TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32787	98584;98585;98586	chr2:178539706;178539705;178539704	chr2:179404433;179404432;179404431
N2AB	31146	93661;93662;93663	chr2:178539706;178539705;178539704	chr2:179404433;179404432;179404431
N2A	30219	90880;90881;90882	chr2:178539706;178539705;178539704	chr2:179404433;179404432;179404431
N2B	23722	71389;71390;71391	chr2:178539706;178539705;178539704	chr2:179404433;179404432;179404431
Novex-1	23847	71764;71765;71766	chr2:178539706;178539705;178539704	chr2:179404433;179404432;179404431
Novex-2	23914	71965;71966;71967	chr2:178539706;178539705;178539704	chr2:179404433;179404432;179404431
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-155
• Domain position: 80
• Structural Position: 171
• Q(SASA): 0.7739
• 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
Y/C	rs1419941913	None	1.0	N	0.795	0.482	0.66614110018	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
Y/C	rs1419941913	None	1.0	N	0.795	0.482	0.66614110018	gnomAD-4.0.0	6.57082E-06	None	None	None	None	I	None	0	6.54536E-05	None	0	0	None	0	0	0	0	0
Y/F	None	None	0.999	N	0.581	0.465	0.568962582336	gnomAD-4.0.0	3.18253E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71608E-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
Y/A	0.3717	ambiguous	0.4484	ambiguous	-0.806	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
Y/C	0.1501	likely_benign	0.183	benign	0.025	Stabilizing	1.0	D	0.795	deleterious	N	0.505102152	None	None	I
Y/D	0.3784	ambiguous	0.4783	ambiguous	0.829	Stabilizing	1.0	D	0.776	deleterious	N	0.39256608	None	None	I
Y/E	0.6691	likely_pathogenic	0.7609	pathogenic	0.821	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
Y/F	0.1091	likely_benign	0.1128	benign	-0.355	Destabilizing	0.999	D	0.581	neutral	N	0.421870267	None	None	I
Y/G	0.349	ambiguous	0.4216	ambiguous	-1.013	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
Y/H	0.2102	likely_benign	0.2643	benign	0.119	Stabilizing	1.0	D	0.741	deleterious	N	0.451883742	None	None	I
Y/I	0.5117	ambiguous	0.5816	pathogenic	-0.272	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
Y/K	0.5678	likely_pathogenic	0.6751	pathogenic	0.085	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
Y/L	0.4725	ambiguous	0.5216	ambiguous	-0.272	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	I
Y/M	0.6036	likely_pathogenic	0.65	pathogenic	-0.142	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
Y/N	0.1715	likely_benign	0.218	benign	-0.111	Destabilizing	1.0	D	0.787	deleterious	N	0.419483322	None	None	I
Y/P	0.6995	likely_pathogenic	0.7497	pathogenic	-0.432	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
Y/Q	0.4819	ambiguous	0.5863	pathogenic	-0.058	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
Y/R	0.4096	ambiguous	0.5118	ambiguous	0.349	Stabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
Y/S	0.1636	likely_benign	0.2033	benign	-0.562	Destabilizing	1.0	D	0.783	deleterious	N	0.3755564	None	None	I
Y/T	0.3307	likely_benign	0.4032	ambiguous	-0.476	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
Y/V	0.3921	ambiguous	0.4544	ambiguous	-0.432	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
Y/W	0.5226	ambiguous	0.5606	ambiguous	-0.423	Destabilizing	1.0	D	0.714	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.