TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24502	73729;73730;73731	chr2:178572628;178572627;178572626	chr2:179437355;179437354;179437353
N2AB	22861	68806;68807;68808	chr2:178572628;178572627;178572626	chr2:179437355;179437354;179437353
N2A	21934	66025;66026;66027	chr2:178572628;178572627;178572626	chr2:179437355;179437354;179437353
N2B	15437	46534;46535;46536	chr2:178572628;178572627;178572626	chr2:179437355;179437354;179437353
Novex-1	15562	46909;46910;46911	chr2:178572628;178572627;178572626	chr2:179437355;179437354;179437353
Novex-2	15629	47110;47111;47112	chr2:178572628;178572627;178572626	chr2:179437355;179437354;179437353
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-132
• Domain position: 72
• Structural Position: 159
• Q(SASA): 0.3811
• 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	None	None	0.958	D	0.475	0.333	0.328222422547	gnomAD-4.0.0	1.36882E-06	None	None	None	None	I	None	0	0	None	0	2.52283E-05	None	0	0	8.99628E-07	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
E/A	0.2661	likely_benign	0.2661	benign	-0.432	Destabilizing	0.919	D	0.613	neutral	N	0.501203372	None	None	I
E/C	0.8787	likely_pathogenic	0.8775	pathogenic	0.196	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
E/D	0.3635	ambiguous	0.3575	ambiguous	-0.539	Destabilizing	0.958	D	0.475	neutral	D	0.52690495	None	None	I
E/F	0.9099	likely_pathogenic	0.9167	pathogenic	-0.644	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
E/G	0.3662	ambiguous	0.3618	ambiguous	-0.639	Destabilizing	0.988	D	0.682	prob.neutral	N	0.516309114	None	None	I
E/H	0.625	likely_pathogenic	0.6072	pathogenic	-0.814	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	I
E/I	0.5116	ambiguous	0.5687	pathogenic	0.079	Stabilizing	0.995	D	0.764	deleterious	None	None	None	None	I
E/K	0.2301	likely_benign	0.2224	benign	0.307	Stabilizing	0.067	N	0.325	neutral	D	0.52468799	None	None	I
E/L	0.6789	likely_pathogenic	0.7034	pathogenic	0.079	Stabilizing	0.991	D	0.738	prob.delet.	None	None	None	None	I
E/M	0.58	likely_pathogenic	0.6072	pathogenic	0.461	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
E/N	0.4452	ambiguous	0.4477	ambiguous	0.101	Stabilizing	0.991	D	0.682	prob.neutral	None	None	None	None	I
E/P	0.9926	likely_pathogenic	0.9929	pathogenic	-0.071	Destabilizing	0.995	D	0.721	prob.delet.	None	None	None	None	I
E/Q	0.1335	likely_benign	0.1315	benign	0.103	Stabilizing	0.958	D	0.612	neutral	N	0.499646436	None	None	I
E/R	0.4091	ambiguous	0.3872	ambiguous	0.249	Stabilizing	0.982	D	0.68	prob.neutral	None	None	None	None	I
E/S	0.2668	likely_benign	0.2603	benign	-0.073	Destabilizing	0.968	D	0.627	neutral	None	None	None	None	I
E/T	0.2293	likely_benign	0.2394	benign	0.094	Stabilizing	0.991	D	0.684	prob.neutral	None	None	None	None	I
E/V	0.31	likely_benign	0.3495	ambiguous	-0.071	Destabilizing	0.988	D	0.74	deleterious	N	0.4971909	None	None	I
E/W	0.9666	likely_pathogenic	0.9652	pathogenic	-0.595	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
E/Y	0.8666	likely_pathogenic	0.8666	pathogenic	-0.414	Destabilizing	0.998	D	0.736	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.