TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1547	4864;4865;4866	chr2:178777426;178777425;178777424	chr2:179642153;179642152;179642151
N2AB	1547	4864;4865;4866	chr2:178777426;178777425;178777424	chr2:179642153;179642152;179642151
N2A	1547	4864;4865;4866	chr2:178777426;178777425;178777424	chr2:179642153;179642152;179642151
N2B	1501	4726;4727;4728	chr2:178777426;178777425;178777424	chr2:179642153;179642152;179642151
Novex-1	1501	4726;4727;4728	chr2:178777426;178777425;178777424	chr2:179642153;179642152;179642151
Novex-2	1501	4726;4727;4728	chr2:178777426;178777425;178777424	chr2:179642153;179642152;179642151
Novex-3	1547	4864;4865;4866	chr2:178777426;178777425;178777424	chr2:179642153;179642152;179642151

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-6
• Domain position: 91
• Structural Position: 177
• Q(SASA): 0.4539
• 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	-0.636	1.0	D	0.852	0.738	0.867169889803	gnomAD-2.1.1	2.41E-05	None	None	None	None	I	None	0	8.7E-05	None	0	0	None	0	None	0	1.78E-05	1.64908E-04
V/M	None	-0.636	1.0	D	0.852	0.738	0.867169889803	gnomAD-4.0.0	7.5274E-06	None	None	None	None	I	None	0	8.95095E-05	None	0	0	None	0	0	6.29624E-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	0.6811	likely_pathogenic	0.7326	pathogenic	-1.745	Destabilizing	0.999	D	0.733	prob.delet.	D	0.796051213	None	None	I
V/C	0.9756	likely_pathogenic	0.9759	pathogenic	-1.77	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
V/D	0.9947	likely_pathogenic	0.9963	pathogenic	-2.815	Highly Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
V/E	0.9784	likely_pathogenic	0.9848	pathogenic	-2.771	Highly Destabilizing	1.0	D	0.797	deleterious	D	0.793960013	None	None	I
V/F	0.9411	likely_pathogenic	0.9499	pathogenic	-1.367	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
V/G	0.9031	likely_pathogenic	0.9253	pathogenic	-2.075	Highly Destabilizing	1.0	D	0.756	deleterious	D	0.793960013	None	None	I
V/H	0.9973	likely_pathogenic	0.9978	pathogenic	-1.525	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
V/I	0.1457	likely_benign	0.142	benign	-0.901	Destabilizing	0.998	D	0.704	prob.neutral	None	None	None	None	I
V/K	0.9861	likely_pathogenic	0.99	pathogenic	-1.489	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
V/L	0.7894	likely_pathogenic	0.7949	pathogenic	-0.901	Destabilizing	0.997	D	0.733	prob.delet.	D	0.686092661	None	None	I
V/M	0.6819	likely_pathogenic	0.7488	pathogenic	-0.963	Destabilizing	1.0	D	0.852	deleterious	D	0.740419789	None	None	I
V/N	0.9807	likely_pathogenic	0.9846	pathogenic	-1.609	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
V/P	0.9816	likely_pathogenic	0.9814	pathogenic	-1.153	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
V/Q	0.9841	likely_pathogenic	0.988	pathogenic	-1.8	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
V/R	0.9795	likely_pathogenic	0.9843	pathogenic	-0.985	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
V/S	0.9025	likely_pathogenic	0.9246	pathogenic	-2.036	Highly Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
V/T	0.6813	likely_pathogenic	0.7265	pathogenic	-1.889	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	I
V/W	0.999	likely_pathogenic	0.9992	pathogenic	-1.63	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
V/Y	0.9962	likely_pathogenic	0.9969	pathogenic	-1.312	Destabilizing	1.0	D	0.847	deleterious	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.