NM_000238.4(KCNH2):c.2669C>G (p.Ser890Cys) AND Long QT syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 29, 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:: RCV003102092.3

Allele description [Variation Report for NM_000238.4(KCNH2):c.2669C>G (p.Ser890Cys)]

NM_000238.4(KCNH2):c.2669C>G (p.Ser890Cys)

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.2669C>G (p.Ser890Cys)

HGVS:

NC_000007.14:g.150948467G>C
NG_008916.1:g.34460C>G
NM_000238.4:c.2669C>GMANE SELECT
NM_001406753.1:c.2381C>G
NM_172057.3:c.1649C>G
NP_000229.1:p.Ser890Cys
NP_000229.1:p.Ser890Cys
NP_001393682.1:p.Ser794Cys
NP_742054.1:p.Ser550Cys
NP_742054.1:p.Ser550Cys
LRG_288t1:c.2669C>G
LRG_288t3:c.1649C>G
LRG_288:g.34460C>G
LRG_288p1:p.Ser890Cys
LRG_288p3:p.Ser550Cys
NC_000007.13:g.150645555G>C
NM_000238.3:c.2669C>G
NM_172057.2:c.1649C>G
NR_176254.1:n.3077C>G
NR_176255.1:n.1950C>G

Protein change:

S550C

Molecular consequence:

NM_000238.4:c.2669C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406753.1:c.2381C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172057.3:c.1649C>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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mitochondrial carnitine/acylcarnitine carrier protein [Eptesicus fuscus]
mitochondrial carnitine/acylcarnitine carrier protein [Eptesicus fuscus]
gi|2472391887|ref|XP_008154062.2|

Protein
PDZ domain-containing protein [Streptomyces angustmyceticus]
PDZ domain-containing protein [Streptomyces angustmyceticus]
gi|2094044594|gnl|PRJNA759542|K7396 0|gb|UAL68958.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003440231	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 29, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24667783, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003440231

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 29, 2022)

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

Genetic analysis, in silico prediction, and family segregation in long QT syndrome.

Riuró H, Campuzano O, Berne P, Arbelo E, Iglesias A, Pérez-Serra A, Coll-Vidal M, Partemi S, Mademont-Soler I, Picó F, Allegue C, Oliva A, Gerstenfeld E, Sarquella-Brugada G, Castro-Urda V, Fernández-Lozano I, Mont L, Brugada J, Scornik FS, Brugada R.

Eur J Hum Genet. 2015 Jan;23(1):79-85. doi: 10.1038/ejhg.2014.54. Epub 2014 Mar 26.

PubMed [citation]

PMID:: 24667783
PMCID:: PMC4266740

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, SCV003440231.2

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

Description

This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 890 of the KCNH2 protein (p.Ser890Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with KCNH2-related conditions (PMID: 24667783). 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. 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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