Titin Variants in Dilated Cardiomyopathy

TTN Transcript / Exon Structure & Truncating Variants in Cardiomyopathy Studies

Titin - Exon 48

Details for Exon 48 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 48 are displayed below.

HG19 Genomic HG38 Genomic Locus Reference Genomic Meta-Transcript
StartEnd StartEnd StartEnd StartEnd
179,616,766 179,610,047 178,752,039 178,745,320
179,616,766 * 179,610,312 *

* Coordinates for protein-coding part of the exon.

Transcripts

Exon 48 occurs in the following Titin transcripts (the number indicates the exon rank of exon 48 in each transcript).

METAN2BAN2BN2ANOVEX-1NOVEX-2NOVEX-3
- - - - - - 46

Functional Data

PSI: As exon 48 of the Novex-3 transcript is a 3' exon, the PSI is unreliable. An alternative method comparing ratio of reads from exons 48 & 364 suggests novex-3 represents 9.4% of transcripts in the DCM cohort and 7.3% of transcripts for GTEx.

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):

StudyCohortPatient IDVariant (CDS)Variant (protein)Variant Type
STM 2015DCM-PRO12FB00047c.13022C>Gp.Ser4341Xnonsense
STM 2015DCM-ES20JL01558c.14470_14471insCACACTCCATAp.R4824fsframeshift
STM 2015WHISRR363549c.16516G>Tp.Glu5506*nonsense
STM 2015WHISRR444813c.16516G>Tp.Glu5506*nonsense
STM 2015WHISRR485694c.16516G>Tp.Glu5506*nonsense
STM 2015WHISRR373048c.16529delTp.Val5510fsframeshift
STM 2015FHS14608c.15305_15305delCp.T5102fsframeshift
STM 2015FHS35c.10443_10443delAp.K3481fsframeshift
STM 2015FHS21984c.13660_13661insAp.I4554fsframeshift
STM 2015FHS13496c.13705G>Tp.E4569*nonsense
STM 2015FHS21368c.13939_13939delGp.E4647fsframeshift
STM 2015JHSJ133254c.13410_13411insAp.K4470fsframeshift

