TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21004	63235;63236;63237	chr2:178588715;178588714;178588713	chr2:179453442;179453441;179453440
N2AB	19363	58312;58313;58314	chr2:178588715;178588714;178588713	chr2:179453442;179453441;179453440
N2A	18436	55531;55532;55533	chr2:178588715;178588714;178588713	chr2:179453442;179453441;179453440
N2B	11939	36040;36041;36042	chr2:178588715;178588714;178588713	chr2:179453442;179453441;179453440
Novex-1	12064	36415;36416;36417	chr2:178588715;178588714;178588713	chr2:179453442;179453441;179453440
Novex-2	12131	36616;36617;36618	chr2:178588715;178588714;178588713	chr2:179453442;179453441;179453440
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: Fn3-40
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.3278
• 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/G	None	None	0.014	N	0.329	0.292	0.413113201963	gnomAD-4.0.0	1.59233E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85997E-06	0	0
E/K	rs769345390	-0.8	0.822	N	0.499	0.338	0.444807159249	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.6E-05	None	0	None	0	0	0
E/K	rs769345390	-0.8	0.822	N	0.499	0.338	0.444807159249	gnomAD-4.0.0	1.59237E-06	None	None	None	None	N	None	0	0	None	0	2.77994E-05	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	0.6854	likely_pathogenic	0.6769	pathogenic	-0.848	Destabilizing	0.698	D	0.458	neutral	N	0.485905095	None	None	N
E/C	0.9823	likely_pathogenic	0.981	pathogenic	-0.616	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
E/D	0.4185	ambiguous	0.4293	ambiguous	-1.384	Destabilizing	0.822	D	0.377	neutral	N	0.496202162	None	None	N
E/F	0.9823	likely_pathogenic	0.9839	pathogenic	-0.237	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
E/G	0.6153	likely_pathogenic	0.6325	pathogenic	-1.253	Destabilizing	0.014	N	0.329	neutral	N	0.488235726	None	None	N
E/H	0.9498	likely_pathogenic	0.9471	pathogenic	-0.723	Destabilizing	0.998	D	0.657	neutral	None	None	None	None	N
E/I	0.9006	likely_pathogenic	0.9028	pathogenic	0.274	Stabilizing	0.978	D	0.785	deleterious	None	None	None	None	N
E/K	0.8131	likely_pathogenic	0.8336	pathogenic	-1.231	Destabilizing	0.822	D	0.499	neutral	N	0.503781495	None	None	N
E/L	0.8732	likely_pathogenic	0.8725	pathogenic	0.274	Stabilizing	0.978	D	0.771	deleterious	None	None	None	None	N
E/M	0.8833	likely_pathogenic	0.8935	pathogenic	0.819	Stabilizing	0.998	D	0.701	prob.neutral	None	None	None	None	N
E/N	0.8333	likely_pathogenic	0.8334	pathogenic	-1.592	Destabilizing	0.956	D	0.64	neutral	None	None	None	None	N
E/P	0.9463	likely_pathogenic	0.9371	pathogenic	-0.079	Destabilizing	0.993	D	0.75	deleterious	None	None	None	None	N
E/Q	0.5406	ambiguous	0.544	ambiguous	-1.372	Destabilizing	0.99	D	0.622	neutral	N	0.474749373	None	None	N
E/R	0.8775	likely_pathogenic	0.8853	pathogenic	-0.95	Destabilizing	0.978	D	0.695	prob.neutral	None	None	None	None	N
E/S	0.809	likely_pathogenic	0.8023	pathogenic	-1.963	Destabilizing	0.86	D	0.514	neutral	None	None	None	None	N
E/T	0.8647	likely_pathogenic	0.8671	pathogenic	-1.634	Destabilizing	0.978	D	0.65	neutral	None	None	None	None	N
E/V	0.7723	likely_pathogenic	0.7852	pathogenic	-0.079	Destabilizing	0.971	D	0.741	deleterious	N	0.489716984	None	None	N
E/W	0.9914	likely_pathogenic	0.9921	pathogenic	-0.104	Destabilizing	0.998	D	0.734	prob.delet.	None	None	None	None	N
E/Y	0.9674	likely_pathogenic	0.9687	pathogenic	-0.067	Destabilizing	0.993	D	0.737	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.