Titin Variants in Dilated Cardiomyopathy
TTN Transcript / Exon Structure & Truncating Variants in Cardiomyopathy Studies
Titin - Exon 28
Details for Exon 28 of the Titin gene - Sequence Coordinates, Associated Transcripts, Functional Data, Truncating Variants and Sequence.
Coordinates
The genomic coordinates of HG19 and Locus Reference Genomic (LRG) and the CDS coordinates of the Titin meta-transcript for exon 28 are displayed below.
| HG19 Genomic | Locus Reference Genomic | Meta-Transcript | |||
|---|---|---|---|---|---|
| Start | End | Start | End | Start | End |
| 179,641,776 | 179,640,083 | 58,754 | 60,447 | 4,815 | 6,508 |
Transcripts
Exon 28 occurs in the following Titin transcripts (the number indicates the exon rank of exon 28 in each transcript).
| META | N2BA | N2B | N2A | NOVEX-1 | NOVEX-2 | NOVEX-3 |
| 28 | 28 | 27 | 28 | 27 | 27 | 28 |
Functional Data
Region: This exon occurs in the near Z-disk / I-band region of the titin protein.
Domains: This exon codes for the following domain(s) - Ig-like 7/8/9/10.
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 assymmetric, i.e. the length of the exon is not a multiple of three and therefore removal of it will 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):
| Study | Cohort | Patient ID | Variant (CDS) | Variant (protein) | Variant Type |
|---|---|---|---|---|---|
| STM 2015 | JHS | J306717 | c.6355G>T | p.E2119* | nonsense |
| NEJM 2012 | DCM-C | TSSDC011-450 | c.6247delG | p.Arg2083fs | frameshift |
Sequence
Size of Exon: 1694 bases
Ensembl ID:
ENSE00002224222
AAATGTTGAAGTTGAGTTTGCAGAGCCTGAGCCAGAGAGAAAGTTAATCATCCCACGGGGGACATATAGAGCAAAGGAGATTGCAGCCCCAGAACTGGAGCCCCTCCATTTGCGATATGG
CCAAGAGCAATGGGAAGAAGGTGATCTCTATGACAAAGAGAAACAACAGAAACCATTTTTCAAGAAAAAACTCACTTCCTTAAGACTTAAGCGCTTTGGGCCTGCCCACTTTGAATGCAG
GCTAACACCCATTGGTGACCCAACGATGGTGGTGGAGTGGCTCCATGATGGAAAGCCACTTGAAGCAGCCAACAGGCTCCGTATGATCAATGAATTTGGGTACTGCAGCCTTGATTATGG
CGTTGCATATTCTAGAGACAGTGGTATCATTACTTGCAGAGCCACTAACAAATATGGAACAGATCACACATCTGCTACCCTTATTGTTAAAGATGAGAAAAGTCTTGTGGAAGAATCCCA
ATTGCCTGAGGGGAGGAAAGGCTTACAGAGAATTGAAGAATTAGAGAGAATGGCTCATGAAGGTGCACTTACAGGTGTAACAACAGATCAGAAAGAAAAGCAAAAGCCAGACATTGTCTT
GTACCCAGAGCCAGTTAGAGTACTTGAAGGGGAGACTGCAAGGTTCCGCTGCAGGGTAACAGGCTACCCTCAGCCCAAAGTCAACTGGTACCTCAATGGACAGCTCATCCGCAAAAGCAA
AAGGTTCAGAGTTCGCTATGATGGTATCCATTACCTGGACATCGTGGACTGCAAATCATATGACACAGGTGAAGTGAAGGTCACCGCGGAAAATCCTGAAGGTGTGATAGAGCATAAAGT
GAAGCTTGAGATTCAACAGAGGGAAGATTTTAGGTCTGTCCTTAGGAGAGCTCCTGAACCAAGGCCTGAGTTTCACGTACATGAACCAGGAAAGCTTCAGTTTGAAGTACAAAAAGTGGA
TAGACCTGTTGACACCACTGAAACCAAAGAAGTTGTGAAGTTGAAAAGGGCTGAAAGAATTACCCATGAAAAAGTGCCTGAAGAGTCGGAAGAGCTGCGCAGTAAATTCAAGCGCAGAAC
AGAAGAGGGCTATTATGAAGCCATTACCGCTGTGGAGCTCAAGTCTCGAAAGAAGGATGAATCCTATGAGGAACTCCTCAGGAAGACAAAAGATGAACTTCTCCACTGGACCAAAGAGTT
AACTGAAGAGGAAAAGAAAGCTCTTGCCGAAGAAGGCAAAATCACGATTCCAACTTTTAAACCTGACAAGATTGAACTAAGTCCTAGTATGGAGGCTCCAAAAATCTTCGAAAGAATCCA
GAGCCAAACAGTGGGCCAAGGATCTGATGCACACTTCCGGGTCAGAGTCGTGGGGAAACCAGACCCCGAATGTGAATGGTACAAAAATGGTGTCAAAATTGAACGGTCTGACCGGATCTA
CTGGTACTGGCCCGAAGACAATGTTTGTGAATTGGTCATAAGAGATGTGACTGCTGAGGACTCTGCCAGCATCATGGTAAAAGCCATCAACATAGCTGGAGAAACCTCCAGTCACGCATT
CTTACTTGTCCAAG
ATGC = coding sequence, ATGC = non-coding sequence
