TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5481	16666;16667;16668	chr2:178732620;178732619;178732618	chr2:179597347;179597346;179597345
N2AB	5164	15715;15716;15717	chr2:178732620;178732619;178732618	chr2:179597347;179597346;179597345
N2A	4237	12934;12935;12936	chr2:178732620;178732619;178732618	chr2:179597347;179597346;179597345
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-38
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.1822
• 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/F	None	None	0.317	N	0.658	0.397	0.381239546501	gnomAD-4.0.0	1.59175E-06	None	None	None	None	N	None	5.65483E-05	0	None	0	0	None	0	0	0	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	0.4689	ambiguous	0.5305	ambiguous	-2.16	Highly Destabilizing	0.035	N	0.61	neutral	None	None	None	None	N
I/C	0.7859	likely_pathogenic	0.8174	pathogenic	-1.393	Destabilizing	0.824	D	0.738	prob.delet.	None	None	None	None	N
I/D	0.9335	likely_pathogenic	0.9626	pathogenic	-1.734	Destabilizing	0.555	D	0.796	deleterious	None	None	None	None	N
I/E	0.8579	likely_pathogenic	0.9116	pathogenic	-1.586	Destabilizing	0.555	D	0.797	deleterious	None	None	None	None	N
I/F	0.2021	likely_benign	0.2509	benign	-1.283	Destabilizing	0.317	N	0.658	neutral	N	0.51394064	None	None	N
I/G	0.8087	likely_pathogenic	0.8611	pathogenic	-2.645	Highly Destabilizing	0.001	N	0.563	neutral	None	None	None	None	N
I/H	0.8136	likely_pathogenic	0.8709	pathogenic	-1.963	Destabilizing	0.935	D	0.835	deleterious	None	None	None	None	N
I/K	0.7697	likely_pathogenic	0.855	pathogenic	-1.5	Destabilizing	0.555	D	0.793	deleterious	None	None	None	None	N
I/L	0.1514	likely_benign	0.1748	benign	-0.813	Destabilizing	0.012	N	0.491	neutral	N	0.518018308	None	None	N
I/M	0.1389	likely_benign	0.162	benign	-0.688	Destabilizing	0.317	N	0.626	neutral	N	0.502340051	None	None	N
I/N	0.653	likely_pathogenic	0.75	pathogenic	-1.561	Destabilizing	0.484	N	0.83	deleterious	D	0.522597126	None	None	N
I/P	0.864	likely_pathogenic	0.905	pathogenic	-1.236	Destabilizing	0.555	D	0.833	deleterious	None	None	None	None	N
I/Q	0.7605	likely_pathogenic	0.8323	pathogenic	-1.528	Destabilizing	0.791	D	0.84	deleterious	None	None	None	None	N
I/R	0.6818	likely_pathogenic	0.7876	pathogenic	-1.147	Destabilizing	0.555	D	0.843	deleterious	None	None	None	None	N
I/S	0.5354	ambiguous	0.5999	pathogenic	-2.322	Highly Destabilizing	0.117	N	0.777	deleterious	D	0.540447892	None	None	N
I/T	0.406	ambiguous	0.4761	ambiguous	-2.032	Highly Destabilizing	0.062	N	0.704	prob.neutral	N	0.510733842	None	None	N
I/V	0.0654	likely_benign	0.0699	benign	-1.236	Destabilizing	None	N	0.221	neutral	N	0.408932681	None	None	N
I/W	0.8528	likely_pathogenic	0.8971	pathogenic	-1.531	Destabilizing	0.935	D	0.836	deleterious	None	None	None	None	N
I/Y	0.6593	likely_pathogenic	0.7476	pathogenic	-1.257	Destabilizing	0.555	D	0.759	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.