TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8109	24550;24551;24552	chr2:178718875;178718874;178718873	chr2:179583602;179583601;179583600
N2AB	7792	23599;23600;23601	chr2:178718875;178718874;178718873	chr2:179583602;179583601;179583600
N2A	6865	20818;20819;20820	chr2:178718875;178718874;178718873	chr2:179583602;179583601;179583600
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: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-66
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.2469
• 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/A	None	None	0.822	D	0.676	0.669	0.736644243634	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
V/I	rs2077903400	None	0.014	N	0.215	0.148	0.395143324098	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs2077903400	None	0.014	N	0.215	0.148	0.395143324098	gnomAD-4.0.0	2.56283E-06	None	None	None	None	I	None	3.38455E-05	0	None	0	0	None	0	0	0	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	0.4028	ambiguous	0.3705	ambiguous	-1.744	Destabilizing	0.822	D	0.676	prob.neutral	D	0.626322647	None	None	I
V/C	0.893	likely_pathogenic	0.875	pathogenic	-1.08	Destabilizing	0.998	D	0.743	deleterious	None	None	None	None	I
V/D	0.8982	likely_pathogenic	0.8944	pathogenic	-2.015	Highly Destabilizing	0.99	D	0.864	deleterious	D	0.627331668	None	None	I
V/E	0.7909	likely_pathogenic	0.7909	pathogenic	-1.878	Destabilizing	0.993	D	0.865	deleterious	None	None	None	None	I
V/F	0.3967	ambiguous	0.3735	ambiguous	-1.042	Destabilizing	0.942	D	0.791	deleterious	D	0.563436387	None	None	I
V/G	0.4392	ambiguous	0.4301	ambiguous	-2.202	Highly Destabilizing	0.971	D	0.863	deleterious	D	0.627331668	None	None	I
V/H	0.9376	likely_pathogenic	0.9256	pathogenic	-1.925	Destabilizing	0.998	D	0.851	deleterious	None	None	None	None	I
V/I	0.1068	likely_benign	0.1077	benign	-0.514	Destabilizing	0.014	N	0.215	neutral	N	0.496856389	None	None	I
V/K	0.8559	likely_pathogenic	0.8498	pathogenic	-1.579	Destabilizing	0.978	D	0.867	deleterious	None	None	None	None	I
V/L	0.3773	ambiguous	0.3659	ambiguous	-0.514	Destabilizing	0.014	N	0.337	neutral	D	0.551238274	None	None	I
V/M	0.3006	likely_benign	0.2991	benign	-0.375	Destabilizing	0.956	D	0.705	prob.neutral	None	None	None	None	I
V/N	0.8273	likely_pathogenic	0.818	pathogenic	-1.605	Destabilizing	0.993	D	0.863	deleterious	None	None	None	None	I
V/P	0.8842	likely_pathogenic	0.8505	pathogenic	-0.893	Destabilizing	0.993	D	0.86	deleterious	None	None	None	None	I
V/Q	0.8192	likely_pathogenic	0.8114	pathogenic	-1.57	Destabilizing	0.993	D	0.867	deleterious	None	None	None	None	I
V/R	0.8328	likely_pathogenic	0.8228	pathogenic	-1.275	Destabilizing	0.993	D	0.858	deleterious	None	None	None	None	I
V/S	0.6526	likely_pathogenic	0.6263	pathogenic	-2.168	Highly Destabilizing	0.978	D	0.863	deleterious	None	None	None	None	I
V/T	0.5178	ambiguous	0.491	ambiguous	-1.906	Destabilizing	0.86	D	0.733	prob.delet.	None	None	None	None	I
V/W	0.9391	likely_pathogenic	0.9261	pathogenic	-1.495	Destabilizing	0.998	D	0.847	deleterious	None	None	None	None	I
V/Y	0.8272	likely_pathogenic	0.7992	pathogenic	-1.118	Destabilizing	0.978	D	0.763	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.