Titin Variants in Dilated Cardiomyopathy
TTN Transcript / Exon Structure & Truncating Variants in Cardiomyopathy Studies
Titin - Exon 336
Details for Exon 336 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 336 are displayed below.
| HG19 Genomic | HG38 Genomic | Locus Reference Genomic | Meta-Transcript | ||||
|---|---|---|---|---|---|---|---|
| Start | End | Start | End | Start | End | Start | End |
| 179,418,123 | 179,416,357 | 178,553,396 | 178,551,630 | 282,407 | 284,173 | 89,504 | 91,270 |
Transcripts
Exon 336 occurs in the following Titin transcripts (the number indicates the exon rank of exon 336 in each transcript).
| META | N2BA | N2B | N2A | NOVEX-1 | NOVEX-2 | NOVEX-3 |
| 335 | 285 | 163 | 284 | 164 | 164 | - |
Functional Data
Region: This exon occurs in the A-band region of the titin protein.
Domains: This exon codes for the following domain(s) - Ig-like 131, Fibronectin type-III 106/107, Ig-like 132, Fibronectin type-III 108/109.
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 97% 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 | 10MV00215 | c.89750dupG | p.Val29918SerfsX3 | frameshift |
| STM 2015 | DCM-PRO | 10TD00812 | c.90086_90088delAAGinsA | p.Glu30029AspfsX7 | frameshift |
| STM 2015 | DCM-ES | 20DB01655 | c.89900_89903delATTA | p.N29967fs | frameshift |
| STM 2015 | DCM-ES | 20AA01165 | c.90322_90323insT | p.Glu30108* | frameshift |
| LMM 2014 | ALL-CASES | 102 | c.90587delA | p.Lys30196ArgfsX94 | frameshift |
| NEJM 2012 | DCM-B | UK-E12 | c.89900_89903delATTA | p.Tyr29967fs | frameshift |
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: 1767 bases
Ensembl ID:
ENSE00001075040
AAGATGAGAAGAATCTTGGCAGTGATGCCAGATACAGCATTGAAAACACTGATTCATCCTCATTACTCACCATTCCTCAAGTTACTCGCAATGATACAGGAAAATATATTCTCACAATAG
AAAATGGAGTTGGTGAACCTAAGTCTTCAACTGTGAGTGTTAAAGTGCTTGACACACCAGCTGCCTGCCAGAAACTACAGGTTAAACATGTTTCTCGAGGCACAGTCACTTTGCTCTGGG
ATCCTCCTCTCATTGATGGAGGATCTCCAATAATTAATTATGTCATTGAAAAGAGAGATGCCACCAAGAGAACATGGTCTGTCGTGTCACACAAATGTTCTAGCACATCCTTCAAGCTAA
TAGATTTGTCGGAGAAGACTCCATTCTTCTTCAGAGTTCTTGCAGAAAATGAAATTGGAATTGGGGAACCCTGTGAAACTACAGAGCCAGTGAAGGCTGCTGAAGTACCAGCTCCTATAC
GTGATCTCTCAATGAAAGACTCAACAAAGACATCTGTCATCCTCAGCTGGACCAAACCTGACTTTGATGGTGGTAGCGTCATCACAGAATATGTTGTAGAAAGGAAAGGTAAAGGTGAAC
AGACGTGGTCCCACGCTGGCATAAGTAAGACATGTGAAATTGAGGTTAGCCAACTTAAGGAGCAGTCAGTCCTGGAGTTCAGAGTGTTTGCCAAAAATGAGAAAGGACTGAGTGATCCTG
TCACTATTGGGCCAATTACAGTGAAAGAACTTATTATTACACCTGAAGTTGACCTGTCAGATATCCCTGGGGCACAAGTCACTGTGAGAATTGGGCACAATGTGCACCTTGAATTACCTT
ATAAGGGAAAACCCAAACCATCCATCAGTTGGCTGAAAGATGGCTTGCCACTGAAAGAAAGTGAATTTGTTCGCTTCAGTAAAACTGAAAACAAAATTACTTTGAGTATTAAGAATGCCA
AGAAGGAGCATGGAGGAAAATACACTGTTATTCTTGATAATGCAGTGTGTAGAATTGCAGTCCCCATTACAGTCATCACCCTTGGCCCACCATCAAAGCCCAAAGGACCCATTCGATTTG
ATGAAATCAAGGCTGATAGTGTCATCCTGTCATGGGATGTACCTGAAGATAATGGAGGAGGAGAAATTACTTGTTACAGCATCGAGAAGCGGGAAACTTCACAAACTAACTGGAAGATGG
TGTGTTCAAGTGTTGCCAGAACGACTTTCAAAGTTCCTAATCTAGTCAAAGATGCTGAGTACCAGTTTAGAGTGAGAGCAGAAAACAGATACGGAGTCAGCCAACCACTTGTCTCAAGCA
TTATTGTGGCAAAACACCAGTTCAGGATTCCTGGTCCCCCAGGAAAGCCAGTTATATACAATGTGACTTCTGATGGCATGTCACTAACTTGGGATGCTCCAGTTTATGATGGTGGTTCAG
AAGTTACTGGATTCCATGTTGAAAAGAAAGAAAGAAATAGCATCCTCTGGCAAAAAGTTAATACATCACCAATCTCTGGAAGAGAATATAGAGCCACTGGACTGGTAGAAGGTCTGGATT
ACCAATTCCGTGTATATGCTGAAAATTCTGCTGGCCTAAGCTCACCTAGTGACCCAAGCAAATTTACCTTAGCTGTTTCTCCAGTAG
ATGC = coding sequence, ATGC = non-coding sequence
