TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5446	16561;16562;16563	chr2:178732840;178732839;178732838	chr2:179597567;179597566;179597565
N2AB	5129	15610;15611;15612	chr2:178732840;178732839;178732838	chr2:179597567;179597566;179597565
N2A	4202	12829;12830;12831	chr2:178732840;178732839;178732838	chr2:179597567;179597566;179597565
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-37
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.2306
• 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	None	None	0.977	D	0.736	0.504	0.741923070755	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
V/L	None	None	0.898	N	0.732	0.339	0.518367700685	gnomAD-4.0.0	1.37366E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80464E-06	0	0
V/M	rs1232217078	None	0.993	D	0.874	0.452	0.618982361579	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/M	rs1232217078	None	0.993	D	0.874	0.452	0.618982361579	gnomAD-4.0.0	6.57091E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47011E-05	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	0.598	likely_pathogenic	0.6456	pathogenic	-1.783	Destabilizing	0.977	D	0.736	prob.delet.	D	0.547625644	None	None	N
V/C	0.9272	likely_pathogenic	0.9355	pathogenic	-1.232	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
V/D	0.9877	likely_pathogenic	0.9924	pathogenic	-1.826	Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
V/E	0.9575	likely_pathogenic	0.9729	pathogenic	-1.787	Destabilizing	0.999	D	0.866	deleterious	D	0.548893091	None	None	N
V/F	0.6182	likely_pathogenic	0.686	pathogenic	-1.264	Destabilizing	0.995	D	0.866	deleterious	None	None	None	None	N
V/G	0.8065	likely_pathogenic	0.8452	pathogenic	-2.143	Highly Destabilizing	0.999	D	0.856	deleterious	D	0.548893091	None	None	N
V/H	0.9835	likely_pathogenic	0.9896	pathogenic	-1.645	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
V/I	0.0816	likely_benign	0.0809	benign	-0.865	Destabilizing	0.15	N	0.547	neutral	None	None	None	None	N
V/K	0.9589	likely_pathogenic	0.9737	pathogenic	-1.428	Destabilizing	0.998	D	0.867	deleterious	None	None	None	None	N
V/L	0.3842	ambiguous	0.403	ambiguous	-0.865	Destabilizing	0.898	D	0.732	prob.delet.	N	0.501110785	None	None	N
V/M	0.4525	ambiguous	0.4986	ambiguous	-0.723	Destabilizing	0.993	D	0.874	deleterious	D	0.530281857	None	None	N
V/N	0.9486	likely_pathogenic	0.9652	pathogenic	-1.289	Destabilizing	0.999	D	0.888	deleterious	None	None	None	None	N
V/P	0.9025	likely_pathogenic	0.9287	pathogenic	-1.139	Destabilizing	0.999	D	0.874	deleterious	None	None	None	None	N
V/Q	0.9359	likely_pathogenic	0.955	pathogenic	-1.437	Destabilizing	0.999	D	0.883	deleterious	None	None	None	None	N
V/R	0.9263	likely_pathogenic	0.9492	pathogenic	-0.932	Destabilizing	0.999	D	0.886	deleterious	None	None	None	None	N
V/S	0.8094	likely_pathogenic	0.8565	pathogenic	-1.847	Destabilizing	0.998	D	0.855	deleterious	None	None	None	None	N
V/T	0.6722	likely_pathogenic	0.732	pathogenic	-1.701	Destabilizing	0.983	D	0.811	deleterious	None	None	None	None	N
V/W	0.9859	likely_pathogenic	0.9909	pathogenic	-1.495	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
V/Y	0.9562	likely_pathogenic	0.9699	pathogenic	-1.215	Destabilizing	0.999	D	0.867	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.