TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30004	90235;90236;90237	chr2:178552890;178552889;178552888	chr2:179417617;179417616;179417615
N2AB	28363	85312;85313;85314	chr2:178552890;178552889;178552888	chr2:179417617;179417616;179417615
N2A	27436	82531;82532;82533	chr2:178552890;178552889;178552888	chr2:179417617;179417616;179417615
N2B	20939	63040;63041;63042	chr2:178552890;178552889;178552888	chr2:179417617;179417616;179417615
Novex-1	21064	63415;63416;63417	chr2:178552890;178552889;178552888	chr2:179417617;179417616;179417615
Novex-2	21131	63616;63617;63618	chr2:178552890;178552889;178552888	chr2:179417617;179417616;179417615
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-106
• Domain position: 72
• Structural Position: 105
• Q(SASA): 0.195
• 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/V	rs1238583004	-2.113	1.0	N	0.72	0.472	0.781133240969	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
F/V	rs1238583004	-2.113	1.0	N	0.72	0.472	0.781133240969	gnomAD-4.0.0	1.59126E-06	None	None	None	None	N	None	0	0	None	0	2.77577E-05	None	0	0	0	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	0.8942	likely_pathogenic	0.8092	pathogenic	-2.691	Highly Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
F/C	0.4842	ambiguous	0.3716	ambiguous	-1.077	Destabilizing	1.0	D	0.779	deleterious	N	0.473631946	None	None	N
F/D	0.9778	likely_pathogenic	0.9596	pathogenic	-3.029	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
F/E	0.9811	likely_pathogenic	0.9667	pathogenic	-2.842	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
F/G	0.956	likely_pathogenic	0.9196	pathogenic	-3.074	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
F/H	0.6993	likely_pathogenic	0.6114	pathogenic	-1.708	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
F/I	0.543	ambiguous	0.3909	ambiguous	-1.433	Destabilizing	1.0	D	0.725	prob.delet.	N	0.485867738	None	None	N
F/K	0.9709	likely_pathogenic	0.9504	pathogenic	-1.528	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
F/L	0.8945	likely_pathogenic	0.8412	pathogenic	-1.433	Destabilizing	0.999	D	0.631	neutral	N	0.474920026	None	None	N
F/M	0.7783	likely_pathogenic	0.6911	pathogenic	-1.02	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
F/N	0.8775	likely_pathogenic	0.8164	pathogenic	-1.947	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
F/P	0.9986	likely_pathogenic	0.9968	pathogenic	-1.864	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
F/Q	0.92	likely_pathogenic	0.8731	pathogenic	-1.937	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
F/R	0.9062	likely_pathogenic	0.8545	pathogenic	-1.113	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
F/S	0.7516	likely_pathogenic	0.6156	pathogenic	-2.464	Highly Destabilizing	1.0	D	0.772	deleterious	N	0.48072849	None	None	N
F/T	0.8617	likely_pathogenic	0.7512	pathogenic	-2.183	Highly Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
F/V	0.524	ambiguous	0.37	ambiguous	-1.864	Destabilizing	1.0	D	0.72	prob.delet.	N	0.479267053	None	None	N
F/W	0.6794	likely_pathogenic	0.6293	pathogenic	-0.38	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
F/Y	0.1142	likely_benign	0.1065	benign	-0.74	Destabilizing	0.999	D	0.564	neutral	N	0.398056752	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.