Titin Variants in Dilated Cardiomyopathy
TTN Transcript / Exon Structure & Truncating Variants in Cardiomyopathy Studies
Titin - Exon 49
Details for Exon 49 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 49 are displayed below.
| HG19 Genomic | HG38 Genomic | Locus Reference Genomic | Meta-Transcript | ||||
|---|---|---|---|---|---|---|---|
| Start | End | Start | End | Start | End | Start | End |
| 179,606,648 | 179,603,868 | 178,741,921 | 178,739,141 | 93,882 | 96,662 | 11,312 | 14,092 |
Transcripts
Exon 49 occurs in the following Titin transcripts (the number indicates the exon rank of exon 49 in each transcript).
| META | N2BA | N2B | N2A | NOVEX-1 | NOVEX-2 | NOVEX-3 |
| 48 | 46 | 45 | - | 46 | 46 | - |
Functional Data
Region: This exon occurs in the I-band region of the titin protein.
Domains: This exon codes for the following domain(s) - Ig-like 21/22/23.
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):
| Study | Cohort | Patient ID | Variant (CDS) | Variant (protein) | Variant Type |
|---|---|---|---|---|---|
| PAED 2016 | CHILDREN | DCM-22 | c.13966C>T | p.Q4656X | nonsense |
| STM 2015 | DCM-PRO | 10DW00512 | c.12643_12644delCA | p.Gln4215ValfsX16 | frameshift |
| STM 2015 | DCM-PRO | 14MW01583 | c.12757C>T | p.Gln4253X | nonsense |
| STM 2015 | DCM-REPL | LW-II-3 | c.11912G>A | p.Trp3971* | nonsense |
| STM 2015 | DCM-REPL | BA-III-3 | c.13900G>T | p.Glu4634* | nonsense |
| STM 2015 | DCM-REPL | L-III-1 | c.14056del | p.Thr4686fs | frameshift |
| LMM 2014 | ALL-CASES | 155 | c.11657delA | p.Asp3886ValfsX22 | frameshift |
| LMM 2014 | ALL-CASES | 157 | c.12587C>A | p.Ser4196X | nonsense |
| NEJM 2012 | DCM-A | HFA-42 | c.13696C>T | p.Gln4566X | nonsense |
| NEJM 2012 | Controls | pv-1 | c.13010delA | p.Lys4337fs | frameshift |
Sequence
Size of Exon: 2781 bases
Ensembl ID:
ENSE00001328652
TTGATTCCGAAAAGGAAGGCACTGGCCCAATTTTCATCAAAGAAGTGTCAAATGCTGATATAAGCATGGGGGATGTGGCTACACTGTCTGTAACTGTCATTGGCATCCCCAAACCTAAAA
TTCAGTGGTTCTTTAATGGAGTGCTATTAACCCCTTCTGCTGACTACAAATTTGTTTTTGACGGTGATGATCATAGCCTGATCATTCTGTTCACCAAATTGGAGGATGAGGGAGAGTATA
CATGTATGGCCAGTAATGACTATGGAAAGACAATATGTAGTGCCTATCTAAAAATTAATTCCAAAGGAGAGGGTCACAAAGACACTGAAACAGAATCAGCAGTGGCAAAATCTCTGGAAA
AGCTGGGAGGTCCTTGTCCTCCTCACTTCCTTAAGGAGTTAAAACCAATTCGCTGTGCTCAAGGGCTTCCTGCCATCTTTGAGTACACAGTGGTTGGAGAGCCTGCCCCTACTGTTACAT
