NM_000238.4(KCNH2):c.2131A>G (p.Ile711Val) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 9, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000181838.11

Allele description [Variation Report for NM_000238.4(KCNH2):c.2131A>G (p.Ile711Val)]

NM_000238.4(KCNH2):c.2131A>G (p.Ile711Val)

Gene:

KCNH2:potassium voltage-gated channel subfamily H member 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q36.1

Genomic location:

Preferred name:

NM_000238.4(KCNH2):c.2131A>G (p.Ile711Val)

Other names:

p.I711V:ATC>GTC

HGVS:

NC_000007.14:g.150950935T>C
NG_008916.1:g.31992A>G
NM_000238.4:c.2131A>GMANE SELECT
NM_001204798.2:c.1111A>G
NM_001406753.1:c.1843A>G
NM_001406755.1:c.1954A>G
NM_001406756.1:c.1843A>G
NM_001406757.1:c.1831A>G
NM_172056.3:c.2131A>G
NM_172057.3:c.1111A>G
NP_000229.1:p.Ile711Val
NP_000229.1:p.Ile711Val
NP_001191727.1:p.Ile371Val
NP_001393682.1:p.Ile615Val
NP_001393684.1:p.Ile652Val
NP_001393685.1:p.Ile615Val
NP_001393686.1:p.Ile611Val
NP_742053.1:p.Ile711Val
NP_742053.1:p.Ile711Val
NP_742054.1:p.Ile371Val
NP_742054.1:p.Ile371Val
LRG_288t1:c.2131A>G
LRG_288t2:c.2131A>G
LRG_288t3:c.1111A>G
LRG_288:g.31992A>G
LRG_288p1:p.Ile711Val
LRG_288p2:p.Ile711Val
LRG_288p3:p.Ile371Val
NC_000007.13:g.150648023T>C
NM_000238.2:c.2131A>G
NM_000238.3:c.2131A>G
NM_172056.2:c.2131A>G
NM_172057.2:c.1111A>G
NR_176254.1:n.2539A>G
NR_176255.1:n.1412A>G
Q12809:p.Ile711Val

Protein change:

I371V

Links:

UniProtKB: Q12809#VAR_074871; dbSNP: rs199473532

NCBI 1000 Genomes Browser:

rs199473532

Molecular consequence:

NM_000238.4:c.2131A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001204798.2:c.1111A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406753.1:c.1843A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406755.1:c.1954A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406756.1:c.1843A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406757.1:c.1831A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172056.3:c.2131A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172057.3:c.1111A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000234141	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (May 9, 2023)	germline	clinical testing	Citation Link,
SCV002502366	AiLife Diagnostics, AiLife Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 18, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19716085, 25637381, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000234141

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(May 9, 2023)

germline

clinical testing

Citation Link,

SCV002502366

AiLife Diagnostics, AiLife Diagnostics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 18, 2021)

germline

clinical testing

PubMed (3)
[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	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.

Kapplinger JD, Tester DJ, Salisbury BA, Carr JL, Harris-Kerr C, Pollevick GD, Wilde AA, Ackerman MJ.

Heart Rhythm. 2009 Sep;6(9):1297-303. doi: 10.1016/j.hrthm.2009.05.021. Epub 2009 Jun 23.

PubMed [citation]

PMID:: 19716085
PMCID:: PMC3049907

Actionable exomic incidental findings in 6503 participants: challenges of variant classification.

Amendola LM, Dorschner MO, Robertson PD, Salama JS, Hart R, Shirts BH, Murray ML, Tokita MJ, Gallego CJ, Kim DS, Bennett JT, Crosslin DR, Ranchalis J, Jones KL, Rosenthal EA, Jarvik ER, Itsara A, Turner EH, Herman DS, Schleit J, Burt A, Jamal SM, et al.

Genome Res. 2015 Mar;25(3):305-15. doi: 10.1101/gr.183483.114. Epub 2015 Jan 30.

PubMed [citation]

PMID:: 25637381
PMCID:: PMC4352885

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000234141.9

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

Description

Has been reported in an individual with LQTS (Kapplinger et al., 2009); Functional studies performed in HEK293 cells transfected with p.(I711V) showed similar expression levels to wild type (Perry et al., 2016); however, Bohnen et al. (2017) suggests that this variant alters channel gating; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25637381, 27807201, 19716085, 26958806)

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

From AiLife Diagnostics, AiLife Diagnostics, SCV002502366.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (3)

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

Last Updated: Nov 3, 2024

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