NM_000890.5(KCNJ5):c.687C>G (p.Ile229Met) AND Long QT syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 20, 2019
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:: RCV001059060.6

Allele description

NM_000890.5(KCNJ5):c.687C>G (p.Ile229Met)

Gene:

KCNJ5:potassium inwardly rectifying channel subfamily J member 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q24.3

Genomic location:

Preferred name:

NM_000890.5(KCNJ5):c.687C>G (p.Ile229Met)

HGVS:

NC_000011.10:g.128911960C>G
NG_023406.2:g.25543C>G
NM_000890.5:c.687C>GMANE SELECT
NM_001354169.2:c.687C>G
NP_000881.3:p.Ile229Met
NP_001341098.1:p.Ile229Met
LRG_333t1:c.687C>G
LRG_333:g.25543C>G
NC_000011.9:g.128781855C>G
NM_000890.3:c.687C>G

Protein change:

I229M

Links:

dbSNP: rs149327599

NCBI 1000 Genomes Browser:

rs149327599

Molecular consequence:

NM_000890.5:c.687C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354169.2:c.687C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Long QT syndrome (LQTS)
Identifiers:: MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976

Recent activity

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PREDICTED: Nomascus leucogenys acetylcholinesterase (Cartwright blood group) (AC...
PREDICTED: Nomascus leucogenys acetylcholinesterase (Cartwright blood group) (ACHE), transcript variant X5, mRNA
gi|1743171732|ref|XM_030797216.1|

Nucleotide
acetylcholinesterase isoform X2 [Nomascus leucogenys]
acetylcholinesterase isoform X2 [Nomascus leucogenys]
gi|1743171733|ref|XP_030653076.1|

Protein
superoxide dismutase, Ni [Actinomadura namibiensis]
superoxide dismutase, Ni [Actinomadura namibiensis]
gi|2811603887|ref|WP_376770245.1|

Protein
AAB30728 (0)
MeSH
prion protein [Rattus norvegicus]
prion protein [Rattus norvegicus]
gi|9653968|gb|AAB30728.2||bbm|33747 |146447

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001223664	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 20, 2019)	germline	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

SCV001223664

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 20, 2019)

germline

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

Citations

PubMed

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 Invitae, SCV001223664.5

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

Description

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. 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"). This variant has not been reported in the literature in individuals with KCNJ5-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with methionine at codon 229 of the KCNJ5 protein (p.Ile229Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine.

#	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: Feb 28, 2024

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