TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32146	96661;96662;96663	chr2:178543537;178543536;178543535	chr2:179408264;179408263;179408262
N2AB	30505	91738;91739;91740	chr2:178543537;178543536;178543535	chr2:179408264;179408263;179408262
N2A	29578	88957;88958;88959	chr2:178543537;178543536;178543535	chr2:179408264;179408263;179408262
N2B	23081	69466;69467;69468	chr2:178543537;178543536;178543535	chr2:179408264;179408263;179408262
Novex-1	23206	69841;69842;69843	chr2:178543537;178543536;178543535	chr2:179408264;179408263;179408262
Novex-2	23273	70042;70043;70044	chr2:178543537;178543536;178543535	chr2:179408264;179408263;179408262
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: Fn3-122
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.2162
• 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/V	rs1455005015	-0.061	1.0	N	0.801	0.55	0.528260413467	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/V	rs1455005015	-0.061	1.0	N	0.801	0.55	0.528260413467	gnomAD-4.0.0	1.59367E-06	None	None	None	None	N	None	0	2.28728E-05	None	0	0	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	0.5377	ambiguous	0.5581	ambiguous	-0.817	Destabilizing	0.999	D	0.619	neutral	N	0.46977585	None	None	N
E/C	0.9805	likely_pathogenic	0.9811	pathogenic	-0.538	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/D	0.2809	likely_benign	0.2949	benign	-1.342	Destabilizing	0.203	N	0.194	neutral	N	0.462262947	None	None	N
E/F	0.9806	likely_pathogenic	0.9813	pathogenic	-0.133	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
E/G	0.6765	likely_pathogenic	0.6737	pathogenic	-1.227	Destabilizing	1.0	D	0.714	prob.delet.	N	0.480335688	None	None	N
E/H	0.9119	likely_pathogenic	0.9199	pathogenic	-0.482	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/I	0.8718	likely_pathogenic	0.887	pathogenic	0.317	Stabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
E/K	0.7147	likely_pathogenic	0.7332	pathogenic	-0.915	Destabilizing	1.0	D	0.523	neutral	N	0.50970739	None	None	N
E/L	0.835	likely_pathogenic	0.8417	pathogenic	0.317	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
E/M	0.8774	likely_pathogenic	0.886	pathogenic	0.805	Stabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/N	0.7444	likely_pathogenic	0.7524	pathogenic	-1.391	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
E/P	0.811	likely_pathogenic	0.8291	pathogenic	-0.039	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
E/Q	0.4934	ambiguous	0.5207	ambiguous	-1.205	Destabilizing	1.0	D	0.635	neutral	N	0.469153512	None	None	N
E/R	0.8351	likely_pathogenic	0.8476	pathogenic	-0.592	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/S	0.695	likely_pathogenic	0.7047	pathogenic	-1.759	Destabilizing	0.999	D	0.567	neutral	None	None	None	None	N
E/T	0.7616	likely_pathogenic	0.7861	pathogenic	-1.419	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/V	0.6899	likely_pathogenic	0.7155	pathogenic	-0.039	Destabilizing	1.0	D	0.801	deleterious	N	0.493667003	None	None	N
E/W	0.9924	likely_pathogenic	0.9929	pathogenic	0.078	Stabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
E/Y	0.9632	likely_pathogenic	0.9655	pathogenic	0.098	Stabilizing	1.0	D	0.818	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.