GGTTCAAAGAAAACAAGCAGCTTTGCACCAGTGTTTATTACACTATCATTCATAACCCTAATGGCTCTGGAACTTTCATTGTCAATGACCCTCAGAGGGAAGACAGTGGCCTCTATATCT
GTAAAGCAGAGAATATGTTGGGTGAGTCCACCTGTGCAGCAGAGCTGCTTGTGCTTCTGGAAGACACAGACATGACTGATACCCCCTGCAAAGCAAAGTCCACACCAGAGGCTCCTGAGG
ATTTTCCACAGACACCCTTAAAGGGTCCCGCAGTTGAAGCACTTGACTCAGAGCAGGAAATTGCAACGTTTGTAAAAGACACCATTTTGAAAGCTGCTTTAATTACAGAAGAAAACCAGC
AACTATCTTATGAGCATATTGCTAAAGCCAATGAATTGAGCAGTCAGCTTCCTTTGGGAGCTCAGGAATTGCAATCCATTTTGGAGCAAGACAAGCTCACTCCTGAAAGCACCAGGGAAT
TTCTTTGCATCAATGGCAGTATTCACTTTCAGCCTCTCAAGGAACCATCTCCCAACCTACAGCTGCAGATTGTACAGTCCCAGAAAACCTTCTCCAAAGAAGGTATTCTAATGCCTGAAG
AGCCTGAGACACAGGCAGTTCTATCAGATACCGAGAAAATCTTCCCAAGTGCCATGTCCATAGAACAAATTAATTCATTAACAGTTGAGCCTCTGAAAACTTTATTAGCTGAACCTGAAG
GGAATTATCCACAGTCTTCAATAGAACCTCCAATGCATTCTTATCTAACCTCTGTGGCTGAGGAAGTACTTTCACCAAAAGAAAAGACAGTATCTGACACCAACAGAGAGCAAAGAGTGA
CTCTTCAAAAGCAAGAGGCACAAAGTGCGCTCATCTTGAGTCAGAGCTTAGCTGAGGGACACGTGGAGAGTCTCCAGAGTCCTGATGTCATGATCTCTCAGGTAAACTATGAGCCCCTAG
TCCCTTCAGAACACTCATGCACAGAAGGAGGTAAAATTTTGATAGAAAGTGCAAATCCACTGGAAAATGCAGGGCAAGATTCTGCGGTCAGAATTGAGGAAGGCAAGTCCTTAAGATTTC
CACTAGCACTTGAAGAAAAGCAGGTACTGCTCAAAGAAGAGCATTCTGACAACGTGGTGATGCCCCCAGACCAAATCATTGAGTCTAAAAGAGAGCCCGTGGCAATAAAGAAAGTGCAGG
AGGTACAGGGAAGGGACCTTCTTTCTAAGGAAAGCTTGCTTTCTGGTATTCCAGAAGAGCAGAGATTAAACCTGAAAATTCAAATCTGCCGGGCTTTGCAAGCAGCCGTGGCCAGCGAGC
AGCCAGGTCTTTTCTCTGAGTGGCTAAGAAATATTGAAAAGGTGGAGGTCGAGGCTGTAAACATCACCCAAGAGCCCAGACACATCATGTGCATGTACCTTGTTACTTCGGCAAAGTCTG
TAACAGAAGAAGTAACCATCATTATTGAAGATGTTGATCCTCAAATGGCTAACCTGAAAATGGAACTTAGGGATGCTTTGTGTGCTATTATATATGAGGAAATAGACATCCTAACAGCTG
AGGGTCCTAGAATTCAGCAAGGAGCCAAAACAAGTTTGCAAGAAGAAATGGATTCTTTTTCAGGTTCACAGAAGGTTGAACCCATTACTGAACCAGAAGTTGAATCTAAATATCTGATCT
CAACTGAAGAGGTCAGTTATTTTAACGTGCAAAGTAGGGTTAAATATTTGGATGCCACACCTGTCACTAAAGGGGTTGCTTCAGCTGTTGTCTCTGACGAAAAACAAGATGAGAGTCTGA
AACCATCAGAGGAAAAAGAGGAGTCTTCCTCTGAAAGTGGTACTGAGGAGGTTGCTACAGTAAAGATACAGGAAGCTGAGGGTGGCTTAATCAAAGAGGATGGCCCCATGATACATACAC
CTTTAGTGGACACTGTTTCTGAGGAAGGTGATATTGTACACCTCACAACATCCATAACAAATGCTAAAGAGGTGAATTGGTATTTTGAGAATAAACTGGTGCCTTCAGATGAAAAGTTCA
AGTGTTTACAAGATCAAAATACATATACGCTAGTCATCGACAAAGTAAATACCGAAGACCATCAAGGAGAGTATGTCTGTGAGGCCTTGAATGACAGCGGAAAAACAGCAACTTCAGCCA
AACTCACTGTAGTAAAAAGAG
ATGC = coding sequence, ATGC = non-coding sequence
