NM_001267550.2(TTN):c.75250C>T (p.Arg25084Ter) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jul 28, 2017
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000184262.12

Allele description [Variation Report for NM_001267550.2(TTN):c.75250C>T (p.Arg25084Ter)]

NM_001267550.2(TTN):c.75250C>T (p.Arg25084Ter)

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.75250C>T (p.Arg25084Ter)

Other names:

p.R23443*:CGA>TGA

HGVS:

NC_000002.12:g.178570882G>A
NG_011618.3:g.264921C>T
NG_051363.1:g.53056G>A
NM_001256850.1:c.70327C>T
NM_001267550.2:c.75250C>TMANE SELECT
NM_003319.4:c.48055C>T
NM_133378.4:c.67546C>T
NM_133432.3:c.48430C>T
NM_133437.4:c.48631C>T
NP_001243779.1:p.Arg23443Ter
NP_001254479.1:p.Arg25084Ter
NP_001254479.2:p.Arg25084Ter
NP_003310.4:p.Arg16019Ter
NP_596869.4:p.Arg22516Ter
NP_597676.3:p.Arg16144Ter
NP_597681.4:p.Arg16211Ter
LRG_391t1:c.75250C>T
LRG_391:g.264921C>T
LRG_391p1:p.Arg25084Ter
NC_000002.11:g.179435609G>A
NM_001267550.1:c.75250C>T
NM_001267550.2:c.75250C>T
NM_003319.4:c.48055C>T
NM_133379.3:c.*174703C>T

Protein change:

R16019*

Links:

dbSNP: rs794729286

NCBI 1000 Genomes Browser:

rs794729286

Molecular consequence:

NM_001256850.1:c.70327C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001267550.2:c.75250C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_003319.4:c.48055C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_133378.4:c.67546C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_133432.3:c.48430C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_133437.4:c.48631C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000236884	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Mar 27, 2013)	germline	clinical testing	Citation Link,
SCV000927360	Blueprint Genetics	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme)	Likely pathogenic (Jul 28, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000236884

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Mar 27, 2013)

germline

clinical testing

Citation Link,

SCV000927360

Blueprint Genetics

criteria provided, single submitter

(Blueprint Genetics Variant Classification Scheme)

Likely pathogenic
(Jul 28, 2017)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000236884.10

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

Description

p.Arg23443Stop (CGA>TGA): c.70327 C>T in exon 276 of the TTN gene (NM_001256850.1). The Arg23443Stop mutation in the TTN gene has not been reported previously as a disease-causing mutation or as a benign polymorphism to our knowledge. Arg23443Stop is predicted to cause loss of normal protein function either due to production of an abnormal, prematurely truncated protein, or by absence of protein product due to nonsense mediated mRNA decay. Other truncating TTN variants have been reported in approximately 3% of control alleles (Herman D et al., 2012). However, Arg23443Stop is located in the A-band region of titin, where the majority of truncating mutations associated with DCM have been reported (Herman D et al., 2012). In summary, Arg23443Stop in the TTN gene is interpreted as a disease-causing mutation. The variant is found in DCM panel(s).

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

From Blueprint Genetics, SCV000927360.1

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

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

Last Updated: Mar 22, 2025

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