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NM_001267550.2(TTN):c.70162C>T (p.Arg23388Ter) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 11, 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:
RCV000554185.7

Allele description [Variation Report for NM_001267550.2(TTN):c.70162C>T (p.Arg23388Ter)]

NM_001267550.2(TTN):c.70162C>T (p.Arg23388Ter)

Genes:
LOC126806422:BRD4-independent group 4 enhancer GRCh37_chr2:179440205-179441404 [Gene]
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.70162C>T (p.Arg23388Ter)
Other names:
p.R21747*:CGA>TGA
HGVS:
  • NC_000002.12:g.178575970G>A
  • NG_011618.3:g.259833C>T
  • NG_051363.1:g.58144G>A
  • NM_001256850.1:c.65239C>T
  • NM_001267550.2:c.70162C>TMANE SELECT
  • NM_003319.4:c.42967C>T
  • NM_133378.4:c.62458C>T
  • NM_133432.3:c.43342C>T
  • NM_133437.4:c.43543C>T
  • NP_001243779.1:p.Arg21747Ter
  • NP_001254479.2:p.Arg23388Ter
  • NP_003310.4:p.Arg14323Ter
  • NP_596869.4:p.Arg20820Ter
  • NP_597676.3:p.Arg14448Ter
  • NP_597681.4:p.Arg14515Ter
  • LRG_391:g.259833C>T
  • NC_000002.11:g.179440697G>A
  • NM_001267550.1:c.70162C>T
  • NM_003319.4:c.42967C>T
  • p.Arg20820*
Protein change:
R14323*
Links:
dbSNP: rs781540455
NCBI 1000 Genomes Browser:
rs781540455
Molecular consequence:
  • NM_001256850.1:c.65239C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001267550.2:c.70162C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_003319.4:c.42967C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_133378.4:c.62458C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_133432.3:c.43342C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_133437.4:c.43543C>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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000642459Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 11, 2023) 		germlineclinical testing

PubMed (8)
[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

Clinical genetics and outcome of left ventricular non-compaction cardiomyopathy.

Sedaghat-Hamedani F, Haas J, Zhu F, Geier C, Kayvanpour E, Liss M, Lai A, Frese K, Pribe-Wolferts R, Amr A, Li DT, Samani OS, Carstensen A, Bordalo DM, Müller M, Fischer C, Shao J, Wang J, Nie M, Yuan L, Haßfeld S, Schwartz C, et al.

Eur Heart J. 2017 Dec 7;38(46):3449-3460. doi: 10.1093/eurheartj/ehx545.

PubMed [citation]
PMID:
29029073

Association Between Titin Loss-of-Function Variants and Early-Onset Atrial Fibrillation.

Choi SH, Weng LC, Roselli C, Lin H, Haggerty CM, Shoemaker MB, Barnard J, Arking DE, Chasman DI, Albert CM, Chaffin M, Tucker NR, Smith JD, Gupta N, Gabriel S, Margolin L, Shea MA, Shaffer CM, Yoneda ZT, Boerwinkle E, Smith NL, Silverman EK, et al.

JAMA. 2018 Dec 11;320(22):2354-2364. doi: 10.1001/jama.2018.18179.

PubMed [citation]
PMID:
30535219
PMCID:
PMC6436530
See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000642459.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This sequence change creates a premature translational stop signal (p.Arg23388*) 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 present in population databases (rs781540455, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with atrial fibrillation, dilated cardiomyopathy, and/or left ventricular non-compaction cardiomyopathy (PMID: 29029073, 30535219, 33190517, 34495297, 36264615; Invitae). ClinVar contains an entry for this variant (Variation ID: 202402). This variant is located in the A band of TTN (PMID: 25589632). Truncating variants in this region are significantly overrepresented in patients affected with dilated cardiomyopathy (PMID: 25589632). Truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). 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: Oct 26, 2024