TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2592	7999;8000;8001	chr2:178773190;178773189;178773188	chr2:179637917;179637916;179637915
N2AB	2592	7999;8000;8001	chr2:178773190;178773189;178773188	chr2:179637917;179637916;179637915
N2A	2592	7999;8000;8001	chr2:178773190;178773189;178773188	chr2:179637917;179637916;179637915
N2B	2546	7861;7862;7863	chr2:178773190;178773189;178773188	chr2:179637917;179637916;179637915
Novex-1	2546	7861;7862;7863	chr2:178773190;178773189;178773188	chr2:179637917;179637916;179637915
Novex-2	2546	7861;7862;7863	chr2:178773190;178773189;178773188	chr2:179637917;179637916;179637915
Novex-3	2592	7999;8000;8001	chr2:178773190;178773189;178773188	chr2:179637917;179637916;179637915

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-15
• Domain position: 60
• Structural Position: 141
• Q(SASA): 0.203
• 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
L/I	None	None	0.005	N	0.093	0.091	0.350746614512	gnomAD-4.0.0	1.59125E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85724E-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
L/A	0.1917	likely_benign	0.1991	benign	-1.658	Destabilizing	0.525	D	0.371	neutral	None	None	None	None	N
L/C	0.428	ambiguous	0.3978	ambiguous	-0.863	Destabilizing	0.998	D	0.41	neutral	None	None	None	None	N
L/D	0.5467	ambiguous	0.531	ambiguous	-1.317	Destabilizing	0.949	D	0.517	neutral	None	None	None	None	N
L/E	0.2304	likely_benign	0.217	benign	-1.353	Destabilizing	0.728	D	0.487	neutral	None	None	None	None	N
L/F	0.1299	likely_benign	0.1316	benign	-1.366	Destabilizing	0.949	D	0.405	neutral	None	None	None	None	N
L/G	0.4203	ambiguous	0.4509	ambiguous	-1.951	Destabilizing	0.842	D	0.481	neutral	None	None	None	None	N
L/H	0.1871	likely_benign	0.173	benign	-1.185	Destabilizing	0.993	D	0.529	neutral	None	None	None	None	N
L/I	0.0712	likely_benign	0.0711	benign	-0.938	Destabilizing	0.005	N	0.093	neutral	N	0.461235397	None	None	N
L/K	0.1783	likely_benign	0.1653	benign	-1.055	Destabilizing	0.728	D	0.445	neutral	None	None	None	None	N
L/M	0.0948	likely_benign	0.1	benign	-0.553	Destabilizing	0.949	D	0.451	neutral	None	None	None	None	N
L/N	0.2349	likely_benign	0.233	benign	-0.795	Destabilizing	0.949	D	0.539	neutral	None	None	None	None	N
L/P	0.4989	ambiguous	0.5227	ambiguous	-1.147	Destabilizing	0.966	D	0.551	neutral	N	0.509489816	None	None	N
L/Q	0.0945	likely_benign	0.096	benign	-1.058	Destabilizing	0.111	N	0.391	neutral	N	0.467777208	None	None	N
L/R	0.1543	likely_benign	0.1438	benign	-0.376	Destabilizing	0.876	D	0.495	neutral	N	0.476116409	None	None	N
L/S	0.1867	likely_benign	0.184	benign	-1.353	Destabilizing	0.172	N	0.339	neutral	None	None	None	None	N
L/T	0.1457	likely_benign	0.1484	benign	-1.28	Destabilizing	0.728	D	0.379	neutral	None	None	None	None	N
L/V	0.0808	likely_benign	0.0822	benign	-1.147	Destabilizing	0.005	N	0.082	neutral	N	0.482147438	None	None	N
L/W	0.2301	likely_benign	0.2201	benign	-1.418	Destabilizing	0.998	D	0.525	neutral	None	None	None	None	N
L/Y	0.3042	likely_benign	0.2938	benign	-1.2	Destabilizing	0.974	D	0.442	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.