TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24606	74041;74042;74043	chr2:178572316;178572315;178572314	chr2:179437043;179437042;179437041
N2AB	22965	69118;69119;69120	chr2:178572316;178572315;178572314	chr2:179437043;179437042;179437041
N2A	22038	66337;66338;66339	chr2:178572316;178572315;178572314	chr2:179437043;179437042;179437041
N2B	15541	46846;46847;46848	chr2:178572316;178572315;178572314	chr2:179437043;179437042;179437041
Novex-1	15666	47221;47222;47223	chr2:178572316;178572315;178572314	chr2:179437043;179437042;179437041
Novex-2	15733	47422;47423;47424	chr2:178572316;178572315;178572314	chr2:179437043;179437042;179437041
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: Fn3-66
• Domain position: 88
• Structural Position: 122
• Q(SASA): 0.2212
• 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/Q	rs1466808448	-0.563	0.976	N	0.629	0.249	0.279370189704	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	6.50195E-04	None	0	None	0	0	0
E/Q	rs1466808448	-0.563	0.976	N	0.629	0.249	0.279370189704	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.93498E-04	None	0	0	0	0	0
E/Q	rs1466808448	-0.563	0.976	N	0.629	0.249	0.279370189704	gnomAD-4.0.0	6.57255E-06	None	None	None	None	N	None	0	0	None	0	1.93498E-04	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	0.3683	ambiguous	0.2267	benign	-0.683	Destabilizing	0.968	D	0.619	neutral	N	0.479910252	None	None	N
E/C	0.93	likely_pathogenic	0.8705	pathogenic	-0.447	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/D	0.3031	likely_benign	0.1874	benign	-0.993	Destabilizing	0.888	D	0.605	neutral	N	0.520574957	None	None	N
E/F	0.9093	likely_pathogenic	0.8007	pathogenic	0.132	Stabilizing	1.0	D	0.732	deleterious	None	None	None	None	N
E/G	0.5387	ambiguous	0.3217	benign	-1.068	Destabilizing	0.999	D	0.582	neutral	N	0.498320903	None	None	N
E/H	0.7974	likely_pathogenic	0.6195	pathogenic	-0.022	Destabilizing	1.0	D	0.61	neutral	None	None	None	None	N
E/I	0.572	likely_pathogenic	0.3999	ambiguous	0.374	Stabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
E/K	0.4778	ambiguous	0.2773	benign	-0.485	Destabilizing	0.429	N	0.369	neutral	N	0.470808899	None	None	N
E/L	0.6845	likely_pathogenic	0.5056	ambiguous	0.374	Stabilizing	0.996	D	0.675	prob.neutral	None	None	None	None	N
E/M	0.6651	likely_pathogenic	0.5104	ambiguous	0.673	Stabilizing	0.998	D	0.749	deleterious	None	None	None	None	N
E/N	0.6086	likely_pathogenic	0.3989	ambiguous	-1.089	Destabilizing	0.991	D	0.617	neutral	None	None	None	None	N
E/P	0.9019	likely_pathogenic	0.7739	pathogenic	0.043	Stabilizing	0.991	D	0.735	deleterious	None	None	None	None	N
E/Q	0.3037	likely_benign	0.2043	benign	-0.917	Destabilizing	0.976	D	0.629	neutral	N	0.480697174	None	None	N
E/R	0.6694	likely_pathogenic	0.4654	ambiguous	-0.106	Destabilizing	0.992	D	0.648	neutral	None	None	None	None	N
E/S	0.4535	ambiguous	0.2832	benign	-1.384	Destabilizing	0.976	D	0.633	neutral	None	None	None	None	N
E/T	0.4387	ambiguous	0.2778	benign	-1.057	Destabilizing	0.997	D	0.663	prob.neutral	None	None	None	None	N
E/V	0.36	ambiguous	0.2436	benign	0.043	Stabilizing	0.993	D	0.706	prob.delet.	N	0.478886748	None	None	N
E/W	0.9816	likely_pathogenic	0.9496	pathogenic	0.436	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/Y	0.8895	likely_pathogenic	0.7537	pathogenic	0.403	Stabilizing	1.0	D	0.763	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.