NM_153766.3(KCNJ1):c.887T>G (p.Val296Gly) AND Bartter syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 5, 2022
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:: RCV002240079.1

Allele description [Variation Report for NM_153766.3(KCNJ1):c.887T>G (p.Val296Gly)]

NM_153766.3(KCNJ1):c.887T>G (p.Val296Gly)

Gene:

KCNJ1:potassium inwardly rectifying channel subfamily J member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q24.3

Genomic location:

Preferred name:

NM_153766.3(KCNJ1):c.887T>G (p.Val296Gly)

HGVS:

NC_000011.10:g.128839357A>C
NG_009379.1:g.33017T>G
NM_000220.6:c.944T>G
NM_153764.3:c.887T>G
NM_153765.3:c.938T>G
NM_153766.3:c.887T>GMANE SELECT
NM_153767.4:c.887T>G
NP_000211.1:p.Val315Gly
NP_722448.1:p.Val296Gly
NP_722449.3:p.Val313Gly
NP_722450.1:p.Val296Gly
NP_722451.1:p.Val296Gly
NC_000011.9:g.128709252A>C
NM_000220.4:c.944T>G

Protein change:

V296G

Links:

dbSNP: rs753949204

NCBI 1000 Genomes Browser:

rs753949204

Molecular consequence:

NM_000220.6:c.944T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_153764.3:c.887T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_153765.3:c.938T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_153766.3:c.887T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_153767.4:c.887T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Bartter syndrome
Synonyms:: Bartter's syndrome; Potassium wasting
Identifiers:: MONDO: MONDO:0015231; MedGen: C0004775; OMIM: PS601678

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002511428	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Apr 5, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19096086, 9015377, 23782368, 9587066, 12081585 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002511428

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Apr 5, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

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

Phenotype-genotype correlation in antenatal and neonatal variants of Bartter syndrome.

Brochard K, Boyer O, Blanchard A, Loirat C, Niaudet P, Macher MA, Deschenes G, Bensman A, Decramer S, Cochat P, Morin D, Broux F, Caillez M, Guyot C, Novo R, Jeunemaître X, Vargas-Poussou R.

Nephrol Dial Transplant. 2009 May;24(5):1455-64. doi: 10.1093/ndt/gfn689. Epub 2008 Dec 18.

PubMed [citation]

PMID:: 19096086

Mutations in the ROMK gene in antenatal Bartter syndrome are associated with impaired K+ channel function.

Derst C, Konrad M, Köckerling A, Károlyi L, Deschenes G, Daut J, Karschin A, Seyberth HW.

Biochem Biophys Res Commun. 1997 Jan 23;230(3):641-5.

PubMed [citation]

PMID:: 9015377

See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002511428.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Variant summary: KCNJ1 c.944T>G (p.Val315Gly) results in a non-conservative amino acid change located in the Inward rectifier potassium channel, C-terminal domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251166 control chromosomes. c.944T>G has been reported in the literature in multiple individuals affected with Bartter Syndrome, Type 2 including homozygous and compound heterozygous individuals (Karolyi_1997, Borchard_2009, Fretzayas_2013). These data indicate that the variant is very likely to be associated with disease. Expression studies showed that the variant lies adjacent to the cAMP-dependent PKA phosphorylation domain in the C-terminal part of the protein and results in an impaired K+ trafficking (Derst_1997). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was 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: Sep 29, 2024

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