TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2688	8287;8288;8289	chr2:178771265;178771264;178771263	chr2:179635992;179635991;179635990
N2AB	2688	8287;8288;8289	chr2:178771265;178771264;178771263	chr2:179635992;179635991;179635990
N2A	2688	8287;8288;8289	chr2:178771265;178771264;178771263	chr2:179635992;179635991;179635990
N2B	2642	8149;8150;8151	chr2:178771265;178771264;178771263	chr2:179635992;179635991;179635990
Novex-1	2642	8149;8150;8151	chr2:178771265;178771264;178771263	chr2:179635992;179635991;179635990
Novex-2	2642	8149;8150;8151	chr2:178771265;178771264;178771263	chr2:179635992;179635991;179635990
Novex-3	2688	8287;8288;8289	chr2:178771265;178771264;178771263	chr2:179635992;179635991;179635990

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-16
• Domain position: 68
• Structural Position: 153
• Q(SASA): 0.5116
• 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/Q	rs748787636	-0.059	0.928	N	0.609	0.312	0.282575091529	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.81E-06	0
E/Q	rs748787636	-0.059	0.928	N	0.609	0.312	0.282575091529	gnomAD-4.0.0	1.5906E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85657E-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	0.2167	likely_benign	0.1995	benign	-0.925	Destabilizing	0.865	D	0.628	neutral	D	0.593428169	None	None	N
E/C	0.8869	likely_pathogenic	0.8624	pathogenic	-0.307	Destabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	N
E/D	0.1592	likely_benign	0.1588	benign	-1.023	Destabilizing	0.928	D	0.542	neutral	N	0.502704508	None	None	N
E/F	0.7451	likely_pathogenic	0.7136	pathogenic	-0.743	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
E/G	0.2998	likely_benign	0.2655	benign	-1.233	Destabilizing	0.978	D	0.689	prob.neutral	D	0.687819398	None	None	N
E/H	0.5237	ambiguous	0.4739	ambiguous	-0.991	Destabilizing	0.998	D	0.647	neutral	None	None	None	None	N
E/I	0.2971	likely_benign	0.2701	benign	-0.099	Destabilizing	0.992	D	0.742	deleterious	None	None	None	None	N
E/K	0.1849	likely_benign	0.1507	benign	-0.293	Destabilizing	0.039	N	0.338	neutral	N	0.501080274	None	None	N
E/L	0.4138	ambiguous	0.3796	ambiguous	-0.099	Destabilizing	0.983	D	0.737	prob.delet.	None	None	None	None	N
E/M	0.44	ambiguous	0.4078	ambiguous	0.428	Stabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	N
E/N	0.2423	likely_benign	0.2386	benign	-0.705	Destabilizing	0.983	D	0.658	neutral	None	None	None	None	N
E/P	0.8207	likely_pathogenic	0.7632	pathogenic	-0.354	Destabilizing	0.992	D	0.752	deleterious	None	None	None	None	N
E/Q	0.1796	likely_benign	0.1643	benign	-0.637	Destabilizing	0.928	D	0.609	neutral	N	0.511977624	None	None	N
E/R	0.342	ambiguous	0.2817	benign	-0.184	Destabilizing	0.968	D	0.653	neutral	None	None	None	None	N
E/S	0.2358	likely_benign	0.2296	benign	-0.986	Destabilizing	0.944	D	0.603	neutral	None	None	None	None	N
E/T	0.1932	likely_benign	0.1865	benign	-0.721	Destabilizing	0.983	D	0.727	prob.delet.	None	None	None	None	N
E/V	0.1997	likely_benign	0.1826	benign	-0.354	Destabilizing	0.978	D	0.745	deleterious	N	0.504868785	None	None	N
E/W	0.9119	likely_pathogenic	0.8857	pathogenic	-0.538	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
E/Y	0.6632	likely_pathogenic	0.6083	pathogenic	-0.477	Destabilizing	0.997	D	0.739	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.