Sequence

Size of Exon: 6720 bases           Ensembl ID: ENSE00001339816

AATTATTCTCTGAGGGGGAATCTGAACATTCAGAAAGGGATACACGTGACGCCTTTTCAGATTCTGAAGACATAGACCACAAATCCATGGCTGCTAAAAGATATGCAAGTAGAATATCAT
CTACAAGCTCCTGGCCTGAATATTTTAAGCCTTCTTTTACCCAGAAACTTACATTTAAATATGTTTTAGAGGGTGAACCGGTTGTTTTTACATGTAGATTAATTGCCTGTCCAACTCCAG
AAATGACTTGGTTTCATAACAATCGGCCCATCCCAACAGGTCTTCGTCGGATTATAAAAGCTGAGAGTGATTTACACCATCACTCTTCCAGCTTAGAGATTAAAAGGGTCCAAGACAGAG
ATTCTGGAAGTTATAGGTTACTAGCAATTAATAGTGAAGGGTCTGCAGAATCAACTGCATCATTGCTTGTTATCCAAAAAGGGCAAGATGAGAAATATTTAGAATTTCTGAAAAGAGCAG
AACGGACACATGAAAATGTGGAGGCTTTAGTTGAAAGGGGAGAAGATAGGATAAAGGTTGACCTGAGGTTTACTGGCTCTCCCTTTAACAAAAAACAAGATGTGGAACAAAAGGGAATGA
TGAGAACTATACATTTTAAGACAATGAGTTCTGCCAAGAAAACAGATTACATGTATGATGAAGAATATTTAGAAAGTAAATCTGACATAAGAGGTTGGCTTAATGTAGGTGAAAGTTTCC
TGGACAAGGAGACCAAAGTGAAGTTGCAACGTTTAAGGGAGGCTAGAAAAACATTAATGGAGAAAAAGAAATTATCTCTTTTAGATACGTCTTCTGAAATAAGCTCAAGAACTTTGAGAA
GTGAAGCTAGTGATAAAGATATTCTGTTCTCTAGAGAGGACATGAAAATCAGATCTATGTCTGATCTAGCTGAAAGTTATAAGGTAGATCATTCAGCTGAGAGTATTGTGCAAAATCCAC
ATGCCCTTTCTAATCAAATGGATCAAAATATAGAATCTGAGGAACTTCCCACAAGCTTTCAAACTATTGTTGATGAAGAAATTTTCCAGACTGAAATAAGAATGAGCCAAGAAGCACTGG
TAAAGGAAAGTCTACCAAAAGACCATTTATATGGTGAAATTCTAGTAAATGAAAATACCCAAGCAAGAGGACAGCTGGAAGAAATTATGGCCAATACTACAATTGGAGAGTCATCCACAT
ATATCACTAATGTATGTGAGAAGGAGGAAGTATATGAGACTCCTGAAAATGTGTCTCAAGCTATTACACCACATGCCAGCGAATCTTTTGGTACACTTGTAAATGTTGAAGAAAGTGAAG
AAATAGCTAGTGAAAGAATAAAAAAGGATGATTTGAGAGAATTACAACTCTCTGCTTCTACACGAATTGATGAATTCAAAACCGAACAGAAGGAAGAAAACATGAGATTTTTTGAAAATT
CTTTTCGAAAACGCCCACAACGTTGCCCACCTTCATTTCTTCAAGAAATTGAATCTCAAGAAGTTTATGAAGGTGACAGTTGTAATTTTGTGTGTCATTTTCAAGGATATCCTCAACCTA
TAGTGACGTGGTATAACAATGACATGCCAATCCCACGTAATCAAAACTTTATCATTCATTCGTTGGAAAACTATTCAATATTAACTCTTTCATCTGTTCATCATCAGAATGAAGGTTCTA
TTACTTGTGTGCTATTTAACCAATATGGAACAGTAAAAACAACCAGTATGCTTAAAGTGAAAGCAAAACAAAAACATGATGTCAAAGCACATAAAGTCCCAGTGTTCCATGACTACTTGG
ATGAGGAAGAAGAGTTAGCATTGGTGTTTGACCAAGCAAAAGGCGCCCATCCATCTATGAGTCAAGAGGGCCAAACAAATCTTCATTTGTTAAAAACTAACCCACCAGTTCCTCCCTCTG
GAGACACAGAATTGCTTTCCTTTCCTGTAGAAATTCAGGTAACAGCAGCTACTCCTATCCCAGAACAGGATAAAGAGTCTAAAGAAGTGTTTCAAACTGAGGAGCTGGAACCTAAAGCAA
TGCCTCAAGATCAAGTTACTCAATCACCAAAACACAGATTTGTATTTTTGTCTGATATTACTAATGAACCACCAAAAATGTTACAAGAAATGCCAAAGCATGCCAGGTGTAGAGAAGGGG
ATTCCATCATTCTTGAATGTTTAATATCTGGTGAGCCCCAGCCAGTTGTAACATGGTTTCAAAATGGAGTCCTTTTAAAGCAGAACCAGAAGTTTCAGTTTGAAGAAGTTAATTGTAGCC
ACCAATTATATATTAAGGATGTTAATTCTCAAGATTCTGGAAAATATAAATGTGTTGCTGAAAACAATTCAGGGGCAGTTGAAAGTGTTTCAGATCTAACAGTGGAGCCTGTCACTTATA
GAGAAAATAGTCAATTCGAAAATATTGGTGAAATTTATGGAAAATATTCCAGAGATCAGCAACTGCAAGACCAGGGAGAATCTGTAAGGGCACATTTTTATGATTATCCAGCTGGTCCCT
