Titin Variants in Dilated Cardiomyopathy

TTN Transcript / Exon Structure & Truncating Variants in Cardiomyopathy Studies

Titin - Exon 353

Details for Exon 353 of the Titin gene - Sequence Coordinates, Associated Transcripts, Functional Data, Truncating Variants and Sequence.

The exon number is based on the LRG numbering, as recommended for clinical reporting.


The genomic coordinates of HG19 and Locus Reference Genomic (LRG) and the CDS coordinates of the Titin meta-transcript for exon 353 are displayed below.

HG19 Genomic Locus Reference Genomic Meta-Transcript
StartEnd StartEnd StartEnd
179,404,693 179,404,109 295,837 296,42198,099 98,683


Exon 353 occurs in the following Titin transcripts (the number indicates the exon rank of exon 353 in each transcript).

352 302 180 301 181 181 -

Functional Data

Region: This exon occurs in the A-band region of the titin protein.

Domains: This exon codes for the following domain(s) - Ig-like 139, Fibronectin type-III 127.

PSI: The "proportion spliced-in" (an estimate of the percentage of TTN transcripts that incorporate this exon based on RNAseq data) is 100% in DCM (LV tissue of 84 end-stage patients) and 100% in GTEx (LV tissue of 105 samples from Genotype-Tissue Expression project). (See Ref. 1 for details)

Symmetry: This exon is symmetric, i.e. the length of the exon is a multiple of three and therefore removal of it will not alter the reading frame.

1. A. M. Roberts, J. S. Ware, D. S. Herman et al. Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease. Sci. Transl. Med. 7, 270ra6 (2015).

Truncating Variants

The following TTN truncating variants affecting this exon have been described in major published studies (click on the study name for more details):

StudyCohortPatient IDVariant (CDS)Variant (protein)Variant Type
STM 2015DCM-PRO10CS01784c.98265_98268dupAACAp.His32757AsnfsX4frameshift
STM 2015DCM-ES20DS01225c.98265_98268dupAACAp.His32757fsframeshift
STM 2015DCM-ES20LB01523c.98299_98300delAGp.R32767fsframeshift
STM 2015DCM-ES20PS01566c.98506C>Tp.R32836*nonsense
STM 2015FHS11733c.98551C>Tp.R32851*nonsense
STM 2015FHS21570c.98551C>Tp.R32851*nonsense
NEJM 2012DCM-B UK-G7c.98299_98300delAGp.Arg32767fsframeshift
NEJM 2012DCM-B UK-G9c.98506C>Tp.Arg32836Xnonsense

The shaded variants are from a cohort (DCM-B of the 2012 NEJM study) that was also included in the 2015 STM study (DCM-ES cohort) and therefore represent redundant mutations.


Size of Exon: 585 bases           Ensembl ID: ENSE00001728573


ATGC = coding sequence, ATGC = non-coding sequence