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NM_000238.4(KCNH2):c.3365dup (p.Ala1124fs)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(1);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
2 (Most recent: Aug 3, 2021)
Last evaluated:
May 21, 2021
Accession:
VCV000945617.4
Variation ID:
945617
Description:
1bp duplication
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NM_000238.4(KCNH2):c.3365dup (p.Ala1124fs)

Allele ID
924750
Variant type
Duplication
Variant length
1 bp
Cytogenetic location
7q36.1
Genomic location
7: 150945479-150945480 (GRCh38) GRCh38 UCSC
7: 150642567-150642568 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000007.13:g.150642572dup
NC_000007.14:g.150945484dup
NG_008916.1:g.37447dup
... more HGVS
Protein change
A1124fs, A784fs
Other names
-
Canonical SPDI
NC_000007.14:150945479:GGGGG:GGGGGG
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
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 Jun 10, 2019 RCV001216294.2
Uncertain significance 1 criteria provided, single submitter May 21, 2021 RCV001544857.2
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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
2026 2097

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Jun 10, 2019)
criteria provided, single submitter
Method: clinical testing
Long QT syndrome
Allele origin: germline
Invitae
Accession: SCV001388084.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (1)
Comment:
This sequence change results in a premature translational stop signal in the KCNH2 gene (p.Ala1124Glyfs*146). While this is not anticipated to result in nonsense mediated … (more)
Uncertain significance
(May 21, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001764072.1
Submitted: (Aug 03, 2021)
Evidence details
Comment:
Not observed in large population cohorts (Lek et al., 2016); Frameshift variant predicted to result in protein truncation as the last 36 amino acids are … (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
Novel C-terminus frameshift mutation, 1122fs/147, of HERG in LQT2: additional amino acids generated by frameshift cause accelerated inactivation. Sasano T Journal of molecular and cellular cardiology 2004 PMID: 15572050

Record last updated Sep 23, 2021