TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24560	73903;73904;73905	chr2:178572454;178572453;178572452	chr2:179437181;179437180;179437179
N2AB	22919	68980;68981;68982	chr2:178572454;178572453;178572452	chr2:179437181;179437180;179437179
N2A	21992	66199;66200;66201	chr2:178572454;178572453;178572452	chr2:179437181;179437180;179437179
N2B	15495	46708;46709;46710	chr2:178572454;178572453;178572452	chr2:179437181;179437180;179437179
Novex-1	15620	47083;47084;47085	chr2:178572454;178572453;178572452	chr2:179437181;179437180;179437179
Novex-2	15687	47284;47285;47286	chr2:178572454;178572453;178572452	chr2:179437181;179437180;179437179
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: Fn3-66
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.0957
• 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
E/A	None	None	0.914	N	0.481	0.395	0.437958778045	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.8992	likely_pathogenic	0.7981	pathogenic	-0.995	Destabilizing	0.914	D	0.481	neutral	N	0.491171787	None	None	N
E/C	0.9942	likely_pathogenic	0.9903	pathogenic	-0.511	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/D	0.7001	likely_pathogenic	0.5649	pathogenic	-1.209	Destabilizing	0.732	D	0.456	neutral	N	0.4638791	None	None	N
E/F	0.9962	likely_pathogenic	0.9918	pathogenic	-0.439	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
E/G	0.9394	likely_pathogenic	0.8812	pathogenic	-1.374	Destabilizing	0.181	N	0.307	neutral	N	0.489058647	None	None	N
E/H	0.9903	likely_pathogenic	0.9801	pathogenic	-0.74	Destabilizing	0.999	D	0.547	neutral	None	None	None	None	N
E/I	0.978	likely_pathogenic	0.9542	pathogenic	0.05	Stabilizing	0.994	D	0.739	prob.delet.	None	None	None	None	N
E/K	0.9689	likely_pathogenic	0.9364	pathogenic	-0.739	Destabilizing	0.109	N	0.263	neutral	N	0.468001423	None	None	N
E/L	0.9699	likely_pathogenic	0.9284	pathogenic	0.05	Stabilizing	0.988	D	0.638	neutral	None	None	None	None	N
E/M	0.9785	likely_pathogenic	0.9513	pathogenic	0.593	Stabilizing	0.997	D	0.677	prob.neutral	None	None	None	None	N
E/N	0.9684	likely_pathogenic	0.929	pathogenic	-1.212	Destabilizing	0.975	D	0.521	neutral	None	None	None	None	N
E/P	0.9818	likely_pathogenic	0.9717	pathogenic	-0.277	Destabilizing	0.963	D	0.642	neutral	None	None	None	None	N
E/Q	0.8937	likely_pathogenic	0.7888	pathogenic	-1.069	Destabilizing	0.99	D	0.541	neutral	N	0.4838015	None	None	N
E/R	0.9784	likely_pathogenic	0.9601	pathogenic	-0.463	Destabilizing	0.989	D	0.526	neutral	None	None	None	None	N
E/S	0.9536	likely_pathogenic	0.9052	pathogenic	-1.56	Destabilizing	0.966	D	0.46	neutral	None	None	None	None	N
E/T	0.978	likely_pathogenic	0.952	pathogenic	-1.241	Destabilizing	0.993	D	0.54	neutral	None	None	None	None	N
E/V	0.9503	likely_pathogenic	0.8986	pathogenic	-0.277	Destabilizing	0.979	D	0.589	neutral	N	0.503542051	None	None	N
E/W	0.9988	likely_pathogenic	0.9978	pathogenic	-0.178	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/Y	0.9929	likely_pathogenic	0.9858	pathogenic	-0.183	Destabilizing	1.0	D	0.706	prob.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.