TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32873	98842;98843;98844	chr2:178539448;178539447;178539446	chr2:179404175;179404174;179404173
N2AB	31232	93919;93920;93921	chr2:178539448;178539447;178539446	chr2:179404175;179404174;179404173
N2A	30305	91138;91139;91140	chr2:178539448;178539447;178539446	chr2:179404175;179404174;179404173
N2B	23808	71647;71648;71649	chr2:178539448;178539447;178539446	chr2:179404175;179404174;179404173
Novex-1	23933	72022;72023;72024	chr2:178539448;178539447;178539446	chr2:179404175;179404174;179404173
Novex-2	24000	72223;72224;72225	chr2:178539448;178539447;178539446	chr2:179404175;179404174;179404173
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: Fn3-127
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.3712
• 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	rs1575354700	None	0.999	N	0.541	0.455	0.335661160332	gnomAD-4.0.0	3.42099E-06	None	None	None	None	N	None	0	0	None	0	1.25964E-04	None	0	0	0	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	0.6852	likely_pathogenic	0.6254	pathogenic	-1.354	Destabilizing	0.999	D	0.692	prob.neutral	N	0.474607561	None	None	N
E/C	0.9721	likely_pathogenic	0.9637	pathogenic	-0.735	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
E/D	0.9185	likely_pathogenic	0.8849	pathogenic	-1.348	Destabilizing	0.999	D	0.445	neutral	N	0.503133523	None	None	N
E/F	0.9832	likely_pathogenic	0.9773	pathogenic	-1.055	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
E/G	0.8159	likely_pathogenic	0.7578	pathogenic	-1.722	Destabilizing	1.0	D	0.774	deleterious	N	0.503133523	None	None	N
E/H	0.9573	likely_pathogenic	0.9411	pathogenic	-1.203	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
E/I	0.8352	likely_pathogenic	0.8033	pathogenic	-0.331	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
E/K	0.6819	likely_pathogenic	0.61	pathogenic	-0.827	Destabilizing	0.999	D	0.541	neutral	N	0.467392312	None	None	N
E/L	0.9306	likely_pathogenic	0.911	pathogenic	-0.331	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
E/M	0.8869	likely_pathogenic	0.8603	pathogenic	0.284	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/N	0.9551	likely_pathogenic	0.9365	pathogenic	-1.188	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/P	0.9981	likely_pathogenic	0.9974	pathogenic	-0.654	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/Q	0.4034	ambiguous	0.3495	ambiguous	-1.079	Destabilizing	1.0	D	0.623	neutral	N	0.489196045	None	None	N
E/R	0.782	likely_pathogenic	0.7341	pathogenic	-0.66	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/S	0.8209	likely_pathogenic	0.7665	pathogenic	-1.701	Destabilizing	0.999	D	0.594	neutral	None	None	None	None	N
E/T	0.8403	likely_pathogenic	0.801	pathogenic	-1.366	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/V	0.6451	likely_pathogenic	0.6034	pathogenic	-0.654	Destabilizing	1.0	D	0.813	deleterious	N	0.456653978	None	None	N
E/W	0.9947	likely_pathogenic	0.9927	pathogenic	-0.844	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/Y	0.9792	likely_pathogenic	0.971	pathogenic	-0.763	Destabilizing	1.0	D	0.83	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.