TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35715	107368;107369;107370	chr2:178528608;178528607;178528606	chr2:179393335;179393334;179393333
N2AB	34074	102445;102446;102447	chr2:178528608;178528607;178528606	chr2:179393335;179393334;179393333
N2A	33147	99664;99665;99666	chr2:178528608;178528607;178528606	chr2:179393335;179393334;179393333
N2B	26650	80173;80174;80175	chr2:178528608;178528607;178528606	chr2:179393335;179393334;179393333
Novex-1	26775	80548;80549;80550	chr2:178528608;178528607;178528606	chr2:179393335;179393334;179393333
Novex-2	26842	80749;80750;80751	chr2:178528608;178528607;178528606	chr2:179393335;179393334;179393333
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-168
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.9111
• 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
E/D	rs1687608057	None	0.117	N	0.373	0.061	0.177238962908	gnomAD-4.0.0	1.59417E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43662E-05	0
E/G	rs1196336342	0.186	0.993	N	0.628	0.477	0.431822907236	gnomAD-2.1.1	4.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.97E-06	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
E/A	0.2566	likely_benign	0.2782	benign	-0.757	Destabilizing	0.977	D	0.619	neutral	N	0.484165866	None	None	I
E/C	0.9751	likely_pathogenic	0.9798	pathogenic	-0.121	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
E/D	0.4906	ambiguous	0.5882	pathogenic	-0.745	Destabilizing	0.117	N	0.373	neutral	N	0.4825525	None	None	I
E/F	0.9699	likely_pathogenic	0.9751	pathogenic	-0.642	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
E/G	0.4202	ambiguous	0.4796	ambiguous	-1.02	Destabilizing	0.993	D	0.628	neutral	N	0.493932221	None	None	I
E/H	0.8524	likely_pathogenic	0.888	pathogenic	-0.776	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
E/I	0.652	likely_pathogenic	0.7055	pathogenic	-0.072	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	I
E/K	0.2242	likely_benign	0.2716	benign	-0.007	Destabilizing	0.977	D	0.585	neutral	N	0.508082876	None	None	I
E/L	0.7884	likely_pathogenic	0.8329	pathogenic	-0.072	Destabilizing	0.998	D	0.75	deleterious	None	None	None	None	I
E/M	0.7582	likely_pathogenic	0.7946	pathogenic	0.343	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
E/N	0.6723	likely_pathogenic	0.7423	pathogenic	-0.371	Destabilizing	0.99	D	0.719	prob.delet.	None	None	None	None	I
E/P	0.8042	likely_pathogenic	0.8997	pathogenic	-0.28	Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	I
E/Q	0.2511	likely_benign	0.2811	benign	-0.333	Destabilizing	0.997	D	0.655	neutral	N	0.503215774	None	None	I
E/R	0.4336	ambiguous	0.4936	ambiguous	0.104	Stabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	I
E/S	0.4596	ambiguous	0.5219	ambiguous	-0.589	Destabilizing	0.983	D	0.595	neutral	None	None	None	None	I
E/T	0.4773	ambiguous	0.5483	ambiguous	-0.371	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	I
E/V	0.4212	ambiguous	0.4745	ambiguous	-0.28	Destabilizing	0.997	D	0.723	prob.delet.	N	0.438297504	None	None	I
E/W	0.9925	likely_pathogenic	0.9938	pathogenic	-0.453	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
E/Y	0.9354	likely_pathogenic	0.95	pathogenic	-0.384	Destabilizing	1.0	D	0.757	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.