TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5311	16156;16157;16158	chr2:178733362;178733361;178733360	chr2:179598089;179598088;179598087
N2AB	4994	15205;15206;15207	chr2:178733362;178733361;178733360	chr2:179598089;179598088;179598087
N2A	4067	12424;12425;12426	chr2:178733362;178733361;178733360	chr2:179598089;179598088;179598087
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-36
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.2002
• 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
F/L	rs768239529	-1.224	0.03	D	0.265	0.174	0.319114376414	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
F/L	rs768239529	-1.224	0.03	D	0.265	0.174	0.319114376414	gnomAD-4.0.0	3.18258E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71647E-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
F/A	0.9487	likely_pathogenic	0.944	pathogenic	-2.183	Highly Destabilizing	0.927	D	0.635	neutral	None	None	None	None	N
F/C	0.798	likely_pathogenic	0.8035	pathogenic	-1.279	Destabilizing	0.999	D	0.666	neutral	D	0.613116445	None	None	N
F/D	0.9846	likely_pathogenic	0.9838	pathogenic	-0.903	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
F/E	0.9782	likely_pathogenic	0.9776	pathogenic	-0.796	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
F/G	0.9733	likely_pathogenic	0.9728	pathogenic	-2.541	Highly Destabilizing	0.995	D	0.695	prob.neutral	None	None	None	None	N
F/H	0.8844	likely_pathogenic	0.8873	pathogenic	-0.81	Destabilizing	1.0	D	0.587	neutral	None	None	None	None	N
F/I	0.6061	likely_pathogenic	0.5797	pathogenic	-1.099	Destabilizing	0.828	D	0.546	neutral	D	0.554119919	None	None	N
F/K	0.9741	likely_pathogenic	0.9756	pathogenic	-1.386	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	N
F/L	0.9391	likely_pathogenic	0.9309	pathogenic	-1.099	Destabilizing	0.03	N	0.265	neutral	D	0.531661587	None	None	N
F/M	0.7717	likely_pathogenic	0.759	pathogenic	-0.85	Destabilizing	0.991	D	0.613	neutral	None	None	None	None	N
F/N	0.9454	likely_pathogenic	0.9443	pathogenic	-1.505	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
F/P	0.9983	likely_pathogenic	0.9982	pathogenic	-1.455	Destabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	N
F/Q	0.9471	likely_pathogenic	0.9473	pathogenic	-1.516	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
F/R	0.942	likely_pathogenic	0.946	pathogenic	-0.785	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
F/S	0.8962	likely_pathogenic	0.8964	pathogenic	-2.318	Highly Destabilizing	0.979	D	0.689	prob.neutral	N	0.510105269	None	None	N
F/T	0.9051	likely_pathogenic	0.9016	pathogenic	-2.109	Highly Destabilizing	0.969	D	0.661	neutral	None	None	None	None	N
F/V	0.6081	likely_pathogenic	0.5887	pathogenic	-1.455	Destabilizing	0.238	N	0.349	neutral	N	0.501504195	None	None	N
F/W	0.7114	likely_pathogenic	0.7253	pathogenic	-0.275	Destabilizing	1.0	D	0.595	neutral	None	None	None	None	N
F/Y	0.3501	ambiguous	0.3591	ambiguous	-0.532	Destabilizing	0.993	D	0.542	neutral	N	0.507037484	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.