TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16939	51040;51041;51042	chr2:178611414;178611413;178611412	chr2:179476141;179476140;179476139
N2AB	15298	46117;46118;46119	chr2:178611414;178611413;178611412	chr2:179476141;179476140;179476139
N2A	14371	43336;43337;43338	chr2:178611414;178611413;178611412	chr2:179476141;179476140;179476139
N2B	7874	23845;23846;23847	chr2:178611414;178611413;178611412	chr2:179476141;179476140;179476139
Novex-1	7999	24220;24221;24222	chr2:178611414;178611413;178611412	chr2:179476141;179476140;179476139
Novex-2	8066	24421;24422;24423	chr2:178611414;178611413;178611412	chr2:179476141;179476140;179476139
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-11
• Domain position: 88
• Structural Position: 120
• Q(SASA): 0.3392
• 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
P/L	rs1321289317	-0.83	1.0	D	0.827	0.465	0.746050308143	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
P/L	rs1321289317	-0.83	1.0	D	0.827	0.465	0.746050308143	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
P/S	None	None	1.0	D	0.747	0.428	0.386558576397	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
P/A	0.1575	likely_benign	0.4427	ambiguous	-1.627	Destabilizing	1.0	D	0.717	prob.delet.	D	0.543720062	None	None	I
P/C	0.8855	likely_pathogenic	0.9859	pathogenic	-1.147	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
P/D	0.9342	likely_pathogenic	0.9881	pathogenic	-1.805	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
P/E	0.8717	likely_pathogenic	0.973	pathogenic	-1.834	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
P/F	0.9009	likely_pathogenic	0.9914	pathogenic	-1.413	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
P/G	0.7457	likely_pathogenic	0.9478	pathogenic	-1.892	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
P/H	0.7805	likely_pathogenic	0.9687	pathogenic	-1.328	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
P/I	0.8505	likely_pathogenic	0.9707	pathogenic	-1.002	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
P/K	0.9438	likely_pathogenic	0.9874	pathogenic	-1.222	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
P/L	0.6685	likely_pathogenic	0.9082	pathogenic	-1.002	Destabilizing	1.0	D	0.827	deleterious	D	0.618810289	None	None	I
P/M	0.8455	likely_pathogenic	0.9727	pathogenic	-0.79	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
P/N	0.9117	likely_pathogenic	0.9859	pathogenic	-1.045	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	I
P/Q	0.796	likely_pathogenic	0.9552	pathogenic	-1.325	Destabilizing	1.0	D	0.788	deleterious	D	0.693330286	None	None	I
P/R	0.8844	likely_pathogenic	0.9712	pathogenic	-0.63	Destabilizing	1.0	D	0.848	deleterious	D	0.607362871	None	None	I
P/S	0.4848	ambiguous	0.86	pathogenic	-1.498	Destabilizing	1.0	D	0.747	deleterious	D	0.630225046	None	None	I
P/T	0.5185	ambiguous	0.8632	pathogenic	-1.435	Destabilizing	1.0	D	0.748	deleterious	D	0.653421975	None	None	I
P/V	0.6932	likely_pathogenic	0.9209	pathogenic	-1.178	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
P/W	0.9552	likely_pathogenic	0.9968	pathogenic	-1.521	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
P/Y	0.9007	likely_pathogenic	0.9901	pathogenic	-1.253	Destabilizing	1.0	D	0.857	deleterious	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.