TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8391	25396;25397;25398	chr2:178717703;178717702;178717701	chr2:179582430;179582429;179582428
N2AB	8074	24445;24446;24447	chr2:178717703;178717702;178717701	chr2:179582430;179582429;179582428
N2A	7147	21664;21665;21666	chr2:178717703;178717702;178717701	chr2:179582430;179582429;179582428
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-69
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.2764
• Predicted PPI site: I

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
V/G	None	None	1.0	D	0.824	0.847	0.911112205665	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
V/A	0.4772	ambiguous	0.4726	ambiguous	-1.501	Destabilizing	0.993	D	0.635	neutral	D	0.577335905	None	None	I
V/C	0.9262	likely_pathogenic	0.9275	pathogenic	-1.145	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
V/D	0.9401	likely_pathogenic	0.9609	pathogenic	-0.872	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
V/E	0.8944	likely_pathogenic	0.9299	pathogenic	-0.765	Destabilizing	0.999	D	0.846	deleterious	D	0.631742797	None	None	I
V/F	0.3805	ambiguous	0.4945	ambiguous	-0.928	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
V/G	0.669	likely_pathogenic	0.6979	pathogenic	-1.933	Destabilizing	1.0	D	0.824	deleterious	D	0.631742797	None	None	I
V/H	0.9624	likely_pathogenic	0.9782	pathogenic	-1.443	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
V/I	0.0873	likely_benign	0.1012	benign	-0.372	Destabilizing	0.969	D	0.583	neutral	None	None	None	None	I
V/K	0.9395	likely_pathogenic	0.9633	pathogenic	-1.035	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
V/L	0.399	ambiguous	0.5156	ambiguous	-0.372	Destabilizing	0.959	D	0.636	neutral	D	0.551112018	None	None	I
V/M	0.374	ambiguous	0.4583	ambiguous	-0.448	Destabilizing	1.0	D	0.714	prob.delet.	D	0.593960679	None	None	I
V/N	0.8798	likely_pathogenic	0.9198	pathogenic	-1.001	Destabilizing	0.998	D	0.854	deleterious	None	None	None	None	I
V/P	0.848	likely_pathogenic	0.8777	pathogenic	-0.714	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	I
V/Q	0.9111	likely_pathogenic	0.944	pathogenic	-0.969	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
V/R	0.9141	likely_pathogenic	0.9493	pathogenic	-0.803	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
V/S	0.7338	likely_pathogenic	0.7721	pathogenic	-1.716	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	I
V/T	0.5395	ambiguous	0.5714	pathogenic	-1.459	Destabilizing	0.724	D	0.384	neutral	None	None	None	None	I
V/W	0.961	likely_pathogenic	0.9785	pathogenic	-1.17	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
V/Y	0.8555	likely_pathogenic	0.9073	pathogenic	-0.823	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I

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.