TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16919	50980;50981;50982	chr2:178611474;178611473;178611472	chr2:179476201;179476200;179476199
N2AB	15278	46057;46058;46059	chr2:178611474;178611473;178611472	chr2:179476201;179476200;179476199
N2A	14351	43276;43277;43278	chr2:178611474;178611473;178611472	chr2:179476201;179476200;179476199
N2B	7854	23785;23786;23787	chr2:178611474;178611473;178611472	chr2:179476201;179476200;179476199
Novex-1	7979	24160;24161;24162	chr2:178611474;178611473;178611472	chr2:179476201;179476200;179476199
Novex-2	8046	24361;24362;24363	chr2:178611474;178611473;178611472	chr2:179476201;179476200;179476199
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-11
• Domain position: 68
• Structural Position: 98
• Q(SASA): 0.2887
• 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
V/A	rs757845759	None	0.977	N	0.414	0.233	0.465038187318	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
V/F	rs2056315018	None	0.993	N	0.745	0.295	0.511677802314	gnomAD-4.0.0	1.36905E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79955E-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
V/A	0.2367	likely_benign	0.2799	benign	-0.87	Destabilizing	0.977	D	0.414	neutral	N	0.478689221	None	None	N
V/C	0.7481	likely_pathogenic	0.8357	pathogenic	-0.805	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
V/D	0.4208	ambiguous	0.4601	ambiguous	-0.556	Destabilizing	0.999	D	0.755	deleterious	N	0.474128025	None	None	N
V/E	0.2867	likely_benign	0.3317	benign	-0.602	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
V/F	0.2021	likely_benign	0.2083	benign	-0.75	Destabilizing	0.993	D	0.745	deleterious	N	0.478417197	None	None	N
V/G	0.3139	likely_benign	0.3686	ambiguous	-1.095	Destabilizing	0.999	D	0.732	prob.delet.	N	0.475792113	None	None	N
V/H	0.6192	likely_pathogenic	0.6907	pathogenic	-0.466	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
V/I	0.0745	likely_benign	0.0798	benign	-0.388	Destabilizing	0.117	N	0.232	neutral	N	0.444135903	None	None	N
V/K	0.4185	ambiguous	0.4768	ambiguous	-0.782	Destabilizing	0.998	D	0.722	prob.delet.	None	None	None	None	N
V/L	0.1598	likely_benign	0.178	benign	-0.388	Destabilizing	0.898	D	0.377	neutral	N	0.467711294	None	None	N
V/M	0.1518	likely_benign	0.1548	benign	-0.505	Destabilizing	0.995	D	0.743	deleterious	None	None	None	None	N
V/N	0.2973	likely_benign	0.362	ambiguous	-0.605	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
V/P	0.7473	likely_pathogenic	0.8168	pathogenic	-0.513	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
V/Q	0.3159	likely_benign	0.3896	ambiguous	-0.774	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
V/R	0.4454	ambiguous	0.5069	ambiguous	-0.251	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
V/S	0.2405	likely_benign	0.2994	benign	-1.05	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
V/T	0.2068	likely_benign	0.2684	benign	-0.982	Destabilizing	0.983	D	0.629	neutral	None	None	None	None	N
V/W	0.8751	likely_pathogenic	0.9069	pathogenic	-0.861	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
V/Y	0.6074	likely_pathogenic	0.6922	pathogenic	-0.573	Destabilizing	0.999	D	0.755	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.