TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7290	22093;22094;22095	chr2:178723139;178723138;178723137	chr2:179587866;179587865;179587864
N2AB	6973	21142;21143;21144	chr2:178723139;178723138;178723137	chr2:179587866;179587865;179587864
N2A	6046	18361;18362;18363	chr2:178723139;178723138;178723137	chr2:179587866;179587865;179587864
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-57
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.2433
• 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
L/M	None	None	0.864	N	0.665	0.249	0.534814951121	gnomAD-4.0.0	6.84321E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9956E-07	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
L/A	0.129	likely_benign	0.1151	benign	-1.173	Destabilizing	0.547	D	0.458	neutral	None	None	None	None	N
L/C	0.3305	likely_benign	0.2773	benign	-0.775	Destabilizing	0.985	D	0.667	neutral	None	None	None	None	N
L/D	0.3718	ambiguous	0.3236	benign	-0.625	Destabilizing	0.945	D	0.749	deleterious	None	None	None	None	N
L/E	0.181	likely_benign	0.1602	benign	-0.695	Destabilizing	0.945	D	0.746	deleterious	None	None	None	None	N
L/F	0.0941	likely_benign	0.0853	benign	-1.121	Destabilizing	0.894	D	0.668	neutral	None	None	None	None	N
L/G	0.2594	likely_benign	0.2266	benign	-1.403	Destabilizing	0.945	D	0.738	prob.delet.	None	None	None	None	N
L/H	0.113	likely_benign	0.0991	benign	-0.663	Destabilizing	0.995	D	0.719	prob.delet.	None	None	None	None	N
L/I	0.0733	likely_benign	0.0726	benign	-0.66	Destabilizing	0.031	N	0.273	neutral	None	None	None	None	N
L/K	0.1275	likely_benign	0.1177	benign	-0.577	Destabilizing	0.945	D	0.716	prob.delet.	None	None	None	None	N
L/M	0.1023	likely_benign	0.0985	benign	-0.414	Destabilizing	0.864	D	0.665	neutral	N	0.490492176	None	None	N
L/N	0.1797	likely_benign	0.1528	benign	-0.321	Destabilizing	0.981	D	0.741	deleterious	None	None	None	None	N
L/P	0.1004	likely_benign	0.0868	benign	-0.798	Destabilizing	0.975	D	0.75	deleterious	N	0.476723472	None	None	N
L/Q	0.0803	likely_benign	0.0753	benign	-0.608	Destabilizing	0.975	D	0.725	prob.delet.	N	0.500944339	None	None	N
L/R	0.0908	likely_benign	0.087	benign	0.036	Stabilizing	0.928	D	0.735	prob.delet.	N	0.495615877	None	None	N
L/S	0.1207	likely_benign	0.1075	benign	-0.886	Destabilizing	0.894	D	0.719	prob.delet.	None	None	None	None	N
L/T	0.1125	likely_benign	0.1005	benign	-0.844	Destabilizing	0.894	D	0.597	neutral	None	None	None	None	N
L/V	0.076	likely_benign	0.0732	benign	-0.798	Destabilizing	0.006	N	0.277	neutral	N	0.51181748	None	None	N
L/W	0.1337	likely_benign	0.1277	benign	-1.107	Destabilizing	0.995	D	0.699	prob.neutral	None	None	None	None	N
L/Y	0.1958	likely_benign	0.1758	benign	-0.847	Destabilizing	0.945	D	0.722	prob.delet.	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.