Titin Variants in Dilated Cardiomyopathy
TTN Transcript / Exon Structure & Truncating Variants in Cardiomyopathy Studies
Titin - Exon 340
Details for Exon 340 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 340 are displayed below.
| HG19 Genomic | Locus Reference Genomic | Meta-Transcript | |||
|---|---|---|---|---|---|
| Start | End | Start | End | Start | End |
| 179,414,200 | 179,412,134 | 286,330 | 288,396 | 92,153 | 94,219 |
Transcripts
Exon 340 occurs in the following Titin transcripts (the number indicates the exon rank of exon 340 in each transcript).
| META | N2BA | N2B | N2A | NOVEX-1 | NOVEX-2 | NOVEX-3 |
| 339 | 289 | 167 | 288 | 168 | 168 | - |
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 112/113, Ig-like 134, Fibronectin type-III 114/115, Ig-like 135, Fibronectin type-III 116.
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 98% 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):
| Study | Cohort | Patient ID | Variant (CDS) | Variant (protein) | Variant Type |
|---|---|---|---|---|---|
| STM 2015 | DCM-PRO | 10KF00073 | c.92683C>T | p.Arg30895X | nonsense |
| STM 2015 | DCM-ES | 20AK01584 | c.93166C>T | p.R31056* | nonsense |
| STM 2015 | JHS | J545771 | c.92288_92289insAAAAG | p.S30763fs | frameshift |
| STM 2015 | JHS | J567853 | c.92288_92289insAAAAG | p.S30763fs | frameshift |
| LMM 2014 | ALL-CASES | 120 | c.93897delT | p.Phe31299LeufsX14 | frameshift |
| NEJM 2012 | DCM-A | HFA-46 | c.94103_94107delTTAAA | p.Thr31366fs | frameshift |
| NEJM 2012 | DCM-A | MBG-121 | c.93451G>T | p.Glu31151X | nonsense |
| NEJM 2012 | DCM-B | UK-C10 | c.93165C>T | p.Arg31056X | nonsense |
| NEJM 2012 | DCM-C | TSFDC002-23 | c.93165C>T | p.Arg31056X | nonsense |
| NEJM 2012 | DCM-C | TSSDC019-268 | c.92876G>A | p.Trp30959X | nonsense |
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: 2067 bases
Ensembl ID:
ENSE00001378255
GAAGAGAAAAGAAAAGCACAAGATGGGTAAAAGTGATCAGCAAACGACCAATCTCTGAAACAAGATTCAAAGTCACTGGTCTGACAGAAGGCAATGAGTATGAATTCCATGTCATGGCTG
AAAATGCTGCAGGAGTTGGACCTGCAAGTGGCATCTCAAGACTCATTAAATGTAGAGAGCCCGTCAACCCACCAGGTCCTCCCACAGTGGTCAAAGTAACAGACACATCAAAGACAACTG
TGAGCTTAGAATGGTCCAAACCAGTGTTTGATGGTGGCATGGAAATAATTGGGTATATTATTGAAATGTGTAAGGCCGACTTAGGAGACTGGCACAAGGTGAATGCAGAGGCATGTGTGA
AAACAAGATATACAGTCACTGATCTACAAGCAGGTGAAGAATACAAATTCCGAGTTAGTGCTATCAATGGTGCTGGAAAAGGCGACAGCTGTGAAGTGACTGGCACAATTAAAGCAGTTG
ACCGGTTAACAGCTCCTGAGTTAGACATAGATGCAAACTTCAAACAGACTCATGTTGTTAGAGCTGGGGCCAGTATTCGCCTCTTCATTGCCTACCAAGGTAGACCTACTCCTACAGCTG
TGTGGAGCAAACCAGACTCTAACCTTAGCCTTCGGGCTGATATCCATACAACAGATTCCTTCAGCACCCTCACTGTGGAAAACTGCAACAGAAATGATGCAGGGAAATATACCCTTACTG
TGGAAAACAACAGTGGTAGTAAGTCAATCACATTCACCGTGAAAGTGCTAGACACTCCAGGCCCACCTGGCCCAATTACCTTCAAAGATGTGACCCGGGGATCTGCTACATTGATGTGGG
ATGCCCCTCTTCTTGACGGTGGTGCCCGAATCCATCATTATGTGGTAGAGAAACGAGAGGCAAGTCGCCGTAGTTGGCAGGTTATCAGTGAAAAATGCACTCGTCAGATCTTCAAGGTCA
ATGACCTGGCCGAAGGTGTTCCGTACTATTTCCGTGTTTCTGCAGTAAATGAGTATGGTGTTGGTGAGCCCTATGAAATGCCAGAACCAATTGTAGCCACAGAACAGCCTGCTCCACCTA
GGAGACTTGATGTTGTTGATACTAGCAAATCCTCCGCAGTCTTAGCTTGGCTTAAACCTGACCACGATGGAGGCAGCCGGATCACTGGCTACCTGCTTGAAATGAGACAAAAGGGATCTG
ACTTCTGGGTTGAAGCTGGTCACACCAAACAGCTAACTTTCACAGTAGAGCGTCTTGTTGAGAAAACTGAATATGAATTCCGTGTGAAGGCCAAGAATGATGCTGGCTATAGTGAACCCA
GAGAAGCCTTCTCTTCTGTCATCATTAAGGAGCCTCAAATCGAGCCCACTGCTGACCTCACTGGAATTACCAATCAGCTTATAACTTGCAAAGCAGGAAGCCCATTTACCATTGACGTAC
CAATCAGTGGTCGTCCTGCCCCCAAAGTAACATGGAAACTGGAAGAAATGAGACTTAAAGAGACAGATCGAGTGAGCATTACAACAACAAAAGACAGAACCACACTGACTGTAAAGGACA
GCATGAGAGGTGACTCTGGAAGATACTTCTTGACCCTGGAAAATACAGCTGGTGTTAAAACATTTAGCGTCACAGTTGTGGTCATTGGAAGGCCAGGTCCAGTAACCGGCCCCATTGAGG
TCTCATCTGTCTCAGCTGAATCGTGTGTCCTGTCATGGGGAGAACCTAAAGATGGAGGAGGCACTGAAATTACTAATTACATAGTTGAAAAGCGTGAATCGGGTACAACAGCTTGGCAGC
TTGTCAATTCCAGTGTCAAGCGCACTCAAATTAAAGTCACTCATCTCACAAAATACATGGAATATTCTTTCCGTGTCAGTTCAGAGAACAGATTTGGTGTCAGCAAACCTCTAGAATCAG
CACCAATAATTGCTGAACATCCATTTG
ATGC = coding sequence, ATGC = non-coding sequence
