TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2718	8377;8378;8379	chr2:178770640;178770639;178770638	chr2:179635367;179635366;179635365
N2AB	2718	8377;8378;8379	chr2:178770640;178770639;178770638	chr2:179635367;179635366;179635365
N2A	2718	8377;8378;8379	chr2:178770640;178770639;178770638	chr2:179635367;179635366;179635365
N2B	2672	8239;8240;8241	chr2:178770640;178770639;178770638	chr2:179635367;179635366;179635365
Novex-1	2672	8239;8240;8241	chr2:178770640;178770639;178770638	chr2:179635367;179635366;179635365
Novex-2	2672	8239;8240;8241	chr2:178770640;178770639;178770638	chr2:179635367;179635366;179635365
Novex-3	2718	8377;8378;8379	chr2:178770640;178770639;178770638	chr2:179635367;179635366;179635365

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-17
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.3481
• 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
V/A	rs2091324546	None	0.999	D	0.481	0.667	0.746317035393	gnomAD-4.0.0	1.59126E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43287E-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
V/A	0.5541	ambiguous	0.6973	pathogenic	-0.501	Destabilizing	0.999	D	0.481	neutral	D	0.54989227	None	None	I
V/C	0.9481	likely_pathogenic	0.9631	pathogenic	-0.519	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	I
V/D	0.9868	likely_pathogenic	0.9927	pathogenic	-0.266	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
V/E	0.9493	likely_pathogenic	0.9618	pathogenic	-0.393	Destabilizing	1.0	D	0.652	neutral	D	0.703029302	None	None	I
V/F	0.8528	likely_pathogenic	0.8979	pathogenic	-0.83	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I
V/G	0.8223	likely_pathogenic	0.9056	pathogenic	-0.622	Destabilizing	1.0	D	0.682	prob.neutral	D	0.702944807	None	None	I
V/H	0.9906	likely_pathogenic	0.9935	pathogenic	-0.296	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
V/I	0.1356	likely_benign	0.1589	benign	-0.338	Destabilizing	0.998	D	0.515	neutral	None	None	None	None	I
V/K	0.9557	likely_pathogenic	0.9593	pathogenic	-0.374	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	I
V/L	0.7328	likely_pathogenic	0.7955	pathogenic	-0.338	Destabilizing	0.997	D	0.517	neutral	D	0.607329521	None	None	I
V/M	0.5489	ambiguous	0.6408	pathogenic	-0.275	Destabilizing	1.0	D	0.725	prob.delet.	D	0.701958867	None	None	I
V/N	0.9605	likely_pathogenic	0.9774	pathogenic	-0.056	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
V/P	0.9968	likely_pathogenic	0.9978	pathogenic	-0.358	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	I
V/Q	0.9382	likely_pathogenic	0.9515	pathogenic	-0.332	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
V/R	0.9433	likely_pathogenic	0.9478	pathogenic	0.131	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
V/S	0.82	likely_pathogenic	0.9013	pathogenic	-0.407	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
V/T	0.6036	likely_pathogenic	0.7102	pathogenic	-0.437	Destabilizing	0.999	D	0.62	neutral	None	None	None	None	I
V/W	0.9983	likely_pathogenic	0.9989	pathogenic	-0.906	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
V/Y	0.9877	likely_pathogenic	0.9919	pathogenic	-0.591	Destabilizing	1.0	D	0.705	prob.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.