TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32845	98758;98759;98760	chr2:178539532;178539531;178539530	chr2:179404259;179404258;179404257
N2AB	31204	93835;93836;93837	chr2:178539532;178539531;178539530	chr2:179404259;179404258;179404257
N2A	30277	91054;91055;91056	chr2:178539532;178539531;178539530	chr2:179404259;179404258;179404257
N2B	23780	71563;71564;71565	chr2:178539532;178539531;178539530	chr2:179404259;179404258;179404257
Novex-1	23905	71938;71939;71940	chr2:178539532;178539531;178539530	chr2:179404259;179404258;179404257
Novex-2	23972	72139;72140;72141	chr2:178539532;178539531;178539530	chr2:179404259;179404258;179404257
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-127
• Domain position: 51
• Structural Position: 67
• Q(SASA): 0.445
• 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
T/I	rs1230480423	0.114	1.0	N	0.782	0.463	0.551634222746	gnomAD-4.0.0	2.73676E-06	None	None	None	None	I	None	0	2.23604E-05	None	0	0	None	0	0	2.6984E-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
T/A	0.1889	likely_benign	0.1428	benign	-0.733	Destabilizing	0.999	D	0.549	neutral	D	0.524695485	None	None	I
T/C	0.6634	likely_pathogenic	0.5556	ambiguous	-0.49	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
T/D	0.8627	likely_pathogenic	0.7611	pathogenic	-0.081	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
T/E	0.7428	likely_pathogenic	0.615	pathogenic	-0.088	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
T/F	0.7616	likely_pathogenic	0.6288	pathogenic	-0.788	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
T/G	0.6221	likely_pathogenic	0.5386	ambiguous	-0.982	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
T/H	0.6768	likely_pathogenic	0.5518	ambiguous	-1.202	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
T/I	0.4107	ambiguous	0.2954	benign	-0.165	Destabilizing	1.0	D	0.782	deleterious	N	0.471257107	None	None	I
T/K	0.5479	ambiguous	0.4222	ambiguous	-0.741	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
T/L	0.2495	likely_benign	0.1816	benign	-0.165	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	I
T/M	0.2003	likely_benign	0.1509	benign	0.012	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
T/N	0.3961	ambiguous	0.2841	benign	-0.641	Destabilizing	1.0	D	0.748	deleterious	N	0.521463179	None	None	I
T/P	0.2559	likely_benign	0.1792	benign	-0.322	Destabilizing	1.0	D	0.782	deleterious	N	0.462993665	None	None	I
T/Q	0.5275	ambiguous	0.4164	ambiguous	-0.79	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
T/R	0.4706	ambiguous	0.3441	ambiguous	-0.482	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
T/S	0.3138	likely_benign	0.241	benign	-0.92	Destabilizing	0.999	D	0.555	neutral	N	0.521500464	None	None	I
T/V	0.2675	likely_benign	0.2038	benign	-0.322	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	I
T/W	0.9231	likely_pathogenic	0.8718	pathogenic	-0.732	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
T/Y	0.7731	likely_pathogenic	0.6466	pathogenic	-0.51	Destabilizing	1.0	D	0.767	deleterious	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.