TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27608	83047;83048;83049	chr2:178563310;178563309;178563308	chr2:179428037;179428036;179428035
N2AB	25967	78124;78125;78126	chr2:178563310;178563309;178563308	chr2:179428037;179428036;179428035
N2A	25040	75343;75344;75345	chr2:178563310;178563309;178563308	chr2:179428037;179428036;179428035
N2B	18543	55852;55853;55854	chr2:178563310;178563309;178563308	chr2:179428037;179428036;179428035
Novex-1	18668	56227;56228;56229	chr2:178563310;178563309;178563308	chr2:179428037;179428036;179428035
Novex-2	18735	56428;56429;56430	chr2:178563310;178563309;178563308	chr2:179428037;179428036;179428035
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-89
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1758
• 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	0.999	N	0.653	0.345	0.30921473904	gnomAD-4.0.0	1.59162E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85881E-06	0	0
E/Q	None	None	1.0	N	0.743	0.342	0.27479166964	gnomAD-4.0.0	3.18322E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71755E-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	0.5104	ambiguous	0.5048	ambiguous	-2.118	Highly Destabilizing	0.999	D	0.697	prob.neutral	D	0.531241411	None	None	N
E/C	0.9627	likely_pathogenic	0.9631	pathogenic	-1.302	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/D	0.7	likely_pathogenic	0.7039	pathogenic	-1.694	Destabilizing	0.999	D	0.653	neutral	N	0.491500956	None	None	N
E/F	0.9606	likely_pathogenic	0.9595	pathogenic	-1.848	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/G	0.7819	likely_pathogenic	0.7841	pathogenic	-2.495	Highly Destabilizing	1.0	D	0.773	deleterious	D	0.533015838	None	None	N
E/H	0.8844	likely_pathogenic	0.8833	pathogenic	-1.769	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
E/I	0.9125	likely_pathogenic	0.8956	pathogenic	-1.028	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
E/K	0.8162	likely_pathogenic	0.8035	pathogenic	-2.127	Highly Destabilizing	0.999	D	0.689	prob.neutral	N	0.503475918	None	None	N
E/L	0.8842	likely_pathogenic	0.8802	pathogenic	-1.028	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/M	0.8104	likely_pathogenic	0.7967	pathogenic	-0.215	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
E/N	0.9072	likely_pathogenic	0.9065	pathogenic	-2.223	Highly Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/P	0.9995	likely_pathogenic	0.9991	pathogenic	-1.38	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/Q	0.2943	likely_benign	0.2965	benign	-1.933	Destabilizing	1.0	D	0.743	deleterious	N	0.515190567	None	None	N
E/R	0.8497	likely_pathogenic	0.8462	pathogenic	-1.867	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/S	0.6371	likely_pathogenic	0.6239	pathogenic	-2.953	Highly Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
E/T	0.7935	likely_pathogenic	0.7721	pathogenic	-2.599	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/V	0.7772	likely_pathogenic	0.7505	pathogenic	-1.38	Destabilizing	1.0	D	0.781	deleterious	N	0.513897625	None	None	N
E/W	0.9866	likely_pathogenic	0.9865	pathogenic	-1.896	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
E/Y	0.9505	likely_pathogenic	0.947	pathogenic	-1.707	Destabilizing	1.0	D	0.805	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.