TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26182	78769;78770;78771	chr2:178567588;178567587;178567586	chr2:179432315;179432314;179432313
N2AB	24541	73846;73847;73848	chr2:178567588;178567587;178567586	chr2:179432315;179432314;179432313
N2A	23614	71065;71066;71067	chr2:178567588;178567587;178567586	chr2:179432315;179432314;179432313
N2B	17117	51574;51575;51576	chr2:178567588;178567587;178567586	chr2:179432315;179432314;179432313
Novex-1	17242	51949;51950;51951	chr2:178567588;178567587;178567586	chr2:179432315;179432314;179432313
Novex-2	17309	52150;52151;52152	chr2:178567588;178567587;178567586	chr2:179432315;179432314;179432313
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-78
• Domain position: 95
• Structural Position: 127
• Q(SASA): 0.3051
• 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
I/V	None	None	0.005	N	0.181	0.092	0.230578612272	gnomAD-4.0.0	2.05771E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70366E-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
I/A	0.8573	likely_pathogenic	0.8799	pathogenic	-2.461	Highly Destabilizing	0.717	D	0.611	neutral	None	None	None	None	N
I/C	0.8961	likely_pathogenic	0.901	pathogenic	-1.628	Destabilizing	0.998	D	0.735	deleterious	None	None	None	None	N
I/D	0.9942	likely_pathogenic	0.9956	pathogenic	-2.724	Highly Destabilizing	0.991	D	0.815	deleterious	None	None	None	None	N
I/E	0.9701	likely_pathogenic	0.9747	pathogenic	-2.482	Highly Destabilizing	0.973	D	0.826	deleterious	None	None	None	None	N
I/F	0.5013	ambiguous	0.5195	ambiguous	-1.452	Destabilizing	0.947	D	0.697	prob.delet.	None	None	None	None	N
I/G	0.9815	likely_pathogenic	0.9855	pathogenic	-3.021	Highly Destabilizing	0.973	D	0.807	deleterious	None	None	None	None	N
I/H	0.9546	likely_pathogenic	0.9592	pathogenic	-2.414	Highly Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
I/K	0.9094	likely_pathogenic	0.9201	pathogenic	-1.935	Destabilizing	0.964	D	0.819	deleterious	N	0.488160733	None	None	N
I/L	0.234	likely_benign	0.2606	benign	-0.839	Destabilizing	0.256	N	0.348	neutral	N	0.459207152	None	None	N
I/M	0.2579	likely_benign	0.2674	benign	-0.706	Destabilizing	0.964	D	0.67	prob.neutral	N	0.490442139	None	None	N
I/N	0.9329	likely_pathogenic	0.9459	pathogenic	-2.314	Highly Destabilizing	0.991	D	0.825	deleterious	None	None	None	None	N
I/P	0.9958	likely_pathogenic	0.9967	pathogenic	-1.361	Destabilizing	0.991	D	0.825	deleterious	None	None	None	None	N
I/Q	0.9331	likely_pathogenic	0.9388	pathogenic	-2.152	Highly Destabilizing	0.991	D	0.795	deleterious	None	None	None	None	N
I/R	0.8782	likely_pathogenic	0.8926	pathogenic	-1.686	Destabilizing	0.964	D	0.822	deleterious	N	0.487653754	None	None	N
I/S	0.9167	likely_pathogenic	0.9329	pathogenic	-3.012	Highly Destabilizing	0.973	D	0.725	deleterious	None	None	None	None	N
I/T	0.7872	likely_pathogenic	0.8106	pathogenic	-2.614	Highly Destabilizing	0.792	D	0.717	prob.delet.	N	0.485372349	None	None	N
I/V	0.0693	likely_benign	0.0713	benign	-1.361	Destabilizing	0.005	N	0.181	neutral	N	0.402064558	None	None	N
I/W	0.9772	likely_pathogenic	0.9788	pathogenic	-1.836	Destabilizing	0.998	D	0.695	prob.delet.	None	None	None	None	N
I/Y	0.9031	likely_pathogenic	0.9119	pathogenic	-1.521	Destabilizing	0.973	D	0.76	deleterious	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.