TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26458	79597;79598;79599	chr2:178566760;178566759;178566758	chr2:179431487;179431486;179431485
N2AB	24817	74674;74675;74676	chr2:178566760;178566759;178566758	chr2:179431487;179431486;179431485
N2A	23890	71893;71894;71895	chr2:178566760;178566759;178566758	chr2:179431487;179431486;179431485
N2B	17393	52402;52403;52404	chr2:178566760;178566759;178566758	chr2:179431487;179431486;179431485
Novex-1	17518	52777;52778;52779	chr2:178566760;178566759;178566758	chr2:179431487;179431486;179431485
Novex-2	17585	52978;52979;52980	chr2:178566760;178566759;178566758	chr2:179431487;179431486;179431485
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: Fn3-80
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.1505
• 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/D	rs1162274016	-1.475	0.958	N	0.598	0.303	0.210429274316	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
E/D	rs1162274016	-1.475	0.958	N	0.598	0.303	0.210429274316	gnomAD-4.0.0	1.59216E-06	None	None	None	None	N	None	0	0	None	0	2.77546E-05	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	0.5652	likely_pathogenic	0.5219	ambiguous	-0.782	Destabilizing	0.958	D	0.631	neutral	N	0.497110043	None	None	N
E/C	0.9412	likely_pathogenic	0.9332	pathogenic	-0.065	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/D	0.8688	likely_pathogenic	0.8641	pathogenic	-1.566	Destabilizing	0.958	D	0.598	neutral	N	0.506593471	None	None	N
E/F	0.9741	likely_pathogenic	0.9738	pathogenic	-0.454	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
E/G	0.8288	likely_pathogenic	0.7886	pathogenic	-1.193	Destabilizing	0.988	D	0.719	prob.delet.	D	0.533345006	None	None	N
E/H	0.9309	likely_pathogenic	0.9278	pathogenic	-0.408	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
E/I	0.8487	likely_pathogenic	0.8606	pathogenic	0.393	Stabilizing	0.995	D	0.834	deleterious	None	None	None	None	N
E/K	0.8611	likely_pathogenic	0.8648	pathogenic	-0.782	Destabilizing	0.919	D	0.603	neutral	N	0.478067509	None	None	N
E/L	0.9179	likely_pathogenic	0.9279	pathogenic	0.393	Stabilizing	0.991	D	0.754	deleterious	None	None	None	None	N
E/M	0.8199	likely_pathogenic	0.8127	pathogenic	1.016	Stabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
E/N	0.9251	likely_pathogenic	0.9191	pathogenic	-1.16	Destabilizing	0.991	D	0.735	prob.delet.	None	None	None	None	N
E/P	0.9991	likely_pathogenic	0.9992	pathogenic	0.017	Stabilizing	0.995	D	0.76	deleterious	None	None	None	None	N
E/Q	0.3031	likely_benign	0.2991	benign	-0.798	Destabilizing	0.414	N	0.389	neutral	N	0.511382258	None	None	N
E/R	0.8927	likely_pathogenic	0.8956	pathogenic	-0.806	Destabilizing	0.982	D	0.737	prob.delet.	None	None	None	None	N
E/S	0.6901	likely_pathogenic	0.6333	pathogenic	-1.711	Destabilizing	0.968	D	0.635	neutral	None	None	None	None	N
E/T	0.8231	likely_pathogenic	0.8206	pathogenic	-1.311	Destabilizing	0.991	D	0.737	prob.delet.	None	None	None	None	N
E/V	0.74	likely_pathogenic	0.7501	pathogenic	0.017	Stabilizing	0.988	D	0.736	prob.delet.	N	0.48473978	None	None	N
E/W	0.9961	likely_pathogenic	0.9959	pathogenic	-0.655	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
E/Y	0.9682	likely_pathogenic	0.9662	pathogenic	-0.275	Destabilizing	0.998	D	0.801	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.