TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16345	49258;49259;49260	chr2:178614481;178614480;178614479	chr2:179479208;179479207;179479206
N2AB	14704	44335;44336;44337	chr2:178614481;178614480;178614479	chr2:179479208;179479207;179479206
N2A	13777	41554;41555;41556	chr2:178614481;178614480;178614479	chr2:179479208;179479207;179479206
N2B	7280	22063;22064;22065	chr2:178614481;178614480;178614479	chr2:179479208;179479207;179479206
Novex-1	7405	22438;22439;22440	chr2:178614481;178614480;178614479	chr2:179479208;179479207;179479206
Novex-2	7472	22639;22640;22641	chr2:178614481;178614480;178614479	chr2:179479208;179479207;179479206
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: Ig-110
• Domain position: 84
• Structural Position: 173
• Q(SASA): 0.4419
• 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/K	None	None	0.978	N	0.534	0.408	0.415690173769	gnomAD-4.0.0	1.61337E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.46839E-05	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	0.3902	ambiguous	0.48	ambiguous	-0.695	Destabilizing	0.989	D	0.623	neutral	N	0.514970404	None	None	N
E/C	0.959	likely_pathogenic	0.9691	pathogenic	-0.114	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
E/D	0.19	likely_benign	0.2068	benign	-0.635	Destabilizing	0.054	N	0.187	neutral	N	0.481897111	None	None	N
E/F	0.9413	likely_pathogenic	0.9592	pathogenic	-0.43	Destabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	N
E/G	0.5359	ambiguous	0.6185	pathogenic	-0.961	Destabilizing	0.978	D	0.659	neutral	D	0.612106042	None	None	N
E/H	0.7808	likely_pathogenic	0.844	pathogenic	-0.497	Destabilizing	0.999	D	0.589	neutral	None	None	None	None	N
E/I	0.7424	likely_pathogenic	0.808	pathogenic	0.001	Stabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
E/K	0.5217	ambiguous	0.6468	pathogenic	0.135	Stabilizing	0.978	D	0.534	neutral	N	0.50495479	None	None	N
E/L	0.7688	likely_pathogenic	0.8375	pathogenic	0.001	Stabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	N
E/M	0.7528	likely_pathogenic	0.823	pathogenic	0.315	Stabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
E/N	0.4463	ambiguous	0.5239	ambiguous	-0.316	Destabilizing	0.983	D	0.575	neutral	None	None	None	None	N
E/P	0.8951	likely_pathogenic	0.9113	pathogenic	-0.21	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
E/Q	0.3262	likely_benign	0.4149	ambiguous	-0.255	Destabilizing	0.989	D	0.536	neutral	N	0.508418966	None	None	N
E/R	0.6983	likely_pathogenic	0.78	pathogenic	0.282	Stabilizing	0.998	D	0.595	neutral	None	None	None	None	N
E/S	0.4398	ambiguous	0.524	ambiguous	-0.505	Destabilizing	0.983	D	0.531	neutral	None	None	None	None	N
E/T	0.4455	ambiguous	0.5375	ambiguous	-0.279	Destabilizing	0.992	D	0.669	neutral	None	None	None	None	N
E/V	0.4936	ambiguous	0.5936	pathogenic	-0.21	Destabilizing	0.999	D	0.676	prob.neutral	N	0.518794202	None	None	N
E/W	0.9829	likely_pathogenic	0.9877	pathogenic	-0.193	Destabilizing	1.0	D	0.628	neutral	None	None	None	None	N
E/Y	0.8932	likely_pathogenic	0.9207	pathogenic	-0.157	Destabilizing	0.999	D	0.72	prob.delet.	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.