TTACTCCCTGGACAAATGTAAAAGAATATTCAGTAAGGGACTATTTTCAAAGCCTTGAGACTATTGAGCAAATAGACCAGAAAGAGCAGGTGCGTTGCATACCTTCTAGAGAAAAAATTC
CCAGATTTGTGCATGGTGCTTCAAGAACCATAAAAATCAGCAAGCCCATCAGGGCTGAATTCATACAATGTCAGGCTGAAGGGAAAGAGAGACATGTAAGTGAAAAATCAAAGCTGCACC
AAGCAGAGGGTACTGTTTATCCATTTGTTGATGATTTCAGTGATGTCACTATTAAGAAAGAAATAAGAAATAATTTTGGAAAACTTGGTAGATCAGAAAAGGAAAATGTACAAGAATGTG
CCCAAAGTGACTATTTACCAAATATTCACTCTGAGAGAATTTCTGACAGTTACAATACAAAAGATTCATCTGCCATTGTATATGAAGAATCCCTTGGTGAAGAGATACACTACCCGGGGA
AAAAGGTGAAGCATAGAATTATCGAATTTGAAAAATTACATGTAGAAAAAGGAGTTCTAGAAAAAAGACCTACCAGAACATCAATTGTTAATCCTCCTCAAAAGAAGATTGATGACAAAG
CCTTTTCATTAAAGCAAAGAGAATCAAGATCAAGCAATCTAAATGCAAATATGTATCAGGCAGAGAAAATGTCTCCAAATACTGAATCAGATTCATCTAACATTGCAATAAATTTAAAGC
TGCTTTCCTCTCAAACTCATAAAGAATTTGACGCACAAGAAAGGGAACAACAGGAAAAAATAAGTCTTATAGATAAACCTGCAATTTCTAAAAGAGCTGAACATGAATCACCTATTACAT
TTGACTTAAAGCAGTTTCACACTCAAATAAAACACACAGATGTGAAATTCCAAGAATTAGATAGTGGTCAACCAGAAGAAGCTTATTTTAAAATCCAACATCCTGCTGACACTGAGAACA
TTGTATTTGATCTAAAACAAATGTATTCTCATATAGGAGATCCAGCTCTGGAGTTCCAAGGGCAAGAAACTAGGGAACAGCAGGAAATACATTATAAAGAAAAAATTCCTAGCCCTGAAA
CGTTACAACCTGACACACACAATATCTCTAAAAGTGTGCAAAATAATGTATTTGCCAGTCAAGAAATTTCTTCCAGTCAAGAGCTTTCAAATAGAACTATGGTGGAGAAAAGTAGTATTG
ATGAAAATTCCATTTCTTTAGAAAAAGAAGTCCGACATGTACAGGAACAAAACTTAGACATTTTAAAAACTGATCTTTCTCTTAAATCCTTTTCTGAAGAAATCTATAGTGAATCATGTG
CCCTACTTCCAACCTCATCTGCAGATATAGAAGAAACTGATCTTTCTGAGAAAAGTTGTCCTCTAGAAAATGGAGGCAGAAGTTCCATCTCACATTTGAAAAAAGCAGCAAGTGAGGAAA
AGCCTTTAGGGGTTGGTGAAATGGAAGAAGAATGCACTCTAGAACCAGAGTTGGCAGCATTTCCAAAGCAGGATGGTGGGACACAGGAATATACAGATGCCACTTTGGAAGACCACAGAG
GTGATGTTCAGGAAGCTGACACACTCCATAGACAGCTCTCCCTGAGTCAGTGCTTCCCACTCTTGATGACTGAAGAACAACAGAATCCAGGTGAACAAATAAGTACAAACATTCATGCCT
CTGGAGAAGAAAAATGTTATGAAGAAGTTCAAGTTCAGAATGAAGCTTCTTTCTCCACTTTAGAAGGAGAAATGATAGAAACTAGTTTTTCTCAAAATATTCCTAAATTAGATGAGGCAC
ATACCACTGAGGCAGCAGAATCTGAGACCTCCCTAACACAATATTTACTTGCTGCTGGAAAGCGTGAGGTTCCTGAAACTAAAGACACCAGAGACCAGGCAAAGCTTGTCCAGAGTGAAT
CAATCACTTCAATGGAGGTGGAAGAAGTAACTTTCAACACTGTGTATGAATACTACAACCAGAAACAGGAATCACTAGGTCGTCCACTTTCTCCTGAGTCTGACATTTCCATTGGTGTGG
GAAGTACAACCAGTGAAGAAATATCTGAGTTAGATCAGTTTTATACCCCACCATCATCTGTTGAATATTTTGAATCTCCAAAGTCCCCTGACTTATATTTTAATCCTTCAGATATAACTA
AACAATCCTCAATACATTCAGGAGGTGAGACAGTTGAAAGATATTCCACACCTTTAGGGGAAGTTGCTGAAAGATATTCAACACCTTCCGAAGGTGAGGTAGGAGAAAGATACTCCACAC
CCCCAGGGGAGACACTAGAGAGATACTCCACACCTCCAGGAGAGACTCTAGAGAGATACTCCACACCCCCAGGAGAGACTCTAGAGAGATATTCCACACCCCCAGGAGAGACTCTGGAGA
GATACTCCACACCCCCAGGAGAGACTCTAGAGCGATATTCCACACCCCCAGGGGAGGCACTAGAGAGATATTCTATTCCTACTGGAGGACCAAACCCCACTGGTACTTTTAAAACATATC
CATCAAAAATAGAAAGGGAAGACGGTACACCAAATGAGCATTTCTACACACCTACAGAAGAGAGGGGTTCAGCTTATGAAATATGGCGTTCCGATTCATTTGGTACACCCAATGAAGCCA
