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NM_000238.4(KCNH2):c.157G>C (p.Gly53Arg)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
3 (Most recent: Oct 23, 2020)
Last evaluated:
Oct 23, 2020
Accession:
VCV000067215.4
Variation ID:
67215
Description:
single nucleotide variant
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NM_000238.4(KCNH2):c.157G>C (p.Gly53Arg)

Allele ID
78111
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
7q36.1
Genomic location
7: 150974861 (GRCh38) GRCh38 UCSC
7: 150671949 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
Q12809:p.Gly53Arg
NC_000007.13:g.150671949C>G
NC_000007.14:g.150974861C>G
... more HGVS
Protein change
G53R
Other names
-
Canonical SPDI
NC_000007.14:150974860:C:G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA004831
UniProtKB: Q12809#VAR_008909
dbSNP: rs199472842
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 Oct 9, 2019 RCV000777695.2
Pathogenic 1 criteria provided, single submitter Oct 23, 2020 RCV001267970.1
not provided 1 no assertion provided - RCV000057924.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
KCNH2 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
2038 2109

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Oct 09, 2019)
criteria provided, single submitter
Method: clinical testing
Arrhythmia
Allele origin: germline
Color Health, Inc
Accession: SCV000913628.2
Submitted: (May 19, 2020)
Comment:
This missense variant replaces glycine with arginine at codon 53 in the cytoplasmic N-terminal PAS domain of the KCNH2 protein. Computational prediction suggests that this … (more)
Evidence details
Pathogenic
(Oct 23, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
(Unknown mechanism)
Allele origin: germline
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446513.1
Submitted: (Oct 23, 2020)
Evidence details
not provided
(-)
no assertion provided
Method: literature only
Congenital long QT syndrome
Allele origin: germline
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust
Accession: SCV000089444.3
Submitted: (Sep 22, 2016)
Evidence details
Publications
PubMed (6)
Comment:
This variant has been reported as associated with Long QT syndrome in the following publications (PMID:10187793;PMID:10973849;PMID:15840476;PMID:21536673;PMID:22396785). This is a literature report, and does not necessarily … (more)

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
Paralogous annotation of disease-causing variants in long QT syndrome genes. Ware JS Human mutation 2012 PMID: 22581653
Changes in channel trafficking and protein stability caused by LQT2 mutations in the PAS domain of the HERG channel. Harley CA PloS one 2012 PMID: 22396785
Rescue of aberrant gating by a genetically encoded PAS (Per-Arnt-Sim) domain in several long QT syndrome mutant human ether-á-go-go-related gene potassium channels. Gianulis EC The Journal of biological chemistry 2011 PMID: 21536673
Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Tester DJ Heart rhythm 2005 PMID: 15840476
Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Splawski I Circulation 2000 PMID: 10973849
Long QT syndrome-associated mutations in the Per-Arnt-Sim (PAS) domain of HERG potassium channels accelerate channel deactivation. Chen J The Journal of biological chemistry 1999 PMID: 10187793

Text-mined citations for rs199472842...

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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 Nov 27, 2021