TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21608	65047;65048;65049	chr2:178584819;178584818;178584817	chr2:179449546;179449545;179449544
N2AB	19967	60124;60125;60126	chr2:178584819;178584818;178584817	chr2:179449546;179449545;179449544
N2A	19040	57343;57344;57345	chr2:178584819;178584818;178584817	chr2:179449546;179449545;179449544
N2B	12543	37852;37853;37854	chr2:178584819;178584818;178584817	chr2:179449546;179449545;179449544
Novex-1	12668	38227;38228;38229	chr2:178584819;178584818;178584817	chr2:179449546;179449545;179449544
Novex-2	12735	38428;38429;38430	chr2:178584819;178584818;178584817	chr2:179449546;179449545;179449544
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-44
• Domain position: 50
• Structural Position: 66
• Q(SASA): 0.3537
• 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
V/I	None	None	0.014	N	0.254	0.132	0.498323335527	gnomAD-4.0.0	1.59195E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85982E-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
V/A	0.2097	likely_benign	0.2466	benign	-1.025	Destabilizing	0.822	D	0.489	neutral	N	0.508109879	None	None	N
V/C	0.6603	likely_pathogenic	0.6818	pathogenic	-0.674	Destabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
V/D	0.4035	ambiguous	0.541	ambiguous	-0.698	Destabilizing	0.99	D	0.771	deleterious	N	0.491025629	None	None	N
V/E	0.2659	likely_benign	0.3673	ambiguous	-0.789	Destabilizing	0.993	D	0.724	prob.delet.	None	None	None	None	N
V/F	0.169	likely_benign	0.194	benign	-1.065	Destabilizing	0.942	D	0.723	prob.delet.	N	0.493527216	None	None	N
V/G	0.2467	likely_benign	0.2849	benign	-1.225	Destabilizing	0.971	D	0.763	deleterious	N	0.475358484	None	None	N
V/H	0.4782	ambiguous	0.5609	ambiguous	-0.731	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
V/I	0.0724	likely_benign	0.0748	benign	-0.622	Destabilizing	0.014	N	0.254	neutral	N	0.475056099	None	None	N
V/K	0.3243	likely_benign	0.436	ambiguous	-0.784	Destabilizing	0.978	D	0.727	prob.delet.	None	None	None	None	N
V/L	0.1733	likely_benign	0.1885	benign	-0.622	Destabilizing	0.247	N	0.406	neutral	N	0.494545936	None	None	N
V/M	0.1183	likely_benign	0.1326	benign	-0.418	Destabilizing	0.956	D	0.7	prob.neutral	None	None	None	None	N
V/N	0.2171	likely_benign	0.2653	benign	-0.457	Destabilizing	0.993	D	0.775	deleterious	None	None	None	None	N
V/P	0.9192	likely_pathogenic	0.9345	pathogenic	-0.72	Destabilizing	0.993	D	0.741	deleterious	None	None	None	None	N
V/Q	0.2462	likely_benign	0.3029	benign	-0.735	Destabilizing	0.993	D	0.743	deleterious	None	None	None	None	N
V/R	0.3474	ambiguous	0.4405	ambiguous	-0.183	Destabilizing	0.993	D	0.775	deleterious	None	None	None	None	N
V/S	0.2141	likely_benign	0.2553	benign	-0.888	Destabilizing	0.978	D	0.731	prob.delet.	None	None	None	None	N
V/T	0.18	likely_benign	0.2123	benign	-0.88	Destabilizing	0.86	D	0.607	neutral	None	None	None	None	N
V/W	0.8072	likely_pathogenic	0.8516	pathogenic	-1.133	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
V/Y	0.4784	ambiguous	0.5461	ambiguous	-0.86	Destabilizing	0.978	D	0.73	prob.delet.	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.