TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28786	86581;86582;86583	chr2:178559776;178559775;178559774	chr2:179424503;179424502;179424501
N2AB	27145	81658;81659;81660	chr2:178559776;178559775;178559774	chr2:179424503;179424502;179424501
N2A	26218	78877;78878;78879	chr2:178559776;178559775;178559774	chr2:179424503;179424502;179424501
N2B	19721	59386;59387;59388	chr2:178559776;178559775;178559774	chr2:179424503;179424502;179424501
Novex-1	19846	59761;59762;59763	chr2:178559776;178559775;178559774	chr2:179424503;179424502;179424501
Novex-2	19913	59962;59963;59964	chr2:178559776;178559775;178559774	chr2:179424503;179424502;179424501
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-144
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.1106
• 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	0.025	D	0.318	0.501	0.664321979793	gnomAD-4.0.0	1.61529E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.89417E-06	0	0
V/I	rs1219680583	None	0.773	N	0.538	0.301	0.682044198124	gnomAD-4.0.0	2.06612E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80612E-06	0	1.66739E-05

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	0.3141	likely_benign	0.292	benign	-1.556	Destabilizing	0.025	N	0.318	neutral	D	0.533921116	None	None	I
V/C	0.7981	likely_pathogenic	0.791	pathogenic	-1.033	Destabilizing	0.997	D	0.772	deleterious	None	None	None	None	I
V/D	0.9561	likely_pathogenic	0.9551	pathogenic	-1.541	Destabilizing	0.983	D	0.853	deleterious	D	0.613866119	None	None	I
V/E	0.9233	likely_pathogenic	0.9277	pathogenic	-1.436	Destabilizing	0.975	D	0.833	deleterious	None	None	None	None	I
V/F	0.5199	ambiguous	0.495	ambiguous	-0.976	Destabilizing	0.983	D	0.765	deleterious	D	0.554846295	None	None	I
V/G	0.6061	likely_pathogenic	0.5678	pathogenic	-1.979	Destabilizing	0.935	D	0.801	deleterious	D	0.597614593	None	None	I
V/H	0.9562	likely_pathogenic	0.9555	pathogenic	-1.566	Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	I
V/I	0.0869	likely_benign	0.0865	benign	-0.449	Destabilizing	0.773	D	0.538	neutral	N	0.506822666	None	None	I
V/K	0.9293	likely_pathogenic	0.9314	pathogenic	-1.335	Destabilizing	0.975	D	0.833	deleterious	None	None	None	None	I
V/L	0.461	ambiguous	0.4375	ambiguous	-0.449	Destabilizing	0.63	D	0.605	neutral	D	0.555523147	None	None	I
V/M	0.3571	ambiguous	0.339	benign	-0.401	Destabilizing	0.996	D	0.708	prob.delet.	None	None	None	None	I
V/N	0.8688	likely_pathogenic	0.8653	pathogenic	-1.318	Destabilizing	0.987	D	0.858	deleterious	None	None	None	None	I
V/P	0.88	likely_pathogenic	0.8758	pathogenic	-0.785	Destabilizing	0.987	D	0.843	deleterious	None	None	None	None	I
V/Q	0.8951	likely_pathogenic	0.8978	pathogenic	-1.319	Destabilizing	0.987	D	0.845	deleterious	None	None	None	None	I
V/R	0.8959	likely_pathogenic	0.8997	pathogenic	-1.007	Destabilizing	0.987	D	0.845	deleterious	None	None	None	None	I
V/S	0.6039	likely_pathogenic	0.5728	pathogenic	-1.893	Destabilizing	0.95	D	0.81	deleterious	None	None	None	None	I
V/T	0.4755	ambiguous	0.451	ambiguous	-1.655	Destabilizing	0.916	D	0.61	neutral	None	None	None	None	I
V/W	0.9783	likely_pathogenic	0.9768	pathogenic	-1.314	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	I
V/Y	0.904	likely_pathogenic	0.8963	pathogenic	-0.949	Destabilizing	0.996	D	0.759	deleterious	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.