TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31183	93772;93773;93774	chr2:178548079;178548078;178548077	chr2:179412806;179412805;179412804
N2AB	29542	88849;88850;88851	chr2:178548079;178548078;178548077	chr2:179412806;179412805;179412804
N2A	28615	86068;86069;86070	chr2:178548079;178548078;178548077	chr2:179412806;179412805;179412804
N2B	22118	66577;66578;66579	chr2:178548079;178548078;178548077	chr2:179412806;179412805;179412804
Novex-1	22243	66952;66953;66954	chr2:178548079;178548078;178548077	chr2:179412806;179412805;179412804
Novex-2	22310	67153;67154;67155	chr2:178548079;178548078;178548077	chr2:179412806;179412805;179412804
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: Fn3-115
• Domain position: 71
• Structural Position: 105
• Q(SASA): 0.224
• 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/G	None	None	0.994	N	0.653	0.477	0.476364732183	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.3382	likely_benign	0.2757	benign	-1.481	Destabilizing	0.994	D	0.591	neutral	N	0.480560706	None	None	N
E/C	0.8904	likely_pathogenic	0.872	pathogenic	-0.846	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/D	0.2841	likely_benign	0.3141	benign	-1.676	Destabilizing	0.104	N	0.257	neutral	N	0.479733986	None	None	N
E/F	0.829	likely_pathogenic	0.8391	pathogenic	-1.038	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/G	0.557	ambiguous	0.4945	ambiguous	-1.906	Destabilizing	0.994	D	0.653	neutral	N	0.512230407	None	None	N
E/H	0.6801	likely_pathogenic	0.6414	pathogenic	-1.083	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
E/I	0.4811	ambiguous	0.4239	ambiguous	-0.261	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/K	0.5223	ambiguous	0.4066	ambiguous	-1.508	Destabilizing	0.994	D	0.571	neutral	N	0.447370852	None	None	N
E/L	0.6006	likely_pathogenic	0.555	ambiguous	-0.261	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
E/M	0.5944	likely_pathogenic	0.5335	ambiguous	0.467	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/N	0.5622	ambiguous	0.5688	pathogenic	-1.788	Destabilizing	0.998	D	0.65	neutral	None	None	None	None	N
E/P	0.9935	likely_pathogenic	0.9922	pathogenic	-0.652	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
E/Q	0.2245	likely_benign	0.1823	benign	-1.495	Destabilizing	0.998	D	0.668	neutral	N	0.443234469	None	None	N
E/R	0.6161	likely_pathogenic	0.5187	ambiguous	-1.319	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
E/S	0.3777	ambiguous	0.3398	benign	-2.46	Highly Destabilizing	0.992	D	0.55	neutral	None	None	None	None	N
E/T	0.3846	ambiguous	0.3361	benign	-2.061	Highly Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
E/V	0.3445	ambiguous	0.2843	benign	-0.652	Destabilizing	0.999	D	0.738	prob.delet.	N	0.426264861	None	None	N
E/W	0.9552	likely_pathogenic	0.9501	pathogenic	-1.046	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/Y	0.7759	likely_pathogenic	0.7785	pathogenic	-0.832	Destabilizing	1.0	D	0.773	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.