TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1843	5752;5753;5754	chr2:178776337;178776336;178776335	chr2:179641064;179641063;179641062
N2AB	1843	5752;5753;5754	chr2:178776337;178776336;178776335	chr2:179641064;179641063;179641062
N2A	1843	5752;5753;5754	chr2:178776337;178776336;178776335	chr2:179641064;179641063;179641062
N2B	1797	5614;5615;5616	chr2:178776337;178776336;178776335	chr2:179641064;179641063;179641062
Novex-1	1797	5614;5615;5616	chr2:178776337;178776336;178776335	chr2:179641064;179641063;179641062
Novex-2	1797	5614;5615;5616	chr2:178776337;178776336;178776335	chr2:179641064;179641063;179641062
Novex-3	1843	5752;5753;5754	chr2:178776337;178776336;178776335	chr2:179641064;179641063;179641062

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-9
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.0955
• 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
I/T	None	None	0.991	D	0.793	0.674	0.823937394785	gnomAD-4.0.0	1.59108E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02151E-05
I/V	None	None	0.58	N	0.445	0.228	0.573784085325	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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
I/A	0.8768	likely_pathogenic	0.9102	pathogenic	-2.595	Highly Destabilizing	0.953	D	0.685	prob.neutral	None	None	None	None	N
I/C	0.9597	likely_pathogenic	0.9725	pathogenic	-1.64	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
I/D	0.9967	likely_pathogenic	0.9985	pathogenic	-3.152	Highly Destabilizing	0.998	D	0.874	deleterious	None	None	None	None	N
I/E	0.9929	likely_pathogenic	0.9964	pathogenic	-2.95	Highly Destabilizing	0.998	D	0.875	deleterious	None	None	None	None	N
I/F	0.3631	ambiguous	0.536	ambiguous	-1.589	Destabilizing	0.982	D	0.739	prob.delet.	N	0.441133524	None	None	N
I/G	0.9896	likely_pathogenic	0.994	pathogenic	-3.101	Highly Destabilizing	0.998	D	0.878	deleterious	None	None	None	None	N
I/H	0.9873	likely_pathogenic	0.9951	pathogenic	-2.618	Highly Destabilizing	0.999	D	0.86	deleterious	None	None	None	None	N
I/K	0.9831	likely_pathogenic	0.9919	pathogenic	-2.083	Highly Destabilizing	0.993	D	0.878	deleterious	None	None	None	None	N
I/L	0.2124	likely_benign	0.2566	benign	-1.127	Destabilizing	0.02	N	0.265	neutral	N	0.511487369	None	None	N
I/M	0.2012	likely_benign	0.257	benign	-0.885	Destabilizing	0.982	D	0.707	prob.neutral	D	0.611191656	None	None	N
I/N	0.9727	likely_pathogenic	0.9852	pathogenic	-2.355	Highly Destabilizing	0.997	D	0.872	deleterious	D	0.704453201	None	None	N
I/P	0.9886	likely_pathogenic	0.9928	pathogenic	-1.6	Destabilizing	0.998	D	0.868	deleterious	None	None	None	None	N
I/Q	0.9868	likely_pathogenic	0.9941	pathogenic	-2.267	Highly Destabilizing	0.998	D	0.873	deleterious	None	None	None	None	N
I/R	0.9732	likely_pathogenic	0.987	pathogenic	-1.697	Destabilizing	0.993	D	0.865	deleterious	None	None	None	None	N
I/S	0.9547	likely_pathogenic	0.9717	pathogenic	-2.955	Highly Destabilizing	0.991	D	0.835	deleterious	D	0.703642021	None	None	N
I/T	0.8247	likely_pathogenic	0.8791	pathogenic	-2.63	Highly Destabilizing	0.991	D	0.793	deleterious	D	0.70318435	None	None	N
I/V	0.1378	likely_benign	0.1391	benign	-1.6	Destabilizing	0.58	D	0.445	neutral	N	0.517321546	None	None	N
I/W	0.9652	likely_pathogenic	0.9875	pathogenic	-2.078	Highly Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
I/Y	0.9232	likely_pathogenic	0.9671	pathogenic	-1.791	Destabilizing	0.993	D	0.778	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.