TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7098	21517;21518;21519	chr2:178723967;178723966;178723965	chr2:179588694;179588693;179588692
N2AB	6781	20566;20567;20568	chr2:178723967;178723966;178723965	chr2:179588694;179588693;179588692
N2A	5854	17785;17786;17787	chr2:178723967;178723966;178723965	chr2:179588694;179588693;179588692
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: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-55
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.219
• 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/I	rs878978917	-0.699	0.003	N	0.311	0.118	0.496099317193	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
V/I	rs878978917	-0.699	0.003	N	0.311	0.118	0.496099317193	gnomAD-4.0.0	2.73726E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59838E-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	0.156	likely_benign	0.166	benign	-1.558	Destabilizing	0.296	N	0.486	neutral	N	0.487147587	None	None	N
V/C	0.6308	likely_pathogenic	0.6672	pathogenic	-1.227	Destabilizing	0.991	D	0.64	neutral	None	None	None	None	N
V/D	0.2493	likely_benign	0.2613	benign	-1.902	Destabilizing	0.879	D	0.732	prob.delet.	N	0.502035838	None	None	N
V/E	0.2374	likely_benign	0.2441	benign	-1.909	Destabilizing	0.906	D	0.68	prob.neutral	None	None	None	None	N
V/F	0.1131	likely_benign	0.1236	benign	-1.384	Destabilizing	0.782	D	0.665	neutral	N	0.484896316	None	None	N
V/G	0.2086	likely_benign	0.2313	benign	-1.862	Destabilizing	0.879	D	0.695	prob.neutral	N	0.501600487	None	None	N
V/H	0.3613	ambiguous	0.3955	ambiguous	-1.417	Destabilizing	0.991	D	0.737	prob.delet.	None	None	None	None	N
V/I	0.0653	likely_benign	0.0654	benign	-0.816	Destabilizing	0.003	N	0.311	neutral	N	0.481801218	None	None	N
V/K	0.2681	likely_benign	0.3064	benign	-1.187	Destabilizing	0.826	D	0.671	neutral	None	None	None	None	N
V/L	0.1393	likely_benign	0.1447	benign	-0.816	Destabilizing	0.001	N	0.175	neutral	N	0.504928793	None	None	N
V/M	0.105	likely_benign	0.1035	benign	-0.632	Destabilizing	0.826	D	0.569	neutral	None	None	None	None	N
V/N	0.1676	likely_benign	0.1858	benign	-1.062	Destabilizing	0.906	D	0.748	deleterious	None	None	None	None	N
V/P	0.8776	likely_pathogenic	0.9224	pathogenic	-1.03	Destabilizing	0.967	D	0.704	prob.neutral	None	None	None	None	N
V/Q	0.2518	likely_benign	0.2773	benign	-1.297	Destabilizing	0.967	D	0.714	prob.delet.	None	None	None	None	N
V/R	0.2123	likely_benign	0.2551	benign	-0.665	Destabilizing	0.906	D	0.749	deleterious	None	None	None	None	N
V/S	0.15	likely_benign	0.1672	benign	-1.543	Destabilizing	0.704	D	0.657	neutral	None	None	None	None	N
V/T	0.1216	likely_benign	0.1244	benign	-1.446	Destabilizing	0.018	N	0.304	neutral	None	None	None	None	N
V/W	0.6377	likely_pathogenic	0.6573	pathogenic	-1.579	Destabilizing	0.991	D	0.743	deleterious	None	None	None	None	N
V/Y	0.3467	ambiguous	0.3911	ambiguous	-1.266	Destabilizing	0.906	D	0.679	prob.neutral	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.