TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5210	15853;15854;15855	chr2:178733761;178733760;178733759	chr2:179598488;179598487;179598486
N2AB	4893	14902;14903;14904	chr2:178733761;178733760;178733759	chr2:179598488;179598487;179598486
N2A	3966	12121;12122;12123	chr2:178733761;178733760;178733759	chr2:179598488;179598487;179598486
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-35
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.3985
• 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	None	None	0.904	D	0.396	0.232	0.400033932507	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	0.1467	likely_benign	0.1768	benign	-0.464	Destabilizing	0.822	D	0.449	neutral	D	0.544684459	None	None	N
E/C	0.8653	likely_pathogenic	0.9225	pathogenic	-0.141	Destabilizing	0.998	D	0.652	neutral	None	None	None	None	N
E/D	0.1212	likely_benign	0.1463	benign	-0.516	Destabilizing	0.002	N	0.155	neutral	N	0.500834419	None	None	N
E/F	0.8307	likely_pathogenic	0.9017	pathogenic	-0.126	Destabilizing	0.993	D	0.599	neutral	None	None	None	None	N
E/G	0.1283	likely_benign	0.1609	benign	-0.734	Destabilizing	0.822	D	0.457	neutral	D	0.558537896	None	None	N
E/H	0.55	ambiguous	0.6556	pathogenic	-0.09	Destabilizing	0.993	D	0.447	neutral	None	None	None	None	N
E/I	0.4689	ambiguous	0.593	pathogenic	0.233	Stabilizing	0.978	D	0.587	neutral	None	None	None	None	N
E/K	0.1561	likely_benign	0.1884	benign	0.112	Stabilizing	0.822	D	0.425	neutral	D	0.615309917	None	None	N
E/L	0.4768	ambiguous	0.5951	pathogenic	0.233	Stabilizing	0.978	D	0.567	neutral	None	None	None	None	N
E/M	0.5261	ambiguous	0.6407	pathogenic	0.381	Stabilizing	0.998	D	0.571	neutral	None	None	None	None	N
E/N	0.247	likely_benign	0.3139	benign	-0.323	Destabilizing	0.754	D	0.415	neutral	None	None	None	None	N
E/P	0.369	ambiguous	0.4644	ambiguous	0.022	Stabilizing	0.978	D	0.465	neutral	None	None	None	None	N
E/Q	0.1649	likely_benign	0.1973	benign	-0.23	Destabilizing	0.904	D	0.396	neutral	D	0.555039172	None	None	N
E/R	0.2952	likely_benign	0.354	ambiguous	0.349	Stabilizing	0.978	D	0.435	neutral	None	None	None	None	N
E/S	0.2046	likely_benign	0.2469	benign	-0.508	Destabilizing	0.86	D	0.409	neutral	None	None	None	None	N
E/T	0.2368	likely_benign	0.3098	benign	-0.284	Destabilizing	0.86	D	0.445	neutral	None	None	None	None	N
E/V	0.2688	likely_benign	0.355	ambiguous	0.022	Stabilizing	0.97	D	0.489	neutral	D	0.583452947	None	None	N
E/W	0.9046	likely_pathogenic	0.946	pathogenic	0.079	Stabilizing	0.998	D	0.667	neutral	None	None	None	None	N
E/Y	0.677	likely_pathogenic	0.7899	pathogenic	0.127	Stabilizing	0.993	D	0.565	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.