TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27181	81766;81767;81768	chr2:178564591;178564590;178564589	chr2:179429318;179429317;179429316
N2AB	25540	76843;76844;76845	chr2:178564591;178564590;178564589	chr2:179429318;179429317;179429316
N2A	24613	74062;74063;74064	chr2:178564591;178564590;178564589	chr2:179429318;179429317;179429316
N2B	18116	54571;54572;54573	chr2:178564591;178564590;178564589	chr2:179429318;179429317;179429316
Novex-1	18241	54946;54947;54948	chr2:178564591;178564590;178564589	chr2:179429318;179429317;179429316
Novex-2	18308	55147;55148;55149	chr2:178564591;178564590;178564589	chr2:179429318;179429317;179429316
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-86
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.3531
• 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/A	rs750155984	-0.616	0.005	N	0.044	0.102	0.401327265625	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	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	0.1759	likely_benign	0.1664	benign	-0.978	Destabilizing	0.005	N	0.044	neutral	N	0.401499702	None	None	N
V/C	0.639	likely_pathogenic	0.6578	pathogenic	-0.74	Destabilizing	0.991	D	0.373	neutral	None	None	None	None	N
V/D	0.3009	likely_benign	0.2502	benign	-0.719	Destabilizing	0.001	N	0.197	neutral	N	0.344048909	None	None	N
V/E	0.2392	likely_benign	0.204	benign	-0.795	Destabilizing	0.002	N	0.145	neutral	None	None	None	None	N
V/F	0.1554	likely_benign	0.152	benign	-0.92	Destabilizing	0.954	D	0.421	neutral	N	0.469322205	None	None	N
V/G	0.2834	likely_benign	0.2737	benign	-1.192	Destabilizing	0.166	N	0.393	neutral	N	0.431110533	None	None	N
V/H	0.4477	ambiguous	0.4376	ambiguous	-0.648	Destabilizing	0.901	D	0.451	neutral	None	None	None	None	N
V/I	0.0707	likely_benign	0.0732	benign	-0.534	Destabilizing	0.662	D	0.29	neutral	N	0.412103485	None	None	N
V/K	0.3524	ambiguous	0.3419	ambiguous	-0.838	Destabilizing	0.39	N	0.411	neutral	None	None	None	None	N
V/L	0.1559	likely_benign	0.1655	benign	-0.534	Destabilizing	0.285	N	0.261	neutral	N	0.455296902	None	None	N
V/M	0.1222	likely_benign	0.1256	benign	-0.411	Destabilizing	0.965	D	0.395	neutral	None	None	None	None	N
V/N	0.2239	likely_benign	0.2089	benign	-0.577	Destabilizing	0.004	N	0.239	neutral	None	None	None	None	N
V/P	0.9359	likely_pathogenic	0.9309	pathogenic	-0.645	Destabilizing	0.722	D	0.451	neutral	None	None	None	None	N
V/Q	0.2836	likely_benign	0.2735	benign	-0.828	Destabilizing	0.39	N	0.45	neutral	None	None	None	None	N
V/R	0.3266	likely_benign	0.324	benign	-0.233	Destabilizing	0.561	D	0.493	neutral	None	None	None	None	N
V/S	0.1759	likely_benign	0.1689	benign	-1.014	Destabilizing	0.209	N	0.362	neutral	None	None	None	None	N
V/T	0.1585	likely_benign	0.1535	benign	-0.988	Destabilizing	0.345	N	0.247	neutral	None	None	None	None	N
V/W	0.7631	likely_pathogenic	0.7582	pathogenic	-1.009	Destabilizing	0.991	D	0.467	neutral	None	None	None	None	N
V/Y	0.4195	ambiguous	0.4227	ambiguous	-0.735	Destabilizing	0.965	D	0.423	neutral	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.