TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8336	25231;25232;25233	chr2:178718000;178717999;178717998	chr2:179582727;179582726;179582725
N2AB	8019	24280;24281;24282	chr2:178718000;178717999;178717998	chr2:179582727;179582726;179582725
N2A	7092	21499;21500;21501	chr2:178718000;178717999;178717998	chr2:179582727;179582726;179582725
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: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-68
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.0714
• Site annotation: disulfide
• 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
C/G	None	None	0.999	D	0.855	0.767	0.925936472269	gnomAD-4.0.0	1.20032E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
C/S	None	None	1.0	D	0.745	0.767	0.862583160585	gnomAD-4.0.0	1.20032E-06	None	None	disulfide	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
C/A	0.9215	likely_pathogenic	0.9473	pathogenic	-1.516	Destabilizing	0.994	D	0.666	neutral	None	None	disulfide	None	N
C/D	0.9998	likely_pathogenic	0.9999	pathogenic	-1.005	Destabilizing	1.0	D	0.875	deleterious	None	None	disulfide	None	N
C/E	0.9998	likely_pathogenic	0.9998	pathogenic	-0.777	Destabilizing	1.0	D	0.875	deleterious	None	None	disulfide	None	N
C/F	0.8318	likely_pathogenic	0.9116	pathogenic	-1.005	Destabilizing	1.0	D	0.849	deleterious	D	0.641459762	disulfide	None	N
C/G	0.9071	likely_pathogenic	0.947	pathogenic	-1.867	Destabilizing	0.999	D	0.855	deleterious	D	0.668612308	disulfide	None	N
C/H	0.9987	likely_pathogenic	0.9993	pathogenic	-2.11	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	disulfide	None	N
C/I	0.8261	likely_pathogenic	0.872	pathogenic	-0.573	Destabilizing	0.999	D	0.763	deleterious	None	None	disulfide	None	N
C/K	0.9998	likely_pathogenic	0.9998	pathogenic	-0.601	Destabilizing	1.0	D	0.865	deleterious	None	None	disulfide	None	N
C/L	0.7745	likely_pathogenic	0.8401	pathogenic	-0.573	Destabilizing	0.996	D	0.732	prob.delet.	None	None	disulfide	None	N
C/M	0.9511	likely_pathogenic	0.9677	pathogenic	-0.02	Destabilizing	0.996	D	0.609	neutral	None	None	disulfide	None	N
C/N	0.9986	likely_pathogenic	0.9991	pathogenic	-1.136	Destabilizing	1.0	D	0.878	deleterious	None	None	disulfide	None	N
C/P	0.9992	likely_pathogenic	0.9996	pathogenic	-0.865	Destabilizing	1.0	D	0.876	deleterious	None	None	disulfide	None	N
C/Q	0.9989	likely_pathogenic	0.9993	pathogenic	-0.696	Destabilizing	1.0	D	0.875	deleterious	None	None	disulfide	None	N
C/R	0.9961	likely_pathogenic	0.9974	pathogenic	-1.112	Destabilizing	1.0	D	0.875	deleterious	D	0.668612308	disulfide	None	N
C/S	0.9785	likely_pathogenic	0.9886	pathogenic	-1.463	Destabilizing	1.0	D	0.745	deleterious	D	0.652592947	disulfide	None	N
C/T	0.983	likely_pathogenic	0.9893	pathogenic	-1.04	Destabilizing	1.0	D	0.763	deleterious	None	None	disulfide	None	N
C/V	0.6929	likely_pathogenic	0.7314	pathogenic	-0.865	Destabilizing	0.998	D	0.743	deleterious	None	None	disulfide	None	N
C/W	0.9924	likely_pathogenic	0.9962	pathogenic	-1.333	Destabilizing	1.0	D	0.845	deleterious	D	0.668612308	disulfide	None	N
C/Y	0.9848	likely_pathogenic	0.9925	pathogenic	-1.105	Destabilizing	1.0	D	0.851	deleterious	D	0.668410504	disulfide	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.