NM_000238.4(KCNH2):c.652A>G (p.Met218Val) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 13, 2023
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:: RCV003298115.1

Allele description [Variation Report for NM_000238.4(KCNH2):c.652A>G (p.Met218Val)]

NM_000238.4(KCNH2):c.652A>G (p.Met218Val)

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.652A>G (p.Met218Val)

HGVS:

NC_000007.14:g.150958323T>C
NG_008916.1:g.24604A>G
NM_000238.4:c.652A>GMANE SELECT
NM_001406753.1:c.364A>G
NM_001406755.1:c.475A>G
NM_001406756.1:c.364A>G
NM_001406757.1:c.352A>G
NM_172056.3:c.652A>G
NP_000229.1:p.Met218Val
NP_000229.1:p.Met218Val
NP_001393682.1:p.Met122Val
NP_001393684.1:p.Met159Val
NP_001393685.1:p.Met122Val
NP_001393686.1:p.Met118Val
NP_742053.1:p.Met218Val
NP_742053.1:p.Met218Val
LRG_288t1:c.652A>G
LRG_288t2:c.652A>G
LRG_288:g.24604A>G
LRG_288p1:p.Met218Val
LRG_288p2:p.Met218Val
NC_000007.13:g.150655411T>C
NM_000238.2:c.652A>G
NM_000238.3:c.652A>G
NM_172056.2:c.652A>G
NR_176254.1:n.1060A>G
Q12809:p.Met218Val

Protein change:

M118V

Links:

UniProtKB: Q12809#VAR_074799; dbSNP: rs199472869

NCBI 1000 Genomes Browser:

rs199472869

Molecular consequence:

NM_000238.4:c.652A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406753.1:c.364A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406755.1:c.475A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406756.1:c.364A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406757.1:c.352A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172056.3:c.652A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003997356	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Uncertain significance (Jun 13, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19716085, 32893267 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003997356

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Uncertain significance
(Jun 13, 2023)

germline

clinical testing

PubMed (2)
[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

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

Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls.

Walsh R, Lahrouchi N, Tadros R, Kyndt F, Glinge C, Postema PG, Amin AS, Nannenberg EA, Ware JS, Whiffin N, Mazzarotto F, Škorić-Milosavljević D, Krijger C, Arbelo E, Babuty D, Barajas-Martinez H, Beckmann BM, Bézieau S, Bos JM, Breckpot J, Campuzano O, Castelletti S, et al.

Genet Med. 2021 Jan;23(1):47-58. doi: 10.1038/s41436-020-00946-5. Epub 2020 Sep 7.

PubMed [citation]

PMID:: 32893267
PMCID:: PMC7790744

Details of each submission

From Ambry Genetics, SCV003997356.1

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

Description

The p.M218V variant (also known as c.652A>G), located in coding exon 4 of the KCNH2 gene, results from an A to G substitution at nucleotide position 652. The methionine at codon 218 is replaced by valine, an amino acid with highly similar properties. This alteration has been reported in long QT syndrome cohorts; however, clinical details were limited (Kapplinger JD et al. Heart Rhythm, 2009 Sep;6:1297-303; Walsh R et al. Genet Med, 2021 Jan;23:47-58). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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 8, 2024

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