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

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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002273761Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Mar 29, 2022)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 24, 2023