NM_001267550.2(TTN):c.92683C>T (p.Arg30895Ter) AND Primary dilated cardiomyopathy

Clinical significance:Likely pathogenic (Last evaluated: Oct 8, 2014)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000209537.1

Allele description [Variation Report for NM_001267550.2(TTN):c.92683C>T (p.Arg30895Ter)]

NM_001267550.2(TTN):c.92683C>T (p.Arg30895Ter)

Genes:
TTN-AS1:TTN antisense RNA 1 [Gene - HGNC]
TTN:titin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.92683C>T (p.Arg30895Ter)
HGVS:
  • NC_000002.12:g.178548943G>A
  • NG_011618.3:g.286860C>T
  • NG_051363.1:g.31117G>A
  • NM_001256850.1:c.87760C>T
  • NM_001267550.2:c.92683C>TMANE SELECT
  • NM_003319.4:c.65488C>T
  • NM_133378.4:c.84979C>T
  • NM_133432.3:c.65863C>T
  • NM_133437.4:c.66064C>T
  • NP_001243779.1:p.Arg29254Ter
  • NP_001254479.2:p.Arg30895Ter
  • NP_003310.4:p.Arg21830Ter
  • NP_596869.4:p.Arg28327Ter
  • NP_597676.3:p.Arg21955Ter
  • NP_597681.4:p.Arg22022Ter
  • LRG_391t1:c.92683C>T
  • LRG_391:g.286860C>T
  • NC_000002.11:g.179413670G>A
Protein change:
R21830*
Links:
dbSNP: rs869312065
NCBI 1000 Genomes Browser:
rs869312065
Molecular consequence:
  • NM_001256850.1:c.87760C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001267550.2:c.92683C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_003319.4:c.65488C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_133378.4:c.84979C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_133432.3:c.65863C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_133437.4:c.66064C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000189673Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust - Unselected DCMcriteria provided, single submitter
Likely pathogenic
(Oct 8, 2014)
germlineresearch

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot provided374not providedresearch

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, SCV000189673.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedresearch 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes374not providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2021

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