Titin Variants in Dilated Cardiomyopathy

TTN Transcript / Exon Structure & Truncating Variants in Cardiomyopathy Studies

Titin - Exon 329

Details for Exon 329 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 329 are displayed below.

HG19 Genomic Locus Reference Genomic Meta-Transcript
StartEnd StartEnd StartEnd
179,422,962 179,422,375 277,568 278,15587,119 87,706

Transcripts

Exon 329 occurs in the following Titin transcripts (the number indicates the exon rank of exon 329 in each transcript).

METAN2BAN2BN2ANOVEX-1NOVEX-2NOVEX-3
328 278 156 277 157 157 -

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 100.

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 95% 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
RECOVERY 2016DCM-REC20BM01499c.87624C>Ap.Y29208Xnonsense
STM 2015DCM-ES20BM01499c.87624C>Ap.Y29208*nonsense
NEJM 2012DCM-B UK-B6c.87624C>Ap.Tyr29208Xnonsense

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.

Sequence

Size of Exon: 588 bases           Ensembl ID: ENSE00001124286

AACCACCTGAAATTGATATGAAGAATTTCCCAAGTCACACTGTATATGTTAGAGCTGGTTCAAACCTTAAAGTTGACATTCCAATCTCTGGAAAACCACTTCCCAAAGTGACCTTATCAA
GAGATGGTGTCCCCCTTAAGGCAACCATGAGATTTAATACCGAAATTACTGCTGAGAACCTGACCATCAATCTCAAAGAAAGTGTTACAGCTGACGCTGGGAGATATGAAATCACTGCTG
CCAACTCCAGTGGTACAACCAAAGCTTTCATTAACATTGTTGTGCTAGACAGGCCTGGTCCTCCAACTGGCCCTGTTGTTATTAGTGATATAACTGAAGAAAGTGTGACTCTCAAATGGG
AGCCACCTAAGTATGACGGTGGAAGTCAAGTTACCAACTACATTCTACTCAAAAGAGAAACAAGTACTGCAGTGTGGACTGAAGTGTCTGCAACAGTTGCAAGAACCATGATGAAAGTCA
TGAAACTGACCACAGGAGAAGAATACCAATTCCGCATCAAGGCAGAAAACCGCTTTGGCATCAGTGATCATATAGATTCAGCTTGTGTGACTGTCAAACTACCATACA

ATGC = coding sequence, ATGC = non-coding sequence