TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19954	60085;60086;60087	chr2:178592044;178592043;178592042	chr2:179456771;179456770;179456769
N2AB	18313	55162;55163;55164	chr2:178592044;178592043;178592042	chr2:179456771;179456770;179456769
N2A	17386	52381;52382;52383	chr2:178592044;178592043;178592042	chr2:179456771;179456770;179456769
N2B	10889	32890;32891;32892	chr2:178592044;178592043;178592042	chr2:179456771;179456770;179456769
Novex-1	11014	33265;33266;33267	chr2:178592044;178592043;178592042	chr2:179456771;179456770;179456769
Novex-2	11081	33466;33467;33468	chr2:178592044;178592043;178592042	chr2:179456771;179456770;179456769
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: Fn3-32
• Domain position: 78
• Structural Position: 111
• Q(SASA): 0.3519
• 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
E/V	rs774004055	0.484	0.999	N	0.777	0.475	0.441636318388	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
E/V	rs774004055	0.484	0.999	N	0.777	0.475	0.441636318388	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.6328	likely_pathogenic	0.6108	pathogenic	-0.31	Destabilizing	0.996	D	0.545	neutral	N	0.472138799	None	None	I
E/C	0.9533	likely_pathogenic	0.9466	pathogenic	-0.507	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
E/D	0.8571	likely_pathogenic	0.8383	pathogenic	-1.268	Destabilizing	0.998	D	0.389	neutral	N	0.50263977	None	None	I
E/F	0.9739	likely_pathogenic	0.968	pathogenic	-1.036	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
E/G	0.8055	likely_pathogenic	0.7971	pathogenic	-0.577	Destabilizing	0.999	D	0.727	prob.delet.	N	0.497866831	None	None	I
E/H	0.9344	likely_pathogenic	0.9143	pathogenic	-1.187	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	I
E/I	0.7224	likely_pathogenic	0.6928	pathogenic	0.382	Stabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
E/K	0.6689	likely_pathogenic	0.6283	pathogenic	-0.65	Destabilizing	0.767	D	0.314	neutral	N	0.473152757	None	None	I
E/L	0.9119	likely_pathogenic	0.8881	pathogenic	0.382	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
E/M	0.8327	likely_pathogenic	0.8038	pathogenic	0.683	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
E/N	0.9137	likely_pathogenic	0.9022	pathogenic	-0.79	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	I
E/P	0.9991	likely_pathogenic	0.9989	pathogenic	0.173	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
E/Q	0.3356	likely_benign	0.297	benign	-0.636	Destabilizing	0.996	D	0.548	neutral	N	0.473379793	None	None	I
E/R	0.7894	likely_pathogenic	0.7563	pathogenic	-0.806	Destabilizing	0.998	D	0.636	neutral	None	None	None	None	I
E/S	0.7359	likely_pathogenic	0.7063	pathogenic	-1.189	Destabilizing	0.997	D	0.472	neutral	None	None	None	None	I
E/T	0.7314	likely_pathogenic	0.7089	pathogenic	-0.94	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
E/V	0.4732	ambiguous	0.4339	ambiguous	0.173	Stabilizing	0.999	D	0.777	deleterious	N	0.466081538	None	None	I
E/W	0.9921	likely_pathogenic	0.9902	pathogenic	-1.464	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
E/Y	0.9669	likely_pathogenic	0.9606	pathogenic	-0.93	Destabilizing	1.0	D	0.805	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.