TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5055	15388;15389;15390	chr2:178734761;178734760;178734759	chr2:179599488;179599487;179599486
N2AB	4738	14437;14438;14439	chr2:178734761;178734760;178734759	chr2:179599488;179599487;179599486
N2A	3811	11656;11657;11658	chr2:178734761;178734760;178734759	chr2:179599488;179599487;179599486
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: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-33
• Domain position: 75
• Structural Position: 157
• Q(SASA): 0.3756
• Predicted PPI site: N

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	0.999	D	0.578	0.294	0.336892272479	gnomAD-4.0.0	1.59185E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43373E-05	0
E/G	rs1185775947	None	1.0	D	0.81	0.595	0.631273993836	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/G	rs1185775947	None	1.0	D	0.81	0.595	0.631273993836	gnomAD-4.0.0	6.57004E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4699E-05	0	0
E/K	None	None	0.999	N	0.663	0.369	0.450152462452	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
E/A	0.3932	ambiguous	0.3324	benign	-1.181	Destabilizing	0.999	D	0.727	prob.delet.	D	0.612462179	None	None	N
E/C	0.967	likely_pathogenic	0.9517	pathogenic	-0.49	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
E/D	0.4931	ambiguous	0.4086	ambiguous	-0.972	Destabilizing	0.999	D	0.578	neutral	D	0.603915509	None	None	N
E/F	0.8878	likely_pathogenic	0.8551	pathogenic	-0.714	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
E/G	0.6174	likely_pathogenic	0.5335	ambiguous	-1.52	Destabilizing	1.0	D	0.81	deleterious	D	0.66799065	None	None	N
E/H	0.6985	likely_pathogenic	0.6129	pathogenic	-0.931	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/I	0.4707	ambiguous	0.4251	ambiguous	-0.253	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
E/K	0.2156	likely_benign	0.1677	benign	-0.405	Destabilizing	0.999	D	0.663	neutral	N	0.498769629	None	None	N
E/L	0.5829	likely_pathogenic	0.5214	ambiguous	-0.253	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
E/M	0.5638	ambiguous	0.5207	ambiguous	0.285	Stabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
E/N	0.6361	likely_pathogenic	0.5392	ambiguous	-0.89	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/P	0.9964	likely_pathogenic	0.9947	pathogenic	-0.543	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
E/Q	0.2064	likely_benign	0.1665	benign	-0.801	Destabilizing	1.0	D	0.695	prob.neutral	N	0.506825913	None	None	N
E/R	0.4118	ambiguous	0.3417	ambiguous	-0.222	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/S	0.4991	ambiguous	0.4212	ambiguous	-1.234	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	N
E/T	0.4153	ambiguous	0.3479	ambiguous	-0.933	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
E/V	0.2974	likely_benign	0.2562	benign	-0.543	Destabilizing	1.0	D	0.854	deleterious	N	0.487148192	None	None	N
E/W	0.9744	likely_pathogenic	0.9679	pathogenic	-0.379	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/Y	0.8591	likely_pathogenic	0.8035	pathogenic	-0.411	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N

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.