TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7780	23563;23564;23565	chr2:178720424;178720423;178720422	chr2:179585151;179585150;179585149
N2AB	7463	22612;22613;22614	chr2:178720424;178720423;178720422	chr2:179585151;179585150;179585149
N2A	6536	19831;19832;19833	chr2:178720424;178720423;178720422	chr2:179585151;179585150;179585149
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-62
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.8367
• 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
V/E	None	None	0.997	N	0.701	0.57	0.839276590097	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
V/L	rs1220083902	-0.038	0.932	N	0.597	0.294	0.482061804652	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
V/L	rs1220083902	-0.038	0.932	N	0.597	0.294	0.482061804652	gnomAD-4.0.0	1.592E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85963E-06	0	0
V/M	None	None	0.999	N	0.733	0.453	0.547681404787	gnomAD-4.0.0	1.592E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85963E-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
V/A	0.2496	likely_benign	0.2511	benign	-0.401	Destabilizing	0.995	D	0.577	neutral	N	0.457078918	None	None	I
V/C	0.9343	likely_pathogenic	0.9217	pathogenic	-0.874	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
V/D	0.902	likely_pathogenic	0.9206	pathogenic	-0.483	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
V/E	0.8094	likely_pathogenic	0.8448	pathogenic	-0.603	Destabilizing	0.997	D	0.701	prob.neutral	N	0.492697903	None	None	I
V/F	0.2487	likely_benign	0.2695	benign	-0.794	Destabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	I
V/G	0.4786	ambiguous	0.492	ambiguous	-0.445	Destabilizing	1.0	D	0.701	prob.neutral	N	0.500571489	None	None	I
V/H	0.9118	likely_pathogenic	0.9269	pathogenic	-0.023	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
V/I	0.1551	likely_benign	0.1705	benign	-0.424	Destabilizing	0.948	D	0.516	neutral	None	None	None	None	I
V/K	0.9409	likely_pathogenic	0.9544	pathogenic	-0.461	Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	I
V/L	0.664	likely_pathogenic	0.6919	pathogenic	-0.424	Destabilizing	0.932	D	0.597	neutral	N	0.512625557	None	None	I
V/M	0.4272	ambiguous	0.4393	ambiguous	-0.644	Destabilizing	0.999	D	0.733	prob.delet.	N	0.497470843	None	None	I
V/N	0.7699	likely_pathogenic	0.7993	pathogenic	-0.279	Destabilizing	0.992	D	0.727	prob.delet.	None	None	None	None	I
V/P	0.9809	likely_pathogenic	0.9854	pathogenic	-0.39	Destabilizing	0.992	D	0.718	prob.delet.	None	None	None	None	I
V/Q	0.8684	likely_pathogenic	0.8841	pathogenic	-0.504	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	I
V/R	0.8845	likely_pathogenic	0.9016	pathogenic	0.014	Stabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	I
V/S	0.4978	ambiguous	0.5184	ambiguous	-0.573	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	I
V/T	0.3996	ambiguous	0.4282	ambiguous	-0.607	Destabilizing	0.991	D	0.674	neutral	None	None	None	None	I
V/W	0.9459	likely_pathogenic	0.9494	pathogenic	-0.831	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
V/Y	0.7548	likely_pathogenic	0.7812	pathogenic	-0.576	Destabilizing	0.999	D	0.703	prob.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.