TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32438	97537;97538;97539	chr2:178542444;178542443;178542442	chr2:179407171;179407170;179407169
N2AB	30797	92614;92615;92616	chr2:178542444;178542443;178542442	chr2:179407171;179407170;179407169
N2A	29870	89833;89834;89835	chr2:178542444;178542443;178542442	chr2:179407171;179407170;179407169
N2B	23373	70342;70343;70344	chr2:178542444;178542443;178542442	chr2:179407171;179407170;179407169
Novex-1	23498	70717;70718;70719	chr2:178542444;178542443;178542442	chr2:179407171;179407170;179407169
Novex-2	23565	70918;70919;70920	chr2:178542444;178542443;178542442	chr2:179407171;179407170;179407169
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: Fn3-124
• Domain position: 40
• Structural Position: 41
• Q(SASA): 0.1228
• 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	1.0	N	0.73	0.32	0.303453137403	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	0.8969	likely_pathogenic	0.9044	pathogenic	-0.582	Destabilizing	0.999	D	0.681	prob.neutral	N	0.518733017	None	None	N
E/C	0.976	likely_pathogenic	0.9805	pathogenic	0.059	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/D	0.7878	likely_pathogenic	0.8144	pathogenic	-1.684	Destabilizing	0.999	D	0.645	neutral	N	0.491171787	None	None	N
E/F	0.9847	likely_pathogenic	0.9878	pathogenic	-0.384	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/G	0.9336	likely_pathogenic	0.9397	pathogenic	-0.951	Destabilizing	1.0	D	0.729	prob.delet.	D	0.536636689	None	None	N
E/H	0.9588	likely_pathogenic	0.9707	pathogenic	-0.296	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
E/I	0.9698	likely_pathogenic	0.973	pathogenic	0.466	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/K	0.9455	likely_pathogenic	0.9537	pathogenic	-0.543	Destabilizing	0.999	D	0.669	neutral	D	0.54017818	None	None	N
E/L	0.9474	likely_pathogenic	0.954	pathogenic	0.466	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/M	0.9443	likely_pathogenic	0.9504	pathogenic	0.912	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/N	0.9709	likely_pathogenic	0.9766	pathogenic	-0.92	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
E/P	0.9997	likely_pathogenic	0.9998	pathogenic	0.132	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/Q	0.6361	likely_pathogenic	0.6641	pathogenic	-0.577	Destabilizing	1.0	D	0.73	prob.delet.	N	0.466925013	None	None	N
E/R	0.9581	likely_pathogenic	0.9636	pathogenic	-0.655	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/S	0.9078	likely_pathogenic	0.9179	pathogenic	-1.363	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
E/T	0.9592	likely_pathogenic	0.9626	pathogenic	-0.994	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/V	0.9269	likely_pathogenic	0.9344	pathogenic	0.132	Stabilizing	1.0	D	0.731	prob.delet.	D	0.530849791	None	None	N
E/W	0.993	likely_pathogenic	0.9946	pathogenic	-0.662	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/Y	0.9753	likely_pathogenic	0.9817	pathogenic	-0.223	Destabilizing	1.0	D	0.742	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.