TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30364	91315;91316;91317	chr2:178551810;178551809;178551808	chr2:179416537;179416536;179416535
N2AB	28723	86392;86393;86394	chr2:178551810;178551809;178551808	chr2:179416537;179416536;179416535
N2A	27796	83611;83612;83613	chr2:178551810;178551809;178551808	chr2:179416537;179416536;179416535
N2B	21299	64120;64121;64122	chr2:178551810;178551809;178551808	chr2:179416537;179416536;179416535
Novex-1	21424	64495;64496;64497	chr2:178551810;178551809;178551808	chr2:179416537;179416536;179416535
Novex-2	21491	64696;64697;64698	chr2:178551810;178551809;178551808	chr2:179416537;179416536;179416535
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-109
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.0843
• 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
K/N	rs1395941923	-1.822	1.0	N	0.742	0.434	0.243972157842	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
K/N	rs1395941923	-1.822	1.0	N	0.742	0.434	0.243972157842	gnomAD-4.0.0	4.10514E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39667E-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
K/A	0.9811	likely_pathogenic	0.9859	pathogenic	-1.631	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
K/C	0.9652	likely_pathogenic	0.9773	pathogenic	-1.384	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
K/D	0.9984	likely_pathogenic	0.9989	pathogenic	-1.86	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/E	0.9756	likely_pathogenic	0.9846	pathogenic	-1.559	Destabilizing	0.999	D	0.541	neutral	N	0.502070339	None	None	N
K/F	0.9964	likely_pathogenic	0.9976	pathogenic	-0.867	Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
K/G	0.9869	likely_pathogenic	0.9908	pathogenic	-2.084	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/H	0.9294	likely_pathogenic	0.9426	pathogenic	-2.02	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
K/I	0.9825	likely_pathogenic	0.9875	pathogenic	-0.332	Destabilizing	1.0	D	0.93	deleterious	N	0.508871195	None	None	N
K/L	0.9497	likely_pathogenic	0.9575	pathogenic	-0.332	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/M	0.8661	likely_pathogenic	0.8985	pathogenic	-0.739	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
K/N	0.9922	likely_pathogenic	0.9948	pathogenic	-1.644	Destabilizing	1.0	D	0.742	deleterious	N	0.49076694	None	None	N
K/P	0.9994	likely_pathogenic	0.9996	pathogenic	-0.748	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
K/Q	0.7611	likely_pathogenic	0.8274	pathogenic	-1.274	Destabilizing	1.0	D	0.724	prob.delet.	N	0.521943181	None	None	N
K/R	0.1609	likely_benign	0.1928	benign	-0.947	Destabilizing	0.999	D	0.549	neutral	N	0.458123776	None	None	N
K/S	0.9925	likely_pathogenic	0.9951	pathogenic	-2.148	Highly Destabilizing	0.999	D	0.578	neutral	None	None	None	None	N
K/T	0.9771	likely_pathogenic	0.9847	pathogenic	-1.605	Destabilizing	1.0	D	0.805	deleterious	N	0.494628054	None	None	N
K/V	0.9697	likely_pathogenic	0.9787	pathogenic	-0.748	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
K/W	0.9939	likely_pathogenic	0.9957	pathogenic	-0.93	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
K/Y	0.9813	likely_pathogenic	0.9853	pathogenic	-0.592	Destabilizing	1.0	D	0.911	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.