TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5810	17653;17654;17655	chr2:178731338;178731337;178731336	chr2:179596065;179596064;179596063
N2AB	5493	16702;16703;16704	chr2:178731338;178731337;178731336	chr2:179596065;179596064;179596063
N2A	4566	13921;13922;13923	chr2:178731338;178731337;178731336	chr2:179596065;179596064;179596063
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-41
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.5152
• 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
I/M	rs762158553	-0.411	0.655	N	0.433	0.184	0.615969100344	gnomAD-4.0.0	7.95641E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85838E-06	5.73148E-05	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
I/A	0.392	ambiguous	0.4191	ambiguous	-1.254	Destabilizing	0.004	N	0.189	neutral	None	None	None	None	I
I/C	0.6766	likely_pathogenic	0.6868	pathogenic	-0.725	Destabilizing	0.836	D	0.498	neutral	None	None	None	None	I
I/D	0.6514	likely_pathogenic	0.6449	pathogenic	-0.781	Destabilizing	0.418	N	0.561	neutral	None	None	None	None	I
I/E	0.5009	ambiguous	0.4759	ambiguous	-0.849	Destabilizing	0.264	N	0.583	neutral	None	None	None	None	I
I/F	0.1294	likely_benign	0.1353	benign	-1.023	Destabilizing	0.716	D	0.389	neutral	None	None	None	None	I
I/G	0.6047	likely_pathogenic	0.636	pathogenic	-1.484	Destabilizing	0.228	N	0.587	neutral	None	None	None	None	I
I/H	0.4822	ambiguous	0.4761	ambiguous	-0.656	Destabilizing	0.836	D	0.549	neutral	None	None	None	None	I
I/K	0.4118	ambiguous	0.3892	ambiguous	-0.81	Destabilizing	0.213	N	0.589	neutral	N	0.409012826	None	None	I
I/L	0.1123	likely_benign	0.1202	benign	-0.737	Destabilizing	0.047	N	0.185	neutral	N	0.46138866	None	None	I
I/M	0.0943	likely_benign	0.0945	benign	-0.569	Destabilizing	0.655	D	0.433	neutral	N	0.443149616	None	None	I
I/N	0.247	likely_benign	0.2381	benign	-0.541	Destabilizing	0.418	N	0.574	neutral	None	None	None	None	I
I/P	0.8291	likely_pathogenic	0.8624	pathogenic	-0.877	Destabilizing	0.836	D	0.559	neutral	None	None	None	None	I
I/Q	0.4138	ambiguous	0.4019	ambiguous	-0.813	Destabilizing	0.027	N	0.417	neutral	None	None	None	None	I
I/R	0.3541	ambiguous	0.3435	ambiguous	-0.126	Destabilizing	0.351	N	0.567	neutral	N	0.466447763	None	None	I
I/S	0.2438	likely_benign	0.2424	benign	-1.036	Destabilizing	0.012	N	0.266	neutral	None	None	None	None	I
I/T	0.2364	likely_benign	0.2408	benign	-1.0	Destabilizing	0.101	N	0.468	neutral	N	0.412941352	None	None	I
I/V	0.0941	likely_benign	0.1002	benign	-0.877	Destabilizing	0.001	N	0.122	neutral	N	0.418925962	None	None	I
I/W	0.6424	likely_pathogenic	0.6578	pathogenic	-1.011	Destabilizing	0.983	D	0.56	neutral	None	None	None	None	I
I/Y	0.3788	ambiguous	0.3708	ambiguous	-0.81	Destabilizing	0.836	D	0.504	neutral	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.