TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9236	27931;27932;27933	chr2:178712124;178712123;178712122	chr2:179576851;179576850;179576849
N2AB	8919	26980;26981;26982	chr2:178712124;178712123;178712122	chr2:179576851;179576850;179576849
N2A	7992	24199;24200;24201	chr2:178712124;178712123;178712122	chr2:179576851;179576850;179576849
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: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-78
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.2651
• 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	rs1034794926	None	0.978	D	0.613	0.661	0.768130985018	gnomAD-4.0.0	2.73685E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59788E-06	0	0
V/I	rs774989128	-0.085	0.37	N	0.209	0.158	None	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
V/I	rs774989128	-0.085	0.37	N	0.209	0.158	None	gnomAD-4.0.0	6.84216E-06	None	None	None	None	I	None	0	2.23664E-05	None	0	0	None	0	0	8.09529E-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	0.6561	likely_pathogenic	0.7575	pathogenic	-1.475	Destabilizing	0.978	D	0.613	neutral	D	0.571531789	None	None	I
V/C	0.9237	likely_pathogenic	0.9433	pathogenic	-1.0	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
V/D	0.9815	likely_pathogenic	0.9918	pathogenic	-1.12	Destabilizing	0.999	D	0.846	deleterious	None	None	None	None	I
V/E	0.9627	likely_pathogenic	0.9809	pathogenic	-1.03	Destabilizing	0.999	D	0.852	deleterious	D	0.630117644	None	None	I
V/F	0.4435	ambiguous	0.5629	ambiguous	-0.927	Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	I
V/G	0.802	likely_pathogenic	0.8775	pathogenic	-1.886	Destabilizing	0.999	D	0.846	deleterious	D	0.630117644	None	None	I
V/H	0.9835	likely_pathogenic	0.992	pathogenic	-1.427	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
V/I	0.076	likely_benign	0.0823	benign	-0.414	Destabilizing	0.37	N	0.209	neutral	N	0.480694858	None	None	I
V/K	0.9695	likely_pathogenic	0.9828	pathogenic	-1.129	Destabilizing	0.999	D	0.854	deleterious	None	None	None	None	I
V/L	0.4638	ambiguous	0.5493	ambiguous	-0.414	Destabilizing	0.9	D	0.551	neutral	D	0.536253481	None	None	I
V/M	0.4171	ambiguous	0.5151	ambiguous	-0.407	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	I
V/N	0.9447	likely_pathogenic	0.9732	pathogenic	-1.063	Destabilizing	0.999	D	0.86	deleterious	None	None	None	None	I
V/P	0.951	likely_pathogenic	0.973	pathogenic	-0.733	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	I
V/Q	0.9596	likely_pathogenic	0.9792	pathogenic	-1.071	Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	I
V/R	0.9574	likely_pathogenic	0.9763	pathogenic	-0.827	Destabilizing	0.999	D	0.862	deleterious	None	None	None	None	I
V/S	0.8541	likely_pathogenic	0.915	pathogenic	-1.691	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	I
V/T	0.7202	likely_pathogenic	0.7958	pathogenic	-1.463	Destabilizing	0.992	D	0.717	prob.delet.	None	None	None	None	I
V/W	0.9777	likely_pathogenic	0.9901	pathogenic	-1.2	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
V/Y	0.9147	likely_pathogenic	0.9526	pathogenic	-0.851	Destabilizing	0.999	D	0.758	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.