TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9264	28015;28016;28017	chr2:178712040;178712039;178712038	chr2:179576767;179576766;179576765
N2AB	8947	27064;27065;27066	chr2:178712040;178712039;178712038	chr2:179576767;179576766;179576765
N2A	8020	24283;24284;24285	chr2:178712040;178712039;178712038	chr2:179576767;179576766;179576765
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-78
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.1136
• 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/C	None	None	0.999	N	0.839	0.665	0.8456673461	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	0.9557	likely_pathogenic	0.9786	pathogenic	-2.576	Highly Destabilizing	0.863	D	0.719	prob.delet.	None	None	None	None	N
F/C	0.6586	likely_pathogenic	0.8348	pathogenic	-1.979	Destabilizing	0.999	D	0.839	deleterious	N	0.512635356	None	None	N
F/D	0.9959	likely_pathogenic	0.9979	pathogenic	-2.977	Highly Destabilizing	0.997	D	0.846	deleterious	None	None	None	None	N
F/E	0.9943	likely_pathogenic	0.9974	pathogenic	-2.727	Highly Destabilizing	0.997	D	0.817	deleterious	None	None	None	None	N
F/G	0.9856	likely_pathogenic	0.9935	pathogenic	-3.068	Highly Destabilizing	0.99	D	0.806	deleterious	None	None	None	None	N
F/H	0.9565	likely_pathogenic	0.9766	pathogenic	-1.96	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
F/I	0.2736	likely_benign	0.4095	ambiguous	-0.969	Destabilizing	0.704	D	0.577	neutral	N	0.350411947	None	None	N
F/K	0.9905	likely_pathogenic	0.9954	pathogenic	-2.037	Highly Destabilizing	0.997	D	0.814	deleterious	None	None	None	None	N
F/L	0.8482	likely_pathogenic	0.9144	pathogenic	-0.969	Destabilizing	0.005	N	0.276	neutral	N	0.409668974	None	None	N
F/M	0.6706	likely_pathogenic	0.7778	pathogenic	-0.974	Destabilizing	0.982	D	0.691	prob.neutral	None	None	None	None	N
F/N	0.9823	likely_pathogenic	0.9908	pathogenic	-2.618	Highly Destabilizing	0.997	D	0.85	deleterious	None	None	None	None	N
F/P	0.9986	likely_pathogenic	0.9994	pathogenic	-1.518	Destabilizing	0.997	D	0.851	deleterious	None	None	None	None	N
F/Q	0.985	likely_pathogenic	0.9931	pathogenic	-2.427	Highly Destabilizing	0.997	D	0.848	deleterious	None	None	None	None	N
F/R	0.9762	likely_pathogenic	0.9889	pathogenic	-1.835	Destabilizing	0.997	D	0.852	deleterious	None	None	None	None	N
F/S	0.9534	likely_pathogenic	0.9783	pathogenic	-3.266	Highly Destabilizing	0.959	D	0.769	deleterious	N	0.512381866	None	None	N
F/T	0.9632	likely_pathogenic	0.9819	pathogenic	-2.883	Highly Destabilizing	0.939	D	0.747	deleterious	None	None	None	None	N
F/V	0.4277	ambiguous	0.5996	pathogenic	-1.518	Destabilizing	0.061	N	0.495	neutral	N	0.452747747	None	None	N
F/W	0.7782	likely_pathogenic	0.8441	pathogenic	-0.204	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	N
F/Y	0.509	ambiguous	0.6086	pathogenic	-0.618	Destabilizing	0.986	D	0.601	neutral	N	0.501114466	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.