TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34981	105166;105167;105168	chr2:178531674;178531673;178531672	chr2:179396401;179396400;179396399
N2AB	33340	100243;100244;100245	chr2:178531674;178531673;178531672	chr2:179396401;179396400;179396399
N2A	32413	97462;97463;97464	chr2:178531674;178531673;178531672	chr2:179396401;179396400;179396399
N2B	25916	77971;77972;77973	chr2:178531674;178531673;178531672	chr2:179396401;179396400;179396399
Novex-1	26041	78346;78347;78348	chr2:178531674;178531673;178531672	chr2:179396401;179396400;179396399
Novex-2	26108	78547;78548;78549	chr2:178531674;178531673;178531672	chr2:179396401;179396400;179396399
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-163
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.2745
• 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/Q	None	None	0.509	N	0.233	0.129	0.250579442822	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	0	0	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	0.1853	likely_benign	0.2894	benign	-0.712	Destabilizing	0.826	D	0.337	neutral	N	0.507393095	None	None	N
E/C	0.9199	likely_pathogenic	0.9528	pathogenic	-0.519	Destabilizing	0.999	D	0.516	neutral	None	None	None	None	N
E/D	0.5505	ambiguous	0.6261	pathogenic	-0.764	Destabilizing	0.92	D	0.315	neutral	N	0.490095414	None	None	N
E/F	0.9309	likely_pathogenic	0.9638	pathogenic	-0.01	Destabilizing	0.982	D	0.481	neutral	None	None	None	None	N
E/G	0.575	likely_pathogenic	0.7071	pathogenic	-1.037	Destabilizing	0.959	D	0.426	neutral	N	0.49138123	None	None	N
E/H	0.8444	likely_pathogenic	0.9135	pathogenic	0.09	Stabilizing	0.991	D	0.372	neutral	None	None	None	None	N
E/I	0.5194	ambiguous	0.6838	pathogenic	0.167	Stabilizing	0.964	D	0.463	neutral	None	None	None	None	N
E/K	0.4224	ambiguous	0.6047	pathogenic	-0.348	Destabilizing	0.852	D	0.314	neutral	N	0.510932046	None	None	N
E/L	0.4795	ambiguous	0.6336	pathogenic	0.167	Stabilizing	0.046	N	0.343	neutral	None	None	None	None	N
E/M	0.5439	ambiguous	0.6851	pathogenic	0.313	Stabilizing	0.982	D	0.461	neutral	None	None	None	None	N
E/N	0.7068	likely_pathogenic	0.8156	pathogenic	-0.948	Destabilizing	0.991	D	0.353	neutral	None	None	None	None	N
E/P	0.4328	ambiguous	0.5769	pathogenic	-0.106	Destabilizing	0.046	N	0.239	neutral	None	None	None	None	N
E/Q	0.2531	likely_benign	0.3615	ambiguous	-0.818	Destabilizing	0.509	D	0.233	neutral	N	0.520418321	None	None	N
E/R	0.6346	likely_pathogenic	0.7737	pathogenic	0.1	Stabilizing	0.982	D	0.353	neutral	None	None	None	None	N
E/S	0.468	ambiguous	0.6182	pathogenic	-1.182	Destabilizing	0.884	D	0.276	neutral	None	None	None	None	N
E/T	0.4827	ambiguous	0.639	pathogenic	-0.907	Destabilizing	0.17	N	0.231	neutral	None	None	None	None	N
E/V	0.3326	likely_benign	0.4796	ambiguous	-0.106	Destabilizing	0.852	D	0.382	neutral	N	0.5102414	None	None	N
E/W	0.9857	likely_pathogenic	0.9932	pathogenic	0.3	Stabilizing	0.999	D	0.589	neutral	None	None	None	None	N
E/Y	0.909	likely_pathogenic	0.9527	pathogenic	0.254	Stabilizing	0.997	D	0.469	neutral	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.