TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18742	56449;56450;56451	chr2:178599677;178599676;178599675	chr2:179464404;179464403;179464402
N2AB	17101	51526;51527;51528	chr2:178599677;178599676;178599675	chr2:179464404;179464403;179464402
N2A	16174	48745;48746;48747	chr2:178599677;178599676;178599675	chr2:179464404;179464403;179464402
N2B	9677	29254;29255;29256	chr2:178599677;178599676;178599675	chr2:179464404;179464403;179464402
Novex-1	9802	29629;29630;29631	chr2:178599677;178599676;178599675	chr2:179464404;179464403;179464402
Novex-2	9869	29830;29831;29832	chr2:178599677;178599676;178599675	chr2:179464404;179464403;179464402
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-116
• Domain position: 55
• Structural Position: 127
• Q(SASA): 0.4871
• 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/A	None	None	0.999	N	0.691	0.476	0.679835815318	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
V/M	None	None	1.0	D	0.725	0.349	0.57179433898	gnomAD-4.0.0	1.36901E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79952E-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	0.2905	likely_benign	0.2232	benign	-0.638	Destabilizing	0.999	D	0.691	prob.neutral	N	0.511644122	None	None	I
V/C	0.8501	likely_pathogenic	0.8042	pathogenic	-0.812	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
V/D	0.7073	likely_pathogenic	0.585	pathogenic	-0.034	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
V/E	0.5774	likely_pathogenic	0.4513	ambiguous	-0.091	Destabilizing	1.0	D	0.783	deleterious	N	0.511644122	None	None	I
V/F	0.3575	ambiguous	0.2699	benign	-0.549	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
V/G	0.5129	ambiguous	0.4109	ambiguous	-0.849	Destabilizing	1.0	D	0.779	deleterious	N	0.489797841	None	None	I
V/H	0.8213	likely_pathogenic	0.7414	pathogenic	-0.304	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
V/I	0.0931	likely_benign	0.0838	benign	-0.207	Destabilizing	0.998	D	0.612	neutral	None	None	None	None	I
V/K	0.7192	likely_pathogenic	0.621	pathogenic	-0.553	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
V/L	0.3447	ambiguous	0.2581	benign	-0.207	Destabilizing	0.997	D	0.673	neutral	N	0.486287104	None	None	I
V/M	0.2665	likely_benign	0.2004	benign	-0.387	Destabilizing	1.0	D	0.725	prob.delet.	D	0.536638567	None	None	I
V/N	0.5972	likely_pathogenic	0.4774	ambiguous	-0.37	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
V/P	0.7919	likely_pathogenic	0.7361	pathogenic	-0.314	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
V/Q	0.6102	likely_pathogenic	0.5127	ambiguous	-0.511	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
V/R	0.6654	likely_pathogenic	0.5745	pathogenic	-0.115	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
V/S	0.445	ambiguous	0.3404	ambiguous	-0.87	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
V/T	0.2706	likely_benign	0.1993	benign	-0.806	Destabilizing	0.999	D	0.74	deleterious	None	None	None	None	I
V/W	0.9351	likely_pathogenic	0.8949	pathogenic	-0.648	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
V/Y	0.7936	likely_pathogenic	0.7159	pathogenic	-0.354	Destabilizing	1.0	D	0.742	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.