TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33664	101215;101216;101217	chr2:178535625;178535624;178535623	chr2:179400352;179400351;179400350
N2AB	32023	96292;96293;96294	chr2:178535625;178535624;178535623	chr2:179400352;179400351;179400350
N2A	31096	93511;93512;93513	chr2:178535625;178535624;178535623	chr2:179400352;179400351;179400350
N2B	24599	74020;74021;74022	chr2:178535625;178535624;178535623	chr2:179400352;179400351;179400350
Novex-1	24724	74395;74396;74397	chr2:178535625;178535624;178535623	chr2:179400352;179400351;179400350
Novex-2	24791	74596;74597;74598	chr2:178535625;178535624;178535623	chr2:179400352;179400351;179400350
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-159
• Domain position: 69
• Structural Position: 151
• Q(SASA): 0.1645
• 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
A/D	None	None	0.946	D	0.66	0.394	0.577897453458	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
A/C	0.7087	likely_pathogenic	0.626	pathogenic	-0.982	Destabilizing	0.998	D	0.53	neutral	None	None	None	None	N
A/D	0.8022	likely_pathogenic	0.6648	pathogenic	-0.935	Destabilizing	0.946	D	0.66	neutral	D	0.523901343	None	None	N
A/E	0.6885	likely_pathogenic	0.5217	ambiguous	-0.985	Destabilizing	0.97	D	0.623	neutral	None	None	None	None	N
A/F	0.8066	likely_pathogenic	0.6801	pathogenic	-1.066	Destabilizing	0.998	D	0.762	deleterious	None	None	None	None	N
A/G	0.2529	likely_benign	0.1937	benign	-1.125	Destabilizing	0.002	N	0.271	neutral	N	0.488153974	None	None	N
A/H	0.8129	likely_pathogenic	0.7152	pathogenic	-1.174	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
A/I	0.7309	likely_pathogenic	0.5827	pathogenic	-0.431	Destabilizing	0.989	D	0.682	prob.neutral	None	None	None	None	N
A/K	0.7913	likely_pathogenic	0.6354	pathogenic	-1.161	Destabilizing	0.989	D	0.619	neutral	None	None	None	None	N
A/L	0.58	likely_pathogenic	0.4715	ambiguous	-0.431	Destabilizing	0.961	D	0.586	neutral	None	None	None	None	N
A/M	0.5578	ambiguous	0.4334	ambiguous	-0.368	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
A/N	0.5918	likely_pathogenic	0.4741	ambiguous	-0.905	Destabilizing	0.73	D	0.665	neutral	None	None	None	None	N
A/P	0.9434	likely_pathogenic	0.8959	pathogenic	-0.545	Destabilizing	0.972	D	0.681	prob.neutral	N	0.506522971	None	None	N
A/Q	0.6156	likely_pathogenic	0.5073	ambiguous	-1.081	Destabilizing	0.994	D	0.693	prob.neutral	None	None	None	None	N
A/R	0.6652	likely_pathogenic	0.5112	ambiguous	-0.766	Destabilizing	0.994	D	0.688	prob.neutral	None	None	None	None	N
A/S	0.1189	likely_benign	0.1015	benign	-1.282	Destabilizing	0.014	N	0.241	neutral	N	0.432316547	None	None	N
A/T	0.1625	likely_benign	0.1131	benign	-1.234	Destabilizing	0.092	N	0.299	neutral	N	0.476955545	None	None	N
A/V	0.4278	ambiguous	0.3038	benign	-0.545	Destabilizing	0.874	D	0.493	neutral	N	0.516263295	None	None	N
A/W	0.9699	likely_pathogenic	0.9384	pathogenic	-1.345	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
A/Y	0.8818	likely_pathogenic	0.7904	pathogenic	-0.958	Destabilizing	0.998	D	0.752	deleterious	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.