NM_000219.6(KCNE1):c.199C>A (p.Arg67Ser) AND Long QT syndrome

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 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:: RCV001859381.2

Allele description

NM_000219.6(KCNE1):c.199C>A (p.Arg67Ser)

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>A (p.Arg67Ser)

HGVS:

NC_000021.9:g.34449436G>T
NG_009091.1:g.66880C>A
NM_000219.6:c.199C>AMANE SELECT
NM_001127668.4:c.199C>A
NM_001127669.4:c.199C>A
NM_001127670.4:c.199C>A
NM_001270402.3:c.199C>A
NM_001270403.2:c.199C>A
NM_001270404.3:c.199C>A
NM_001270405.3:c.199C>A
NP_000210.2:p.Arg67Ser
NP_001121140.1:p.Arg67Ser
NP_001121141.1:p.Arg67Ser
NP_001121142.1:p.Arg67Ser
NP_001257331.1:p.Arg67Ser
NP_001257332.1:p.Arg67Ser
NP_001257333.1:p.Arg67Ser
NP_001257334.1:p.Arg67Ser
LRG_290t1:c.199C>A
LRG_290:g.66880C>A
NC_000021.8:g.35821734G>T
NM_000219.3:c.199C>A

Protein change:

R67S

Links:

dbSNP: rs199473645

NCBI 1000 Genomes Browser:

rs199473645

Molecular consequence:

NM_000219.6:c.199C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127668.4:c.199C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127669.4:c.199C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127670.4:c.199C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270402.3:c.199C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270403.2:c.199C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270404.3:c.199C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270405.3:c.199C>A - 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
SCV002273761	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 29, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31941373, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002273761

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 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

An International Multicenter Evaluation of Type 5 Long QT Syndrome: A Low Penetrant Primary Arrhythmic Condition.

Roberts JD, Asaki SY, Mazzanti A, Bos JM, Tuleta I, Muir AR, Crotti L, Krahn AD, Kutyifa V, Shoemaker MB, Johnsrude CL, Aiba T, Marcondes L, Baban A, Udupa S, Dechert B, Fischbach P, Knight LM, Vittinghoff E, Kukavica D, Stallmeyer B, Giudicessi JR, et al.

Circulation. 2020 Feb 11;141(6):429-439. doi: 10.1161/CIRCULATIONAHA.119.043114. Epub 2020 Jan 16.

PubMed [citation]

PMID:: 31941373
PMCID:: PMC7035205

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, SCV002273761.2

#	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 arginine, which is basic and polar, with serine, which is neutral and polar, at codon 67 of the KCNE1 protein (p.Arg67Ser). This variant is present in population databases (rs199473645, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with KCNE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1193618). 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. This variant disrupts the p.Arg67 amino acid residue in KCNE1. Other variant(s) that disrupt this residue have been observed in individuals with KCNE1-related conditions (PMID: 31941373), which suggests that this may be a clinically significant amino acid residue. 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: Dec 24, 2023

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