TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14893	44902;44903;44904	chr2:178624603;178624602;178624601	chr2:179489330;179489329;179489328
N2AB	13252	39979;39980;39981	chr2:178624603;178624602;178624601	chr2:179489330;179489329;179489328
N2A	12325	37198;37199;37200	chr2:178624603;178624602;178624601	chr2:179489330;179489329;179489328
N2B	5828	17707;17708;17709	chr2:178624603;178624602;178624601	chr2:179489330;179489329;179489328
Novex-1	5953	18082;18083;18084	chr2:178624603;178624602;178624601	chr2:179489330;179489329;179489328
Novex-2	6020	18283;18284;18285	chr2:178624603;178624602;178624601	chr2:179489330;179489329;179489328
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-100
• Domain position: 41
• Structural Position: 59
• Q(SASA): 0.6617
• 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/F	None	None	0.003	N	0.187	0.143	0.461323234107	gnomAD-4.0.0	1.59357E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86239E-06	0	0
L/P	None	None	0.954	N	0.395	0.299	0.778704876926	gnomAD-4.0.0	3.42315E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49937E-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	0.1439	likely_benign	0.1369	benign	-0.626	Destabilizing	0.345	N	0.371	neutral	None	None	None	None	N
L/C	0.4403	ambiguous	0.3412	ambiguous	-0.935	Destabilizing	0.991	D	0.351	neutral	None	None	None	None	N
L/D	0.4525	ambiguous	0.3989	ambiguous	-0.195	Destabilizing	0.561	D	0.452	neutral	None	None	None	None	N
L/E	0.1875	likely_benign	0.1631	benign	-0.246	Destabilizing	0.561	D	0.449	neutral	None	None	None	None	N
L/F	0.1313	likely_benign	0.1014	benign	-0.561	Destabilizing	0.003	N	0.187	neutral	N	0.452045081	None	None	N
L/G	0.3126	likely_benign	0.2949	benign	-0.77	Destabilizing	0.561	D	0.444	neutral	None	None	None	None	N
L/H	0.1108	likely_benign	0.088	benign	0.074	Stabilizing	None	N	0.195	neutral	N	0.461197284	None	None	N
L/I	0.0936	likely_benign	0.0832	benign	-0.346	Destabilizing	0.326	N	0.31	neutral	N	0.448261878	None	None	N
L/K	0.1058	likely_benign	0.1085	benign	-0.456	Destabilizing	0.209	N	0.41	neutral	None	None	None	None	N
L/M	0.1291	likely_benign	0.1153	benign	-0.733	Destabilizing	0.901	D	0.321	neutral	None	None	None	None	N
L/N	0.1892	likely_benign	0.1764	benign	-0.459	Destabilizing	0.561	D	0.451	neutral	None	None	None	None	N
L/P	0.1544	likely_benign	0.138	benign	-0.412	Destabilizing	0.954	D	0.395	neutral	N	0.444675148	None	None	N
L/Q	0.0756	likely_benign	0.0662	benign	-0.569	Destabilizing	0.561	D	0.415	neutral	None	None	None	None	N
L/R	0.0959	likely_benign	0.0792	benign	-0.003	Destabilizing	0.001	N	0.192	neutral	N	0.340591696	None	None	N
L/S	0.1561	likely_benign	0.1354	benign	-0.887	Destabilizing	0.561	D	0.439	neutral	None	None	None	None	N
L/T	0.1258	likely_benign	0.1193	benign	-0.831	Destabilizing	0.722	D	0.419	neutral	None	None	None	None	N
L/V	0.0888	likely_benign	0.0805	benign	-0.412	Destabilizing	0.285	N	0.323	neutral	N	0.436451595	None	None	N
L/W	0.2578	likely_benign	0.1711	benign	-0.579	Destabilizing	0.991	D	0.341	neutral	None	None	None	None	N
L/Y	0.2694	likely_benign	0.2173	benign	-0.368	Destabilizing	0.39	N	0.416	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.