NM_153766.3(KCNJ1):c.584C>T (p.Ala195Val) AND Bartter disease type 2

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Mar 14, 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:: RCV000009727.3

Allele description [Variation Report for NM_153766.3(KCNJ1):c.584C>T (p.Ala195Val)]

NM_153766.3(KCNJ1):c.584C>T (p.Ala195Val)

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.584C>T (p.Ala195Val)

HGVS:

NC_000011.10:g.128839660G>A
NG_009379.1:g.32714C>T
NM_000220.6:c.641C>T
NM_153764.3:c.584C>T
NM_153765.3:c.635C>T
NM_153766.3:c.584C>TMANE SELECT
NM_153767.4:c.584C>T
NP_000211.1:p.Ala214Val
NP_722448.1:p.Ala195Val
NP_722449.3:p.Ala212Val
NP_722450.1:p.Ala195Val
NP_722451.1:p.Ala195Val
NC_000011.9:g.128709555G>A

Protein change:

A195V; ALA195VAL

Links:

OMIM: 600359.0005; dbSNP: rs104894246

NCBI 1000 Genomes Browser:

rs104894246

Molecular consequence:

NM_000220.6:c.641C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_153764.3:c.584C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_153765.3:c.635C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_153766.3:c.584C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_153767.4:c.584C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Bartter disease type 2
Synonyms:: HYPOKALEMIC ALKALOSIS WITH HYPERCALCIURIA 2, ANTENATAL; Hyperprostaglandin E syndrome 2; Bartter syndrome, type 2, antenatal
Identifiers:: MONDO: MONDO:0009424; MedGen: C1855849; Orphanet: 112; OMIM: 241200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000029948	OMIM	no assertion criteria provided	Pathogenic (Jun 1, 1998)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 8841184, 9580661
SCV002803923	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 14, 2022)	unknown	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

SCV000029948

OMIM

no assertion criteria provided

Pathogenic
(Jun 1, 1998)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV002803923

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 14, 2022)

unknown

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK.

Simon DB, Karet FE, Rodriguez-Soriano J, Hamdan JH, DiPietro A, Trachtman H, Sanjad SA, Lifton RP.

Nat Genet. 1996 Oct;14(2):152-6.

PubMed [citation]

PMID:: 8841184

Functional consequences of ROMK mutants linked to antenatal Bartter's syndrome and implications for treatment.

Schwalbe RA, Bianchi L, Accili EA, Brown AM.

Hum Mol Genet. 1998 Jun;7(6):975-80.

PubMed [citation]

PMID:: 9580661

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000029948.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In nonconsanguineous family BAR206, Simon et al. (1996) found compound heterozygosity for mutations in the KCNJ1 gene in members affected by antenatal Bartter syndrome (BARTS2; 241200). One variant represented a 4-bp deletion, spanning the last base of codon 313 and all of codon 314, resulting in a frameshift mutation and altering the encoded protein from amino acid 315 onward and ending at a new stop codon at position 350. The second variant in this kindred arose from substitution of valine for alanine at amino acid 195 in the cytoplasmic C-terminal region of ROMK.

Schwalbe et al. (1998) studied this mutation in rat Kcnj1 and determined that it hindered phosphorylation of a nearby serine and lead to fast channel rundown.

#	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 Fulgent Genetics, Fulgent Genetics, SCV002803923.1

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

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

Last Updated: Feb 20, 2024

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