NM_001267550.2(TTN):c.106629del (p.Ala35544fs) AND Primary dilated cardiomyopathy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 8, 2014
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000209272.1

Allele description [Variation Report for NM_001267550.2(TTN):c.106629del (p.Ala35544fs)]

NM_001267550.2(TTN):c.106629del (p.Ala35544fs)

Genes:

TTN-AS1:TTN antisense RNA 1 [Gene - HGNC]
TTN:titin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.106629del (p.Ala35544fs)

HGVS:

NC_000002.12:g.178529126del
NG_011618.3:g.306681del
NG_051363.1:g.11300del
NM_001256850.1:c.101706del
NM_001267550.2:c.106629delMANE SELECT
NM_003319.4:c.79434del
NM_133378.4:c.98925del
NM_133432.3:c.79809del
NM_133437.4:c.80010del
NP_001243779.1:p.Ala33903fs
NP_001254479.2:p.Ala35544fs
NP_003310.4:p.Ala26479fs
NP_596869.4:p.Ala32976fs
NP_597676.3:p.Ala26604fs
NP_597681.4:p.Ala26671fs
LRG_391t1:c.106629delA
LRG_391:g.306681del
NC_000002.11:g.179393853del

Protein change:

A26479fs

Links:

dbSNP: rs869312069

NCBI 1000 Genomes Browser:

rs869312069

Molecular consequence:

NM_001256850.1:c.101706del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001267550.2:c.106629del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003319.4:c.79434del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_133378.4:c.98925del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_133432.3:c.79809del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_133437.4:c.80010del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Primary dilated cardiomyopathy (DCM)
Synonyms:: Dilated Cardiomyopathy
Identifiers:: EFO: EFO_0000407; MONDO: MONDO:0005021; MeSH: D002311; MedGen: C0007193; Human Phenotype Ontology: HP:0001644

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000189678	Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust - Unselected DCM	criteria provided, single submitter (Roberts et al. 2015)	Likely pathogenic (Oct 8, 2014)	germline	research	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000189678

Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust - Unselected DCM

criteria provided, single submitter

(Roberts et al. 2015)

Likely pathogenic
(Oct 8, 2014)

germline

research

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	374	not provided	research

Citations

PubMed

Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease.

Roberts AM, Ware JS, Herman DS, Schafer S, Baksi J, Bick AG, Buchan RJ, Walsh R, John S, Wilkinson S, Mazzarotto F, Felkin LE, Gong S, MacArthur JA, Cunningham F, Flannick J, Gabriel SB, Altshuler DM, Macdonald PS, Heinig M, Keogh AM, Hayward CS, et al.

Sci Transl Med. 2015 Jan 14;7(270):270ra6. doi: 10.1126/scitranslmed.3010134.

PubMed [citation]

PMID:: 25589632
PMCID:: PMC4560092

Details of each submission

From Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust - Unselected DCM, SCV000189678.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	PubMed (1)

Description

This TTN truncating variant (TTNtv) was identified in one individual in this cohort and is located in an exon that is highly expressed in the heart. In the seven cohorts assessed, TTNtv were found in 14% of ambulant DCM, 22% end-stage or familial DCM, and 2% controls. Heterozygous nonsense, frameshift and canonical splice-disrupting variants found in constitutive and other highly utilised exons are highly likely to be pathogenic when identified in individuals with phenotypically confirmed DCM. TTNtv found incidentally in healthy individuals (excluding familial assessment of DCM relatives) are thought to have low penetrance, particularly when identified in exons that are not constitutively expressed in the heart.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	374	not provided	not provided		1	not provided	not provided	not provided

Last Updated: May 16, 2025

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