TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24499	73720;73721;73722	chr2:178572637;178572636;178572635	chr2:179437364;179437363;179437362
N2AB	22858	68797;68798;68799	chr2:178572637;178572636;178572635	chr2:179437364;179437363;179437362
N2A	21931	66016;66017;66018	chr2:178572637;178572636;178572635	chr2:179437364;179437363;179437362
N2B	15434	46525;46526;46527	chr2:178572637;178572636;178572635	chr2:179437364;179437363;179437362
Novex-1	15559	46900;46901;46902	chr2:178572637;178572636;178572635	chr2:179437364;179437363;179437362
Novex-2	15626	47101;47102;47103	chr2:178572637;178572636;178572635	chr2:179437364;179437363;179437362
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-132
• Domain position: 69
• Structural Position: 156
• Q(SASA): 0.1224
• 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
L/P	rs769255289	None	0.994	N	0.825	0.599	0.776129731606	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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	0.9444	likely_pathogenic	0.9423	pathogenic	-2.393	Highly Destabilizing	0.916	D	0.699	prob.neutral	None	None	None	None	I
L/C	0.8901	likely_pathogenic	0.8852	pathogenic	-1.723	Destabilizing	0.999	D	0.738	prob.delet.	None	None	None	None	I
L/D	0.9999	likely_pathogenic	0.9999	pathogenic	-2.42	Highly Destabilizing	0.996	D	0.825	deleterious	None	None	None	None	I
L/E	0.9989	likely_pathogenic	0.9987	pathogenic	-2.249	Highly Destabilizing	0.996	D	0.827	deleterious	None	None	None	None	I
L/F	0.8259	likely_pathogenic	0.8344	pathogenic	-1.528	Destabilizing	0.975	D	0.738	prob.delet.	None	None	None	None	I
L/G	0.9957	likely_pathogenic	0.9955	pathogenic	-2.905	Highly Destabilizing	0.987	D	0.822	deleterious	None	None	None	None	I
L/H	0.997	likely_pathogenic	0.9966	pathogenic	-2.314	Highly Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	I
L/I	0.179	likely_benign	0.1874	benign	-0.947	Destabilizing	0.025	N	0.439	neutral	N	0.491417126	None	None	I
L/K	0.9978	likely_pathogenic	0.9974	pathogenic	-1.81	Destabilizing	0.987	D	0.799	deleterious	None	None	None	None	I
L/M	0.3743	ambiguous	0.374	ambiguous	-0.822	Destabilizing	0.975	D	0.696	prob.neutral	None	None	None	None	I
L/N	0.999	likely_pathogenic	0.9987	pathogenic	-1.999	Destabilizing	0.996	D	0.839	deleterious	None	None	None	None	I
L/P	0.9987	likely_pathogenic	0.9985	pathogenic	-1.406	Destabilizing	0.994	D	0.825	deleterious	N	0.501499411	None	None	I
L/Q	0.9934	likely_pathogenic	0.9924	pathogenic	-1.945	Destabilizing	0.994	D	0.816	deleterious	N	0.501499411	None	None	I
L/R	0.9946	likely_pathogenic	0.994	pathogenic	-1.436	Destabilizing	0.994	D	0.808	deleterious	N	0.501499411	None	None	I
L/S	0.9962	likely_pathogenic	0.9958	pathogenic	-2.721	Highly Destabilizing	0.987	D	0.793	deleterious	None	None	None	None	I
L/T	0.978	likely_pathogenic	0.9764	pathogenic	-2.403	Highly Destabilizing	0.975	D	0.742	deleterious	None	None	None	None	I
L/V	0.1766	likely_benign	0.1768	benign	-1.406	Destabilizing	0.099	N	0.385	neutral	N	0.47240729	None	None	I
L/W	0.9931	likely_pathogenic	0.9928	pathogenic	-1.854	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	I
L/Y	0.9925	likely_pathogenic	0.9923	pathogenic	-1.564	Destabilizing	0.987	D	0.733	prob.delet.	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.