NM_001267550.2(TTN):c.3034C>T (p.Arg1012Ter) AND Primary dilated cardiomyopathy

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 7, 2015
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:
RCV000040169.3

Allele description

NM_001267550.2(TTN):c.3034C>T (p.Arg1012Ter)

Gene:
TTN:titin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.3034C>T (p.Arg1012Ter)
HGVS:
  • NC_000002.12:g.178782872G>A
  • NG_011618.3:g.52931C>T
  • NM_001256850.1:c.3034C>T
  • NM_001267550.2:c.3034C>TMANE SELECT
  • NM_003319.4:c.2896C>T
  • NM_133378.4:c.3034C>T
  • NM_133379.5:c.3034C>T
  • NM_133432.3:c.2896C>T
  • NM_133437.4:c.2896C>T
  • NP_001243779.1:p.Arg1012Ter
  • NP_001254479.2:p.Arg1012Ter
  • NP_003310.4:p.Arg966Ter
  • NP_596869.4:p.Arg1012Ter
  • NP_596870.2:p.Arg1012Ter
  • NP_597676.3:p.Arg966Ter
  • NP_597681.4:p.Arg966Ter
  • LRG_391:g.52931C>T
  • NC_000002.11:g.179647599G>A
  • c.3034C>T
  • p.Arg1012X
Protein change:
R1012*
Links:
dbSNP: rs397517547
NCBI 1000 Genomes Browser:
rs397517547
Molecular consequence:
  • NM_001256850.1:c.3034C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001267550.2:c.3034C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_003319.4:c.2896C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_133378.4:c.3034C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_133379.5:c.3034C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_133432.3:c.2896C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_133437.4:c.2896C>T - nonsense - [Sequence Ontology: SO:0001587]
Observations:
1

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000063860Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Likely pathogenic
(May 7, 2015) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided31not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000063860.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (1)

Description

The p.Arg1012X variant in TTN has not been previously reported in individuals wi th cardiomyopathy or in large population studies. This nonsense variant leads to a premature termination codon at position 1012, which is predicted to lead to a truncated or absent protein. Nonsense and other truncating variants in TTN are strongly associated with DCM if they are located in the exons encoding for the A -band (Herman 2012, Pugh 2014) and/or are located in an exon that is highly expr essed in the heart (Roberts 2015). The p.Arg1012X variant is located in the high ly expressed exon 18 in the near Z-disk band. In summary, although additional st udies are required to fully establish its clinical significance, the p.Arg1012X variant is likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided3not provided1not provided

Last Updated: Apr 8, 2022