TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7037	21334;21335;21336	chr2:178724266;178724265;178724264	chr2:179588993;179588992;179588991
N2AB	6720	20383;20384;20385	chr2:178724266;178724265;178724264	chr2:179588993;179588992;179588991
N2A	5793	17602;17603;17604	chr2:178724266;178724265;178724264	chr2:179588993;179588992;179588991
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: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-54
• Domain position: 90
• Structural Position: 176
• Q(SASA): 1.1794
• 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/I	None	None	0.002	N	0.515	0.237	0.566335693254	gnomAD-4.0.0	1.59646E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86786E-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	0.6756	likely_pathogenic	0.6621	pathogenic	-1.631	Destabilizing	0.334	N	0.685	prob.neutral	D	0.583461473	None	None	I
V/C	0.954	likely_pathogenic	0.9581	pathogenic	-1.424	Destabilizing	0.982	D	0.73	prob.delet.	None	None	None	None	I
V/D	0.9746	likely_pathogenic	0.9781	pathogenic	-1.976	Destabilizing	0.781	D	0.732	prob.delet.	D	0.568047525	None	None	I
V/E	0.955	likely_pathogenic	0.9582	pathogenic	-1.978	Destabilizing	0.826	D	0.702	prob.neutral	None	None	None	None	I
V/F	0.6747	likely_pathogenic	0.6781	pathogenic	-1.428	Destabilizing	0.638	D	0.723	prob.delet.	D	0.567442112	None	None	I
V/G	0.8054	likely_pathogenic	0.8108	pathogenic	-1.927	Destabilizing	0.781	D	0.707	prob.neutral	D	0.584066886	None	None	I
V/H	0.9868	likely_pathogenic	0.9872	pathogenic	-1.42	Destabilizing	0.982	D	0.751	deleterious	None	None	None	None	I
V/I	0.1006	likely_benign	0.0965	benign	-0.908	Destabilizing	0.002	N	0.515	neutral	N	0.507788245	None	None	I
V/K	0.9624	likely_pathogenic	0.9634	pathogenic	-1.277	Destabilizing	0.826	D	0.702	prob.neutral	None	None	None	None	I
V/L	0.6347	likely_pathogenic	0.6242	pathogenic	-0.908	Destabilizing	0.034	N	0.693	prob.neutral	D	0.57159773	None	None	I
V/M	0.5985	likely_pathogenic	0.5892	pathogenic	-0.83	Destabilizing	0.7	D	0.753	deleterious	None	None	None	None	I
V/N	0.9367	likely_pathogenic	0.9395	pathogenic	-1.193	Destabilizing	0.935	D	0.74	deleterious	None	None	None	None	I
V/P	0.9504	likely_pathogenic	0.9461	pathogenic	-1.117	Destabilizing	0.935	D	0.711	prob.delet.	None	None	None	None	I
V/Q	0.9632	likely_pathogenic	0.9634	pathogenic	-1.431	Destabilizing	0.935	D	0.721	prob.delet.	None	None	None	None	I
V/R	0.9396	likely_pathogenic	0.9435	pathogenic	-0.756	Destabilizing	0.826	D	0.739	prob.delet.	None	None	None	None	I
V/S	0.8497	likely_pathogenic	0.8493	pathogenic	-1.676	Destabilizing	0.826	D	0.687	prob.neutral	None	None	None	None	I
V/T	0.6934	likely_pathogenic	0.6925	pathogenic	-1.576	Destabilizing	0.399	N	0.717	prob.delet.	None	None	None	None	I
V/W	0.9942	likely_pathogenic	0.9943	pathogenic	-1.583	Destabilizing	0.982	D	0.716	prob.delet.	None	None	None	None	I
V/Y	0.9656	likely_pathogenic	0.9668	pathogenic	-1.275	Destabilizing	0.826	D	0.727	prob.delet.	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.