TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13695	41308;41309;41310	chr2:178636644;178636643;178636642	chr2:179501371;179501370;179501369
N2AB	12054	36385;36386;36387	chr2:178636644;178636643;178636642	chr2:179501371;179501370;179501369
N2A	11127	33604;33605;33606	chr2:178636644;178636643;178636642	chr2:179501371;179501370;179501369
N2B	4630	14113;14114;14115	chr2:178636644;178636643;178636642	chr2:179501371;179501370;179501369
Novex-1	4755	14488;14489;14490	chr2:178636644;178636643;178636642	chr2:179501371;179501370;179501369
Novex-2	4822	14689;14690;14691	chr2:178636644;178636643;178636642	chr2:179501371;179501370;179501369
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-87
• Domain position: 12
• Structural Position: 18
• Q(SASA): 0.4063
• 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
T/R	None	None	0.062	N	0.485	0.071	0.225215365344	gnomAD-4.0.0	1.59221E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85982E-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
T/A	0.1744	likely_benign	0.1295	benign	-0.829	Destabilizing	0.027	N	0.385	neutral	N	0.456935694	None	None	N
T/C	0.8029	likely_pathogenic	0.7502	pathogenic	-0.548	Destabilizing	0.935	D	0.491	neutral	None	None	None	None	N
T/D	0.6092	likely_pathogenic	0.5384	ambiguous	0.004	Stabilizing	0.149	N	0.451	neutral	None	None	None	None	N
T/E	0.3619	ambiguous	0.3181	benign	0.047	Stabilizing	0.035	N	0.421	neutral	None	None	None	None	N
T/F	0.7086	likely_pathogenic	0.6548	pathogenic	-0.786	Destabilizing	0.791	D	0.583	neutral	None	None	None	None	N
T/G	0.3485	ambiguous	0.2837	benign	-1.124	Destabilizing	0.149	N	0.502	neutral	None	None	None	None	N
T/H	0.431	ambiguous	0.3456	ambiguous	-1.308	Destabilizing	0.555	D	0.561	neutral	None	None	None	None	N
T/I	0.5357	ambiguous	0.493	ambiguous	-0.127	Destabilizing	0.484	N	0.531	neutral	N	0.48174152	None	None	N
T/K	0.1483	likely_benign	0.1275	benign	-0.556	Destabilizing	None	N	0.197	neutral	N	0.430046525	None	None	N
T/L	0.2519	likely_benign	0.2048	benign	-0.127	Destabilizing	0.149	N	0.491	neutral	None	None	None	None	N
T/M	0.203	likely_benign	0.1705	benign	-0.034	Destabilizing	0.791	D	0.501	neutral	None	None	None	None	N
T/N	0.2286	likely_benign	0.1841	benign	-0.629	Destabilizing	0.149	N	0.444	neutral	None	None	None	None	N
T/P	0.2441	likely_benign	0.1438	benign	-0.328	Destabilizing	0.211	N	0.533	neutral	N	0.472643997	None	None	N
T/Q	0.2023	likely_benign	0.178	benign	-0.687	Destabilizing	0.002	N	0.216	neutral	None	None	None	None	N
T/R	0.2132	likely_benign	0.1666	benign	-0.429	Destabilizing	0.062	N	0.485	neutral	N	0.467835469	None	None	N
T/S	0.1857	likely_benign	0.1447	benign	-0.961	Destabilizing	0.027	N	0.442	neutral	N	0.445703448	None	None	N
T/V	0.3796	ambiguous	0.3502	ambiguous	-0.328	Destabilizing	0.149	N	0.451	neutral	None	None	None	None	N
T/W	0.8813	likely_pathogenic	0.8679	pathogenic	-0.737	Destabilizing	0.935	D	0.581	neutral	None	None	None	None	N
T/Y	0.683	likely_pathogenic	0.6429	pathogenic	-0.478	Destabilizing	0.791	D	0.579	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.