TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31289	94090;94091;94092	chr2:178547761;178547760;178547759	chr2:179412488;179412487;179412486
N2AB	29648	89167;89168;89169	chr2:178547761;178547760;178547759	chr2:179412488;179412487;179412486
N2A	28721	86386;86387;86388	chr2:178547761;178547760;178547759	chr2:179412488;179412487;179412486
N2B	22224	66895;66896;66897	chr2:178547761;178547760;178547759	chr2:179412488;179412487;179412486
Novex-1	22349	67270;67271;67272	chr2:178547761;178547760;178547759	chr2:179412488;179412487;179412486
Novex-2	22416	67471;67472;67473	chr2:178547761;178547760;178547759	chr2:179412488;179412487;179412486
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-151
• Domain position: 72
• Structural Position: 157
• Q(SASA): 0.1617
• 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/I	None	None	0.978	N	0.75	0.319	0.451504584351	gnomAD-4.0.0	6.84167E-07	None	None	None	None	N	None	2.98793E-05	0	None	0	0	None	0	0	0	0	0
T/N	rs371666313	-1.335	0.997	D	0.727	0.347	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
T/N	rs371666313	-1.335	0.997	D	0.727	0.347	None	gnomAD-4.0.0	1.85897E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.54267E-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	0.1352	likely_benign	0.1464	benign	-1.17	Destabilizing	0.948	D	0.635	neutral	N	0.488365809	None	None	N
T/C	0.4339	ambiguous	0.4339	ambiguous	-0.861	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
T/D	0.6075	likely_pathogenic	0.6633	pathogenic	-1.127	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
T/E	0.4139	ambiguous	0.4472	ambiguous	-0.954	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
T/F	0.3022	likely_benign	0.3191	benign	-0.803	Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
T/G	0.4274	ambiguous	0.4712	ambiguous	-1.575	Destabilizing	0.992	D	0.757	deleterious	None	None	None	None	N
T/H	0.2679	likely_benign	0.2813	benign	-1.661	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
T/I	0.1435	likely_benign	0.1613	benign	-0.117	Destabilizing	0.978	D	0.75	deleterious	N	0.498946971	None	None	N
T/K	0.3106	likely_benign	0.3301	benign	-0.644	Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	N
T/L	0.1044	likely_benign	0.115	benign	-0.117	Destabilizing	0.983	D	0.682	prob.neutral	None	None	None	None	N
T/M	0.0936	likely_benign	0.0926	benign	-0.111	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
T/N	0.1867	likely_benign	0.202	benign	-1.189	Destabilizing	0.997	D	0.727	prob.delet.	D	0.536483851	None	None	N
T/P	0.679	likely_pathogenic	0.7493	pathogenic	-0.436	Destabilizing	0.999	D	0.799	deleterious	N	0.516384792	None	None	N
T/Q	0.2552	likely_benign	0.2658	benign	-1.025	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
T/R	0.2599	likely_benign	0.2723	benign	-0.782	Destabilizing	0.999	D	0.8	deleterious	None	None	None	None	N
T/S	0.1498	likely_benign	0.1559	benign	-1.466	Destabilizing	0.775	D	0.413	neutral	N	0.505064866	None	None	N
T/V	0.1356	likely_benign	0.143	benign	-0.436	Destabilizing	0.611	D	0.431	neutral	None	None	None	None	N
T/W	0.6626	likely_pathogenic	0.703	pathogenic	-0.873	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
T/Y	0.3287	likely_benign	0.3469	ambiguous	-0.537	Destabilizing	1.0	D	0.809	deleterious	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.