NM_001267550.2(TTN):c.41473C>T (p.Arg13825Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 31, 2025
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:: RCV000552893.7

Allele description [Variation Report for NM_001267550.2(TTN):c.41473C>T (p.Arg13825Ter)]

NM_001267550.2(TTN):c.41473C>T (p.Arg13825Ter)

Gene:

TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.41473C>T (p.Arg13825Ter)

HGVS:

NC_000002.12:g.178636098G>A
NG_011618.3:g.199705C>T
NM_001256850.1:c.36550C>T
NM_001267550.2:c.41473C>TMANE SELECT
NM_003319.4:c.14278C>T
NM_133378.4:c.33769C>T
NM_133432.3:c.14653C>T
NM_133437.4:c.14854C>T
NP_001243779.1:p.Arg12184Ter
NP_001254479.2:p.Arg13825Ter
NP_003310.4:p.Arg4760Ter
NP_596869.4:p.Arg11257Ter
NP_597676.3:p.Arg4885Ter
NP_597681.4:p.Arg4952Ter
LRG_391t1:c.41473C>T
LRG_391:g.199705C>T
NC_000002.11:g.179500825G>A
NM_001267550.1:c.41473C>T
NM_003319.4:c.14278C>T

Protein change:

R11257*

Links:

dbSNP: rs869312043

Molecular consequence:

NM_001256850.1:c.36550C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001267550.2:c.41473C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_003319.4:c.14278C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_133378.4:c.33769C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_133432.3:c.14653C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_133437.4:c.14854C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Dilated cardiomyopathy 1G (CMD1G)
Identifiers:: MONDO: MONDO:0011400; MedGen: C1858763; Orphanet: 154; OMIM: 604145

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2J (LGMDR10)
Synonyms:: Limb-girdle muscular dystrophy, type 2J; MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 10
Identifiers:: MONDO: MONDO:0012127; MedGen: C1837342; Orphanet: 140922; OMIM: 608807

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000643141	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 31, 2025)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 31251381, 31983221, 25589632, 23975875, 27869827, 32964742, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000643141

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 31, 2025)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Association of Titin-Truncating Genetic Variants With Life-threatening Cardiac Arrhythmias in Patients With Dilated Cardiomyopathy and Implanted Defibrillators.

Corden B, Jarman J, Whiffin N, Tayal U, Buchan R, Sehmi J, Harper A, Midwinter W, Lascelles K, Markides V, Mason M, Baksi J, Pantazis A, Pennell DJ, Barton PJ, Prasad SK, Wong T, Cook SA, Ware JS.

JAMA Netw Open. 2019 Jun 5;2(6):e196520. doi: 10.1001/jamanetworkopen.2019.6520.

PubMed [citation]

PMID:: 31251381
PMCID:: PMC6604081

Reevaluating the Genetic Contribution of Monogenic Dilated Cardiomyopathy.

Mazzarotto F, Tayal U, Buchan RJ, Midwinter W, Wilk A, Whiffin N, Govind R, Mazaika E, de Marvao A, Dawes TJW, Felkin LE, Ahmad M, Theotokis PI, Edwards E, Ing AY, Thomson KL, Chan LLH, Sim D, Baksi AJ, Pantazis A, Roberts AM, Watkins H, et al.

Circulation. 2020 Feb 4;141(5):387-398. doi: 10.1161/CIRCULATIONAHA.119.037661. Epub 2020 Jan 27.

PubMed [citation]

PMID:: 31983221
PMCID:: PMC7004454

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000643141.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change creates a premature translational stop signal (p.Arg13825*) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with clinical features of dilated cardiomyopathy (PMID: 25589632, 31251381, 31983221; internal data). ClinVar contains an entry for this variant (Variation ID: 223274). This variant is located in the I band of TTN (PMID: 25589632). Truncating variants in this region have been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875, internal data). Truncating variants in this region have also been identified in individuals affected with autosomal dominant dilated cardiomyopathy and/or cardio-related conditions (PMID: 27869827, 32964742, internal data). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Apr 12, 2026

ClinVar

Relating variation to medicine