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NM_001267550.2(TTN):c.40963G>T (p.Glu13655Ter)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(2);Uncertain significance(2)

Review status:
criteria provided, conflicting interpretations
Submissions:
4 (Most recent: Jan 7, 2021)
Last evaluated:
Apr 30, 2020
Accession:
VCV000167788.7
Variation ID:
167788
Description:
single nucleotide variant
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NM_001267550.2(TTN):c.40963G>T (p.Glu13655Ter)

Allele ID
177075
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2q31.2
Genomic location
2: 178636764 (GRCh38) GRCh38 UCSC
2: 179501491 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000002.11:g.179501491C>A
NC_000002.12:g.178636764C>A
NM_001267550.2:c.40963G>T MANE Select NP_001254479.2:p.Glu13655Ter nonsense
... more HGVS
Protein change
E11087*, E13655*, E4590*, E12014*, E4715*, E4782*
Other names
-
Canonical SPDI
NC_000002.12:178636763:C:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00003
Links
ClinGen: CA235126
dbSNP: rs727504198
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Apr 30, 2020 RCV000560235.5
Likely pathogenic 1 criteria provided, single submitter Sep 13, 2019 RCV000618763.1
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Mar 30, 2018 RCV000760496.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
TTN - - GRCh38
GRCh37
7416 17422

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Mar 30, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000890386.1
Submitted: (Mar 13, 2019)
Evidence details
Comment:
The E12014X likely pathogenic variant in the TTN gene has not been published as pathogenic or benign to our knowledge. This variant has not been … (more)
Uncertain significance
(Dec 22, 2015)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000226712.5
Submitted: (Jun 30, 2017)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Likely pathogenic
(Sep 13, 2019)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000737324.3
Submitted: (Nov 30, 2020)
Evidence details
Comment:
The p.E4590* variant (also known as c.13768G>T), located in coding exon 52 of the TTN gene, results from a G to T substitution at nucleotide … (more)
Uncertain significance
(Apr 30, 2020)
criteria provided, single submitter
Method: clinical testing
Dilated cardiomyopathy 1G
Limb-girdle muscular dystrophy, type 2J
Allele origin: germline
Invitae
Accession: SCV000643133.5
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change results in a premature translational stop signal in the TTN gene (p.Glu13655*). While this is not anticipated to result in nonsense mediated … (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
Prevalence of Titin Truncating Variants in General Population. Akinrinade O PloS one 2015 PMID: 26701604
Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease. Roberts AM Science translational medicine 2015 PMID: 25589632
Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy. Ceyhan-Birsoy O Neurology 2013 PMID: 23975875
Truncations of titin causing dilated cardiomyopathy. Herman DS The New England journal of medicine 2012 PMID: 22335739
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=TTN - - - -

Text-mined citations for rs727504198...

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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 Apr 08, 2021