NM_153766.3(KCNJ1):c.155C>T (p.Thr52Met) AND Bartter syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 31, 2024
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:: RCV003226388.2

Allele description [Variation Report for NM_153766.3(KCNJ1):c.155C>T (p.Thr52Met)]

NM_153766.3(KCNJ1):c.155C>T (p.Thr52Met)

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.155C>T (p.Thr52Met)

HGVS:

NC_000011.10:g.128840089G>A
NG_009379.1:g.32285C>T
NM_000220.6:c.212C>T
NM_153764.3:c.155C>T
NM_153765.3:c.206C>T
NM_153766.3:c.155C>TMANE SELECT
NM_153767.4:c.155C>T
NP_000211.1:p.Thr71Met
NP_722448.1:p.Thr52Met
NP_722449.3:p.Thr69Met
NP_722450.1:p.Thr52Met
NP_722451.1:p.Thr52Met
NC_000011.9:g.128709984G>A
NM_000220.4:c.212C>T

Protein change:

T52M

Links:

dbSNP: rs373367600

NCBI 1000 Genomes Browser:

rs373367600

Molecular consequence:

NM_000220.6:c.212C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_153764.3:c.155C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_153765.3:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_153766.3:c.155C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_153767.4:c.155C>T - 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
SCV003922571	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jul 31, 2024)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 12911542, 31441846, 34751387, 34663630, 32251469, 35006361, 31731488 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003922571

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jul 31, 2024)

germline

clinical testing

PubMed (7)
[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

Classification and rescue of ROMK mutations underlying hyperprostaglandin E syndrome/antenatal Bartter syndrome.

Peters M, Ermert S, Jeck N, Derst C, Pechmann U, Weber S, Schlingmann KP, Seyberth HW, Waldegger S, Konrad M.

Kidney Int. 2003 Sep;64(3):923-32.

PubMed [citation]

PMID:: 12911542

A novel compound heterozygous KCNJ1 gene mutation presenting as late-onset Bartter syndrome: Case report.

Li J, Hu S, Nie Y, Wang R, Tan M, Li H, Zhu S.

Medicine (Baltimore). 2019 Aug;98(34):e16738. doi: 10.1097/MD.0000000000016738.

PubMed [citation]

PMID:: 31441846
PMCID:: PMC6716717

See all PubMed Citations (7)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003922571.2

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

Description

Variant summary: KCNJ1 c.212C>T (p.Thr71Met) results in a non-conservative amino acid change located in the Potassium channel, inwardly rectifying, transmembrane domain (IPR040445) 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 2.8e-05 in 251480 control chromosomes. c.212C>T has been reported in the literature in multiple individuals affected with Bartter Syndrome, Type 2 in cluding in multiple homozygous individuals (Peters_2003, Sinha_2022) with evidence of co-segregation (London_2022), as well as in compound heterozygotes (Li_2019, Mani_2021). These data indicate that the variant is very likely to be associated with disease. One publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (Peters_2003). The following publications have been ascertained in the context of this evaluation (PMID: 31441846, 34751387, 34663630, 12911542, 32251469, 35006361, 31731488). ClinVar contains an entry for this variant (Variation ID: 631655). 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: Oct 20, 2024

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