TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19843	59752;59753;59754	chr2:178592478;178592477;178592476	chr2:179457205;179457204;179457203
N2AB	18202	54829;54830;54831	chr2:178592478;178592477;178592476	chr2:179457205;179457204;179457203
N2A	17275	52048;52049;52050	chr2:178592478;178592477;178592476	chr2:179457205;179457204;179457203
N2B	10778	32557;32558;32559	chr2:178592478;178592477;178592476	chr2:179457205;179457204;179457203
Novex-1	10903	32932;32933;32934	chr2:178592478;178592477;178592476	chr2:179457205;179457204;179457203
Novex-2	10970	33133;33134;33135	chr2:178592478;178592477;178592476	chr2:179457205;179457204;179457203
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-119
• Domain position: 54
• Structural Position: 139
• Q(SASA): 0.2124
• 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/K	rs1185186867	-1.34	0.99	N	0.621	0.341	0.415055319159	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
E/K	rs1185186867	-1.34	0.99	N	0.621	0.341	0.415055319159	gnomAD-4.0.0	5.47452E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19664E-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	0.5016	ambiguous	0.461	ambiguous	-1.096	Destabilizing	0.98	D	0.641	neutral	N	0.483237248	None	None	N
E/C	0.9258	likely_pathogenic	0.9241	pathogenic	-0.78	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
E/D	0.4338	ambiguous	0.3846	ambiguous	-1.574	Destabilizing	0.997	D	0.595	neutral	N	0.493721407	None	None	N
E/F	0.8915	likely_pathogenic	0.878	pathogenic	-0.898	Destabilizing	0.991	D	0.768	deleterious	None	None	None	None	N
E/G	0.695	likely_pathogenic	0.6713	pathogenic	-1.47	Destabilizing	0.999	D	0.729	prob.delet.	N	0.498494347	None	None	N
E/H	0.7375	likely_pathogenic	0.7322	pathogenic	-1.171	Destabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	N
E/I	0.5141	ambiguous	0.4998	ambiguous	-0.06	Destabilizing	0.991	D	0.741	deleterious	None	None	None	None	N
E/K	0.6349	likely_pathogenic	0.6366	pathogenic	-1.069	Destabilizing	0.99	D	0.621	neutral	N	0.48874862	None	None	N
E/L	0.6856	likely_pathogenic	0.6634	pathogenic	-0.06	Destabilizing	0.971	D	0.694	prob.neutral	None	None	None	None	N
E/M	0.6822	likely_pathogenic	0.6761	pathogenic	0.464	Stabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
E/N	0.735	likely_pathogenic	0.6953	pathogenic	-1.344	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
E/P	0.9951	likely_pathogenic	0.9964	pathogenic	-0.385	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
E/Q	0.3148	likely_benign	0.2996	benign	-1.197	Destabilizing	0.999	D	0.671	neutral	N	0.481457288	None	None	N
E/R	0.6868	likely_pathogenic	0.706	pathogenic	-0.94	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
E/S	0.5835	likely_pathogenic	0.5446	ambiguous	-1.848	Destabilizing	0.993	D	0.622	neutral	None	None	None	None	N
E/T	0.4983	ambiguous	0.4787	ambiguous	-1.516	Destabilizing	0.985	D	0.703	prob.neutral	None	None	None	None	N
E/V	0.3187	likely_benign	0.3043	benign	-0.385	Destabilizing	0.4	N	0.531	neutral	N	0.473856525	None	None	N
E/W	0.95	likely_pathogenic	0.9503	pathogenic	-0.851	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/Y	0.8587	likely_pathogenic	0.8469	pathogenic	-0.667	Destabilizing	0.671	D	0.521	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.