NM_153766.3(KCNJ1):c.506G>A (p.Arg169His) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 25, 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:: RCV001901980.5

Allele description [Variation Report for NM_153766.3(KCNJ1):c.506G>A (p.Arg169His)]

NM_153766.3(KCNJ1):c.506G>A (p.Arg169His)

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.506G>A (p.Arg169His)

HGVS:

NC_000011.10:g.128839738C>T
NG_009379.1:g.32636G>A
NM_000220.6:c.563G>A
NM_153764.3:c.506G>A
NM_153765.3:c.557G>A
NM_153766.3:c.506G>AMANE SELECT
NM_153767.4:c.506G>A
NP_000211.1:p.Arg188His
NP_722448.1:p.Arg169His
NP_722449.3:p.Arg186His
NP_722450.1:p.Arg169His
NP_722451.1:p.Arg169His
NC_000011.9:g.128709633C>T

Protein change:

R169H

Links:

dbSNP: rs759992526

NCBI 1000 Genomes Browser:

rs759992526

Molecular consequence:

NM_000220.6:c.563G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_153764.3:c.506G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_153765.3:c.557G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_153766.3:c.506G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_153767.4:c.506G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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molybdopterin biosynthesis protein B [Shigella flexneri 2a str. 301]
molybdopterin biosynthesis protein B [Shigella flexneri 2a str. 301]
gi|24112150|ref|NP_706660.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002133895	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 25, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20926634, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002133895

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 25, 2022)

germline

clinical testing

PubMed (2)
[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

Hypertension resistance polymorphisms in ROMK (Kir1.1) alter channel function by different mechanisms.

Fang L, Li D, Welling PA.

Am J Physiol Renal Physiol. 2010 Dec;299(6):F1359-64. doi: 10.1152/ajprenal.00257.2010. Epub 2010 Oct 6.

PubMed [citation]

PMID:: 20926634
PMCID:: PMC3006317

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002133895.2

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

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 188 of the KCNJ1 protein (p.Arg188His). This variant is present in population databases (rs759992526, gnomAD 0.08%). This missense change has been observed in individual(s) with clinical features of Bartter syndrome (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects KCNJ1 function (PMID: 20926634). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 26, 2024

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