TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23901	71926;71927;71928	chr2:178574431;178574430;178574429	chr2:179439158;179439157;179439156
N2AB	22260	67003;67004;67005	chr2:178574431;178574430;178574429	chr2:179439158;179439157;179439156
N2A	21333	64222;64223;64224	chr2:178574431;178574430;178574429	chr2:179439158;179439157;179439156
N2B	14836	44731;44732;44733	chr2:178574431;178574430;178574429	chr2:179439158;179439157;179439156
Novex-1	14961	45106;45107;45108	chr2:178574431;178574430;178574429	chr2:179439158;179439157;179439156
Novex-2	15028	45307;45308;45309	chr2:178574431;178574430;178574429	chr2:179439158;179439157;179439156
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: Fn3-61
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.1076
• 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	0.994	D	0.698	0.745	0.73031271798	gnomAD-4.0.0	1.36861E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79915E-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	0.6218	likely_pathogenic	0.661	pathogenic	-2.634	Highly Destabilizing	0.63	D	0.615	neutral	D	0.556264876	None	None	N
V/C	0.9195	likely_pathogenic	0.9234	pathogenic	-2.067	Highly Destabilizing	0.999	D	0.782	deleterious	None	None	None	None	N
V/D	0.9944	likely_pathogenic	0.9962	pathogenic	-3.431	Highly Destabilizing	0.975	D	0.886	deleterious	None	None	None	None	N
V/E	0.9884	likely_pathogenic	0.9912	pathogenic	-3.122	Highly Destabilizing	0.967	D	0.865	deleterious	D	0.655021777	None	None	N
V/F	0.8647	likely_pathogenic	0.9	pathogenic	-1.359	Destabilizing	0.987	D	0.788	deleterious	None	None	None	None	N
V/G	0.8194	likely_pathogenic	0.8562	pathogenic	-3.211	Highly Destabilizing	0.967	D	0.857	deleterious	D	0.655021777	None	None	N
V/H	0.9967	likely_pathogenic	0.9978	pathogenic	-2.938	Highly Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
V/I	0.1054	likely_benign	0.1194	benign	-0.941	Destabilizing	0.818	D	0.563	neutral	None	None	None	None	N
V/K	0.9946	likely_pathogenic	0.9958	pathogenic	-2.011	Highly Destabilizing	0.975	D	0.865	deleterious	None	None	None	None	N
V/L	0.6257	likely_pathogenic	0.707	pathogenic	-0.941	Destabilizing	0.63	D	0.626	neutral	D	0.524723493	None	None	N
V/M	0.6339	likely_pathogenic	0.7104	pathogenic	-1.32	Destabilizing	0.994	D	0.698	prob.neutral	D	0.545162061	None	None	N
V/N	0.9727	likely_pathogenic	0.9807	pathogenic	-2.652	Highly Destabilizing	0.975	D	0.885	deleterious	None	None	None	None	N
V/P	0.9923	likely_pathogenic	0.9937	pathogenic	-1.49	Destabilizing	0.987	D	0.876	deleterious	None	None	None	None	N
V/Q	0.9883	likely_pathogenic	0.9907	pathogenic	-2.305	Highly Destabilizing	0.987	D	0.878	deleterious	None	None	None	None	N
V/R	0.9891	likely_pathogenic	0.9909	pathogenic	-2.049	Highly Destabilizing	0.975	D	0.895	deleterious	None	None	None	None	N
V/S	0.8686	likely_pathogenic	0.8975	pathogenic	-3.155	Highly Destabilizing	0.95	D	0.839	deleterious	None	None	None	None	N
V/T	0.6852	likely_pathogenic	0.7491	pathogenic	-2.7	Highly Destabilizing	0.033	N	0.32	neutral	None	None	None	None	N
V/W	0.9982	likely_pathogenic	0.9989	pathogenic	-1.874	Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
V/Y	0.9884	likely_pathogenic	0.9919	pathogenic	-1.66	Destabilizing	0.996	D	0.793	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.