TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5662	17209;17210;17211	chr2:178731891;178731890;178731889	chr2:179596618;179596617;179596616
N2AB	5345	16258;16259;16260	chr2:178731891;178731890;178731889	chr2:179596618;179596617;179596616
N2A	4418	13477;13478;13479	chr2:178731891;178731890;178731889	chr2:179596618;179596617;179596616
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-40
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.4061
• Predicted PPI site: I

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
G/D	rs760089168	-0.682	1.0	D	0.799	0.536	0.655917873618	gnomAD-2.1.1	2.14E-05	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	3.13E-05	0
G/D	rs760089168	-0.682	1.0	D	0.799	0.536	0.655917873618	gnomAD-3.1.2	3.29E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	5.88E-05	2.07211E-04	0
G/D	rs760089168	-0.682	1.0	D	0.799	0.536	0.655917873618	gnomAD-4.0.0	2.47895E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	3.29164E-04	2.62773E-05	3.29402E-05	6.40512E-05

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
G/A	0.6864	likely_pathogenic	0.6799	pathogenic	-0.507	Destabilizing	1.0	D	0.759	deleterious	D	0.557660836	None	None	I
G/C	0.9585	likely_pathogenic	0.9621	pathogenic	-0.462	Destabilizing	1.0	D	0.703	prob.neutral	D	0.620041688	None	None	I
G/D	0.9851	likely_pathogenic	0.9875	pathogenic	-1.033	Destabilizing	1.0	D	0.799	deleterious	D	0.586559976	None	None	I
G/E	0.9852	likely_pathogenic	0.9887	pathogenic	-1.046	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
G/F	0.9941	likely_pathogenic	0.9955	pathogenic	-0.822	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
G/H	0.9959	likely_pathogenic	0.9975	pathogenic	-1.05	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
G/I	0.9862	likely_pathogenic	0.9902	pathogenic	-0.111	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
G/K	0.9943	likely_pathogenic	0.9961	pathogenic	-0.947	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
G/L	0.9886	likely_pathogenic	0.9909	pathogenic	-0.111	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
G/M	0.9923	likely_pathogenic	0.9943	pathogenic	-0.223	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
G/N	0.9894	likely_pathogenic	0.9926	pathogenic	-0.632	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
G/P	0.9969	likely_pathogenic	0.9978	pathogenic	-0.205	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
G/Q	0.9903	likely_pathogenic	0.993	pathogenic	-0.749	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
G/R	0.9825	likely_pathogenic	0.9864	pathogenic	-0.71	Destabilizing	1.0	D	0.788	deleterious	D	0.594099968	None	None	I
G/S	0.7724	likely_pathogenic	0.8164	pathogenic	-0.83	Destabilizing	1.0	D	0.812	deleterious	D	0.545668637	None	None	I
G/T	0.9585	likely_pathogenic	0.9696	pathogenic	-0.762	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
G/V	0.9634	likely_pathogenic	0.9714	pathogenic	-0.205	Destabilizing	1.0	D	0.751	deleterious	D	0.61963808	None	None	I
G/W	0.9912	likely_pathogenic	0.9942	pathogenic	-1.238	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
G/Y	0.9938	likely_pathogenic	0.9958	pathogenic	-0.757	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I

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.