TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31905	95938;95939;95940	chr2:178545397;178545396;178545395	chr2:179410124;179410123;179410122
N2AB	30264	91015;91016;91017	chr2:178545397;178545396;178545395	chr2:179410124;179410123;179410122
N2A	29337	88234;88235;88236	chr2:178545397;178545396;178545395	chr2:179410124;179410123;179410122
N2B	22840	68743;68744;68745	chr2:178545397;178545396;178545395	chr2:179410124;179410123;179410122
Novex-1	22965	69118;69119;69120	chr2:178545397;178545396;178545395	chr2:179410124;179410123;179410122
Novex-2	23032	69319;69320;69321	chr2:178545397;178545396;178545395	chr2:179410124;179410123;179410122
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: Fn3-120
• Domain position: 99
• Structural Position: 132
• Q(SASA): 1.167
• 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	rs777381153	0.395	0.993	N	0.628	0.229	0.216624796971	gnomAD-2.1.1	4.5E-06	None	None	None	None	N	None	0	0	None	0	0	None	4.13E-05	None	0	0	0
E/Q	rs777381153	0.395	0.993	N	0.628	0.229	0.216624796971	gnomAD-4.0.0	2.11808E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.78444E-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	0.211	likely_benign	0.2264	benign	-0.199	Destabilizing	0.976	D	0.72	deleterious	N	0.445306408	None	None	N
E/C	0.8658	likely_pathogenic	0.8952	pathogenic	-0.199	Destabilizing	1.0	D	0.721	deleterious	None	None	None	None	N
E/D	0.0983	likely_benign	0.1154	benign	-0.333	Destabilizing	0.026	N	0.388	neutral	N	0.334677278	None	None	N
E/F	0.7711	likely_pathogenic	0.8033	pathogenic	-0.117	Destabilizing	1.0	D	0.579	neutral	None	None	None	None	N
E/G	0.2537	likely_benign	0.2863	benign	-0.356	Destabilizing	0.953	D	0.477	neutral	N	0.467201833	None	None	N
E/H	0.645	likely_pathogenic	0.6738	pathogenic	0.376	Stabilizing	1.0	D	0.65	prob.neutral	None	None	None	None	N
E/I	0.4135	ambiguous	0.4345	ambiguous	0.169	Stabilizing	0.998	D	0.617	neutral	None	None	None	None	N
E/K	0.3446	ambiguous	0.3558	ambiguous	0.363	Stabilizing	0.953	D	0.709	prob.delet.	N	0.476994752	None	None	N
E/L	0.4297	ambiguous	0.4478	ambiguous	0.169	Stabilizing	0.995	D	0.638	neutral	None	None	None	None	N
E/M	0.5102	ambiguous	0.5243	ambiguous	0.022	Stabilizing	1.0	D	0.611	neutral	None	None	None	None	N
E/N	0.3022	likely_benign	0.3328	benign	0.042	Stabilizing	0.99	D	0.685	prob.delet.	None	None	None	None	N
E/P	0.4861	ambiguous	0.5344	ambiguous	0.065	Stabilizing	0.998	D	0.623	neutral	None	None	None	None	N
E/Q	0.2307	likely_benign	0.2352	benign	0.066	Stabilizing	0.993	D	0.628	neutral	N	0.493233641	None	None	N
E/R	0.5045	ambiguous	0.5407	ambiguous	0.634	Stabilizing	0.995	D	0.689	prob.delet.	None	None	None	None	N
E/S	0.2669	likely_benign	0.2954	benign	-0.099	Destabilizing	0.964	D	0.716	prob.delet.	None	None	None	None	N
E/T	0.3161	likely_benign	0.3455	ambiguous	0.035	Stabilizing	0.995	D	0.654	prob.neutral	None	None	None	None	N
E/V	0.246	likely_benign	0.258	benign	0.065	Stabilizing	0.998	D	0.574	neutral	N	0.466335041	None	None	N
E/W	0.927	likely_pathogenic	0.938	pathogenic	-0.003	Destabilizing	1.0	D	0.731	deleterious	None	None	None	None	N
E/Y	0.6264	likely_pathogenic	0.6771	pathogenic	0.122	Stabilizing	1.0	D	0.511	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.