMed [citation]

PMID:: 15579781

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003439573.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 254 of the KCNJ11 protein (p.Pro254Leu). This variant is present in population databases (rs104894237, gnomAD 0.003%). This missense change has been observed in individuals with autosomal recessive hyperinsulinism (PMID: 15579781, 27188453). ClinVar contains an entry for this variant (Variation ID: 8675). 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: 15579781). 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.

#	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: Oct 8, 2024

ClinVar

Relating variation to medicine