TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9273	28042;28043;28044	chr2:178712013;178712012;178712011	chr2:179576740;179576739;179576738
N2AB	8956	27091;27092;27093	chr2:178712013;178712012;178712011	chr2:179576740;179576739;179576738
N2A	8029	24310;24311;24312	chr2:178712013;178712012;178712011	chr2:179576740;179576739;179576738
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: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-78
• Domain position: 69
• Structural Position: 152
• Q(SASA): 0.2406
• 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/E	None	None	1.0	D	0.841	0.832	0.821358977847	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
G/R	None	None	1.0	D	0.835	0.826	0.873837890407	gnomAD-4.0.0	1.59157E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43386E-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	0.2405	likely_benign	0.3213	benign	-0.277	Destabilizing	1.0	D	0.759	deleterious	D	0.549395785	None	None	I
G/C	0.6554	likely_pathogenic	0.8193	pathogenic	-0.434	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
G/D	0.686	likely_pathogenic	0.8209	pathogenic	-0.137	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
G/E	0.8128	likely_pathogenic	0.907	pathogenic	-0.127	Destabilizing	1.0	D	0.841	deleterious	D	0.640675777	None	None	I
G/F	0.9586	likely_pathogenic	0.9818	pathogenic	-0.519	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
G/H	0.9193	likely_pathogenic	0.9704	pathogenic	-0.995	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
G/I	0.9392	likely_pathogenic	0.9754	pathogenic	0.307	Stabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
G/K	0.9204	likely_pathogenic	0.9683	pathogenic	-0.522	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
G/L	0.9063	likely_pathogenic	0.9557	pathogenic	0.307	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
G/M	0.9166	likely_pathogenic	0.9654	pathogenic	0.149	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
G/N	0.7971	likely_pathogenic	0.8955	pathogenic	-0.321	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	I
G/P	0.9957	likely_pathogenic	0.9977	pathogenic	0.157	Stabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/Q	0.8215	likely_pathogenic	0.9183	pathogenic	-0.328	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
G/R	0.7941	likely_pathogenic	0.9112	pathogenic	-0.518	Destabilizing	1.0	D	0.835	deleterious	D	0.656725498	None	None	I
G/S	0.2027	likely_benign	0.3181	benign	-0.728	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	I
G/T	0.6495	likely_pathogenic	0.813	pathogenic	-0.601	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
G/V	0.8381	likely_pathogenic	0.9291	pathogenic	0.157	Stabilizing	1.0	D	0.795	deleterious	D	0.640675777	None	None	I
G/W	0.9283	likely_pathogenic	0.9731	pathogenic	-1.01	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
G/Y	0.9444	likely_pathogenic	0.9787	pathogenic	-0.452	Destabilizing	1.0	D	0.759	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.