TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8377	25354;25355;25356	chr2:178717745;178717744;178717743	chr2:179582472;179582471;179582470
N2AB	8060	24403;24404;24405	chr2:178717745;178717744;178717743	chr2:179582472;179582471;179582470
N2A	7133	21622;21623;21624	chr2:178717745;178717744;178717743	chr2:179582472;179582471;179582470
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-69
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.2032
• 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	0.709	N	0.262	0.144	0.273070737957	gnomAD-4.0.0	1.36895E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79931E-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	0.2812	likely_benign	0.2533	benign	-1.947	Destabilizing	0.709	D	0.262	neutral	N	0.465126241	None	None	I
V/C	0.927	likely_pathogenic	0.9232	pathogenic	-1.449	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
V/D	0.9774	likely_pathogenic	0.9748	pathogenic	-2.233	Highly Destabilizing	1.0	D	0.842	deleterious	N	0.510415591	None	None	I
V/E	0.9363	likely_pathogenic	0.9336	pathogenic	-2.061	Highly Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	I
V/F	0.6032	likely_pathogenic	0.5573	ambiguous	-1.196	Destabilizing	1.0	D	0.801	deleterious	N	0.453278442	None	None	I
V/G	0.709	likely_pathogenic	0.7079	pathogenic	-2.447	Highly Destabilizing	0.997	D	0.78	deleterious	N	0.477814705	None	None	I
V/H	0.9769	likely_pathogenic	0.9747	pathogenic	-2.046	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
V/I	0.1022	likely_benign	0.0904	benign	-0.581	Destabilizing	0.853	D	0.596	neutral	N	0.498529525	None	None	I
V/K	0.941	likely_pathogenic	0.9426	pathogenic	-1.7	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	I
V/L	0.4057	ambiguous	0.3532	ambiguous	-0.581	Destabilizing	0.853	D	0.445	neutral	N	0.493102276	None	None	I
V/M	0.3549	ambiguous	0.3081	benign	-0.545	Destabilizing	0.985	D	0.425	neutral	None	None	None	None	I
V/N	0.9356	likely_pathogenic	0.9272	pathogenic	-1.861	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	I
V/P	0.9825	likely_pathogenic	0.9808	pathogenic	-1.006	Destabilizing	0.995	D	0.829	deleterious	None	None	None	None	I
V/Q	0.9095	likely_pathogenic	0.9098	pathogenic	-1.785	Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	I
V/R	0.9005	likely_pathogenic	0.9088	pathogenic	-1.423	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
V/S	0.7054	likely_pathogenic	0.6802	pathogenic	-2.484	Highly Destabilizing	0.992	D	0.775	deleterious	None	None	None	None	I
V/T	0.409	ambiguous	0.3699	ambiguous	-2.165	Highly Destabilizing	0.99	D	0.627	neutral	None	None	None	None	I
V/W	0.9901	likely_pathogenic	0.9879	pathogenic	-1.605	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
V/Y	0.9563	likely_pathogenic	0.9498	pathogenic	-1.231	Destabilizing	1.0	D	0.79	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.