TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24820	74683;74684;74685	chr2:178571674;178571673;178571672	chr2:179436401;179436400;179436399
N2AB	23179	69760;69761;69762	chr2:178571674;178571673;178571672	chr2:179436401;179436400;179436399
N2A	22252	66979;66980;66981	chr2:178571674;178571673;178571672	chr2:179436401;179436400;179436399
N2B	15755	47488;47489;47490	chr2:178571674;178571673;178571672	chr2:179436401;179436400;179436399
Novex-1	15880	47863;47864;47865	chr2:178571674;178571673;178571672	chr2:179436401;179436400;179436399
Novex-2	15947	48064;48065;48066	chr2:178571674;178571673;178571672	chr2:179436401;179436400;179436399
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-68
• Domain position: 13
• Structural Position: 14
• Q(SASA): 0.2969
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
E/Q	None	None	0.983	N	0.58	0.284	0.338834610459	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
E/A	0.264	likely_benign	0.2291	benign	-0.535	Destabilizing	0.892	D	0.575	neutral	N	0.472204932	None	None	N
E/C	0.9037	likely_pathogenic	0.8812	pathogenic	-0.038	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
E/D	0.1301	likely_benign	0.1096	benign	-0.503	Destabilizing	0.011	N	0.134	neutral	N	0.460606721	None	None	N
E/F	0.8767	likely_pathogenic	0.8488	pathogenic	-0.429	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
E/G	0.3866	ambiguous	0.3193	benign	-0.773	Destabilizing	0.892	D	0.539	neutral	N	0.467204956	None	None	N
E/H	0.6532	likely_pathogenic	0.6073	pathogenic	-0.463	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	N
E/I	0.612	likely_pathogenic	0.5761	pathogenic	0.069	Stabilizing	0.987	D	0.707	prob.neutral	None	None	None	None	N
E/K	0.3484	ambiguous	0.3177	benign	0.089	Stabilizing	0.892	D	0.505	neutral	N	0.521868611	None	None	N
E/L	0.6748	likely_pathogenic	0.6229	pathogenic	0.069	Stabilizing	0.987	D	0.693	prob.neutral	None	None	None	None	N
E/M	0.6309	likely_pathogenic	0.5956	pathogenic	0.345	Stabilizing	0.999	D	0.603	neutral	None	None	None	None	N
E/N	0.3598	ambiguous	0.2901	benign	-0.2	Destabilizing	0.95	D	0.591	neutral	None	None	None	None	N
E/P	0.9854	likely_pathogenic	0.9706	pathogenic	-0.112	Destabilizing	0.987	D	0.689	prob.neutral	None	None	None	None	N
E/Q	0.2912	likely_benign	0.264	benign	-0.156	Destabilizing	0.983	D	0.58	neutral	N	0.48319607	None	None	N
E/R	0.5335	ambiguous	0.4862	ambiguous	0.238	Stabilizing	0.987	D	0.642	neutral	None	None	None	None	N
E/S	0.3018	likely_benign	0.2523	benign	-0.396	Destabilizing	0.916	D	0.507	neutral	None	None	None	None	N
E/T	0.3457	ambiguous	0.3064	benign	-0.208	Destabilizing	0.975	D	0.624	neutral	None	None	None	None	N
E/V	0.4019	ambiguous	0.3728	ambiguous	-0.112	Destabilizing	0.983	D	0.647	neutral	N	0.499325316	None	None	N
E/W	0.9632	likely_pathogenic	0.9516	pathogenic	-0.279	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	N
E/Y	0.7798	likely_pathogenic	0.7312	pathogenic	-0.195	Destabilizing	0.999	D	0.626	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.