TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26332	79219;79220;79221	chr2:178567138;178567137;178567136	chr2:179431865;179431864;179431863
N2AB	24691	74296;74297;74298	chr2:178567138;178567137;178567136	chr2:179431865;179431864;179431863
N2A	23764	71515;71516;71517	chr2:178567138;178567137;178567136	chr2:179431865;179431864;179431863
N2B	17267	52024;52025;52026	chr2:178567138;178567137;178567136	chr2:179431865;179431864;179431863
Novex-1	17392	52399;52400;52401	chr2:178567138;178567137;178567136	chr2:179431865;179431864;179431863
Novex-2	17459	52600;52601;52602	chr2:178567138;178567137;178567136	chr2:179431865;179431864;179431863
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-79
• Domain position: 47
• Structural Position: 63
• Q(SASA): 1.09
• Predicted PPI site: I

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
L/I	None	None	0.919	N	0.493	0.237	0.365703291355	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
L/A	0.8686	likely_pathogenic	0.8906	pathogenic	-0.441	Destabilizing	0.968	D	0.604	neutral	None	None	None	None	I
L/C	0.9589	likely_pathogenic	0.9702	pathogenic	-0.795	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
L/D	0.9918	likely_pathogenic	0.9937	pathogenic	-0.188	Destabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	I
L/E	0.961	likely_pathogenic	0.9657	pathogenic	-0.277	Destabilizing	0.995	D	0.721	prob.delet.	None	None	None	None	I
L/F	0.7826	likely_pathogenic	0.8016	pathogenic	-0.594	Destabilizing	0.988	D	0.647	neutral	N	0.498614072	None	None	I
L/G	0.9739	likely_pathogenic	0.9768	pathogenic	-0.539	Destabilizing	0.995	D	0.715	prob.delet.	None	None	None	None	I
L/H	0.9315	likely_pathogenic	0.9441	pathogenic	0.116	Stabilizing	0.999	D	0.741	deleterious	N	0.473672962	None	None	I
L/I	0.2401	likely_benign	0.2371	benign	-0.303	Destabilizing	0.919	D	0.493	neutral	N	0.510976826	None	None	I
L/K	0.8987	likely_pathogenic	0.9083	pathogenic	-0.324	Destabilizing	0.991	D	0.675	prob.neutral	None	None	None	None	I
L/M	0.3653	ambiguous	0.3939	ambiguous	-0.612	Destabilizing	0.862	D	0.509	neutral	None	None	None	None	I
L/N	0.9538	likely_pathogenic	0.9631	pathogenic	-0.202	Destabilizing	0.995	D	0.733	prob.delet.	None	None	None	None	I
L/P	0.9089	likely_pathogenic	0.9279	pathogenic	-0.322	Destabilizing	0.998	D	0.733	prob.delet.	N	0.519364236	None	None	I
L/Q	0.8779	likely_pathogenic	0.8993	pathogenic	-0.37	Destabilizing	0.995	D	0.703	prob.neutral	None	None	None	None	I
L/R	0.8583	likely_pathogenic	0.8693	pathogenic	0.126	Stabilizing	0.994	D	0.697	prob.neutral	N	0.50326142	None	None	I
L/S	0.9602	likely_pathogenic	0.97	pathogenic	-0.589	Destabilizing	0.991	D	0.679	prob.neutral	None	None	None	None	I
L/T	0.8714	likely_pathogenic	0.91	pathogenic	-0.579	Destabilizing	0.991	D	0.639	neutral	None	None	None	None	I
L/V	0.3739	ambiguous	0.4026	ambiguous	-0.322	Destabilizing	0.919	D	0.536	neutral	N	0.484598302	None	None	I
L/W	0.8801	likely_pathogenic	0.8948	pathogenic	-0.613	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
L/Y	0.9254	likely_pathogenic	0.9368	pathogenic	-0.38	Destabilizing	0.995	D	0.675	prob.neutral	None	None	None	None	I

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.