Titin Variants in Dilated Cardiomyopathy

TTN Transcript / Exon Structure & Truncating Variants in Cardiomyopathy Studies


Titin Variant Study - NEJM 2012

New England Journal of Medicine paper describing titin truncations as a major cause of DCM. (2012)

Truncations of titin causing dilated cardiomyopathy.
Herman DS, Lam L, Taylor MR, Wang L, Teekakirikul P, Christodoulou D, Conner L, DePalma SR, McDonough B, Sparks E, Teodorescu DL, Cirino AL, Banner NR, Pennell DJ, Graw S, Merlo M, Di Lenarda A, Sinagra G, Bos JM, Ackerman MJ, Mitchell RN, Murry CE, Lakdawala NK, Ho CY, Barton PJ, Cook SA, Mestroni L, Seidman JG, Seidman CE
N Engl J Med. 2012 366(7):619-28.

Patient cohorts analysed in this study

CohortDescriptionStatusSizeTTNtv %
DCM-ABrigham and Women's HospitalDCM9240.2%
DCM-B *Royal Brompton and Harefield NHS TrustDCM7125.4%
DCM-CFamilial Dilated Cardiomyopathy Registry - Colorado / ItalyDCM1498.7%
HCMBrigham and Women's Hospital / Mayo ClinicHCM2310.9%
ControlsSubjects without cardiomyopathy (multiple sites)CONTROL2492.8%

* Please note the patients in this cohort were also included in DCM-ES cohort from the 2015 STM study.

