NM_133379.5(TTN):c.14460_14470dup (p.Arg4824fs) AND Primary dilated cardiomyopathy

Germline classification:: Uncertain significance (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:: RCV000209797.1

Allele description [Variation Report for NM_133379.5(TTN):c.14460_14470dup (p.Arg4824fs)]

NM_133379.5(TTN):c.14460_14470dup (p.Arg4824fs)

Genes:

LOC126806432:CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:179611985-179613184 [Gene]
TTN:titin [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_133379.5(TTN):c.14460_14470dup (p.Arg4824fs)

HGVS:

NC_000002.12:g.178747931_178747941dup
NG_011618.3:g.87863_87873dup
NM_001256850.1:c.10360+5184_10360+5194dup
NM_001267550.2:c.11311+5184_11311+5194dupMANE SELECT
NM_003319.4:c.10222+5184_10222+5194dup
NM_133378.4:c.10360+5184_10360+5194dup
NM_133379.5:c.14460_14470dup
NM_133432.3:c.10597+5184_10597+5194dup
NM_133437.4:c.10798+5184_10798+5194dup
NP_596870.2:p.Arg4824fs
LRG_391t2:c.14460_14470dup
LRG_391:g.87863_87873dup
NC_000002.11:g.179612658_179612668dup

Protein change:

R4824fs

Links:

dbSNP: rs869312088

NCBI 1000 Genomes Browser:

rs869312088

Molecular consequence:

NM_133379.5:c.14460_14470dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001256850.1:c.10360+5184_10360+5194dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001267550.2:c.11311+5184_11311+5194dup - intron variant - [Sequence Ontology: SO:0001627]
NM_003319.4:c.10222+5184_10222+5194dup - intron variant - [Sequence Ontology: SO:0001627]
NM_133378.4:c.10360+5184_10360+5194dup - intron variant - [Sequence Ontology: SO:0001627]
NM_133432.3:c.10597+5184_10597+5194dup - intron variant - [Sequence Ontology: SO:0001627]
NM_133437.4:c.10798+5184_10798+5194dup - intron variant - [Sequence Ontology: SO:0001627]

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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SAMN02728965 (1)
SRA
Hepacivirus hominis polyprotein, core protein region, (POLY) gene, partial cds.
Hepacivirus hominis polyprotein, core protein region, (POLY) gene, partial cds.
PopSet: 2708441698

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000189714	Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust - Endstage DCM	criteria provided, single submitter (Roberts et al. 2015)	Uncertain significance (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

SCV000189714

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

criteria provided, single submitter

(Roberts et al. 2015)

Uncertain significance
(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	155	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 - Endstage DCM, SCV000189714.1

#	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. It affects only the Novex-3 isoform, which does not span the sarcomere and has not been implicated in DCM. 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	155	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Apr 6, 2024

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