TTGAGCCAAAAGACAATGAAATGCCTCCATCTTTTATTGAACCTCTGACCAAAAGGAAGGTATATGAAAACACAACACTAGGCTTCATTGTTGAAGTTGAAGGTCTTCCAGTTCCTGGTG
TGAAATGGTATCGAAATAAATCTTTACTAGAGCCAGATGAAAGAATCAAAATGGAAAGAGTGGGTAATGTGTGTTCACTGGAAATTTCTAACATTCAAAAAGGAGAAGGGGGAGAGTACA
TGTGTCATGCTGTAAACATCATAGGGGAAGCAAAGAGCTTTGCAAATGTAGACATAATGCCCCAGGAAGAAAGAGTGGTGGCACTACCACCTCCAGTAACACATCAGCATGTCATGGAGT
TTGATTTGGAACACACCACATCATCAAGAACACCTTCTCCTCAAGAAATTGTCCTGGAAGTTGAATTAAGTGAAAAAGACGTTAAAGAATTTGAGAAGCAGGTGAAAATAGTGACAGTTC
CCGAATTTACTCCTGACCATAAAAGTATGATTGTGAGTCTAGATGTTCTTCCATTTAATTTTGTAGATCCAAATATGGATTCAAGGGAGGGAGAAGACAAAGAACTAAAAATTGATTTAG
AAGTATTTGAAATGCCTCCTCGCTTTATAATGCCTATTTGTGATTTTAAAATTCCAGAAAATTCAGATGCTGTATTCAAATGTTCAGTCATAGGGATCCCGACTCCCGAAGTTAAGTGGT
ATAAAGAATATATGTGTATTGAGCCAGATAATATTAAATACGTGATTAGCGAGGAGAAGGGAAGTCACACTCTTAAAATTCGAAATGTCTGTCTTTCTGATAGTGCAACATACAGGTGCA
GAGCTGTGAATTGTGTAGGAGAGGCTATCTGTCGGGGATTCCTCACCATGGGAGATTCTGAAATATTTGCTGTGATAGCAAAGAAAAGCAAAGTGACTTTAAGCAGTTTAATGGAAGAAT
TGGTCTTAAAGAGCAACTACACAGACAGTTTTTTTGAATTTCAGGTGGTGGAAGGGCCTCCCAGGTTTATCAAAGGTATTTCTGACTGTTATGCACCAATAGGTACAGCAGCATATTTTC
AGTGCTTAGTTCGTGGCTCTCCAAGACCCACGGTTTACTGGTACAAAGATGGAAAATTAGTCCAAGGAAGAAGGTTCACTGTTGAGGAAAGTGGCACAGGGTTCCATAACCTGTTTATAA
CAAGCTTAGTAAAGAGTGATGAAGGAGAGTATAGGTGTGTAGCTACAAACAAATCAGGAATGGCTGAGAGCTTTGCAGCACTCACCTTAACTTAAAATGTAATGTTTTAGTGCCTCAGTA
ATTATTAGCATTGATCTGAGTGCTTTCATATTTTCCAAATTATGTGGATCTAATAAACTTCCAAACAGGTCCACCATATTTGAATTCATTACCTTGGAGACCCCTAAAGAAATAATCTCT
ATGTAGAAATCTCATCTTTGTAATACATGTAAATATTTTGTTATCTGAACTGTGGAATCATCACTTGTGTCAATCATGCTGTGTAATATCAAACACAATTAAATCTCTCCTTGGCTACCT
AATTGTTTGTACTTCTATTTACCCTCATGCCTCCTCCACAAAGTGTTTCAGTGGAATGGACTCTCTTTTAGCAGATAAACCATATATGCAAAAGTACAATGTAAAAGTGGAGACCATATC
AGATGACCACGCAGACAAATTGGTAAGGGCAAATCTCTCTGCTCCCATTCTAAGTTATTTTTGGAATTTTAACCCCTTTGCATCCAAACTCATGTTTATTTACTTTGACTTAGAATAGGC
AAAACAAACAACAAAAACCAGCTTCTCCCAATTGGCAACTAACTCTATAATCTGTTTGACATTTCAATCTTAATATATTAACTTCATCTCTTTTAAAAATGTTTTCGTTATTAATATTCC
TCTTCATAAGTGCTTTAATTCTCACTGGCTTCAAGGGACCAATTGTGCTCTTTGTGGGCAGGGTTCACCTAGACATTTGCAAAATAAGCAAATAGATCTTTCCACTTTTGGAGATACCTT
ATTTTTCTCCATTTTTGAGATGACATCAAGTGTAAAATGCAGCAATAATTTAGTATTGGCCTGGGGAAAAAAGGGAAACTATCATATTGTGTTTACATATAGATTTTAAAACTGTATTCT
GATTTCAGAATCTTTAAAATTTAAAAAAAGGTGGGATATTTTTAGAATTGAGACAATATGGTAATTTGTATTTCAGATTATATATAAATAACAAGATAACAAGCTTTCCTATCAGTTTCA
CTGAATTTCATCTTTAAAACGAATATAGCTTAATAAGCATTCAATTTTTATTGTGATGTTTATGTTTCTAAAGTAACTCTTTAATTTTGTCTTTTAAAATTAAAATAACAGTAAATTAAC
ATACTCCTTAATATCTTACCTATATACTAATGTGGACCCAAGTCTTCTCATATAAGACTCGACAAATATAAAAAA


ATGC = coding sequence, ATGC = non-coding sequence