NM_000219.6(KCNE1):c.199C>G (p.Arg67Gly) AND Long QT syndrome

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 9, 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:: RCV000798265.4

Allele description

NM_000219.6(KCNE1):c.199C>G (p.Arg67Gly)

Gene:

KCNE1:potassium voltage-gated channel subfamily E regulatory subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

21q22.12

Genomic location:

Preferred name:

NM_000219.6(KCNE1):c.199C>G (p.Arg67Gly)

HGVS:

NC_000021.9:g.34449436G>C
NG_009091.1:g.66880C>G
NM_000219.6:c.199C>GMANE SELECT
NM_001127668.4:c.199C>G
NM_001127669.4:c.199C>G
NM_001127670.4:c.199C>G
NM_001270402.3:c.199C>G
NM_001270403.2:c.199C>G
NM_001270404.3:c.199C>G
NM_001270405.3:c.199C>G
NP_000210.2:p.Arg67Gly
NP_001121140.1:p.Arg67Gly
NP_001121141.1:p.Arg67Gly
NP_001121142.1:p.Arg67Gly
NP_001257331.1:p.Arg67Gly
NP_001257332.1:p.Arg67Gly
NP_001257333.1:p.Arg67Gly
NP_001257334.1:p.Arg67Gly
LRG_290:g.66880C>G
NC_000021.8:g.35821734G>C
NM_000219.5:c.199C>G

Protein change:

R67G

Links:

dbSNP: rs199473645

NCBI 1000 Genomes Browser:

rs199473645

Molecular consequence:

NM_000219.6:c.199C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127668.4:c.199C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127669.4:c.199C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127670.4:c.199C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001270402.3:c.199C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001270403.2:c.199C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001270404.3:c.199C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001270405.3:c.199C>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
SCV000937871	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 9, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 21576493, 30020974, 31941373, 32058015, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000937871

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 9, 2022)

germline

clinical testing

PubMed (5)
[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

KCNE1 enhances phosphatidylinositol 4,5-bisphosphate (PIP2) sensitivity of IKs to modulate channel activity.

Li Y, Zaydman MA, Wu D, Shi J, Guan M, Virgin-Downey B, Cui J.

Proc Natl Acad Sci U S A. 2011 May 31;108(22):9095-100. doi: 10.1073/pnas.1100872108. Epub 2011 May 16.

PubMed [citation]

PMID:: 21576493
PMCID:: PMC3107281

Role of genetic and electrolyte abnormalities in prolonged QTc interval and sudden cardiac death in end-stage renal disease patients.

Coll M, Ferrer-Costa C, Pich S, Allegue C, Rodrigo E, Fernández-Fresnedo G, Barreda P, Mates J, Martinez de Francisco AL, Ortega I, Iglesias A, Campuzano O, Salas E, Arias M, Brugada R.

PLoS One. 2018;13(7):e0200756. doi: 10.1371/journal.pone.0200756.

PubMed [citation]

PMID:: 30020974
PMCID:: PMC6051653

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000937871.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

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. This variant disrupts the p.Arg67 amino acid residue in KCNE1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21576493, 30020974, 31941373, 32058015; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 644369). This variant has not been reported in the literature in individuals affected with KCNE1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 67 of the KCNE1 protein (p.Arg67Gly).

#	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: Aug 18, 2024

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