NM_000238.4(KCNH2):c.346A>C (p.Lys116Gln) AND Long QT syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 10, 2021
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:: RCV002899900.3

Allele description [Variation Report for NM_000238.4(KCNH2):c.346A>C (p.Lys116Gln)]

NM_000238.4(KCNH2):c.346A>C (p.Lys116Gln)

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.346A>C (p.Lys116Gln)

HGVS:

NC_000007.14:g.150959698T>G
NG_008916.1:g.23229A>C
NM_000238.4:c.346A>CMANE SELECT
NM_001406753.1:c.58A>C
NM_001406755.1:c.169A>C
NM_001406756.1:c.58A>C
NM_001406757.1:c.46A>C
NM_172056.3:c.346A>C
NP_000229.1:p.Lys116Gln
NP_000229.1:p.Lys116Gln
NP_001393682.1:p.Lys20Gln
NP_001393684.1:p.Lys57Gln
NP_001393685.1:p.Lys20Gln
NP_001393686.1:p.Lys16Gln
NP_742053.1:p.Lys116Gln
NP_742053.1:p.Lys116Gln
LRG_288t1:c.346A>C
LRG_288t2:c.346A>C
LRG_288:g.23229A>C
LRG_288p1:p.Lys116Gln
LRG_288p2:p.Lys116Gln
NC_000007.13:g.150656786T>G
NM_000238.3:c.346A>C
NM_172056.2:c.346A>C
NR_176254.1:n.754A>C

Protein change:

K116Q

Molecular consequence:

NM_000238.4:c.346A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406753.1:c.58A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406755.1:c.169A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406756.1:c.58A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406757.1:c.46A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_172056.3:c.346A>C - 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
SCV003245329	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 10, 2021)	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

SCV003245329

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 10, 2021)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003245329.2

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

Description

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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with KCNH2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 116 of the KCNH2 protein (p.Lys116Gln). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.

#	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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