Truncating variants identified in this study

CohortPatient IDExonBandVariant (CDS)Variant (protein)Variant Type
DCM-AHFA-42 I-bandc.13696C>Tp.Gln4566Xnonsense
DCM-AHFA-9 I-bandc.20134delGp.Ser6712fsframeshift
DCM-AD13KD-1 I-bandc.31427-1G>Aessential splice site
DCM-AHFA-26 I-bandc.40558+1G>Aessential splice site
DCM-AHFA-41 I-bandc.40558+1G>Aessential splice site
DCM-AMIY-11 I-bandc.42947-2A>Gessential splice site
DCM-AMDT-11 I-bandc.43544_43545insAp.Ala14514fsframeshift
DCM-AHFA-68 A-bandc.49259delAp.Glu16420fsframeshift
DCM-AMDD-22 A-bandc.49648+2delTessential splice site
DCM-AMIV-14 A-bandc.49648+2delTessential splice site
DCM-AHFA-71 A-bandc.53287+1G>Tessential splice site
DCM-AHFA-63 A-bandc.58858delCp.Glu19619fsframeshift
DCM-AMGR-11 A-bandc.59926+1G>Aessential splice site
DCM-AMDJ-21 A-bandc.61495C>Tp.Arg20499Xnonsense
DCM-AMEH-11 A-bandc.61290T>Ap.Cys20430Xnonsense
DCM-AMEW-11 A-bandc.61876C>Tp.Arg20626Xnonsense
DCM-AMAO-92 A-bandc.63601C>Tp.Arg21201Xnonsense
DCM-ASS-201 A-bandc.65070delCp.Pro21690fsframeshift
DCM-AMAM-12 A-bandc.67348+5G>Aother splice site
DCM-AMIS-11 A-bandc.68328A>Gother splice site
DCM-AMCL-15 A-bandc.68824+5G>Cessential splice site
DCM-AHFA-57 A-bandc.77101_77102insTp.Gln25700fsframeshift
DCM-AMEK-111 A-bandc.72668delTp.Pro24223fsframeshift
DCM-AMGW-11 A-bandc.85768C>Tp.Arg28590Xnonsense
DCM-AMHG-23 A-bandc.71980_71986delGCATATGinsTAp.Ala23994fsframeshift
DCM-AMID-1 A-bandc.81988C>Tp.Gln27330Xnonsense
DCM-AMIP-13 A-bandc.86363G>Ap.Trp28788Xnonsense
DCM-ASS-287-15 A-bandc.77646_77662delinsAGAp.Ser25882fsframeshift
DCM-ASS-725 A-bandc.81988C>Tp.Gln27330Xnonsense
DCM-AMIA-1 A-bandc.86821+2T>Aessential splice site
DCM-AHFA-46 A-bandc.94103_94107delTTAAAp.Thr31366fsframeshift
DCM-AMBG-121 A-bandc.93451G>Tp.Glu31151Xnonsense
DCM-AMHQ-12 A-bandc.95164C>Tp.Gln31722Xnonsense
DCM-ASS-723 A-bandc.95416+2insCCTessential splice site
DCM-AHFA-66 A-bandc.97492+1G>Cessential splice site
DCM-AHFA-83 A-bandc.97492+1G>Cessential splice site
DCM-AMHX-11 A-bandc.99034A>Tp.Lys33012Xnonsense
DCM-BUK-B12 I-bandc.40558G>Cother splice site
DCM-BUK-H11 I-bandc.46236C>Ap.Cys15412Xnonsense
DCM-BUK-G1 A-bandc.50245delTp.Phe16749fsframeshift
DCM-BUK-A3 A-bandc.53488G>Tp.Gly17830Xnonsense
DCM-BUK-B1 A-bandc.59345-5T>Aother splice site
DCM-BUK-B12 A-bandc.59627-1G>Aessential splice site
DCM-BUK-A10 A-bandc.67495C>Tp.Arg22499Xnonsense
DCM-BUK-B2 A-bandc.69412+1G>Aessential splice site
DCM-BUK-H2 A-bandc.69848delTp.Lys23281fsframeshift
DCM-BUK-C8 A-bandc.70790delAp.Glu23597fsframeshift
DCM-BUK-C6 A-bandc.86459_86460delCTp.Ser28820fsframeshift
DCM-BUK-B6 A-bandc.87624C>Ap.Tyr29208Xnonsense
DCM-BUK-E12 A-bandc.89900_89903delATTAp.Tyr29967fsframeshift
DCM-BUK-C10 A-bandc.93165C>Tp.Arg31056Xnonsense
DCM-BUK-E4 A-bandc.96460_96461insAp.Thr32154fsframeshift
DCM-BUK-G7 A-bandc.98299_98300delAGp.Arg32767fsframeshift
DCM-BUK-G9 A-bandc.98506C>Tp.Arg32836Xnonsense
DCM-BUK-C9 A-bandc.100445C>Ap.Ser33482Xnonsense
DCM-CTSSDC011-450 near Z-disk / I-bandc.6247delGp.Arg2083fsframeshift
DCM-CDNFDC144-05-0444 A-bandc.54000G>Ap.Trp18000Xnonsense
DCM-CTSFDC023-300 A-bandc.55269+3A>Gother splice site
DCM-CDNFDC116-04-1545 A-bandc.56806G>Ap.Arg18936Xnonsense
DCM-CTSFDC050-115 A-bandc.57331C>Tp.Arg19111Xnonsense
DCM-CTSFDC017-253-2 A-bandc.58068_58069insGp.Glu19356fsframeshift
DCM-CDNFDC103-03-0941 A-bandc.58270G>Tp.Glu19424Xnonsense
DCM-CDNFDC142-05-0569 A-bandc.61876C>Tp.Arg20626Xnonsense
DCM-CDNFDC081-02-1564 A-bandc.85969A>Tp.Lys28657Xnonsense
DCM-CDNFDC088-02-1900 A-bandc.84819G>Ap.Trp28273Xnonsense
DCM-CTSFDC002-23 A-bandc.93165C>Tp.Arg31056Xnonsense
DCM-CTSSDC019-268 A-bandc.92876G>Ap.Trp30959Xnonsense
DCM-CTSFDC033-434 A-bandc.95966delAp.Asn31989fsframeshift
HCMPA-1 I-bandc.24749_24761delGTCAAGATATCTGp.Gly8250fsframeshift
HCMSS-333 I-bandc.35308+1G>Tessential splice site
Controlspv-75 Z-diskc.1246-3delTother splice site
ControlsN-50 near Z-diskc.3101-2A>Tessential splice site
Controlspv-1 I-bandc.13010delAp.Lys4337fsframeshift
Controls12s-C11 I-bandc.39211G>Tother splice site
Controls12s-G11 A-bandc.55120+3A>Gother splice site
ControlsA-15 A-bandc.76697_76698delTTp.Leu25566fsframeshift
Controlspv-35 A-bandc.99865+2T>Cessential splice site