TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21254	63985;63986;63987	chr2:178587549;178587548;178587547	chr2:179452276;179452275;179452274
N2AB	19613	59062;59063;59064	chr2:178587549;178587548;178587547	chr2:179452276;179452275;179452274
N2A	18686	56281;56282;56283	chr2:178587549;178587548;178587547	chr2:179452276;179452275;179452274
N2B	12189	36790;36791;36792	chr2:178587549;178587548;178587547	chr2:179452276;179452275;179452274
Novex-1	12314	37165;37166;37167	chr2:178587549;178587548;178587547	chr2:179452276;179452275;179452274
Novex-2	12381	37366;37367;37368	chr2:178587549;178587548;178587547	chr2:179452276;179452275;179452274
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-123
• Domain position: 78
• Structural Position: 165
• Q(SASA): 0.4722
• 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/K	None	None	0.955	N	0.603	0.345	0.309530620856	gnomAD-4.0.0	1.20034E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-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
E/A	0.3595	ambiguous	0.3576	ambiguous	-0.229	Destabilizing	0.977	D	0.655	neutral	N	0.489570805	None	None	I
E/C	0.9401	likely_pathogenic	0.9375	pathogenic	-0.03	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
E/D	0.3277	likely_benign	0.3396	benign	-0.311	Destabilizing	0.977	D	0.48	neutral	N	0.496091718	None	None	I
E/F	0.9428	likely_pathogenic	0.9401	pathogenic	-0.137	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
E/G	0.3838	ambiguous	0.3742	ambiguous	-0.4	Destabilizing	0.993	D	0.646	neutral	N	0.494712593	None	None	I
E/H	0.7248	likely_pathogenic	0.7089	pathogenic	0.224	Stabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	I
E/I	0.6855	likely_pathogenic	0.672	pathogenic	0.18	Stabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	I
E/K	0.282	likely_benign	0.2501	benign	0.508	Stabilizing	0.955	D	0.603	neutral	N	0.471720297	None	None	I
E/L	0.759	likely_pathogenic	0.7501	pathogenic	0.18	Stabilizing	0.995	D	0.705	prob.neutral	None	None	None	None	I
E/M	0.7049	likely_pathogenic	0.6941	pathogenic	0.15	Stabilizing	0.999	D	0.7	prob.neutral	None	None	None	None	I
E/N	0.5239	ambiguous	0.5324	ambiguous	0.127	Stabilizing	0.995	D	0.723	prob.delet.	None	None	None	None	I
E/P	0.9234	likely_pathogenic	0.9307	pathogenic	0.064	Stabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	I
E/Q	0.1872	likely_benign	0.1827	benign	0.161	Stabilizing	0.568	D	0.299	neutral	N	0.51285763	None	None	I
E/R	0.478	ambiguous	0.4449	ambiguous	0.698	Stabilizing	0.99	D	0.712	prob.delet.	None	None	None	None	I
E/S	0.332	likely_benign	0.337	benign	0.008	Stabilizing	0.983	D	0.676	prob.neutral	None	None	None	None	I
E/T	0.3907	ambiguous	0.3899	ambiguous	0.156	Stabilizing	0.995	D	0.672	neutral	None	None	None	None	I
E/V	0.4603	ambiguous	0.4444	ambiguous	0.064	Stabilizing	0.997	D	0.716	prob.delet.	D	0.529040591	None	None	I
E/W	0.9778	likely_pathogenic	0.9746	pathogenic	-0.01	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
E/Y	0.8909	likely_pathogenic	0.8795	pathogenic	0.109	Stabilizing	0.999	D	0.727	prob.delet.	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.