TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27918	83977;83978;83979	chr2:178562380;178562379;178562378	chr2:179427107;179427106;179427105
N2AB	26277	79054;79055;79056	chr2:178562380;178562379;178562378	chr2:179427107;179427106;179427105
N2A	25350	76273;76274;76275	chr2:178562380;178562379;178562378	chr2:179427107;179427106;179427105
N2B	18853	56782;56783;56784	chr2:178562380;178562379;178562378	chr2:179427107;179427106;179427105
Novex-1	18978	57157;57158;57159	chr2:178562380;178562379;178562378	chr2:179427107;179427106;179427105
Novex-2	19045	57358;57359;57360	chr2:178562380;178562379;178562378	chr2:179427107;179427106;179427105
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-91
• Domain position: 56
• Structural Position: 88
• Q(SASA): 0.5582
• 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
T/S	None	None	0.309	N	0.309	0.106	0.168933306366	gnomAD-4.0.0	1.59739E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.865E-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	0.0725	likely_benign	0.0773	benign	-0.849	Destabilizing	0.012	N	0.073	neutral	N	0.407372456	None	None	N
T/C	0.3058	likely_benign	0.3572	ambiguous	-0.62	Destabilizing	0.996	D	0.376	neutral	None	None	None	None	N
T/D	0.3639	ambiguous	0.4	ambiguous	-0.318	Destabilizing	0.953	D	0.384	neutral	None	None	None	None	N
T/E	0.3525	ambiguous	0.3984	ambiguous	-0.225	Destabilizing	0.854	D	0.367	neutral	None	None	None	None	N
T/F	0.1708	likely_benign	0.2059	benign	-1.013	Destabilizing	0.91	D	0.403	neutral	None	None	None	None	N
T/G	0.1594	likely_benign	0.1697	benign	-1.118	Destabilizing	0.59	D	0.343	neutral	None	None	None	None	N
T/H	0.2426	likely_benign	0.2726	benign	-0.994	Destabilizing	0.996	D	0.392	neutral	None	None	None	None	N
T/I	0.1279	likely_benign	0.1632	benign	-0.194	Destabilizing	0.003	N	0.157	neutral	N	0.492356567	None	None	N
T/K	0.3015	likely_benign	0.3353	benign	-0.293	Destabilizing	0.742	D	0.374	neutral	None	None	None	None	N
T/L	0.0766	likely_benign	0.0914	benign	-0.194	Destabilizing	0.17	N	0.371	neutral	None	None	None	None	N
T/M	0.0682	likely_benign	0.0762	benign	-0.388	Destabilizing	0.91	D	0.384	neutral	None	None	None	None	N
T/N	0.0828	likely_benign	0.089	benign	-0.651	Destabilizing	0.979	D	0.367	neutral	N	0.482118144	None	None	N
T/P	0.3122	likely_benign	0.3264	benign	-0.384	Destabilizing	0.939	D	0.4	neutral	N	0.501570696	None	None	N
T/Q	0.2497	likely_benign	0.2745	benign	-0.597	Destabilizing	0.984	D	0.403	neutral	None	None	None	None	N
T/R	0.278	likely_benign	0.3108	benign	-0.135	Destabilizing	0.953	D	0.401	neutral	None	None	None	None	N
T/S	0.0857	likely_benign	0.0885	benign	-0.963	Destabilizing	0.309	N	0.309	neutral	N	0.43409491	None	None	N
T/V	0.0962	likely_benign	0.1177	benign	-0.384	Destabilizing	0.17	N	0.293	neutral	None	None	None	None	N
T/W	0.5731	likely_pathogenic	0.6273	pathogenic	-1.094	Destabilizing	0.996	D	0.445	neutral	None	None	None	None	N
T/Y	0.2259	likely_benign	0.2651	benign	-0.735	Destabilizing	0.953	D	0.405	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.