TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3096	9511;9512;9513	chr2:178768033;178768032;178768031	chr2:179632760;179632759;179632758
N2AB	3096	9511;9512;9513	chr2:178768033;178768032;178768031	chr2:179632760;179632759;179632758
N2A	3096	9511;9512;9513	chr2:178768033;178768032;178768031	chr2:179632760;179632759;179632758
N2B	3050	9373;9374;9375	chr2:178768033;178768032;178768031	chr2:179632760;179632759;179632758
Novex-1	3050	9373;9374;9375	chr2:178768033;178768032;178768031	chr2:179632760;179632759;179632758
Novex-2	3050	9373;9374;9375	chr2:178768033;178768032;178768031	chr2:179632760;179632759;179632758
Novex-3	3096	9511;9512;9513	chr2:178768033;178768032;178768031	chr2:179632760;179632759;179632758

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-21
• Domain position: 39
• Structural Position: 56
• Q(SASA): 0.6973
• 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	None	None	0.822	N	0.548	0.508	0.489938136499	gnomAD-4.0.0	1.36815E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79859E-06	0	0
E/D	None	None	0.822	N	0.516	0.131	0.262662153117	gnomAD-4.0.0	1.59054E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.0217E-05
E/V	rs772499668	0.095	0.942	D	0.55	0.497	0.621312436561	gnomAD-2.1.1	7.96E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.53E-05	None	0	0	0
E/V	rs772499668	0.095	0.942	D	0.55	0.497	0.621312436561	gnomAD-4.0.0	4.78853E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.95588E-05	1.65579E-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	0.3295	likely_benign	0.2545	benign	-0.437	Destabilizing	0.822	D	0.548	neutral	N	0.511545165	None	None	N
E/C	0.9608	likely_pathogenic	0.9423	pathogenic	-0.23	Destabilizing	0.998	D	0.692	prob.neutral	None	None	None	None	N
E/D	0.3797	ambiguous	0.2884	benign	-0.471	Destabilizing	0.822	D	0.516	neutral	N	0.503957792	None	None	N
E/F	0.8977	likely_pathogenic	0.8701	pathogenic	-0.204	Destabilizing	0.915	D	0.689	prob.neutral	None	None	None	None	N
E/G	0.5114	ambiguous	0.4165	ambiguous	-0.671	Destabilizing	0.971	D	0.549	neutral	D	0.692499475	None	None	N
E/H	0.8309	likely_pathogenic	0.7637	pathogenic	-0.064	Destabilizing	0.956	D	0.549	neutral	None	None	None	None	N
E/I	0.4901	ambiguous	0.4025	ambiguous	0.157	Stabilizing	0.956	D	0.685	prob.neutral	None	None	None	None	N
E/K	0.4604	ambiguous	0.3702	ambiguous	-0.004	Destabilizing	0.698	D	0.545	neutral	N	0.510101189	None	None	N
E/L	0.5662	likely_pathogenic	0.4945	ambiguous	0.157	Stabilizing	0.915	D	0.593	neutral	None	None	None	None	N
E/M	0.6237	likely_pathogenic	0.5551	ambiguous	0.207	Stabilizing	0.998	D	0.637	neutral	None	None	None	None	N
E/N	0.6316	likely_pathogenic	0.5126	ambiguous	-0.293	Destabilizing	0.978	D	0.535	neutral	None	None	None	None	N
E/P	0.5144	ambiguous	0.4286	ambiguous	-0.02	Destabilizing	0.993	D	0.613	neutral	None	None	None	None	N
E/Q	0.327	likely_benign	0.2679	benign	-0.236	Destabilizing	0.294	N	0.301	neutral	D	0.550364197	None	None	N
E/R	0.6606	likely_pathogenic	0.5722	pathogenic	0.276	Stabilizing	0.956	D	0.533	neutral	None	None	None	None	N
E/S	0.5575	ambiguous	0.4374	ambiguous	-0.488	Destabilizing	0.86	D	0.533	neutral	None	None	None	None	N
E/T	0.5144	ambiguous	0.4147	ambiguous	-0.304	Destabilizing	0.978	D	0.552	neutral	None	None	None	None	N
E/V	0.3245	likely_benign	0.2596	benign	-0.02	Destabilizing	0.942	D	0.55	neutral	D	0.541029134	None	None	N
E/W	0.9794	likely_pathogenic	0.9725	pathogenic	-0.04	Destabilizing	0.994	D	0.677	prob.neutral	None	None	None	None	N
E/Y	0.8596	likely_pathogenic	0.8241	pathogenic	0.027	Stabilizing	0.043	N	0.333	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.