TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26204	78835;78836;78837	chr2:178567522;178567521;178567520	chr2:179432249;179432248;179432247
N2AB	24563	73912;73913;73914	chr2:178567522;178567521;178567520	chr2:179432249;179432248;179432247
N2A	23636	71131;71132;71133	chr2:178567522;178567521;178567520	chr2:179432249;179432248;179432247
N2B	17139	51640;51641;51642	chr2:178567522;178567521;178567520	chr2:179432249;179432248;179432247
Novex-1	17264	52015;52016;52017	chr2:178567522;178567521;178567520	chr2:179432249;179432248;179432247
Novex-2	17331	52216;52217;52218	chr2:178567522;178567521;178567520	chr2:179432249;179432248;179432247
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-137
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.3987
• 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/M	None	None	0.994	N	0.516	0.372	0.613122972663	gnomAD-4.0.0	2.74056E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.60023E-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	0.299	likely_benign	0.3391	benign	-1.069	Destabilizing	0.63	D	0.43	neutral	N	0.493797086	None	None	I
V/C	0.8313	likely_pathogenic	0.8271	pathogenic	-0.758	Destabilizing	0.999	D	0.589	neutral	None	None	None	None	I
V/D	0.684	likely_pathogenic	0.7655	pathogenic	-0.706	Destabilizing	0.975	D	0.687	prob.neutral	None	None	None	None	I
V/E	0.4986	ambiguous	0.5625	ambiguous	-0.743	Destabilizing	0.967	D	0.595	neutral	N	0.487476755	None	None	I
V/F	0.2792	likely_benign	0.3172	benign	-0.868	Destabilizing	0.987	D	0.593	neutral	None	None	None	None	I
V/G	0.5199	ambiguous	0.5839	pathogenic	-1.331	Destabilizing	0.967	D	0.6	neutral	D	0.529070997	None	None	I
V/H	0.7134	likely_pathogenic	0.7551	pathogenic	-0.838	Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	I
V/I	0.0754	likely_benign	0.0725	benign	-0.479	Destabilizing	0.818	D	0.447	neutral	None	None	None	None	I
V/K	0.5684	likely_pathogenic	0.6349	pathogenic	-0.96	Destabilizing	0.975	D	0.627	neutral	None	None	None	None	I
V/L	0.228	likely_benign	0.2481	benign	-0.479	Destabilizing	0.63	D	0.447	neutral	N	0.496723601	None	None	I
V/M	0.1794	likely_benign	0.1886	benign	-0.398	Destabilizing	0.994	D	0.516	neutral	N	0.494356971	None	None	I
V/N	0.4977	ambiguous	0.5365	ambiguous	-0.732	Destabilizing	0.975	D	0.694	prob.neutral	None	None	None	None	I
V/P	0.8045	likely_pathogenic	0.8329	pathogenic	-0.639	Destabilizing	0.987	D	0.668	neutral	None	None	None	None	I
V/Q	0.4899	ambiguous	0.528	ambiguous	-0.907	Destabilizing	0.987	D	0.671	neutral	None	None	None	None	I
V/R	0.5048	ambiguous	0.5777	pathogenic	-0.434	Destabilizing	0.975	D	0.705	prob.neutral	None	None	None	None	I
V/S	0.3622	ambiguous	0.4046	ambiguous	-1.209	Destabilizing	0.845	D	0.508	neutral	None	None	None	None	I
V/T	0.167	likely_benign	0.1697	benign	-1.138	Destabilizing	0.014	N	0.202	neutral	None	None	None	None	I
V/W	0.8828	likely_pathogenic	0.8994	pathogenic	-1.026	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	I
V/Y	0.7113	likely_pathogenic	0.743	pathogenic	-0.733	Destabilizing	0.996	D	0.607	neutral	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.