TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16994	51205;51206;51207	chr2:178611149;178611148;178611147	chr2:179475876;179475875;179475874
N2AB	15353	46282;46283;46284	chr2:178611149;178611148;178611147	chr2:179475876;179475875;179475874
N2A	14426	43501;43502;43503	chr2:178611149;178611148;178611147	chr2:179475876;179475875;179475874
N2B	7929	24010;24011;24012	chr2:178611149;178611148;178611147	chr2:179475876;179475875;179475874
Novex-1	8054	24385;24386;24387	chr2:178611149;178611148;178611147	chr2:179475876;179475875;179475874
Novex-2	8121	24586;24587;24588	chr2:178611149;178611148;178611147	chr2:179475876;179475875;179475874
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-111
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.6504
• 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	rs1230487887	None	0.004	D	0.281	0.087	0.115124310173	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/D	rs1230487887	None	0.004	D	0.281	0.087	0.115124310173	gnomAD-4.0.0	6.57999E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47202E-05	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	0.1141	likely_benign	0.1104	benign	-0.495	Destabilizing	0.581	D	0.677	prob.neutral	N	0.511545165	None	None	N
E/C	0.8088	likely_pathogenic	0.8245	pathogenic	-0.243	Destabilizing	0.993	D	0.741	deleterious	None	None	None	None	N
E/D	0.1069	likely_benign	0.1077	benign	-0.403	Destabilizing	0.004	N	0.281	neutral	D	0.53426907	None	None	N
E/F	0.7049	likely_pathogenic	0.735	pathogenic	-0.303	Destabilizing	0.993	D	0.722	prob.delet.	None	None	None	None	N
E/G	0.1968	likely_benign	0.1912	benign	-0.711	Destabilizing	0.83	D	0.644	neutral	D	0.613595762	None	None	N
E/H	0.4789	ambiguous	0.5126	ambiguous	-0.079	Destabilizing	0.98	D	0.689	prob.neutral	None	None	None	None	N
E/I	0.236	likely_benign	0.2443	benign	0.05	Stabilizing	0.929	D	0.735	prob.delet.	None	None	None	None	N
E/K	0.174	likely_benign	0.2001	benign	-0.011	Destabilizing	0.581	D	0.623	neutral	D	0.554119919	None	None	N
E/L	0.3063	likely_benign	0.3105	benign	0.05	Stabilizing	0.929	D	0.731	prob.delet.	None	None	None	None	N
E/M	0.3635	ambiguous	0.3583	ambiguous	0.11	Stabilizing	0.993	D	0.704	prob.neutral	None	None	None	None	N
E/N	0.2073	likely_benign	0.2163	benign	-0.255	Destabilizing	0.764	D	0.695	prob.neutral	None	None	None	None	N
E/P	0.3176	likely_benign	0.2932	benign	-0.111	Destabilizing	0.929	D	0.739	prob.delet.	None	None	None	None	N
E/Q	0.1663	likely_benign	0.1746	benign	-0.215	Destabilizing	0.83	D	0.636	neutral	D	0.556879528	None	None	N
E/R	0.3294	likely_benign	0.3634	ambiguous	0.292	Stabilizing	0.866	D	0.718	prob.delet.	None	None	None	None	N
E/S	0.2097	likely_benign	0.2082	benign	-0.465	Destabilizing	0.48	N	0.647	neutral	None	None	None	None	N
E/T	0.1779	likely_benign	0.176	benign	-0.297	Destabilizing	0.866	D	0.708	prob.delet.	None	None	None	None	N
E/V	0.1383	likely_benign	0.1356	benign	-0.111	Destabilizing	0.908	D	0.717	prob.delet.	N	0.514027164	None	None	N
E/W	0.8848	likely_pathogenic	0.9001	pathogenic	-0.137	Destabilizing	0.993	D	0.749	deleterious	None	None	None	None	N
E/Y	0.5834	likely_pathogenic	0.6173	pathogenic	-0.072	Destabilizing	0.993	D	0.711	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.