TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7698	23317;23318;23319	chr2:178720927;178720926;178720925	chr2:179585654;179585653;179585652
N2AB	7381	22366;22367;22368	chr2:178720927;178720926;178720925	chr2:179585654;179585653;179585652
N2A	6454	19585;19586;19587	chr2:178720927;178720926;178720925	chr2:179585654;179585653;179585652
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-61
• Domain position: 91
• Structural Position: 177
• Q(SASA): 0.3066
• 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	rs1346948752	-1.4	0.91	D	0.721	0.727	0.955249955587	gnomAD-2.1.1	4.13E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.7E-05	0	0
V/G	rs1346948752	-1.4	0.91	D	0.721	0.727	0.955249955587	gnomAD-4.0.0	1.00154E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.50823E-05	0	3.0275E-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	0.8931	likely_pathogenic	0.8921	pathogenic	-1.508	Destabilizing	0.298	N	0.611	neutral	D	0.630358732	None	None	N
V/C	0.9805	likely_pathogenic	0.9769	pathogenic	-1.67	Destabilizing	0.979	D	0.719	prob.delet.	None	None	None	None	N
V/D	0.9962	likely_pathogenic	0.9956	pathogenic	-2.248	Highly Destabilizing	0.997	D	0.739	prob.delet.	None	None	None	None	N
V/E	0.985	likely_pathogenic	0.9808	pathogenic	-2.243	Highly Destabilizing	0.974	D	0.712	prob.delet.	D	0.647215671	None	None	N
V/F	0.7325	likely_pathogenic	0.7324	pathogenic	-1.419	Destabilizing	0.904	D	0.721	prob.delet.	None	None	None	None	N
V/G	0.9477	likely_pathogenic	0.9443	pathogenic	-1.791	Destabilizing	0.91	D	0.721	prob.delet.	D	0.647215671	None	None	N
V/H	0.9961	likely_pathogenic	0.9947	pathogenic	-1.272	Destabilizing	0.984	D	0.722	prob.delet.	None	None	None	None	N
V/I	0.074	likely_benign	0.0799	benign	-0.82	Destabilizing	None	N	0.468	neutral	None	None	None	None	N
V/K	0.9907	likely_pathogenic	0.9869	pathogenic	-1.237	Destabilizing	0.991	D	0.712	prob.delet.	None	None	None	None	N
V/L	0.5236	ambiguous	0.5273	ambiguous	-0.82	Destabilizing	0.012	N	0.64	neutral	D	0.593515992	None	None	N
V/M	0.537	ambiguous	0.5011	ambiguous	-0.858	Destabilizing	0.835	D	0.727	prob.delet.	D	0.646812062	None	None	N
V/N	0.9837	likely_pathogenic	0.9779	pathogenic	-1.279	Destabilizing	0.98	D	0.743	deleterious	None	None	None	None	N
V/P	0.9838	likely_pathogenic	0.9897	pathogenic	-1.019	Destabilizing	0.98	D	0.721	prob.delet.	None	None	None	None	N
V/Q	0.9847	likely_pathogenic	0.9789	pathogenic	-1.529	Destabilizing	0.996	D	0.731	prob.delet.	None	None	None	None	N
V/R	0.9843	likely_pathogenic	0.9783	pathogenic	-0.731	Destabilizing	0.996	D	0.741	deleterious	None	None	None	None	N
V/S	0.9593	likely_pathogenic	0.9531	pathogenic	-1.735	Destabilizing	0.8	D	0.693	prob.neutral	None	None	None	None	N
V/T	0.9002	likely_pathogenic	0.8927	pathogenic	-1.625	Destabilizing	0.185	N	0.691	prob.neutral	None	None	None	None	N
V/W	0.9942	likely_pathogenic	0.9937	pathogenic	-1.593	Destabilizing	0.996	D	0.688	prob.neutral	None	None	None	None	N
V/Y	0.9813	likely_pathogenic	0.9789	pathogenic	-1.242	Destabilizing	0.881	D	0.727	prob.delet.	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.