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NM_001267550.2(TTN):c.57331C>T (p.Arg19111Ter) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 31, 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:
RCV001213420.15

Allele description [Variation Report for NM_001267550.2(TTN):c.57331C>T (p.Arg19111Ter)]

NM_001267550.2(TTN):c.57331C>T (p.Arg19111Ter)

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.57331C>T (p.Arg19111Ter)
Other names:
p.R17470*:CGA>TGA
HGVS:
  • NC_000002.12:g.178597751G>A
  • NG_011618.3:g.238052C>T
  • NG_051363.1:g.79925G>A
  • NM_001256850.1:c.52408C>T
  • NM_001267550.2:c.57331C>TMANE SELECT
  • NM_003319.4:c.30136C>T
  • NM_133378.4:c.49627C>T
  • NM_133432.3:c.30511C>T
  • NM_133437.4:c.30712C>T
  • NP_001243779.1:p.Arg17470Ter
  • NP_001254479.1:p.Arg19111Ter
  • NP_001254479.2:p.Arg19111Ter
  • NP_003310.4:p.Arg10046Ter
  • NP_596869.4:p.Arg16543Ter
  • NP_597676.3:p.Arg10171Ter
  • NP_597681.4:p.Arg10238Ter
  • LRG_391t1:c.57331C>T
  • LRG_391:g.238052C>T
  • LRG_391p1:p.Arg19111Ter
  • NC_000002.11:g.179462478G>A
  • NM_001267550.1:c.57331C>T
  • NM_003319.4:c.30136C>T
  • NM_133379.3:c.*147834C>T
  • c.49627C>T
  • p.Arg16543X
Protein change:
R10046*
Links:
dbSNP: rs72646831
NCBI 1000 Genomes Browser:
rs72646831
Molecular consequence:
  • NM_001256850.1:c.52408C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001267550.2:c.57331C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_003319.4:c.30136C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_133378.4:c.49627C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_133432.3:c.30511C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_133437.4:c.30712C>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
SCV001385049Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 31, 2024) 		germlineclinical testing

PubMed (5)
[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

Truncations of titin causing dilated cardiomyopathy.

Herman DS, Lam L, Taylor MR, Wang L, Teekakirikul P, Christodoulou D, Conner L, DePalma SR, McDonough B, Sparks E, Teodorescu DL, Cirino AL, Banner NR, Pennell DJ, Graw S, Merlo M, Di Lenarda A, Sinagra G, Bos JM, Ackerman MJ, Mitchell RN, Murry CE, et al.

N Engl J Med. 2012 Feb 16;366(7):619-28. doi: 10.1056/NEJMoa1110186.

PubMed [citation]
PMID:
22335739
PMCID:
PMC3660031

Genetic Risk of Arrhythmic Phenotypes in Patients With Dilated Cardiomyopathy.

Gigli M, Merlo M, Graw SL, Barbati G, Rowland TJ, Slavov DB, Stolfo D, Haywood ME, Dal Ferro M, Altinier A, Ramani F, Brun F, Cocciolo A, Puggia I, Morea G, McKenna WJ, La Rosa FG, Taylor MRG, Sinagra G, Mestroni L.

J Am Coll Cardiol. 2019 Sep 17;74(11):1480-1490. doi: 10.1016/j.jacc.2019.06.072.

PubMed [citation]
PMID:
31514951
PMCID:
PMC6750731
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001385049.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Arg19111*) 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 dilated cardiomyopathy (PMID: 22335739, 31514951). ClinVar contains an entry for this variant (Variation ID: 47121). 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: Apr 20, 2024