NM_001267550.2(TTN):c.41473C>T (p.Arg13825Ter) AND Dilated cardiomyopathy 1G

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 17, 2023
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:: RCV004786558.1

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005398224	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 17, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25589632, 31983221, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005398224

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jul 17, 2023)

germline

clinical testing

PubMed (3)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

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

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 (3)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV005398224.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0102 - Loss of function is known mechanism of disease in this gene. In addition, dominant-negative is also a suggested mechanism. (PMID: 25589632). (I) 0108 - This gene is associated with both recessive and dominant disease (OMIM). (I) 0112 - The condition associated with this gene has incomplete penetrance. Variants in this gene that result in a premature truncating codon (PTC) are known to have reduced penetrance in DCM (PMID: 25589632). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0600 - Variant is located in the annotated I-band and the exon has a PSI score of 100 (PMID: 25589632). (I) 0703 - Other NMD-predicted variants comparable to the one identified in this case have moderate previous evidence for pathogenicity (ClinVar). (SP) 0803 - This variant has limited previous evidence of pathogenicity in unrelated individuals. It has been reported in at least three individuals with DCM (PMIDs: 25589632, 31983221; ClinVar, personal communication). It has been reported by clinical testing laboratories as likely pathogenic and VUS (ClinVar). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#	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: Apr 12, 2026

ClinVar

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