TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25952	78079;78080;78081	chr2:178568278;178568277;178568276	chr2:179433005;179433004;179433003
N2AB	24311	73156;73157;73158	chr2:178568278;178568277;178568276	chr2:179433005;179433004;179433003
N2A	23384	70375;70376;70377	chr2:178568278;178568277;178568276	chr2:179433005;179433004;179433003
N2B	16887	50884;50885;50886	chr2:178568278;178568277;178568276	chr2:179433005;179433004;179433003
Novex-1	17012	51259;51260;51261	chr2:178568278;178568277;178568276	chr2:179433005;179433004;179433003
Novex-2	17079	51460;51461;51462	chr2:178568278;178568277;178568276	chr2:179433005;179433004;179433003
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-76
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.0945
• 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	None	None	0.998	D	0.637	0.437	0.60773865089	gnomAD-4.0.0	1.59176E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85922E-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	0.4825	ambiguous	0.544	ambiguous	-1.826	Destabilizing	0.998	D	0.637	neutral	D	0.526933288	None	None	N
V/C	0.8822	likely_pathogenic	0.889	pathogenic	-1.518	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/D	0.9937	likely_pathogenic	0.9934	pathogenic	-1.913	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
V/E	0.9807	likely_pathogenic	0.9796	pathogenic	-1.694	Destabilizing	1.0	D	0.811	deleterious	D	0.544757899	None	None	N
V/F	0.657	likely_pathogenic	0.6079	pathogenic	-1.086	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
V/G	0.8371	likely_pathogenic	0.8575	pathogenic	-2.373	Highly Destabilizing	1.0	D	0.833	deleterious	D	0.533401594	None	None	N
V/H	0.9921	likely_pathogenic	0.9909	pathogenic	-2.054	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
V/I	0.0883	likely_benign	0.0876	benign	-0.317	Destabilizing	0.813	D	0.253	neutral	None	None	None	None	N
V/K	0.9918	likely_pathogenic	0.9907	pathogenic	-1.535	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
V/L	0.5875	likely_pathogenic	0.5626	ambiguous	-0.317	Destabilizing	0.981	D	0.627	neutral	N	0.466542938	None	None	N
V/M	0.4938	ambiguous	0.4665	ambiguous	-0.425	Destabilizing	0.999	D	0.766	deleterious	N	0.521373725	None	None	N
V/N	0.9702	likely_pathogenic	0.9668	pathogenic	-1.842	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/P	0.9829	likely_pathogenic	0.9883	pathogenic	-0.79	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
V/Q	0.9798	likely_pathogenic	0.9775	pathogenic	-1.642	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/R	0.9869	likely_pathogenic	0.9861	pathogenic	-1.455	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/S	0.8628	likely_pathogenic	0.8776	pathogenic	-2.542	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
V/T	0.7608	likely_pathogenic	0.7722	pathogenic	-2.153	Highly Destabilizing	0.998	D	0.661	neutral	None	None	None	None	N
V/W	0.9937	likely_pathogenic	0.9925	pathogenic	-1.509	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
V/Y	0.9622	likely_pathogenic	0.955	pathogenic	-1.104	Destabilizing	1.0	D	0.784	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.