TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5251	15976;15977;15978	chr2:178733638;178733637;178733636	chr2:179598365;179598364;179598363
N2AB	4934	15025;15026;15027	chr2:178733638;178733637;178733636	chr2:179598365;179598364;179598363
N2A	4007	12244;12245;12246	chr2:178733638;178733637;178733636	chr2:179598365;179598364;179598363
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-35
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.1099
• 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
S/C	rs770408836	-0.085	0.005	N	0.401	0.226	0.354610295913	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
S/C	rs770408836	-0.085	0.005	N	0.401	0.226	0.354610295913	gnomAD-4.0.0	1.59477E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86727E-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
S/A	0.0858	likely_benign	0.0958	benign	-0.771	Destabilizing	0.267	N	0.508	neutral	N	0.477052756	None	None	N
S/C	0.0732	likely_benign	0.0909	benign	-0.398	Destabilizing	0.005	N	0.401	neutral	N	0.442771451	None	None	N
S/D	0.8994	likely_pathogenic	0.9072	pathogenic	0.029	Stabilizing	0.971	D	0.735	prob.delet.	None	None	None	None	N
S/E	0.9506	likely_pathogenic	0.9471	pathogenic	0.072	Stabilizing	0.971	D	0.737	prob.delet.	None	None	None	None	N
S/F	0.5961	likely_pathogenic	0.67	pathogenic	-0.774	Destabilizing	0.989	D	0.788	deleterious	D	0.542548489	None	None	N
S/G	0.1378	likely_benign	0.1664	benign	-1.069	Destabilizing	0.915	D	0.685	prob.neutral	None	None	None	None	N
S/H	0.8285	likely_pathogenic	0.8351	pathogenic	-1.41	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
S/I	0.4108	ambiguous	0.4995	ambiguous	-0.069	Destabilizing	0.949	D	0.791	deleterious	None	None	None	None	N
S/K	0.986	likely_pathogenic	0.9883	pathogenic	-0.444	Destabilizing	0.971	D	0.739	prob.delet.	None	None	None	None	N
S/L	0.2451	likely_benign	0.3214	benign	-0.069	Destabilizing	0.728	D	0.704	prob.neutral	None	None	None	None	N
S/M	0.3867	ambiguous	0.471	ambiguous	0.089	Stabilizing	0.991	D	0.747	deleterious	None	None	None	None	N
S/N	0.4766	ambiguous	0.4807	ambiguous	-0.483	Destabilizing	0.971	D	0.728	prob.delet.	None	None	None	None	N
S/P	0.9654	likely_pathogenic	0.9805	pathogenic	-0.268	Destabilizing	0.989	D	0.786	deleterious	D	0.6870667	None	None	N
S/Q	0.9147	likely_pathogenic	0.9199	pathogenic	-0.534	Destabilizing	0.991	D	0.76	deleterious	None	None	None	None	N
S/R	0.9626	likely_pathogenic	0.9665	pathogenic	-0.472	Destabilizing	0.991	D	0.786	deleterious	None	None	None	None	N
S/T	0.112	likely_benign	0.1358	benign	-0.511	Destabilizing	0.801	D	0.679	prob.neutral	N	0.508428844	None	None	N
S/V	0.3043	likely_benign	0.3751	ambiguous	-0.268	Destabilizing	0.842	D	0.732	prob.delet.	None	None	None	None	N
S/W	0.7761	likely_pathogenic	0.8182	pathogenic	-0.751	Destabilizing	0.998	D	0.78	deleterious	None	None	None	None	N
S/Y	0.5657	likely_pathogenic	0.6077	pathogenic	-0.466	Destabilizing	0.989	D	0.766	deleterious	D	0.566178997	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.