TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2730	8413;8414;8415	chr2:178770604;178770603;178770602	chr2:179635331;179635330;179635329
N2AB	2730	8413;8414;8415	chr2:178770604;178770603;178770602	chr2:179635331;179635330;179635329
N2A	2730	8413;8414;8415	chr2:178770604;178770603;178770602	chr2:179635331;179635330;179635329
N2B	2684	8275;8276;8277	chr2:178770604;178770603;178770602	chr2:179635331;179635330;179635329
Novex-1	2684	8275;8276;8277	chr2:178770604;178770603;178770602	chr2:179635331;179635330;179635329
Novex-2	2684	8275;8276;8277	chr2:178770604;178770603;178770602	chr2:179635331;179635330;179635329
Novex-3	2730	8413;8414;8415	chr2:178770604;178770603;178770602	chr2:179635331;179635330;179635329

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-17
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.0696
• 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/P	None	None	1.0	D	0.851	0.816	0.8892766192	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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	0.8834	likely_pathogenic	0.9216	pathogenic	-3.282	Highly Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
L/C	0.9044	likely_pathogenic	0.9421	pathogenic	-2.712	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
L/D	0.9977	likely_pathogenic	0.9989	pathogenic	-3.976	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/E	0.9907	likely_pathogenic	0.9952	pathogenic	-3.673	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/F	0.6744	likely_pathogenic	0.8037	pathogenic	-1.832	Destabilizing	1.0	D	0.803	deleterious	D	0.630499019	None	None	N
L/G	0.9733	likely_pathogenic	0.9842	pathogenic	-3.867	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/H	0.9834	likely_pathogenic	0.9925	pathogenic	-3.331	Highly Destabilizing	1.0	D	0.843	deleterious	D	0.672805842	None	None	N
L/I	0.2162	likely_benign	0.2832	benign	-1.513	Destabilizing	0.999	D	0.566	neutral	N	0.491240675	None	None	N
L/K	0.988	likely_pathogenic	0.9937	pathogenic	-2.678	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/M	0.2854	likely_benign	0.351	ambiguous	-1.771	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
L/N	0.9865	likely_pathogenic	0.9933	pathogenic	-3.334	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/P	0.9904	likely_pathogenic	0.9956	pathogenic	-2.096	Highly Destabilizing	1.0	D	0.851	deleterious	D	0.672805842	None	None	N
L/Q	0.973	likely_pathogenic	0.9869	pathogenic	-3.028	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
L/R	0.9781	likely_pathogenic	0.988	pathogenic	-2.486	Highly Destabilizing	1.0	D	0.854	deleterious	D	0.672805842	None	None	N
L/S	0.9788	likely_pathogenic	0.9899	pathogenic	-3.919	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/T	0.8894	likely_pathogenic	0.9313	pathogenic	-3.469	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
L/V	0.2273	likely_benign	0.2786	benign	-2.096	Highly Destabilizing	0.999	D	0.558	neutral	N	0.480989714	None	None	N
L/W	0.9648	likely_pathogenic	0.9847	pathogenic	-2.265	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/Y	0.9654	likely_pathogenic	0.9846	pathogenic	-2.162	Highly Destabilizing	1.0	D	0.861	deleterious	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.