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NM_001267550.2(TTN):c.12405del (p.Asn4135fs)

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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:
Oct 15, 2020
Accession:
VCV000166237.5
Variation ID:
166237
Description:
1bp deletion
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NM_001267550.2(TTN):c.12405del (p.Asn4135fs)

Allele ID
173403
Variant type
Deletion
Variant length
1 bp
Cytogenetic location
2q31.2
Genomic location
2: 178740828 (GRCh38) GRCh38 UCSC
2: 179605555 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000002.11:g.179605555del
NC_000002.12:g.178740828del
NM_001267550.2:c.12405del MANE Select NP_001254479.2:p.Asn4135fs frameshift
... more HGVS
Protein change
N3772fs, N3818fs, N3897fs, N3964fs, N4135fs
Other names
-
Canonical SPDI
NC_000002.12:178740827:A:
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA273279
dbSNP: rs727503658
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 Apr 17, 2013 RCV000152420.2
Uncertain significance 1 criteria provided, single submitter Oct 9, 2014 RCV000184415.1
Likely pathogenic 1 criteria provided, single submitter Feb 2, 2017 RCV000618476.1
Uncertain significance 1 criteria provided, single submitter Oct 15, 2020 RCV001299176.1
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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
Uncertain significance
(Oct 09, 2014)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
GeneDx
Accession: SCV000237040.2
Submitted: (Jun 04, 2015)
Evidence details
Comment:
c.11454delT: p.Asn3818LysfsX33 (N3818KfsX33) in exon 46 of the TTN gene (NM_001256850.1). The normal sequence with the base that is deleted in braces is: TCAA{T}GGCA. A … (more)
Likely pathogenic
(Apr 17, 2013)
criteria provided, single submitter
Method: clinical testing
Primary dilated cardiomyopathy
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000201459.5
Submitted: (Mar 21, 2019)
Evidence details
Comment:
The Asn3897fs variant in TTN has been identified by our laboratory in 1 Caucasia n individual with DCM (LMM unpublished data). Data from large population … (more)
Likely pathogenic
(Feb 02, 2017)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000736757.3
Submitted: (Nov 30, 2020)
Evidence details
Comment:
The c.11316delT variant, located in coding exon 44 of the TTN gene, results from a deletion of one nucleotide at nucleotide position 11316, causing a … (more)
Uncertain significance
(Oct 15, 2020)
criteria provided, single submitter
Method: clinical testing
Dilated cardiomyopathy 1G
Limb-girdle muscular dystrophy, type 2J
Allele origin: germline
Invitae
Accession: SCV001488255.1
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.Asn4135Lysfs*33). 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

Text-mined citations for rs727503658...

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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 Jul 29, 2021