TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20751	62476;62477;62478	chr2:178589474;178589473;178589472	chr2:179454201;179454200;179454199
N2AB	19110	57553;57554;57555	chr2:178589474;178589473;178589472	chr2:179454201;179454200;179454199
N2A	18183	54772;54773;54774	chr2:178589474;178589473;178589472	chr2:179454201;179454200;179454199
N2B	11686	35281;35282;35283	chr2:178589474;178589473;178589472	chr2:179454201;179454200;179454199
Novex-1	11811	35656;35657;35658	chr2:178589474;178589473;178589472	chr2:179454201;179454200;179454199
Novex-2	11878	35857;35858;35859	chr2:178589474;178589473;178589472	chr2:179454201;179454200;179454199
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: Fn3-38
• Domain position: 84
• Structural Position: 116
• Q(SASA): 0.4233
• 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/K	rs926520394	None	0.999	N	0.753	0.423	0.362758974969	gnomAD-4.0.0	3.18416E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.8659E-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
E/A	0.3744	ambiguous	0.3463	ambiguous	-0.838	Destabilizing	0.999	D	0.728	prob.delet.	N	0.477592184	None	None	N
E/C	0.93	likely_pathogenic	0.9283	pathogenic	-0.479	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/D	0.4238	ambiguous	0.3593	ambiguous	-1.201	Destabilizing	0.999	D	0.616	neutral	N	0.495177868	None	None	N
E/F	0.886	likely_pathogenic	0.8733	pathogenic	-0.512	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/G	0.6273	likely_pathogenic	0.5604	ambiguous	-1.181	Destabilizing	1.0	D	0.776	deleterious	N	0.470706767	None	None	N
E/H	0.877	likely_pathogenic	0.8499	pathogenic	-0.883	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
E/I	0.509	ambiguous	0.5137	ambiguous	0.09	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/K	0.5657	likely_pathogenic	0.553	ambiguous	-0.81	Destabilizing	0.999	D	0.753	deleterious	N	0.489964049	None	None	N
E/L	0.706	likely_pathogenic	0.6926	pathogenic	0.09	Stabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
E/M	0.6645	likely_pathogenic	0.6727	pathogenic	0.592	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/N	0.6622	likely_pathogenic	0.6125	pathogenic	-1.131	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/P	0.8477	likely_pathogenic	0.7285	pathogenic	-0.198	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/Q	0.3995	ambiguous	0.3877	ambiguous	-1.016	Destabilizing	1.0	D	0.73	prob.delet.	N	0.473802518	None	None	N
E/R	0.7519	likely_pathogenic	0.7191	pathogenic	-0.581	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
E/S	0.5347	ambiguous	0.5145	ambiguous	-1.442	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
E/T	0.4963	ambiguous	0.4898	ambiguous	-1.168	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/V	0.3476	ambiguous	0.3538	ambiguous	-0.198	Destabilizing	1.0	D	0.811	deleterious	N	0.441516741	None	None	N
E/W	0.9768	likely_pathogenic	0.9705	pathogenic	-0.358	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/Y	0.8829	likely_pathogenic	0.8649	pathogenic	-0.305	Destabilizing	1.0	D	0.801	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.