TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2420	7483;7484;7485	chr2:178773910;178773909;178773908	chr2:179638637;179638636;179638635
N2AB	2420	7483;7484;7485	chr2:178773910;178773909;178773908	chr2:179638637;179638636;179638635
N2A	2420	7483;7484;7485	chr2:178773910;178773909;178773908	chr2:179638637;179638636;179638635
N2B	2374	7345;7346;7347	chr2:178773910;178773909;178773908	chr2:179638637;179638636;179638635
Novex-1	2374	7345;7346;7347	chr2:178773910;178773909;178773908	chr2:179638637;179638636;179638635
Novex-2	2374	7345;7346;7347	chr2:178773910;178773909;178773908	chr2:179638637;179638636;179638635
Novex-3	2420	7483;7484;7485	chr2:178773910;178773909;178773908	chr2:179638637;179638636;179638635

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-13
• Domain position: 65
• Structural Position: 148
• Q(SASA): 0.4951
• 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/G	None	None	0.978	D	0.491	0.658	0.725532541758	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
E/A	0.1085	likely_benign	0.1131	benign	-0.101	Destabilizing	0.989	D	0.548	neutral	D	0.566491451	None	None	N
E/C	0.7837	likely_pathogenic	0.8102	pathogenic	0.022	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
E/D	0.075	likely_benign	0.0768	benign	-0.216	Destabilizing	0.054	N	0.249	neutral	N	0.507721204	None	None	N
E/F	0.6847	likely_pathogenic	0.7103	pathogenic	-0.183	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
E/G	0.1157	likely_benign	0.1277	benign	-0.221	Destabilizing	0.978	D	0.491	neutral	D	0.595591065	None	None	N
E/H	0.4301	ambiguous	0.4602	ambiguous	0.282	Stabilizing	1.0	D	0.563	neutral	None	None	None	None	N
E/I	0.3367	likely_benign	0.3592	ambiguous	0.156	Stabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	N
E/K	0.15	likely_benign	0.1697	benign	0.494	Stabilizing	0.978	D	0.507	neutral	D	0.595461448	None	None	N
E/L	0.3488	ambiguous	0.37	ambiguous	0.156	Stabilizing	0.998	D	0.68	prob.neutral	None	None	None	None	N
E/M	0.3974	ambiguous	0.421	ambiguous	0.109	Stabilizing	1.0	D	0.615	neutral	None	None	None	None	N
E/N	0.1751	likely_benign	0.1874	benign	0.301	Stabilizing	0.995	D	0.559	neutral	None	None	None	None	N
E/P	0.632	likely_pathogenic	0.646	pathogenic	0.088	Stabilizing	0.999	D	0.601	neutral	None	None	None	None	N
E/Q	0.1521	likely_benign	0.1608	benign	0.308	Stabilizing	0.997	D	0.558	neutral	D	0.586186968	None	None	N
E/R	0.2675	likely_benign	0.2947	benign	0.642	Stabilizing	0.998	D	0.583	neutral	None	None	None	None	N
E/S	0.1421	likely_benign	0.1511	benign	0.152	Stabilizing	0.983	D	0.509	neutral	None	None	None	None	N
E/T	0.1696	likely_benign	0.1801	benign	0.255	Stabilizing	0.998	D	0.559	neutral	None	None	None	None	N
E/V	0.1933	likely_benign	0.2046	benign	0.088	Stabilizing	0.999	D	0.622	neutral	D	0.69407314	None	None	N
E/W	0.8331	likely_pathogenic	0.8581	pathogenic	-0.135	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/Y	0.5382	ambiguous	0.5721	pathogenic	0.04	Stabilizing	1.0	D	0.625	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.