TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4808	14647;14648;14649	chr2:178736024;178736023;178736022	chr2:179600751;179600750;179600749
N2AB	4491	13696;13697;13698	chr2:178736024;178736023;178736022	chr2:179600751;179600750;179600749
N2A	3564	10915;10916;10917	chr2:178736024;178736023;178736022	chr2:179600751;179600750;179600749
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-31
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.3055
• 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
V/M	None	None	0.999	N	0.495	0.248	0.367042808489	gnomAD-4.0.0	1.59814E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87054E-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	0.1461	likely_benign	0.1832	benign	-1.034	Destabilizing	0.948	D	0.427	neutral	N	0.366836648	None	None	I
V/C	0.8249	likely_pathogenic	0.8846	pathogenic	-0.761	Destabilizing	1.0	D	0.528	neutral	None	None	None	None	I
V/D	0.6312	likely_pathogenic	0.796	pathogenic	-0.293	Destabilizing	0.998	D	0.684	prob.neutral	None	None	None	None	I
V/E	0.3534	ambiguous	0.4887	ambiguous	-0.292	Destabilizing	0.997	D	0.533	neutral	N	0.280864608	None	None	I
V/F	0.3222	likely_benign	0.452	ambiguous	-0.691	Destabilizing	1.0	D	0.508	neutral	None	None	None	None	I
V/G	0.3522	ambiguous	0.4863	ambiguous	-1.337	Destabilizing	0.989	D	0.609	neutral	N	0.445512688	None	None	I
V/H	0.698	likely_pathogenic	0.8152	pathogenic	-0.757	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
V/I	0.0954	likely_benign	0.0998	benign	-0.321	Destabilizing	0.99	D	0.428	neutral	None	None	None	None	I
V/K	0.4414	ambiguous	0.5723	pathogenic	-0.765	Destabilizing	0.998	D	0.541	neutral	None	None	None	None	I
V/L	0.3241	likely_benign	0.3983	ambiguous	-0.321	Destabilizing	0.987	D	0.441	neutral	N	0.321118044	None	None	I
V/M	0.2241	likely_benign	0.3065	benign	-0.345	Destabilizing	0.999	D	0.495	neutral	N	0.35508346	None	None	I
V/N	0.5194	ambiguous	0.6626	pathogenic	-0.582	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	I
V/P	0.6341	likely_pathogenic	0.7306	pathogenic	-0.522	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	I
V/Q	0.403	ambiguous	0.5223	ambiguous	-0.686	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	I
V/R	0.3531	ambiguous	0.4719	ambiguous	-0.347	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	I
V/S	0.2367	likely_benign	0.3121	benign	-1.18	Destabilizing	0.914	D	0.373	neutral	None	None	None	None	I
V/T	0.1661	likely_benign	0.1993	benign	-1.056	Destabilizing	0.983	D	0.431	neutral	None	None	None	None	I
V/W	0.8925	likely_pathogenic	0.9522	pathogenic	-0.849	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
V/Y	0.7553	likely_pathogenic	0.8423	pathogenic	-0.538	Destabilizing	1.0	D	0.518	neutral	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.