TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2550	7873;7874;7875	chr2:178773316;178773315;178773314	chr2:179638043;179638042;179638041
N2AB	2550	7873;7874;7875	chr2:178773316;178773315;178773314	chr2:179638043;179638042;179638041
N2A	2550	7873;7874;7875	chr2:178773316;178773315;178773314	chr2:179638043;179638042;179638041
N2B	2504	7735;7736;7737	chr2:178773316;178773315;178773314	chr2:179638043;179638042;179638041
Novex-1	2504	7735;7736;7737	chr2:178773316;178773315;178773314	chr2:179638043;179638042;179638041
Novex-2	2504	7735;7736;7737	chr2:178773316;178773315;178773314	chr2:179638043;179638042;179638041
Novex-3	2550	7873;7874;7875	chr2:178773316;178773315;178773314	chr2:179638043;179638042;179638041

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-15
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.0981
• Predicted PPI site: N

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	0.942	D	0.677	0.296	0.456830177556	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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	0.1932	likely_benign	0.2134	benign	-1.88	Destabilizing	0.822	D	0.563	neutral	N	0.440790131	None	None	N
V/C	0.8338	likely_pathogenic	0.8469	pathogenic	-1.428	Destabilizing	0.998	D	0.734	prob.delet.	None	None	None	None	N
V/D	0.9109	likely_pathogenic	0.8953	pathogenic	-2.206	Highly Destabilizing	0.993	D	0.788	deleterious	None	None	None	None	N
V/E	0.8001	likely_pathogenic	0.784	pathogenic	-2.044	Highly Destabilizing	0.971	D	0.768	deleterious	D	0.615427103	None	None	N
V/F	0.5792	likely_pathogenic	0.5744	pathogenic	-1.191	Destabilizing	0.915	D	0.779	deleterious	None	None	None	None	N
V/G	0.5354	ambiguous	0.5497	ambiguous	-2.37	Highly Destabilizing	0.971	D	0.795	deleterious	N	0.510493637	None	None	N
V/H	0.9377	likely_pathogenic	0.9342	pathogenic	-2.045	Highly Destabilizing	0.998	D	0.766	deleterious	None	None	None	None	N
V/I	0.1122	likely_benign	0.1172	benign	-0.55	Destabilizing	0.559	D	0.519	neutral	None	None	None	None	N
V/K	0.8346	likely_pathogenic	0.8204	pathogenic	-1.699	Destabilizing	0.978	D	0.765	deleterious	None	None	None	None	N
V/L	0.5107	ambiguous	0.5497	ambiguous	-0.55	Destabilizing	0.006	N	0.275	neutral	N	0.52073822	None	None	N
V/M	0.3098	likely_benign	0.3388	benign	-0.504	Destabilizing	0.942	D	0.677	prob.neutral	D	0.575605201	None	None	N
V/N	0.8102	likely_pathogenic	0.7943	pathogenic	-1.841	Destabilizing	0.993	D	0.796	deleterious	None	None	None	None	N
V/P	0.9708	likely_pathogenic	0.9694	pathogenic	-0.962	Destabilizing	0.993	D	0.741	deleterious	None	None	None	None	N
V/Q	0.8026	likely_pathogenic	0.7969	pathogenic	-1.771	Destabilizing	0.993	D	0.758	deleterious	None	None	None	None	N
V/R	0.7857	likely_pathogenic	0.7702	pathogenic	-1.409	Destabilizing	0.978	D	0.795	deleterious	None	None	None	None	N
V/S	0.5122	ambiguous	0.5115	ambiguous	-2.446	Highly Destabilizing	0.978	D	0.758	deleterious	None	None	None	None	N
V/T	0.2485	likely_benign	0.2685	benign	-2.139	Highly Destabilizing	0.86	D	0.628	neutral	None	None	None	None	N
V/W	0.983	likely_pathogenic	0.9843	pathogenic	-1.618	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
V/Y	0.9058	likely_pathogenic	0.904	pathogenic	-1.24	Destabilizing	0.978	D	0.753	deleterious	None	None	None	None	N

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.