TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6126	18601;18602;18603	chr2:178729877;178729876;178729875	chr2:179594604;179594603;179594602
N2AB	5809	17650;17651;17652	chr2:178729877;178729876;178729875	chr2:179594604;179594603;179594602
N2A	4882	14869;14870;14871	chr2:178729877;178729876;178729875	chr2:179594604;179594603;179594602
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-45
• Domain position: 22
• Structural Position: 31
• Q(SASA): 0.3382
• 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/A	rs1328808708	-0.906	0.822	N	0.513	0.418	0.534719010399	gnomAD-2.1.1	3.22E-05	None	None	None	None	N	None	0	2.32585E-04	None	0	0	None	0	None	0	0	0
E/A	rs1328808708	-0.906	0.822	N	0.513	0.418	0.534719010399	gnomAD-4.0.0	7.52765E-06	None	None	None	None	N	None	0	1.79083E-04	None	0	0	None	0	0	8.99528E-07	0	3.31444E-05
E/G	rs1328808708	None	0.822	N	0.629	0.591	0.634345301216	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	rs1328808708	None	0.822	N	0.629	0.591	0.634345301216	gnomAD-4.0.0	5.57816E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.62893E-06	0	0
E/Q	rs1332146833	-0.704	0.126	N	0.367	0.187	0.264081493735	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
E/Q	rs1332146833	-0.704	0.126	N	0.367	0.187	0.264081493735	gnomAD-4.0.0	3.18387E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71772E-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	0.1783	likely_benign	0.1876	benign	-0.736	Destabilizing	0.822	D	0.513	neutral	N	0.488721431	None	None	N
E/C	0.8703	likely_pathogenic	0.8904	pathogenic	-0.302	Destabilizing	0.998	D	0.665	neutral	None	None	None	None	N
E/D	0.234	likely_benign	0.2446	benign	-1.081	Destabilizing	0.014	N	0.399	neutral	D	0.52218919	None	None	N
E/F	0.7434	likely_pathogenic	0.7914	pathogenic	-0.481	Destabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
E/G	0.246	likely_benign	0.2767	benign	-1.064	Destabilizing	0.822	D	0.629	neutral	N	0.510650801	None	None	N
E/H	0.3911	ambiguous	0.4364	ambiguous	-0.806	Destabilizing	0.994	D	0.613	neutral	None	None	None	None	N
E/I	0.3486	ambiguous	0.379	ambiguous	0.144	Stabilizing	0.978	D	0.735	prob.delet.	None	None	None	None	N
E/K	0.1395	likely_benign	0.1544	benign	-0.383	Destabilizing	0.698	D	0.433	neutral	N	0.485238711	None	None	N
E/L	0.4095	ambiguous	0.4585	ambiguous	0.144	Stabilizing	0.956	D	0.707	prob.neutral	None	None	None	None	N
E/M	0.4692	ambiguous	0.5102	ambiguous	0.57	Stabilizing	0.998	D	0.701	prob.neutral	None	None	None	None	N
E/N	0.3375	likely_benign	0.3639	ambiguous	-0.755	Destabilizing	0.915	D	0.584	neutral	None	None	None	None	N
E/P	0.8361	likely_pathogenic	0.8415	pathogenic	-0.128	Destabilizing	0.978	D	0.714	prob.delet.	None	None	None	None	N
E/Q	0.105	likely_benign	0.1111	benign	-0.67	Destabilizing	0.126	N	0.367	neutral	N	0.514300425	None	None	N
E/R	0.2178	likely_benign	0.2502	benign	-0.246	Destabilizing	0.915	D	0.58	neutral	None	None	None	None	N
E/S	0.2115	likely_benign	0.2234	benign	-1.04	Destabilizing	0.86	D	0.465	neutral	None	None	None	None	N
E/T	0.2055	likely_benign	0.2157	benign	-0.77	Destabilizing	0.956	D	0.687	prob.neutral	None	None	None	None	N
E/V	0.2282	likely_benign	0.2413	benign	-0.128	Destabilizing	0.971	D	0.699	prob.neutral	N	0.498066728	None	None	N
E/W	0.8862	likely_pathogenic	0.9161	pathogenic	-0.314	Destabilizing	0.998	D	0.655	neutral	None	None	None	None	N
E/Y	0.6322	likely_pathogenic	0.6813	pathogenic	-0.234	Destabilizing	0.993	D	0.718	prob.delet.	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.