TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7659	23200;23201;23202	chr2:178721044;178721043;178721042	chr2:179585771;179585770;179585769
N2AB	7342	22249;22250;22251	chr2:178721044;178721043;178721042	chr2:179585771;179585770;179585769
N2A	6415	19468;19469;19470	chr2:178721044;178721043;178721042	chr2:179585771;179585770;179585769
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: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-61
• Domain position: 52
• Structural Position: 127
• Q(SASA): 0.295
• 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	None	None	0.871	N	0.542	0.248	0.416956310301	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
F/A	0.9387	likely_pathogenic	0.9315	pathogenic	-1.926	Destabilizing	0.995	D	0.72	prob.delet.	None	None	None	None	N
F/C	0.845	likely_pathogenic	0.812	pathogenic	-1.156	Destabilizing	1.0	D	0.808	deleterious	N	0.512622129	None	None	N
F/D	0.9768	likely_pathogenic	0.9749	pathogenic	-0.04	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
F/E	0.9782	likely_pathogenic	0.9765	pathogenic	0.064	Stabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
F/G	0.9738	likely_pathogenic	0.9726	pathogenic	-2.264	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
F/H	0.8836	likely_pathogenic	0.8933	pathogenic	-0.58	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
F/I	0.5542	ambiguous	0.5667	pathogenic	-0.925	Destabilizing	0.503	D	0.367	neutral	D	0.53113396	None	None	N
F/K	0.9777	likely_pathogenic	0.9797	pathogenic	-0.996	Destabilizing	0.999	D	0.81	deleterious	None	None	None	None	N
F/L	0.9406	likely_pathogenic	0.9437	pathogenic	-0.925	Destabilizing	0.871	D	0.542	neutral	N	0.493519721	None	None	N
F/M	0.7862	likely_pathogenic	0.7844	pathogenic	-0.794	Destabilizing	0.966	D	0.753	deleterious	None	None	None	None	N
F/N	0.9334	likely_pathogenic	0.9244	pathogenic	-1.044	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
F/P	0.9978	likely_pathogenic	0.9983	pathogenic	-1.25	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
F/Q	0.9605	likely_pathogenic	0.9597	pathogenic	-1.029	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
F/R	0.9478	likely_pathogenic	0.9508	pathogenic	-0.493	Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
F/S	0.8843	likely_pathogenic	0.8705	pathogenic	-1.953	Destabilizing	0.999	D	0.783	deleterious	N	0.516164507	None	None	N
F/T	0.9096	likely_pathogenic	0.9029	pathogenic	-1.753	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
F/V	0.5349	ambiguous	0.5333	ambiguous	-1.25	Destabilizing	0.922	D	0.655	neutral	N	0.520242176	None	None	N
F/W	0.7498	likely_pathogenic	0.7953	pathogenic	-0.032	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
F/Y	0.3822	ambiguous	0.3997	ambiguous	-0.266	Destabilizing	0.989	D	0.63	neutral	N	0.510507971	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.