TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17203	51832;51833;51834	chr2:178609816;178609815;178609814	chr2:179474543;179474542;179474541
N2AB	15562	46909;46910;46911	chr2:178609816;178609815;178609814	chr2:179474543;179474542;179474541
N2A	14635	44128;44129;44130	chr2:178609816;178609815;178609814	chr2:179474543;179474542;179474541
N2B	8138	24637;24638;24639	chr2:178609816;178609815;178609814	chr2:179474543;179474542;179474541
Novex-1	8263	25012;25013;25014	chr2:178609816;178609815;178609814	chr2:179474543;179474542;179474541
Novex-2	8330	25213;25214;25215	chr2:178609816;178609815;178609814	chr2:179474543;179474542;179474541
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-13
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.5143
• 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
P/S	rs1559763601	None	1.0	N	0.747	0.419	0.347879110917	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	2.75482E-04	None	0	0	0	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
P/A	0.4863	ambiguous	0.5052	ambiguous	-0.788	Destabilizing	1.0	D	0.693	prob.neutral	N	0.489406689	None	None	I
P/C	0.9584	likely_pathogenic	0.9602	pathogenic	-0.859	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
P/D	0.8431	likely_pathogenic	0.8518	pathogenic	-0.34	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
P/E	0.7859	likely_pathogenic	0.789	pathogenic	-0.369	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
P/F	0.9775	likely_pathogenic	0.9789	pathogenic	-0.583	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
P/G	0.7157	likely_pathogenic	0.7103	pathogenic	-1.019	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
P/H	0.7077	likely_pathogenic	0.7238	pathogenic	-0.348	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
P/I	0.9611	likely_pathogenic	0.9649	pathogenic	-0.288	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
P/K	0.8464	likely_pathogenic	0.8512	pathogenic	-0.722	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
P/L	0.7279	likely_pathogenic	0.7508	pathogenic	-0.288	Destabilizing	1.0	D	0.731	prob.delet.	N	0.469443	None	None	I
P/M	0.9226	likely_pathogenic	0.9314	pathogenic	-0.493	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
P/N	0.7537	likely_pathogenic	0.7597	pathogenic	-0.677	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
P/Q	0.6234	likely_pathogenic	0.6374	pathogenic	-0.797	Destabilizing	1.0	D	0.734	prob.delet.	N	0.510744753	None	None	I
P/R	0.7334	likely_pathogenic	0.7378	pathogenic	-0.242	Destabilizing	1.0	D	0.708	prob.delet.	N	0.493583144	None	None	I
P/S	0.4894	ambiguous	0.5061	ambiguous	-1.142	Destabilizing	1.0	D	0.747	deleterious	N	0.454275395	None	None	I
P/T	0.5731	likely_pathogenic	0.6026	pathogenic	-1.055	Destabilizing	1.0	D	0.737	prob.delet.	N	0.455734045	None	None	I
P/V	0.8953	likely_pathogenic	0.9037	pathogenic	-0.419	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
P/W	0.9792	likely_pathogenic	0.9803	pathogenic	-0.713	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
P/Y	0.9504	likely_pathogenic	0.9502	pathogenic	-0.416	Destabilizing	1.0	D	0.701	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.