NM_000238.4(KCNH2):c.724C>G (p.Arg242Gly) AND Long QT syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 17, 2020
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:: RCV001854210.5

Allele description [Variation Report for NM_000238.4(KCNH2):c.724C>G (p.Arg242Gly)]

NM_000238.4(KCNH2):c.724C>G (p.Arg242Gly)

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.724C>G (p.Arg242Gly)

HGVS:

NC_000007.14:g.150958251G>C
NG_008916.1:g.24676C>G
NM_000238.4:c.724C>GMANE SELECT
NM_001406753.1:c.436C>G
NM_001406755.1:c.547C>G
NM_001406756.1:c.436C>G
NM_001406757.1:c.424C>G
NM_172056.3:c.724C>G
NP_000229.1:p.Arg242Gly
NP_000229.1:p.Arg242Gly
NP_001393682.1:p.Arg146Gly
NP_001393684.1:p.Arg183Gly
NP_001393685.1:p.Arg146Gly
NP_001393686.1:p.Arg142Gly
NP_742053.1:p.Arg242Gly
NP_742053.1:p.Arg242Gly
LRG_288t1:c.724C>G
LRG_288t2:c.724C>G
LRG_288:g.24676C>G
LRG_288p1:p.Arg242Gly
LRG_288p2:p.Arg242Gly
NC_000007.13:g.150655339G>C
NM_000238.3:c.724C>G
NM_172056.2:c.724C>G
NR_176254.1:n.1132C>G
Q12809:p.Arg242Gly

Protein change:

R142G

Links:

UniProtKB: Q12809#VAR_074800; dbSNP: rs199472872

NCBI 1000 Genomes Browser:

rs199472872

Molecular consequence:

NM_000238.4:c.724C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406753.1:c.436C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406755.1:c.547C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406756.1:c.436C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406757.1:c.424C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172056.3:c.724C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002241207	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 17, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19716085, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002241207

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 17, 2020)

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

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

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, SCV002241207.3

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

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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with long QT syndrome (PMID: 19716085). ClinVar contains an entry for this variant (Variation ID: 67521). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces arginine with glycine at codon 242 of the KCNH2 protein (p.Arg242Gly). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and glycine.

#	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: Sep 29, 2024

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