NM_001267550.2(TTN):c.45316_45320dup (p.Arg15108fs) AND Cardiovascular phenotype

Clinical significance:Likely pathogenic (Last evaluated: Feb 11, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_001267550.2(TTN):c.45316_45320dup (p.Arg15108fs)]

NM_001267550.2(TTN):c.45316_45320dup (p.Arg15108fs)

TTN:titin [Gene - OMIM - HGNC]
Variant type:
Cytogenetic location:
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.45316_45320dup (p.Arg15108fs)
  • NC_000002.12:g.178621504_178621508dup
  • NG_011618.3:g.214295_214299dup
  • NG_051363.1:g.103678_103682dup
  • NM_001256850.1:c.40393_40397dup
  • NM_001267550.2:c.45316_45320dupMANE SELECT
  • NM_003319.4:c.18121_18125dup
  • NM_133378.4:c.37612_37616dup
  • NM_133432.3:c.18496_18500dup
  • NM_133437.4:c.18697_18701dup
  • NP_001243779.1:p.Arg13467fs
  • NP_001254479.2:p.Arg15108fs
  • NP_003310.4:p.Arg6043fs
  • NP_596869.4:p.Arg12540fs
  • NP_597676.3:p.Arg6168fs
  • NP_597681.4:p.Arg6235fs
  • LRG_391:g.214295_214299dup
  • NC_000002.11:g.179486230_179486231insGAGCT
  • NC_000002.11:g.179486231_179486235dup
  • NM_001256850.1:c.40393_40397dupAGCTC
  • NM_003319.4:c.18121_18125dupAGCTC
  • p.R13467AfsX71
Protein change:
dbSNP: rs794729390
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001256850.1:c.40393_40397dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001267550.2:c.45316_45320dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_003319.4:c.18121_18125dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_133378.4:c.37612_37616dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_133432.3:c.18496_18500dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_133437.4:c.18697_18701dup - frameshift variant - [Sequence Ontology: SO:0001589]


Cardiovascular phenotype
MedGen: CN230736

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000735922Ambry Geneticscriteria provided, single submitter
Likely pathogenic
(Feb 11, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Details of each submission

From Ambry Genetics, SCV000735922.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided


The c.18121_18125dupAGCTC variant, located in coding exon 72 of the TTN gene, results from a duplication of AGCTC at nucleotide position 18121, causing a translational frameshift with a predicted alternate stop codon (p.R6043Afs*71). This exon is located in the I-band region of the N2-B isoform of the titin protein and is constitutively expressed in TTN transcripts (percent spliced in or PSI 100%). While truncating variants in TTN are present in 1-3% of the general population, truncating variants in the A-band are the most common cause of dilated cardiomyopathy (DCM) (Herman DS et al. N. Engl. J. Med. 2012 Feb;366:619-28; Roberts AM et al. Sci Transl Med. 2015 Jan;7:270ra6). TTN truncating variants encoded in constitutive exons (PSI >90%) have been found to be significantly associated with DCM regardless of their position in titin (Schafer S et al. Nat. Genet. 2017 Jan;49:46-53). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as likely pathogenic.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Apr 12, 2021

Support Center