TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5191	15796;15797;15798	chr2:178733818;178733817;178733816	chr2:179598545;179598544;179598543
N2AB	4874	14845;14846;14847	chr2:178733818;178733817;178733816	chr2:179598545;179598544;179598543
N2A	3947	12064;12065;12066	chr2:178733818;178733817;178733816	chr2:179598545;179598544;179598543
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-35
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1554
• 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
V/G	None	None	0.928	D	0.849	0.774	0.937896326255	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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	0.5945	likely_pathogenic	0.7294	pathogenic	-1.605	Destabilizing	0.645	D	0.599	neutral	D	0.529165583	None	None	N
V/C	0.9232	likely_pathogenic	0.9577	pathogenic	-1.105	Destabilizing	0.995	D	0.799	deleterious	None	None	None	None	N
V/D	0.9939	likely_pathogenic	0.9969	pathogenic	-1.488	Destabilizing	0.945	D	0.854	deleterious	None	None	None	None	N
V/E	0.9776	likely_pathogenic	0.987	pathogenic	-1.293	Destabilizing	0.928	D	0.84	deleterious	D	0.7616757	None	None	N
V/F	0.4779	ambiguous	0.5634	ambiguous	-0.839	Destabilizing	0.894	D	0.818	deleterious	None	None	None	None	N
V/G	0.8174	likely_pathogenic	0.8925	pathogenic	-2.13	Highly Destabilizing	0.928	D	0.849	deleterious	D	0.686585467	None	None	N
V/H	0.9897	likely_pathogenic	0.9951	pathogenic	-1.838	Destabilizing	0.995	D	0.851	deleterious	None	None	None	None	N
V/I	0.0834	likely_benign	0.0904	benign	-0.168	Destabilizing	0.007	N	0.189	neutral	None	None	None	None	N
V/K	0.981	likely_pathogenic	0.989	pathogenic	-1.157	Destabilizing	0.945	D	0.841	deleterious	None	None	None	None	N
V/L	0.2912	likely_benign	0.3782	ambiguous	-0.168	Destabilizing	0.114	N	0.56	neutral	D	0.533733894	None	None	N
V/M	0.3483	ambiguous	0.4498	ambiguous	-0.242	Destabilizing	0.864	D	0.749	deleterious	D	0.740956048	None	None	N
V/N	0.9719	likely_pathogenic	0.9868	pathogenic	-1.334	Destabilizing	0.981	D	0.872	deleterious	None	None	None	None	N
V/P	0.9766	likely_pathogenic	0.9876	pathogenic	-0.616	Destabilizing	0.981	D	0.844	deleterious	None	None	None	None	N
V/Q	0.9687	likely_pathogenic	0.983	pathogenic	-1.174	Destabilizing	0.981	D	0.856	deleterious	None	None	None	None	N
V/R	0.9691	likely_pathogenic	0.981	pathogenic	-1.103	Destabilizing	0.945	D	0.871	deleterious	None	None	None	None	N
V/S	0.8596	likely_pathogenic	0.9253	pathogenic	-2.046	Highly Destabilizing	0.945	D	0.834	deleterious	None	None	None	None	N
V/T	0.6616	likely_pathogenic	0.7912	pathogenic	-1.698	Destabilizing	0.707	D	0.684	prob.neutral	None	None	None	None	N
V/W	0.9841	likely_pathogenic	0.9914	pathogenic	-1.279	Destabilizing	0.995	D	0.831	deleterious	None	None	None	None	N
V/Y	0.9433	likely_pathogenic	0.9677	pathogenic	-0.86	Destabilizing	0.945	D	0.813	deleterious	None	None	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.