TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17890	53893;53894;53895	chr2:178605627;178605626;178605625	chr2:179470354;179470353;179470352
N2AB	16249	48970;48971;48972	chr2:178605627;178605626;178605625	chr2:179470354;179470353;179470352
N2A	15322	46189;46190;46191	chr2:178605627;178605626;178605625	chr2:179470354;179470353;179470352
N2B	8825	26698;26699;26700	chr2:178605627;178605626;178605625	chr2:179470354;179470353;179470352
Novex-1	8950	27073;27074;27075	chr2:178605627;178605626;178605625	chr2:179470354;179470353;179470352
Novex-2	9017	27274;27275;27276	chr2:178605627;178605626;178605625	chr2:179470354;179470353;179470352
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-18
• Domain position: 29
• Structural Position: 31
• Q(SASA): 0.4287
• 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	rs756643886	-0.773	0.978	N	0.815	0.377	0.328752806141	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	0	None	9.81E-05	None	0	0	0
G/D	rs756643886	-0.773	0.978	N	0.815	0.377	0.328752806141	gnomAD-4.0.0	7.53421E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00259E-07	1.04517E-04	1.65893E-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	0.9246	likely_pathogenic	0.9004	pathogenic	-0.334	Destabilizing	0.961	D	0.731	prob.delet.	N	0.475140993	None	None	I
G/C	0.9725	likely_pathogenic	0.9651	pathogenic	-0.832	Destabilizing	1.0	D	0.868	deleterious	D	0.528581612	None	None	I
G/D	0.9935	likely_pathogenic	0.9909	pathogenic	-0.663	Destabilizing	0.978	D	0.815	deleterious	N	0.487218087	None	None	I
G/E	0.9963	likely_pathogenic	0.9949	pathogenic	-0.827	Destabilizing	0.991	D	0.875	deleterious	None	None	None	None	I
G/F	0.9957	likely_pathogenic	0.9952	pathogenic	-1.104	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	I
G/H	0.9955	likely_pathogenic	0.9944	pathogenic	-0.628	Destabilizing	0.998	D	0.873	deleterious	None	None	None	None	I
G/I	0.9967	likely_pathogenic	0.996	pathogenic	-0.442	Destabilizing	0.999	D	0.884	deleterious	None	None	None	None	I
G/K	0.9965	likely_pathogenic	0.9959	pathogenic	-0.782	Destabilizing	0.983	D	0.879	deleterious	None	None	None	None	I
G/L	0.9942	likely_pathogenic	0.9938	pathogenic	-0.442	Destabilizing	0.991	D	0.879	deleterious	None	None	None	None	I
G/M	0.9976	likely_pathogenic	0.9972	pathogenic	-0.364	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
G/N	0.9899	likely_pathogenic	0.9876	pathogenic	-0.407	Destabilizing	0.193	N	0.663	neutral	None	None	None	None	I
G/P	0.9993	likely_pathogenic	0.9991	pathogenic	-0.372	Destabilizing	0.996	D	0.897	deleterious	None	None	None	None	I
G/Q	0.994	likely_pathogenic	0.9927	pathogenic	-0.722	Destabilizing	0.998	D	0.895	deleterious	None	None	None	None	I
G/R	0.986	likely_pathogenic	0.983	pathogenic	-0.326	Destabilizing	0.989	D	0.89	deleterious	N	0.47924237	None	None	I
G/S	0.9228	likely_pathogenic	0.8894	pathogenic	-0.557	Destabilizing	0.978	D	0.787	deleterious	N	0.474785372	None	None	I
G/T	0.99	likely_pathogenic	0.9856	pathogenic	-0.652	Destabilizing	0.991	D	0.865	deleterious	None	None	None	None	I
G/V	0.9944	likely_pathogenic	0.9925	pathogenic	-0.372	Destabilizing	0.994	D	0.881	deleterious	N	0.494094622	None	None	I
G/W	0.9916	likely_pathogenic	0.9905	pathogenic	-1.255	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	I
G/Y	0.9942	likely_pathogenic	0.9921	pathogenic	-0.894	Destabilizing	1.0	D	0.879	deleterious	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.