TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24434	73525;73526;73527	chr2:178572832;178572831;178572830	chr2:179437559;179437558;179437557
N2AB	22793	68602;68603;68604	chr2:178572832;178572831;178572830	chr2:179437559;179437558;179437557
N2A	21866	65821;65822;65823	chr2:178572832;178572831;178572830	chr2:179437559;179437558;179437557
N2B	15369	46330;46331;46332	chr2:178572832;178572831;178572830	chr2:179437559;179437558;179437557
Novex-1	15494	46705;46706;46707	chr2:178572832;178572831;178572830	chr2:179437559;179437558;179437557
Novex-2	15561	46906;46907;46908	chr2:178572832;178572831;178572830	chr2:179437559;179437558;179437557
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-132
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.6243
• 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
L/P	rs778199323	-0.287	0.998	D	0.739	0.57	0.880231576817	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
L/P	rs778199323	-0.287	0.998	D	0.739	0.57	0.880231576817	gnomAD-4.0.0	1.59207E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85964E-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
L/A	0.902	likely_pathogenic	0.9214	pathogenic	-1.511	Destabilizing	0.938	D	0.611	neutral	None	None	None	None	I
L/C	0.9019	likely_pathogenic	0.918	pathogenic	-0.936	Destabilizing	0.334	N	0.46	neutral	None	None	None	None	I
L/D	0.9946	likely_pathogenic	0.9952	pathogenic	-0.771	Destabilizing	0.998	D	0.74	deleterious	None	None	None	None	I
L/E	0.9784	likely_pathogenic	0.9826	pathogenic	-0.781	Destabilizing	0.998	D	0.736	prob.delet.	None	None	None	None	I
L/F	0.5216	ambiguous	0.5501	ambiguous	-1.086	Destabilizing	0.995	D	0.689	prob.neutral	None	None	None	None	I
L/G	0.9712	likely_pathogenic	0.974	pathogenic	-1.824	Destabilizing	0.995	D	0.721	prob.delet.	None	None	None	None	I
L/H	0.914	likely_pathogenic	0.9249	pathogenic	-1.089	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
L/I	0.4231	ambiguous	0.4763	ambiguous	-0.733	Destabilizing	0.968	D	0.558	neutral	None	None	None	None	I
L/K	0.9562	likely_pathogenic	0.961	pathogenic	-1.027	Destabilizing	0.995	D	0.687	prob.neutral	None	None	None	None	I
L/M	0.2332	likely_benign	0.2659	benign	-0.583	Destabilizing	0.998	D	0.678	prob.neutral	D	0.528576444	None	None	I
L/N	0.959	likely_pathogenic	0.9656	pathogenic	-0.758	Destabilizing	0.998	D	0.738	prob.delet.	None	None	None	None	I
L/P	0.9949	likely_pathogenic	0.9949	pathogenic	-0.96	Destabilizing	0.998	D	0.739	prob.delet.	D	0.526411198	None	None	I
L/Q	0.8715	likely_pathogenic	0.893	pathogenic	-0.922	Destabilizing	0.998	D	0.706	prob.neutral	D	0.525904219	None	None	I
L/R	0.9285	likely_pathogenic	0.9332	pathogenic	-0.479	Destabilizing	0.998	D	0.706	prob.neutral	D	0.525904219	None	None	I
L/S	0.9446	likely_pathogenic	0.9566	pathogenic	-1.377	Destabilizing	0.991	D	0.706	prob.neutral	None	None	None	None	I
L/T	0.8785	likely_pathogenic	0.9033	pathogenic	-1.264	Destabilizing	0.991	D	0.695	prob.neutral	None	None	None	None	I
L/V	0.4627	ambiguous	0.5273	ambiguous	-0.96	Destabilizing	0.958	D	0.574	neutral	D	0.53365419	None	None	I
L/W	0.8626	likely_pathogenic	0.8685	pathogenic	-1.132	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
L/Y	0.8847	likely_pathogenic	0.8928	pathogenic	-0.921	Destabilizing	0.998	D	0.719	prob.delet.	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.