TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19859	59800;59801;59802	chr2:178592430;178592429;178592428	chr2:179457157;179457156;179457155
N2AB	18218	54877;54878;54879	chr2:178592430;178592429;178592428	chr2:179457157;179457156;179457155
N2A	17291	52096;52097;52098	chr2:178592430;178592429;178592428	chr2:179457157;179457156;179457155
N2B	10794	32605;32606;32607	chr2:178592430;178592429;178592428	chr2:179457157;179457156;179457155
Novex-1	10919	32980;32981;32982	chr2:178592430;178592429;178592428	chr2:179457157;179457156;179457155
Novex-2	10986	33181;33182;33183	chr2:178592430;178592429;178592428	chr2:179457157;179457156;179457155
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-119
• Domain position: 70
• Structural Position: 158
• Q(SASA): 0.0594
• 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	rs778885421	-1.65	0.999	N	0.742	0.582	0.636570122401	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	1.78E-05	0
V/M	rs778885421	-1.65	0.999	N	0.742	0.582	0.636570122401	gnomAD-4.0.0	3.42179E-06	None	None	None	None	N	None	0	0	None	0	1.00918E-04	None	0	0	8.99604E-07	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	0.2841	likely_benign	0.3221	benign	-1.731	Destabilizing	0.543	D	0.337	neutral	N	0.432828261	None	None	N
V/C	0.8982	likely_pathogenic	0.905	pathogenic	-1.62	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
V/D	0.9964	likely_pathogenic	0.9978	pathogenic	-2.011	Highly Destabilizing	0.999	D	0.858	deleterious	None	None	None	None	N
V/E	0.9898	likely_pathogenic	0.9932	pathogenic	-1.962	Destabilizing	0.998	D	0.832	deleterious	D	0.5316228	None	None	N
V/F	0.9137	likely_pathogenic	0.9166	pathogenic	-1.36	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
V/G	0.7367	likely_pathogenic	0.8094	pathogenic	-2.093	Highly Destabilizing	0.997	D	0.79	deleterious	D	0.534854629	None	None	N
V/H	0.9984	likely_pathogenic	0.9988	pathogenic	-1.645	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/I	0.126	likely_benign	0.1081	benign	-0.808	Destabilizing	0.99	D	0.561	neutral	None	None	None	None	N
V/K	0.9951	likely_pathogenic	0.997	pathogenic	-1.389	Destabilizing	0.999	D	0.836	deleterious	None	None	None	None	N
V/L	0.485	ambiguous	0.4837	ambiguous	-0.808	Destabilizing	0.973	D	0.629	neutral	N	0.485772603	None	None	N
V/M	0.5732	likely_pathogenic	0.5778	pathogenic	-0.845	Destabilizing	0.999	D	0.742	deleterious	N	0.508492116	None	None	N
V/N	0.9901	likely_pathogenic	0.9928	pathogenic	-1.374	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/P	0.9937	likely_pathogenic	0.9966	pathogenic	-1.083	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
V/Q	0.9894	likely_pathogenic	0.993	pathogenic	-1.518	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
V/R	0.9898	likely_pathogenic	0.9936	pathogenic	-0.947	Destabilizing	0.999	D	0.86	deleterious	None	None	None	None	N
V/S	0.8475	likely_pathogenic	0.8776	pathogenic	-1.941	Destabilizing	0.995	D	0.794	deleterious	None	None	None	None	N
V/T	0.6222	likely_pathogenic	0.6435	pathogenic	-1.773	Destabilizing	0.992	D	0.65	neutral	None	None	None	None	N
V/W	0.999	likely_pathogenic	0.9993	pathogenic	-1.593	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/Y	0.995	likely_pathogenic	0.9962	pathogenic	-1.266	Destabilizing	1.0	D	0.834	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.