NM_000219.4:c.[172A>C;176T>C] AND Long QT syndrome

Clinical significance:Likely pathogenic (Last evaluated: Dec 30, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001244610.1

Allele description [Variation Report for NM_000219.4:c.[172A>C;176T>C]]

NM_000219.6(KCNE1):c.172_177delinsCCCCCT (p.Thr58_Leu59delinsProPro)

Gene:
KCNE1:potassium voltage-gated channel subfamily E regulatory subunit 1 [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
21q22.12
Genomic location:
Preferred name:
NM_000219.6(KCNE1):c.172_177delinsCCCCCT (p.Thr58_Leu59delinsProPro)
HGVS:
  • NC_000021.9:g.34449458_34449463delinsAGGGGG
  • NG_009091.1:g.66853_66858delinsCCCCCT
  • NM_000219.6:c.172_177delinsCCCCCTMANE SELECT
  • NM_001127668.3:c.172_177delinsCCCCCT
  • NM_001127669.4:c.172_177delinsCCCCCT
  • NM_001127670.3:c.172_177delinsCCCCCT
  • NM_001270402.2:c.172_177delinsCCCCCT
  • NM_001270403.2:c.172_177delinsCCCCCT
  • NM_001270404.2:c.172_177delinsCCCCCT
  • NM_001270405.2:c.172_177delinsCCCCCT
  • NP_000210.2:p.Thr58_Leu59delinsProPro
  • NP_001121140.1:p.Thr58_Leu59delinsProPro
  • NP_001121141.1:p.Thr58_Leu59delinsProPro
  • NP_001121142.1:p.Thr58_Leu59delinsProPro
  • NP_001257331.1:p.Thr58_Leu59delinsProPro
  • NP_001257332.1:p.Thr58_Leu59delinsProPro
  • NP_001257333.1:p.Thr58_Leu59delinsProPro
  • NP_001257334.1:p.Thr58_Leu59delinsProPro
  • LRG_290t1:c.172_177delACCCTGinsCCCCCT
  • LRG_290:g.66853_66858delinsCCCCCT
  • NC_000021.8:g.35821756_35821761delinsAGGGGG
  • NM_000219.3:c.172_177delACCCTGinsCCCCCT
  • NM_000219.5:c.172_177delinsCCCCCT
Protein change:
THR59PRO AND LEU60PRO
Links:
OMIM: 176261.0001; dbSNP: rs281865421
NCBI 1000 Genomes Browser:
rs281865421
Molecular consequence:
  • NM_000219.6:c.172_177delinsCCCCCT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127668.3:c.172_177delinsCCCCCT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127669.4:c.172_177delinsCCCCCT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127670.3:c.172_177delinsCCCCCT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270402.2:c.172_177delinsCCCCCT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270403.2:c.172_177delinsCCCCCT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270404.2:c.172_177delinsCCCCCT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270405.2:c.172_177delinsCCCCCT - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Long QT syndrome (LQTS)
Identifiers:
MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976; OMIM: PS192500

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001417840Invitaecriteria provided, single submitter
Likely pathogenic
(Dec 30, 2019)
germlineclinical testing

PubMed (5)
[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

IsK and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome.

Tyson J, Tranebjaerg L, Bellman S, Wren C, Taylor JF, Bathen J, Aslaksen B, Sørland SJ, Lund O, Malcolm S, Pembrey M, Bhattacharya S, Bitner-Glindzicz M.

Hum Mol Genet. 1997 Nov;6(12):2179-85.

PubMed [citation]
PMID:
9328483

Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.

Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT.

Circulation. 2000 Sep 5;102(10):1178-85.

PubMed [citation]
PMID:
10973849
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001417840.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces adjacent threonine and leucine with two proline residues at codons 58 and 59 of the KCNE1 protein (p.Thr58_Leu59delinsProPro). This variant is reported as three separate entries in the ExAC population database (c.172A>C, ExAC 0.003%, c.176T>C, 0.003% and c.177G>T, 0.003%). This variant has been observed in an individual with long QT syndrome (PMID: 10973849), and was shown to segregate with Jervell and Lange-Nielsen syndrome (JLNS) in a family (PMID: 9328483). This variant is also known as T59P/L60P in the literature. ClinVar contains an entry for this variant (Variation ID: 13475). This variant has been reported to affect KCNE1 protein function (PMID: 19907016, 11530100). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Sep 29, 2021

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