TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1852	5779;5780;5781	chr2:178776310;178776309;178776308	chr2:179641037;179641036;179641035
N2AB	1852	5779;5780;5781	chr2:178776310;178776309;178776308	chr2:179641037;179641036;179641035
N2A	1852	5779;5780;5781	chr2:178776310;178776309;178776308	chr2:179641037;179641036;179641035
N2B	1806	5641;5642;5643	chr2:178776310;178776309;178776308	chr2:179641037;179641036;179641035
Novex-1	1806	5641;5642;5643	chr2:178776310;178776309;178776308	chr2:179641037;179641036;179641035
Novex-2	1806	5641;5642;5643	chr2:178776310;178776309;178776308	chr2:179641037;179641036;179641035
Novex-3	1852	5779;5780;5781	chr2:178776310;178776309;178776308	chr2:179641037;179641036;179641035

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-9
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1434
• 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
V/I	None	None	0.997	D	0.466	0.417	0.774770343904	gnomAD-4.0.0	6.84119E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99306E-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
V/A	0.6319	likely_pathogenic	0.7172	pathogenic	-1.768	Destabilizing	0.999	D	0.478	neutral	N	0.518150283	None	None	N
V/C	0.8982	likely_pathogenic	0.9182	pathogenic	-1.159	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
V/D	0.9881	likely_pathogenic	0.9936	pathogenic	-1.725	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
V/E	0.9603	likely_pathogenic	0.9756	pathogenic	-1.671	Destabilizing	1.0	D	0.699	prob.neutral	D	0.68859566	None	None	N
V/F	0.7878	likely_pathogenic	0.8585	pathogenic	-1.189	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
V/G	0.7835	likely_pathogenic	0.841	pathogenic	-2.15	Highly Destabilizing	1.0	D	0.718	prob.delet.	D	0.622406438	None	None	N
V/H	0.9832	likely_pathogenic	0.99	pathogenic	-1.676	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
V/I	0.1323	likely_benign	0.152	benign	-0.785	Destabilizing	0.997	D	0.466	neutral	D	0.545862481	None	None	N
V/K	0.9608	likely_pathogenic	0.974	pathogenic	-1.461	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
V/L	0.6134	likely_pathogenic	0.6852	pathogenic	-0.785	Destabilizing	0.997	D	0.491	neutral	D	0.579797902	None	None	N
V/M	0.5901	likely_pathogenic	0.6948	pathogenic	-0.631	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
V/N	0.9518	likely_pathogenic	0.9738	pathogenic	-1.317	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
V/P	0.9897	likely_pathogenic	0.9921	pathogenic	-1.08	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
V/Q	0.9431	likely_pathogenic	0.9654	pathogenic	-1.429	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
V/R	0.9488	likely_pathogenic	0.9637	pathogenic	-0.985	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
V/S	0.8339	likely_pathogenic	0.895	pathogenic	-1.891	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
V/T	0.6572	likely_pathogenic	0.7411	pathogenic	-1.726	Destabilizing	0.999	D	0.62	neutral	None	None	None	None	N
V/W	0.9959	likely_pathogenic	0.9975	pathogenic	-1.451	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	N
V/Y	0.9772	likely_pathogenic	0.9851	pathogenic	-1.161	Destabilizing	1.0	D	0.729	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.