TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21842	65749;65750;65751	chr2:178583658;178583657;178583656	chr2:179448385;179448384;179448383
N2AB	20201	60826;60827;60828	chr2:178583658;178583657;178583656	chr2:179448385;179448384;179448383
N2A	19274	58045;58046;58047	chr2:178583658;178583657;178583656	chr2:179448385;179448384;179448383
N2B	12777	38554;38555;38556	chr2:178583658;178583657;178583656	chr2:179448385;179448384;179448383
Novex-1	12902	38929;38930;38931	chr2:178583658;178583657;178583656	chr2:179448385;179448384;179448383
Novex-2	12969	39130;39131;39132	chr2:178583658;178583657;178583656	chr2:179448385;179448384;179448383
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-46
• Domain position: 86
• Structural Position: 117
• Q(SASA): 0.3579
• Predicted PPI site: I

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
I/T	None	None	0.061	N	0.378	0.165	0.50557994651	gnomAD-4.0.0	1.36998E-06	None	None	None	None	I	None	0	0	None	0	2.53575E-05	None	0	0	0	0	1.6592E-05

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
I/A	0.4934	ambiguous	0.3578	ambiguous	-1.166	Destabilizing	0.863	D	0.507	neutral	None	None	None	None	I
I/C	0.7465	likely_pathogenic	0.622	pathogenic	-0.775	Destabilizing	0.999	D	0.624	neutral	None	None	None	None	I
I/D	0.8105	likely_pathogenic	0.6607	pathogenic	-0.251	Destabilizing	0.991	D	0.674	neutral	None	None	None	None	I
I/E	0.7351	likely_pathogenic	0.5883	pathogenic	-0.295	Destabilizing	0.991	D	0.665	neutral	None	None	None	None	I
I/F	0.2257	likely_benign	0.1566	benign	-0.895	Destabilizing	0.988	D	0.632	neutral	N	0.48225143	None	None	I
I/G	0.8117	likely_pathogenic	0.6797	pathogenic	-1.42	Destabilizing	0.969	D	0.662	neutral	None	None	None	None	I
I/H	0.6689	likely_pathogenic	0.5129	ambiguous	-0.627	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	I
I/K	0.639	likely_pathogenic	0.4844	ambiguous	-0.637	Destabilizing	0.991	D	0.67	neutral	None	None	None	None	I
I/L	0.1284	likely_benign	0.1033	benign	-0.581	Destabilizing	0.509	D	0.303	neutral	N	0.454448753	None	None	I
I/M	0.1444	likely_benign	0.1085	benign	-0.482	Destabilizing	0.988	D	0.647	neutral	N	0.48132871	None	None	I
I/N	0.4181	ambiguous	0.2907	benign	-0.401	Destabilizing	0.988	D	0.683	prob.neutral	N	0.49979704	None	None	I
I/P	0.8315	likely_pathogenic	0.7633	pathogenic	-0.742	Destabilizing	0.997	D	0.685	prob.neutral	None	None	None	None	I
I/Q	0.6207	likely_pathogenic	0.4782	ambiguous	-0.597	Destabilizing	0.997	D	0.682	prob.neutral	None	None	None	None	I
I/R	0.5297	ambiguous	0.3777	ambiguous	-0.087	Destabilizing	0.991	D	0.689	prob.neutral	None	None	None	None	I
I/S	0.434	ambiguous	0.2994	benign	-1.013	Destabilizing	0.852	D	0.619	neutral	N	0.476344178	None	None	I
I/T	0.3157	likely_benign	0.2151	benign	-0.938	Destabilizing	0.061	N	0.378	neutral	N	0.464492388	None	None	I
I/V	0.0811	likely_benign	0.0716	benign	-0.742	Destabilizing	0.061	N	0.234	neutral	N	0.405772159	None	None	I
I/W	0.8344	likely_pathogenic	0.7403	pathogenic	-0.898	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	I
I/Y	0.5935	likely_pathogenic	0.4606	ambiguous	-0.667	Destabilizing	0.997	D	0.649	neutral	None	None	None	None	I

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.