TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6185	18778;18779;18780	chr2:178729700;178729699;178729698	chr2:179594427;179594426;179594425
N2AB	5868	17827;17828;17829	chr2:178729700;178729699;178729698	chr2:179594427;179594426;179594425
N2A	4941	15046;15047;15048	chr2:178729700;178729699;178729698	chr2:179594427;179594426;179594425
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: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-45
• Domain position: 81
• Structural Position: 164
• Q(SASA): 0.2309
• 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
G/S	rs1460731482	-0.345	1.0	D	0.808	0.543	0.582074046126	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
G/S	rs1460731482	-0.345	1.0	D	0.808	0.543	0.582074046126	gnomAD-4.0.0	3.18279E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85865E-06	1.43283E-05	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
G/A	0.5642	likely_pathogenic	0.6283	pathogenic	-0.412	Destabilizing	1.0	D	0.755	deleterious	D	0.625140387	None	None	I
G/C	0.8821	likely_pathogenic	0.9061	pathogenic	-0.81	Destabilizing	1.0	D	0.813	deleterious	D	0.663729722	None	None	I
G/D	0.7492	likely_pathogenic	0.7653	pathogenic	-0.998	Destabilizing	1.0	D	0.863	deleterious	D	0.616873541	None	None	I
G/E	0.8218	likely_pathogenic	0.8388	pathogenic	-1.182	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
G/F	0.9595	likely_pathogenic	0.9685	pathogenic	-1.248	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
G/H	0.9398	likely_pathogenic	0.9517	pathogenic	-0.668	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
G/I	0.9512	likely_pathogenic	0.961	pathogenic	-0.607	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
G/K	0.9194	likely_pathogenic	0.933	pathogenic	-0.927	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
G/L	0.9412	likely_pathogenic	0.9572	pathogenic	-0.607	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
G/M	0.9551	likely_pathogenic	0.968	pathogenic	-0.459	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
G/N	0.8524	likely_pathogenic	0.8764	pathogenic	-0.512	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
G/P	0.9954	likely_pathogenic	0.9969	pathogenic	-0.511	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
G/Q	0.8754	likely_pathogenic	0.8912	pathogenic	-0.882	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
G/R	0.8404	likely_pathogenic	0.8562	pathogenic	-0.384	Destabilizing	1.0	D	0.873	deleterious	D	0.646701339	None	None	I
G/S	0.4216	ambiguous	0.4932	ambiguous	-0.578	Destabilizing	1.0	D	0.808	deleterious	D	0.611069424	None	None	I
G/T	0.8207	likely_pathogenic	0.858	pathogenic	-0.712	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
G/V	0.8945	likely_pathogenic	0.9131	pathogenic	-0.511	Destabilizing	1.0	D	0.844	deleterious	D	0.647508556	None	None	I
G/W	0.9442	likely_pathogenic	0.9526	pathogenic	-1.367	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/Y	0.9397	likely_pathogenic	0.9537	pathogenic	-1.042	Destabilizing	1.0	D	0.844	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.