TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27611	83056;83057;83058	chr2:178563301;178563300;178563299	chr2:179428028;179428027;179428026
N2AB	25970	78133;78134;78135	chr2:178563301;178563300;178563299	chr2:179428028;179428027;179428026
N2A	25043	75352;75353;75354	chr2:178563301;178563300;178563299	chr2:179428028;179428027;179428026
N2B	18546	55861;55862;55863	chr2:178563301;178563300;178563299	chr2:179428028;179428027;179428026
Novex-1	18671	56236;56237;56238	chr2:178563301;178563300;178563299	chr2:179428028;179428027;179428026
Novex-2	18738	56437;56438;56439	chr2:178563301;178563300;178563299	chr2:179428028;179428027;179428026
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: Fn3-89
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.3341
• 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/D	None	None	0.001	N	0.229	0.053	0.276065633971	gnomAD-4.0.0	1.59159E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85878E-06	0	0
E/G	None	None	0.22	N	0.595	0.312	0.31077124679	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/Q	rs759363145	-0.366	0.331	N	0.524	0.137	0.243972157842	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/Q	rs759363145	-0.366	0.331	N	0.524	0.137	0.243972157842	gnomAD-4.0.0	3.18315E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71765E-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	0.1422	likely_benign	0.1377	benign	-0.915	Destabilizing	0.124	N	0.539	neutral	N	0.499069109	None	None	N
E/C	0.878	likely_pathogenic	0.873	pathogenic	-0.475	Destabilizing	0.968	D	0.731	prob.delet.	None	None	None	None	N
E/D	0.1502	likely_benign	0.1494	benign	-1.099	Destabilizing	0.001	N	0.229	neutral	N	0.468727559	None	None	N
E/F	0.855	likely_pathogenic	0.8462	pathogenic	-0.271	Destabilizing	0.567	D	0.722	prob.delet.	None	None	None	None	N
E/G	0.2384	likely_benign	0.197	benign	-1.289	Destabilizing	0.22	N	0.595	neutral	N	0.47325857	None	None	N
E/H	0.6105	likely_pathogenic	0.5872	pathogenic	-0.44	Destabilizing	0.909	D	0.547	neutral	None	None	None	None	N
E/I	0.4104	ambiguous	0.3955	ambiguous	0.112	Stabilizing	0.003	N	0.459	neutral	None	None	None	None	N
E/K	0.2201	likely_benign	0.1978	benign	-0.606	Destabilizing	0.001	N	0.265	neutral	N	0.473074586	None	None	N
E/L	0.3461	ambiguous	0.3406	ambiguous	0.112	Stabilizing	0.06	N	0.618	neutral	None	None	None	None	N
E/M	0.4525	ambiguous	0.4466	ambiguous	0.545	Stabilizing	0.832	D	0.681	prob.neutral	None	None	None	None	N
E/N	0.3118	likely_benign	0.3028	benign	-1.148	Destabilizing	0.567	D	0.513	neutral	None	None	None	None	N
E/P	0.3788	ambiguous	0.3615	ambiguous	-0.209	Destabilizing	0.726	D	0.643	neutral	None	None	None	None	N
E/Q	0.1888	likely_benign	0.1768	benign	-0.998	Destabilizing	0.331	N	0.524	neutral	N	0.472116027	None	None	N
E/R	0.3838	ambiguous	0.3467	ambiguous	-0.257	Destabilizing	0.396	N	0.525	neutral	None	None	None	None	N
E/S	0.2788	likely_benign	0.2635	benign	-1.454	Destabilizing	0.157	N	0.46	neutral	None	None	None	None	N
E/T	0.2877	likely_benign	0.2702	benign	-1.14	Destabilizing	0.272	N	0.558	neutral	None	None	None	None	N
E/V	0.2167	likely_benign	0.2055	benign	-0.209	Destabilizing	0.046	N	0.585	neutral	N	0.482475282	None	None	N
E/W	0.9445	likely_pathogenic	0.9395	pathogenic	0.021	Stabilizing	0.968	D	0.727	prob.delet.	None	None	None	None	N
E/Y	0.7638	likely_pathogenic	0.7476	pathogenic	-0.006	Destabilizing	0.726	D	0.708	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.