TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20578	61957;61958;61959	chr2:178589993;178589992;178589991	chr2:179454720;179454719;179454718
N2AB	18937	57034;57035;57036	chr2:178589993;178589992;178589991	chr2:179454720;179454719;179454718
N2A	18010	54253;54254;54255	chr2:178589993;178589992;178589991	chr2:179454720;179454719;179454718
N2B	11513	34762;34763;34764	chr2:178589993;178589992;178589991	chr2:179454720;179454719;179454718
Novex-1	11638	35137;35138;35139	chr2:178589993;178589992;178589991	chr2:179454720;179454719;179454718
Novex-2	11705	35338;35339;35340	chr2:178589993;178589992;178589991	chr2:179454720;179454719;179454718
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-37
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.2802
• 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
V/L	None	None	0.015	D	0.36	0.121	0.263140351381	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.5294	ambiguous	0.5783	pathogenic	-1.512	Destabilizing	0.165	N	0.42	neutral	N	0.507533876	None	None	N
V/C	0.8835	likely_pathogenic	0.8822	pathogenic	-1.223	Destabilizing	0.932	D	0.651	neutral	None	None	None	None	N
V/D	0.9789	likely_pathogenic	0.9756	pathogenic	-0.861	Destabilizing	0.773	D	0.709	prob.delet.	D	0.528602201	None	None	N
V/E	0.9562	likely_pathogenic	0.9504	pathogenic	-0.765	Destabilizing	0.563	D	0.647	neutral	None	None	None	None	N
V/F	0.5919	likely_pathogenic	0.6451	pathogenic	-0.956	Destabilizing	0.627	D	0.656	neutral	N	0.476221084	None	None	N
V/G	0.7743	likely_pathogenic	0.7733	pathogenic	-1.921	Destabilizing	0.492	N	0.677	prob.neutral	N	0.498127682	None	None	N
V/H	0.9848	likely_pathogenic	0.9835	pathogenic	-1.334	Destabilizing	0.981	D	0.701	prob.neutral	None	None	None	None	N
V/I	0.0905	likely_benign	0.0994	benign	-0.455	Destabilizing	0.001	N	0.185	neutral	N	0.47398145	None	None	N
V/K	0.9753	likely_pathogenic	0.9693	pathogenic	-1.128	Destabilizing	0.563	D	0.633	neutral	None	None	None	None	N
V/L	0.4998	ambiguous	0.5134	ambiguous	-0.455	Destabilizing	0.015	N	0.36	neutral	D	0.525871708	None	None	N
V/M	0.4411	ambiguous	0.4752	ambiguous	-0.551	Destabilizing	0.054	N	0.363	neutral	None	None	None	None	N
V/N	0.9296	likely_pathogenic	0.9226	pathogenic	-1.111	Destabilizing	0.818	D	0.714	prob.delet.	None	None	None	None	N
V/P	0.7937	likely_pathogenic	0.8012	pathogenic	-0.773	Destabilizing	0.932	D	0.679	prob.neutral	None	None	None	None	N
V/Q	0.9591	likely_pathogenic	0.9546	pathogenic	-1.084	Destabilizing	0.818	D	0.674	neutral	None	None	None	None	N
V/R	0.968	likely_pathogenic	0.9614	pathogenic	-0.84	Destabilizing	0.818	D	0.708	prob.delet.	None	None	None	None	N
V/S	0.8328	likely_pathogenic	0.8398	pathogenic	-1.801	Destabilizing	0.241	N	0.566	neutral	None	None	None	None	N
V/T	0.5952	likely_pathogenic	0.624	pathogenic	-1.553	Destabilizing	0.004	N	0.171	neutral	None	None	None	None	N
V/W	0.9851	likely_pathogenic	0.986	pathogenic	-1.153	Destabilizing	0.981	D	0.703	prob.neutral	None	None	None	None	N
V/Y	0.9329	likely_pathogenic	0.9398	pathogenic	-0.835	Destabilizing	0.818	D	0.657	neutral	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.