TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20629	62110;62111;62112	chr2:178589840;178589839;178589838	chr2:179454567;179454566;179454565
N2AB	18988	57187;57188;57189	chr2:178589840;178589839;178589838	chr2:179454567;179454566;179454565
N2A	18061	54406;54407;54408	chr2:178589840;178589839;178589838	chr2:179454567;179454566;179454565
N2B	11564	34915;34916;34917	chr2:178589840;178589839;178589838	chr2:179454567;179454566;179454565
Novex-1	11689	35290;35291;35292	chr2:178589840;178589839;178589838	chr2:179454567;179454566;179454565
Novex-2	11756	35491;35492;35493	chr2:178589840;178589839;178589838	chr2:179454567;179454566;179454565
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-37
• Domain position: 61
• Structural Position: 93
• Q(SASA): 0.3897
• 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
K/E	None	None	0.999	N	0.629	0.482	0.377451072189	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.7952	likely_pathogenic	0.7028	pathogenic	-0.286	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	I
K/C	0.8977	likely_pathogenic	0.8387	pathogenic	-0.315	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
K/D	0.9154	likely_pathogenic	0.8644	pathogenic	-0.068	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	I
K/E	0.5998	likely_pathogenic	0.5071	ambiguous	-0.026	Destabilizing	0.999	D	0.629	neutral	N	0.498004961	None	None	I
K/F	0.9539	likely_pathogenic	0.9244	pathogenic	-0.306	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
K/G	0.8954	likely_pathogenic	0.8325	pathogenic	-0.569	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
K/H	0.5373	ambiguous	0.4688	ambiguous	-0.966	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
K/I	0.7242	likely_pathogenic	0.5935	pathogenic	0.404	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
K/L	0.7618	likely_pathogenic	0.6579	pathogenic	0.404	Stabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
K/M	0.6375	likely_pathogenic	0.5342	ambiguous	0.374	Stabilizing	1.0	D	0.725	prob.delet.	N	0.519268236	None	None	I
K/N	0.8446	likely_pathogenic	0.7679	pathogenic	-0.085	Destabilizing	1.0	D	0.641	neutral	N	0.475292351	None	None	I
K/P	0.8862	likely_pathogenic	0.804	pathogenic	0.204	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
K/Q	0.3383	likely_benign	0.2698	benign	-0.275	Destabilizing	1.0	D	0.637	neutral	N	0.467276953	None	None	I
K/R	0.1302	likely_benign	0.118	benign	-0.327	Destabilizing	0.999	D	0.61	neutral	N	0.516652005	None	None	I
K/S	0.8333	likely_pathogenic	0.7569	pathogenic	-0.668	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	I
K/T	0.4556	ambiguous	0.3785	ambiguous	-0.449	Destabilizing	1.0	D	0.695	prob.neutral	N	0.496372733	None	None	I
K/V	0.6429	likely_pathogenic	0.5347	ambiguous	0.204	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
K/W	0.9481	likely_pathogenic	0.9139	pathogenic	-0.218	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
K/Y	0.891	likely_pathogenic	0.8289	pathogenic	0.104	Stabilizing	1.0	D	0.764	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.