TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9701	29326;29327;29328	chr2:178706895;178706894;178706893	chr2:179571622;179571621;179571620
N2AB	9384	28375;28376;28377	chr2:178706895;178706894;178706893	chr2:179571622;179571621;179571620
N2A	8457	25594;25595;25596	chr2:178706895;178706894;178706893	chr2:179571622;179571621;179571620
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-83
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.484
• 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	0.901	None	0.464	0.202	0.466655310336	gnomAD-4.0.0	1.36981E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79987E-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	0.5013	ambiguous	0.3004	benign	-1.0	Destabilizing	0.008	N	0.137	neutral	None	None	None	None	I
V/C	0.8985	likely_pathogenic	0.8313	pathogenic	-0.677	Destabilizing	0.989	D	0.518	neutral	None	None	None	None	I
V/D	0.8328	likely_pathogenic	0.5971	pathogenic	-0.103	Destabilizing	0.961	D	0.619	neutral	None	None	None	None	I
V/E	0.6478	likely_pathogenic	0.4769	ambiguous	-0.102	Destabilizing	0.901	D	0.549	neutral	None	None	None	None	I
V/F	0.4134	ambiguous	0.2432	benign	-0.678	Destabilizing	0.923	D	0.515	neutral	None	None	None	None	I
V/G	0.7222	likely_pathogenic	0.4572	ambiguous	-1.29	Destabilizing	0.565	D	0.508	neutral	None	None	None	None	I
V/H	0.8479	likely_pathogenic	0.6888	pathogenic	-0.638	Destabilizing	0.996	D	0.63	neutral	None	None	None	None	I
V/I	0.0857	likely_benign	0.0768	benign	-0.324	Destabilizing	0.005	N	0.13	neutral	None	None	None	None	I
V/K	0.6435	likely_pathogenic	0.5062	ambiguous	-0.615	Destabilizing	0.923	D	0.558	neutral	None	None	None	None	I
V/L	0.3274	likely_benign	0.2221	benign	-0.324	Destabilizing	0.156	N	0.36	neutral	None	None	None	None	I
V/M	0.3561	ambiguous	0.2491	benign	-0.348	Destabilizing	0.901	D	0.464	neutral	None	None	None	None	I
V/N	0.7257	likely_pathogenic	0.4815	ambiguous	-0.464	Destabilizing	0.961	D	0.607	neutral	None	None	None	None	I
V/P	0.9521	likely_pathogenic	0.851	pathogenic	-0.513	Destabilizing	0.961	D	0.605	neutral	None	None	None	None	I
V/Q	0.6167	likely_pathogenic	0.4526	ambiguous	-0.566	Destabilizing	0.961	D	0.593	neutral	None	None	None	None	I
V/R	0.5915	likely_pathogenic	0.4165	ambiguous	-0.199	Destabilizing	0.923	D	0.606	neutral	None	None	None	None	I
V/S	0.6016	likely_pathogenic	0.3609	ambiguous	-1.077	Destabilizing	0.633	D	0.502	neutral	None	None	None	None	I
V/T	0.4875	ambiguous	0.3218	benign	-0.954	Destabilizing	0.775	D	0.385	neutral	None	None	None	None	I
V/W	0.9505	likely_pathogenic	0.8796	pathogenic	-0.821	Destabilizing	0.996	D	0.722	prob.delet.	None	None	None	None	I
V/Y	0.8216	likely_pathogenic	0.6599	pathogenic	-0.506	Destabilizing	0.961	D	0.503	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.