NM_000238.4(KCNH2):c.203T>G (p.Phe68Cys) AND Long QT syndrome

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 10, 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:: RCV001209799.8

Allele description

NM_000238.4(KCNH2):c.203T>G (p.Phe68Cys)

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.203T>G (p.Phe68Cys)

HGVS:

NC_000007.14:g.150974815A>C
NG_008916.1:g.8112T>G
NM_000238.4:c.203T>GMANE SELECT
NM_001406755.1:c.26T>G
NM_172056.3:c.203T>G
NP_000229.1:p.Phe68Cys
NP_000229.1:p.Phe68Cys
NP_001393684.1:p.Phe9Cys
NP_742053.1:p.Phe68Cys
NP_742053.1:p.Phe68Cys
LRG_288t1:c.203T>G
LRG_288t2:c.203T>G
LRG_288:g.8112T>G
LRG_288p1:p.Phe68Cys
LRG_288p2:p.Phe68Cys
NC_000007.13:g.150671903A>C
NM_000238.3:c.203T>G
NM_172056.2:c.203T>G
NR_176254.1:n.611T>G

Protein change:

F68C

Links:

dbSNP: rs1801935420

NCBI 1000 Genomes Browser:

rs1801935420

Molecular consequence:

NM_000238.4:c.203T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406755.1:c.26T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172056.3:c.203T>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: Homo sapiens hypocretin receptor 2 (HCRTR2), transcript variant X1, m...
PREDICTED: Homo sapiens hypocretin receptor 2 (HCRTR2), transcript variant X1, mRNA
gi|2462608124|ref|XM_054355266.1|

Nucleotide
Thryssa baelama isolate WJC3430 12S ribosomal RNA gene, partial sequence; mitoch...
Thryssa baelama isolate WJC3430 12S ribosomal RNA gene, partial sequence; mitochondrial
gi|1584454492|gb|MH380831.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001381249	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 10, 2022)	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

SCV001381249

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 10, 2022)

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, SCV001381249.5

#	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"). ClinVar contains an entry for this variant (Variation ID: 940257). This variant has not been reported in the literature in individuals affected with KCNH2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 68 of the KCNH2 protein (p.Phe68Cys).

#	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 20, 2024

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