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NM_000219.4:c.[172A>C;176T>C]

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Interpretation:
Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
3 (Most recent: Sep 2, 2021)
Last evaluated:
Dec 30, 2019
Accession:
VCV000013475.5
Variation ID:
13475
Description:
6bp indel
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NM_000219.6(KCNE1):c.172_177delinsCCCCCT (p.Thr58_Leu59delinsProPro)

Allele ID
28514
Variant type
Indel
Variant length
6 bp
Cytogenetic location
21q22.12
Genomic location
21: 34449458-34449463 (GRCh38) GRCh38 UCSC
21: 35821756-35821761 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_290:g.66853_66858delinsCCCCCT
NC_000021.8:g.35821756_35821761delinsAGGGGG
NC_000021.9:g.34449458_34449463delinsAGGGGG
... more HGVS
Protein change
-
Other names
-
Canonical SPDI
NC_000021.9:34449457:CAGGGT:AGGGGG
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA085426
OMIM: 176261.0001
dbSNP: rs281865421
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 1 criteria provided, single submitter Dec 30, 2019 RCV001244610.1
Likely pathogenic 1 criteria provided, single submitter Dec 23, 2019 RCV001588813.3
Pathogenic 1 no assertion criteria provided Nov 1, 1997 RCV000014417.25
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
KCNE1 - - GRCh38
GRCh37
254 329

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Dec 30, 2019)
criteria provided, single submitter
Method: clinical testing
Long QT syndrome
Allele origin: germline
Invitae
Accession: SCV001417840.1
Submitted: (Feb 06, 2020)
Evidence details
Publications
PubMed (4)
Comment:
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 … (more)
Likely pathogenic
(Dec 23, 2019)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001822422.1
Submitted: (Sep 02, 2021)
Evidence details
Comment:
Published functional studies demonstrate that the T58P/L59P variant severely weakens the interaction of KCNE1 with KCNQ1 and leads to an inability to modulate channel gating … (more)
Pathogenic
(Nov 01, 1997)
no assertion criteria provided
Method: literature only
JERVELL AND LANGE-NIELSEN SYNDROME 2
Allele origin: germline
OMIM
Accession: SCV000034666.1
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Mechanisms of disease pathogenesis in long QT syndrome type 5. Harmer SC American journal of physiology. Cell physiology 2010 PMID: 19907016
A spectrum of functional effects for disease causing mutations in the Jervell and Lange-Nielsen syndrome. Huang L Cardiovascular research 2001 PMID: 11530100
Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Splawski I Circulation 2000 PMID: 10973849
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 Human molecular genetics 1997 PMID: 9328483

Text-mined citations for rs281865421...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 29, 2021