TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7448	22567;22568;22569	chr2:178722445;178722444;178722443	chr2:179587172;179587171;179587170
N2AB	7131	21616;21617;21618	chr2:178722445;178722444;178722443	chr2:179587172;179587171;179587170
N2A	6204	18835;18836;18837	chr2:178722445;178722444;178722443	chr2:179587172;179587171;179587170
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-59
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1352
• 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
I/T	rs878854293	None	0.98	N	0.635	0.375	0.756846489486	gnomAD-4.0.0	4.80129E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.25001E-06	0	0
I/V	rs1349950887	None	0.689	N	0.425	0.143	0.52851136469	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs1349950887	None	0.689	N	0.425	0.143	0.52851136469	gnomAD-4.0.0	2.56325E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.78863E-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
I/A	0.7562	likely_pathogenic	0.7745	pathogenic	-2.243	Highly Destabilizing	0.97	D	0.55	neutral	None	None	None	None	I
I/C	0.9335	likely_pathogenic	0.9363	pathogenic	-1.455	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	I
I/D	0.9822	likely_pathogenic	0.9842	pathogenic	-1.679	Destabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	I
I/E	0.9591	likely_pathogenic	0.9593	pathogenic	-1.571	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	I
I/F	0.3088	likely_benign	0.3493	ambiguous	-1.426	Destabilizing	0.071	N	0.349	neutral	N	0.49353037	None	None	I
I/G	0.9434	likely_pathogenic	0.9499	pathogenic	-2.694	Highly Destabilizing	0.996	D	0.695	prob.neutral	None	None	None	None	I
I/H	0.9288	likely_pathogenic	0.9314	pathogenic	-1.911	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
I/K	0.902	likely_pathogenic	0.9022	pathogenic	-1.577	Destabilizing	0.996	D	0.698	prob.neutral	None	None	None	None	I
I/L	0.1011	likely_benign	0.1105	benign	-1.006	Destabilizing	0.689	D	0.34	neutral	N	0.459847078	None	None	I
I/M	0.1481	likely_benign	0.1721	benign	-0.826	Destabilizing	0.489	N	0.315	neutral	N	0.506430303	None	None	I
I/N	0.8419	likely_pathogenic	0.8527	pathogenic	-1.517	Destabilizing	0.998	D	0.731	prob.delet.	N	0.520535395	None	None	I
I/P	0.8762	likely_pathogenic	0.8728	pathogenic	-1.392	Destabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	I
I/Q	0.8912	likely_pathogenic	0.8978	pathogenic	-1.556	Destabilizing	0.996	D	0.729	prob.delet.	None	None	None	None	I
I/R	0.8624	likely_pathogenic	0.8585	pathogenic	-1.11	Destabilizing	0.996	D	0.731	prob.delet.	None	None	None	None	I
I/S	0.7922	likely_pathogenic	0.8045	pathogenic	-2.265	Highly Destabilizing	0.994	D	0.649	neutral	N	0.518551452	None	None	I
I/T	0.7661	likely_pathogenic	0.7842	pathogenic	-2.017	Highly Destabilizing	0.98	D	0.635	neutral	N	0.488099093	None	None	I
I/V	0.1131	likely_benign	0.1196	benign	-1.392	Destabilizing	0.689	D	0.425	neutral	N	0.49173021	None	None	I
I/W	0.9353	likely_pathogenic	0.9424	pathogenic	-1.58	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
I/Y	0.8181	likely_pathogenic	0.8361	pathogenic	-1.359	Destabilizing	0.983	D	0.663	neutral	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.