Titin Variants in Dilated Cardiomyopathy

TTN Transcript / Exon Structure & Truncating Variants in Cardiomyopathy Studies

Titin - Exon 220

Details for Exon 220 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 220 are displayed below.

HG19 Genomic Locus Reference Genomic Meta-Transcript
StartEnd StartEnd StartEnd
179,507,044 179,506,964 193,486 193,56640,478 40,558


Exon 220 occurs in the following Titin transcripts (the number indicates the exon rank of exon 220 in each transcript).

219 169 47 168 48 48 -

Functional Data

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

Domains: This exon codes for the following domain(s) - PEVK27.

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 96% 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-ES20VW01643c.40558G>Cp.Val13520Leuother splice site
STM 2015FHS530c.40558+1G>Aessential splice site
NEJM 2012DCM-AHFA-26c.40558+1G>Aessential splice site
NEJM 2012DCM-AHFA-41c.40558+1G>Aessential splice site
NEJM 2012DCM-B UK-B12c.40558G>Cother splice site

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: 81 bases           Ensembl ID: ENSE00002292542


ATGC = coding sequence, ATGC = non-coding sequence