TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8333	25222;25223;25224	chr2:178718009;178718008;178718007	chr2:179582736;179582735;179582734
N2AB	8016	24271;24272;24273	chr2:178718009;178718008;178718007	chr2:179582736;179582735;179582734
N2A	7089	21490;21491;21492	chr2:178718009;178718008;178718007	chr2:179582736;179582735;179582734
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-68
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.504
• 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	rs1438182051	-0.651	0.797	N	0.519	0.316	0.233785782151	gnomAD-2.1.1	3.18E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
E/D	rs1438182051	-0.651	0.797	N	0.519	0.316	0.233785782151	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
E/D	rs1438182051	-0.651	0.797	N	0.519	0.316	0.233785782151	gnomAD-4.0.0	2.56224E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.78675E-06	0	0
E/G	rs770811407	-1.337	0.99	N	0.627	0.515	0.556183318313	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
E/G	rs770811407	-1.337	0.99	N	0.627	0.515	0.556183318313	gnomAD-4.0.0	7.95689E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.76464E-05	0	2.85873E-06	0	6.04778E-05

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	0.1507	likely_benign	0.1919	benign	-0.881	Destabilizing	0.861	D	0.544	neutral	N	0.506507661	None	None	I
E/C	0.8343	likely_pathogenic	0.8943	pathogenic	-0.437	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	I
E/D	0.1884	likely_benign	0.2281	benign	-1.194	Destabilizing	0.797	D	0.519	neutral	N	0.502005918	None	None	I
E/F	0.6308	likely_pathogenic	0.7082	pathogenic	-0.466	Destabilizing	0.992	D	0.717	prob.delet.	None	None	None	None	I
E/G	0.241	likely_benign	0.3315	benign	-1.249	Destabilizing	0.99	D	0.627	neutral	N	0.500989562	None	None	I
E/H	0.4109	ambiguous	0.5127	ambiguous	-0.835	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	I
E/I	0.2245	likely_benign	0.2708	benign	0.123	Stabilizing	0.896	D	0.609	neutral	None	None	None	None	I
E/K	0.1207	likely_benign	0.1497	benign	-0.639	Destabilizing	0.983	D	0.519	neutral	N	0.486727035	None	None	I
E/L	0.3186	likely_benign	0.3831	ambiguous	0.123	Stabilizing	0.051	N	0.426	neutral	None	None	None	None	I
E/M	0.3492	ambiguous	0.4099	ambiguous	0.658	Stabilizing	0.916	D	0.707	prob.neutral	None	None	None	None	I
E/N	0.2553	likely_benign	0.3152	benign	-1.091	Destabilizing	0.983	D	0.591	neutral	None	None	None	None	I
E/P	0.6379	likely_pathogenic	0.756	pathogenic	-0.19	Destabilizing	0.982	D	0.665	neutral	None	None	None	None	I
E/Q	0.1202	likely_benign	0.1485	benign	-0.948	Destabilizing	0.998	D	0.58	neutral	N	0.496637384	None	None	I
E/R	0.2161	likely_benign	0.2751	benign	-0.453	Destabilizing	0.996	D	0.598	neutral	None	None	None	None	I
E/S	0.2132	likely_benign	0.2674	benign	-1.414	Destabilizing	0.909	D	0.511	neutral	None	None	None	None	I
E/T	0.1784	likely_benign	0.21	benign	-1.103	Destabilizing	0.27	N	0.313	neutral	None	None	None	None	I
E/V	0.1426	likely_benign	0.1697	benign	-0.19	Destabilizing	0.111	N	0.392	neutral	N	0.453790684	None	None	I
E/W	0.85	likely_pathogenic	0.9017	pathogenic	-0.263	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
E/Y	0.5406	ambiguous	0.6373	pathogenic	-0.223	Destabilizing	1.0	D	0.711	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.