TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5761	17506;17507;17508	chr2:178731485;178731484;178731483	chr2:179596212;179596211;179596210
N2AB	5444	16555;16556;16557	chr2:178731485;178731484;178731483	chr2:179596212;179596211;179596210
N2A	4517	13774;13775;13776	chr2:178731485;178731484;178731483	chr2:179596212;179596211;179596210
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-41
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.2054
• 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	0.78	D	0.636	0.686	0.760823172197	gnomAD-4.0.0	4.78995E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.49747E-06	0	3.31367E-05
V/L	None	None	0.64	D	0.491	0.421	0.61844985043	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	0.6634	likely_pathogenic	0.6177	pathogenic	-1.588	Destabilizing	0.78	D	0.636	neutral	D	0.571996119	None	None	I
V/C	0.9496	likely_pathogenic	0.9455	pathogenic	-0.963	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
V/D	0.9909	likely_pathogenic	0.9858	pathogenic	-1.505	Destabilizing	0.952	D	0.821	deleterious	None	None	None	None	I
V/E	0.9716	likely_pathogenic	0.9619	pathogenic	-1.421	Destabilizing	0.103	N	0.595	neutral	D	0.589024501	None	None	I
V/F	0.599	likely_pathogenic	0.5914	pathogenic	-1.08	Destabilizing	0.976	D	0.744	deleterious	None	None	None	None	I
V/G	0.8833	likely_pathogenic	0.8495	pathogenic	-1.999	Destabilizing	0.984	D	0.821	deleterious	D	0.589024501	None	None	I
V/H	0.9895	likely_pathogenic	0.9871	pathogenic	-1.629	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	I
V/I	0.088	likely_benign	0.0963	benign	-0.518	Destabilizing	0.015	N	0.226	neutral	None	None	None	None	I
V/K	0.9781	likely_pathogenic	0.971	pathogenic	-1.254	Destabilizing	0.976	D	0.825	deleterious	None	None	None	None	I
V/L	0.4737	ambiguous	0.4991	ambiguous	-0.518	Destabilizing	0.64	D	0.491	neutral	D	0.57578879	None	None	I
V/M	0.3663	ambiguous	0.3775	ambiguous	-0.38	Destabilizing	0.968	D	0.609	neutral	D	0.55658217	None	None	I
V/N	0.9665	likely_pathogenic	0.952	pathogenic	-1.168	Destabilizing	0.988	D	0.859	deleterious	None	None	None	None	I
V/P	0.9759	likely_pathogenic	0.9644	pathogenic	-0.841	Destabilizing	0.996	D	0.851	deleterious	None	None	None	None	I
V/Q	0.9705	likely_pathogenic	0.9629	pathogenic	-1.208	Destabilizing	0.976	D	0.851	deleterious	None	None	None	None	I
V/R	0.9714	likely_pathogenic	0.9629	pathogenic	-0.901	Destabilizing	0.976	D	0.858	deleterious	None	None	None	None	I
V/S	0.8877	likely_pathogenic	0.8601	pathogenic	-1.748	Destabilizing	0.919	D	0.822	deleterious	None	None	None	None	I
V/T	0.6552	likely_pathogenic	0.5761	pathogenic	-1.535	Destabilizing	0.919	D	0.633	neutral	None	None	None	None	I
V/W	0.9901	likely_pathogenic	0.9894	pathogenic	-1.408	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	I
V/Y	0.9572	likely_pathogenic	0.951	pathogenic	-1.052	Destabilizing	0.996	D	0.731	prob.delet.	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.