TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22215	66868;66869;66870	chr2:178581625;178581624;178581623	chr2:179446352;179446351;179446350
N2AB	20574	61945;61946;61947	chr2:178581625;178581624;178581623	chr2:179446352;179446351;179446350
N2A	19647	59164;59165;59166	chr2:178581625;178581624;178581623	chr2:179446352;179446351;179446350
N2B	13150	39673;39674;39675	chr2:178581625;178581624;178581623	chr2:179446352;179446351;179446350
Novex-1	13275	40048;40049;40050	chr2:178581625;178581624;178581623	chr2:179446352;179446351;179446350
Novex-2	13342	40249;40250;40251	chr2:178581625;178581624;178581623	chr2:179446352;179446351;179446350
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: Fn3-49
• Domain position: 60
• Structural Position: 89
• Q(SASA): 0.2567
• 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/N	None	None	0.998	N	0.623	0.377	0.354610295913	gnomAD-4.0.0	1.59361E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43345E-05	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	0.222	likely_benign	0.1943	benign	-0.764	Destabilizing	0.919	D	0.483	neutral	N	0.488311405	None	None	N
T/C	0.4627	ambiguous	0.4165	ambiguous	-0.411	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
T/D	0.6813	likely_pathogenic	0.6564	pathogenic	-0.381	Destabilizing	0.998	D	0.686	prob.neutral	None	None	None	None	N
T/E	0.5506	ambiguous	0.5514	ambiguous	-0.217	Destabilizing	0.995	D	0.654	neutral	None	None	None	None	N
T/F	0.7083	likely_pathogenic	0.6652	pathogenic	-0.741	Destabilizing	0.991	D	0.757	deleterious	None	None	None	None	N
T/G	0.4105	ambiguous	0.3892	ambiguous	-1.121	Destabilizing	0.995	D	0.665	neutral	None	None	None	None	N
T/H	0.5738	likely_pathogenic	0.5405	ambiguous	-1.046	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
T/I	0.5766	likely_pathogenic	0.5339	ambiguous	0.151	Stabilizing	0.919	D	0.553	neutral	N	0.507999049	None	None	N
T/K	0.4023	ambiguous	0.3989	ambiguous	0.006	Stabilizing	0.995	D	0.674	neutral	None	None	None	None	N
T/L	0.1611	likely_benign	0.1479	benign	0.151	Stabilizing	0.938	D	0.488	neutral	None	None	None	None	N
T/M	0.1382	likely_benign	0.125	benign	-0.024	Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
T/N	0.1639	likely_benign	0.1387	benign	-0.594	Destabilizing	0.998	D	0.623	neutral	N	0.472636232	None	None	N
T/P	0.1973	likely_benign	0.1613	benign	-0.123	Destabilizing	0.998	D	0.704	prob.neutral	N	0.477195363	None	None	N
T/Q	0.3567	ambiguous	0.3453	ambiguous	-0.409	Destabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	N
T/R	0.3756	ambiguous	0.3761	ambiguous	-0.097	Destabilizing	0.995	D	0.727	prob.delet.	None	None	None	None	N
T/S	0.2719	likely_benign	0.2267	benign	-0.937	Destabilizing	0.979	D	0.437	neutral	N	0.48078976	None	None	N
T/V	0.3799	ambiguous	0.3517	ambiguous	-0.123	Destabilizing	0.086	N	0.425	neutral	None	None	None	None	N
T/W	0.8979	likely_pathogenic	0.8849	pathogenic	-0.854	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
T/Y	0.608	likely_pathogenic	0.5844	pathogenic	-0.431	Destabilizing	0.995	D	0.762	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.