TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16207	48844;48845;48846	chr2:178615326;178615325;178615324	chr2:179480053;179480052;179480051
N2AB	14566	43921;43922;43923	chr2:178615326;178615325;178615324	chr2:179480053;179480052;179480051
N2A	13639	41140;41141;41142	chr2:178615326;178615325;178615324	chr2:179480053;179480052;179480051
N2B	7142	21649;21650;21651	chr2:178615326;178615325;178615324	chr2:179480053;179480052;179480051
Novex-1	7267	22024;22025;22026	chr2:178615326;178615325;178615324	chr2:179480053;179480052;179480051
Novex-2	7334	22225;22226;22227	chr2:178615326;178615325;178615324	chr2:179480053;179480052;179480051
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-5
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.6054
• 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
E/Q	rs1372711773	0.388	0.722	N	0.511	0.195	0.306377322295	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
E/Q	rs1372711773	0.388	0.722	N	0.511	0.195	0.306377322295	gnomAD-4.0.0	3.18884E-06	None	None	None	None	N	None	0	0	None	0	2.78319E-05	None	0	0	0	0	3.03196E-05

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
E/A	0.1275	likely_benign	0.1405	benign	-0.011	Destabilizing	0.722	D	0.552	neutral	N	0.472733887	None	None	N
E/C	0.7706	likely_pathogenic	0.7732	pathogenic	-0.445	Destabilizing	0.996	D	0.758	deleterious	None	None	None	None	N
E/D	0.0603	likely_benign	0.0634	benign	-0.517	Destabilizing	0.001	N	0.145	neutral	N	0.437041958	None	None	N
E/F	0.6142	likely_pathogenic	0.6334	pathogenic	-0.117	Destabilizing	0.987	D	0.678	prob.neutral	None	None	None	None	N
E/G	0.1499	likely_benign	0.1528	benign	-0.086	Destabilizing	0.722	D	0.542	neutral	N	0.476632558	None	None	N
E/H	0.3935	ambiguous	0.3989	ambiguous	0.609	Stabilizing	0.987	D	0.531	neutral	None	None	None	None	N
E/I	0.2559	likely_benign	0.2809	benign	0.126	Stabilizing	0.961	D	0.665	neutral	None	None	None	None	N
E/K	0.1288	likely_benign	0.1306	benign	0.187	Stabilizing	0.722	D	0.516	neutral	N	0.472535976	None	None	N
E/L	0.277	likely_benign	0.3027	benign	0.126	Stabilizing	0.961	D	0.632	neutral	None	None	None	None	N
E/M	0.3536	ambiguous	0.3785	ambiguous	-0.201	Destabilizing	0.996	D	0.661	neutral	None	None	None	None	N
E/N	0.1318	likely_benign	0.1495	benign	-0.004	Destabilizing	0.633	D	0.515	neutral	None	None	None	None	N
E/P	0.2357	likely_benign	0.2397	benign	0.096	Stabilizing	0.961	D	0.57	neutral	None	None	None	None	N
E/Q	0.1367	likely_benign	0.1374	benign	-0.017	Destabilizing	0.722	D	0.511	neutral	N	0.481574543	None	None	N
E/R	0.2809	likely_benign	0.2689	benign	0.451	Stabilizing	0.961	D	0.527	neutral	None	None	None	None	N
E/S	0.1265	likely_benign	0.1394	benign	-0.14	Destabilizing	0.775	D	0.51	neutral	None	None	None	None	N
E/T	0.1543	likely_benign	0.1694	benign	-0.068	Destabilizing	0.775	D	0.555	neutral	None	None	None	None	N
E/V	0.1659	likely_benign	0.1853	benign	0.096	Stabilizing	0.949	D	0.557	neutral	N	0.460445931	None	None	N
E/W	0.874	likely_pathogenic	0.8643	pathogenic	-0.108	Destabilizing	0.996	D	0.768	deleterious	None	None	None	None	N
E/Y	0.4856	ambiguous	0.4937	ambiguous	0.087	Stabilizing	0.987	D	0.664	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.