NM_001267550.2(TTN):c.46773T>A (p.Tyr15591Ter) AND Primary dilated cardiomyopathy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 5, 2013
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:: RCV000040273.5

Allele description [Variation Report for NM_001267550.2(TTN):c.46773T>A (p.Tyr15591Ter)]

NM_001267550.2(TTN):c.46773T>A (p.Tyr15591Ter)

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.46773T>A (p.Tyr15591Ter)

HGVS:

NC_000002.12:g.178618777A>T
NG_011618.3:g.217026T>A
NG_051363.1:g.100951A>T
NM_001256850.1:c.41850T>A
NM_001267550.2:c.46773T>AMANE SELECT
NM_003319.4:c.19578T>A
NM_133378.4:c.39069T>A
NM_133432.3:c.19953T>A
NM_133437.4:c.20154T>A
NP_001243779.1:p.Tyr13950Ter
NP_001254479.2:p.Tyr15591Ter
NP_003310.4:p.Tyr6526Ter
NP_596869.4:p.Tyr13023Ter
NP_597676.3:p.Tyr6651Ter
NP_597681.4:p.Tyr6718Ter
LRG_391:g.217026T>A
NC_000002.11:g.179483504A>T
c.39069T>A
p.Tyr13023X

Protein change:

Y13023*

Links:

dbSNP: rs397517586

NCBI 1000 Genomes Browser:

rs397517586

Molecular consequence:

NM_001256850.1:c.41850T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001267550.2:c.46773T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_003319.4:c.19578T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_133378.4:c.39069T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_133432.3:c.19953T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_133437.4:c.20154T>A - nonsense - [Sequence Ontology: SO:0001587]

Observations:

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
SCV000063964	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely pathogenic (Jul 5, 2013)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000063964

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely pathogenic
(Jul 5, 2013)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	1	1	not provided	not provided	not provided	clinical 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, Mass General Brigham Personalized Medicine, SCV000063964.6

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

Description

The Tyr13023X variant in TTN has been identified by our laboratory in 1 Caucasia n individual with DCM (LMM unpublished data) and was not identified in large pop ulation studies. This nonsense variant leads to a premature termination codon at position 13023, which is predicted to lead to a truncated or absent protein. He terozygous loss of function of the TTN gene is strongly associated with DCM (Her man 2012). In summary, this variant is likely to be pathogenic, though additiona l data is needed to establish this with confidence.

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

Last Updated: Apr 6, 2024

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