TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16343	49252;49253;49254	chr2:178614487;178614486;178614485	chr2:179479214;179479213;179479212
N2AB	14702	44329;44330;44331	chr2:178614487;178614486;178614485	chr2:179479214;179479213;179479212
N2A	13775	41548;41549;41550	chr2:178614487;178614486;178614485	chr2:179479214;179479213;179479212
N2B	7278	22057;22058;22059	chr2:178614487;178614486;178614485	chr2:179479214;179479213;179479212
Novex-1	7403	22432;22433;22434	chr2:178614487;178614486;178614485	chr2:179479214;179479213;179479212
Novex-2	7470	22633;22634;22635	chr2:178614487;178614486;178614485	chr2:179479214;179479213;179479212
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-110
• Domain position: 82
• Structural Position: 171
• Q(SASA): 0.5202
• 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	rs2056942530	None	0.667	N	0.586	0.165	0.619546946635	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

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	0.3731	ambiguous	0.3961	ambiguous	-0.62	Destabilizing	0.055	N	0.456	neutral	N	0.472578396	None	None	I
V/C	0.8709	likely_pathogenic	0.8806	pathogenic	-0.739	Destabilizing	0.909	D	0.655	neutral	None	None	None	None	I
V/D	0.8537	likely_pathogenic	0.8845	pathogenic	-0.447	Destabilizing	0.567	D	0.712	prob.delet.	None	None	None	None	I
V/E	0.6791	likely_pathogenic	0.7495	pathogenic	-0.542	Destabilizing	0.497	N	0.712	prob.delet.	N	0.45181701	None	None	I
V/F	0.4441	ambiguous	0.4903	ambiguous	-0.699	Destabilizing	0.726	D	0.677	prob.neutral	None	None	None	None	I
V/G	0.6577	likely_pathogenic	0.68	pathogenic	-0.785	Destabilizing	0.22	N	0.712	prob.delet.	D	0.596752704	None	None	I
V/H	0.8784	likely_pathogenic	0.9093	pathogenic	-0.31	Destabilizing	0.968	D	0.747	deleterious	None	None	None	None	I
V/I	0.1175	likely_benign	0.1247	benign	-0.325	Destabilizing	0.072	N	0.443	neutral	None	None	None	None	I
V/K	0.7253	likely_pathogenic	0.807	pathogenic	-0.645	Destabilizing	0.567	D	0.713	prob.delet.	None	None	None	None	I
V/L	0.4817	ambiguous	0.5274	ambiguous	-0.325	Destabilizing	0.055	N	0.463	neutral	N	0.509458945	None	None	I
V/M	0.2546	likely_benign	0.2983	benign	-0.41	Destabilizing	0.667	D	0.586	neutral	N	0.510943125	None	None	I
V/N	0.6585	likely_pathogenic	0.6992	pathogenic	-0.423	Destabilizing	0.567	D	0.716	prob.delet.	None	None	None	None	I
V/P	0.9346	likely_pathogenic	0.9361	pathogenic	-0.387	Destabilizing	0.726	D	0.725	prob.delet.	None	None	None	None	I
V/Q	0.6771	likely_pathogenic	0.7424	pathogenic	-0.652	Destabilizing	0.726	D	0.748	deleterious	None	None	None	None	I
V/R	0.7194	likely_pathogenic	0.7894	pathogenic	-0.104	Destabilizing	0.567	D	0.751	deleterious	None	None	None	None	I
V/S	0.4907	ambiguous	0.5261	ambiguous	-0.796	Destabilizing	0.157	N	0.648	neutral	None	None	None	None	I
V/T	0.2128	likely_benign	0.2367	benign	-0.789	Destabilizing	None	N	0.21	neutral	None	None	None	None	I
V/W	0.9621	likely_pathogenic	0.9675	pathogenic	-0.791	Destabilizing	0.968	D	0.767	deleterious	None	None	None	None	I
V/Y	0.8608	likely_pathogenic	0.876	pathogenic	-0.502	Destabilizing	0.726	D	0.666	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.