TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9753	29482;29483;29484	chr2:178706617;178706616;178706615	chr2:179571344;179571343;179571342
N2AB	9436	28531;28532;28533	chr2:178706617;178706616;178706615	chr2:179571344;179571343;179571342
N2A	8509	25750;25751;25752	chr2:178706617;178706616;178706615	chr2:179571344;179571343;179571342
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-83
• Domain position: 56
• Structural Position: 135
• Q(SASA): 0.4887
• 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
E/D	None	None	0.434	None	0.254	0.04	0.315903272564	gnomAD-4.0.0	1.59096E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8577E-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
E/A	0.4983	ambiguous	0.3314	benign	-0.724	Destabilizing	0.998	D	0.649	neutral	None	None	None	None	I
E/C	0.9828	likely_pathogenic	0.9664	pathogenic	-0.416	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
E/D	0.5027	ambiguous	0.3172	benign	-1.178	Destabilizing	0.434	N	0.254	neutral	None	None	None	None	I
E/F	0.9402	likely_pathogenic	0.878	pathogenic	-0.512	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
E/G	0.7784	likely_pathogenic	0.5429	ambiguous	-1.06	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	I
E/H	0.8883	likely_pathogenic	0.7709	pathogenic	-0.902	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
E/I	0.5543	ambiguous	0.4307	ambiguous	0.175	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
E/K	0.49	ambiguous	0.2812	benign	-0.706	Destabilizing	0.998	D	0.571	neutral	None	None	None	None	I
E/L	0.7827	likely_pathogenic	0.6429	pathogenic	0.175	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
E/M	0.7331	likely_pathogenic	0.5836	pathogenic	0.624	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
E/N	0.7613	likely_pathogenic	0.5682	pathogenic	-1.024	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	I
E/P	0.9981	likely_pathogenic	0.9909	pathogenic	-0.103	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
E/Q	0.4214	ambiguous	0.2742	benign	-0.907	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	I
E/R	0.7307	likely_pathogenic	0.5103	ambiguous	-0.547	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
E/S	0.6543	likely_pathogenic	0.4695	ambiguous	-1.311	Destabilizing	0.997	D	0.61	neutral	None	None	None	None	I
E/T	0.4778	ambiguous	0.3392	benign	-1.044	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
E/V	0.3743	ambiguous	0.2655	benign	-0.103	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
E/W	0.9894	likely_pathogenic	0.9716	pathogenic	-0.413	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
E/Y	0.9184	likely_pathogenic	0.8394	pathogenic	-0.313	Destabilizing	1.0	D	0.722	prob.delet.	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.