Titin Variants in Dilated Cardiomyopathy

TTN Transcript / Exon Structure & Truncating Variants in Cardiomyopathy Studies

Titin - Exon 263

Details for Exon 263 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.

Coordinates

The genomic coordinates of HG19 and Locus Reference Genomic (LRG) and the CDS coordinates of the Titin meta-transcript for exon 263 are displayed below.

HG19 Genomic Locus Reference Genomic Meta-Transcript
StartEnd StartEnd StartEnd
179,479,075 179,478,779 221,455 221,75149,049 49,345

Transcripts

Exon 263 occurs in the following Titin transcripts (the number indicates the exon rank of exon 263 in each transcript).

METAN2BAN2BN2ANOVEX-1NOVEX-2NOVEX-3
262 212 90 211 91 91 -

Functional Data

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

Domains: This exon codes for the following domain(s) - Fibronectin type-III 6.

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.

References
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
NEJM 2012DCM-AHFA-68c.49259delAp.Glu16420fsframeshift

Sequence

Size of Exon: 297 bases           Ensembl ID: ENSE00002217670

ATAAACCCGGACCACCAGCTGCCTTTGACATCACAGATGTAACCAATGAGTCATGTCTTCTAACATGGAACCCACCACGCGATGATGGTGGATCTAAGATCACAAACTATGTTGTGGAGA
GACGAGCAACTGATAGTGAAGTGTGGCACAAGCTCTCATCCACCGTCAAGGATACAAACTTCAAGGCCACCAAATTAATCCCCAATAAAGAGTACATCTTCAGAGTTGCTGCAGAAAACA
TGTATGGTGTTGGTGAACCAGTTCAGGCCTCTCCAATAACAGCCAAATATCAGTTTG

ATGC = coding sequence, ATGC = non-coding sequence