U.S. flag

An official website of the United States government

NM_001267550.2(TTN):c.35794G>T (p.Glu11932Ter) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 4, 2024
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:
RCV000231913.7

Allele description [Variation Report for NM_001267550.2(TTN):c.35794G>T (p.Glu11932Ter)]

NM_001267550.2(TTN):c.35794G>T (p.Glu11932Ter)

Gene:
TTN:titin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.35794G>T (p.Glu11932Ter)
HGVS:
  • NC_000002.12:g.178667239C>A
  • NG_011618.3:g.168564G>T
  • NM_001256850.1:c.34264+2979G>T
  • NM_001267550.2:c.35794G>TMANE SELECT
  • NM_003319.4:c.13283-24922G>T
  • NM_133378.4:c.31483+2979G>T
  • NM_133432.3:c.13658-24922G>T
  • NM_133437.4:c.13859-24922G>T
  • NP_001254479.2:p.Glu11932Ter
  • LRG_391:g.168564G>T
  • NC_000002.11:g.179531966C>A
  • NM_001267550.1:c.35794G>T
Protein change:
E11932*
Links:
dbSNP: rs878854299
NCBI 1000 Genomes Browser:
rs878854299
Molecular consequence:
  • NM_003319.4:c.13283-24922G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133378.4:c.31483+2979G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133432.3:c.13658-24922G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133437.4:c.13859-24922G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001267550.2:c.35794G>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

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000286600Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 4, 2024) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Congenital Titinopathy: Comprehensive characterization and pathogenic insights.

Oates EC, Jones KJ, Donkervoort S, Charlton A, Brammah S, Smith JE 3rd, Ware JS, Yau KS, Swanson LC, Whiffin N, Peduto AJ, Bournazos A, Waddell LB, Farrar MA, Sampaio HA, Teoh HL, Lamont PJ, Mowat D, Fitzsimons RB, Corbett AJ, Ryan MM, O'Grady GL, et al.

Ann Neurol. 2018 Jun;83(6):1105-1124. doi: 10.1002/ana.25241.

PubMed [citation]
PMID:
29691892
PMCID:
PMC6105519

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
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000286600.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Glu11932*) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with clinical features of autosomal recessive centronuclear myopathy (PMID: 29691892). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant has been reported in individual(s) with autosomal dominant non-ischemic cardiomyopathy (internal data); however, the role of the variant in this condition is currently unclear. ClinVar contains an entry for this variant (Variation ID: 238750). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 22, 2025