TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17379	52360;52361;52362	chr2:178608876;178608875;178608874	chr2:179473603;179473602;179473601
N2AB	15738	47437;47438;47439	chr2:178608876;178608875;178608874	chr2:179473603;179473602;179473601
N2A	14811	44656;44657;44658	chr2:178608876;178608875;178608874	chr2:179473603;179473602;179473601
N2B	8314	25165;25166;25167	chr2:178608876;178608875;178608874	chr2:179473603;179473602;179473601
Novex-1	8439	25540;25541;25542	chr2:178608876;178608875;178608874	chr2:179473603;179473602;179473601
Novex-2	8506	25741;25742;25743	chr2:178608876;178608875;178608874	chr2:179473603;179473602;179473601
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: Fn3-14
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.4565
• 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/G	rs1323809346	-1.062	0.939	N	0.604	0.467	0.404034981753	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	8.71E-05	None	0	0	None	0	None	0	0	0
E/G	rs1323809346	-1.062	0.939	N	0.604	0.467	0.404034981753	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
E/G	rs1323809346	-1.062	0.939	N	0.604	0.467	0.404034981753	gnomAD-4.0.0	3.8559E-06	None	None	None	None	N	None	0	5.09096E-05	None	0	0	None	0	0	0	0	0
E/Q	rs770795675	-0.275	0.991	N	0.561	0.274	0.256283259241	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	1.78E-05	0
E/Q	rs770795675	-0.275	0.991	N	0.561	0.274	0.256283259241	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/Q	rs770795675	-0.275	0.991	N	0.561	0.274	0.256283259241	gnomAD-4.0.0	1.67598E-05	None	None	None	None	N	None	2.67451E-05	0	None	0	0	None	0	0	2.12019E-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	0.3222	likely_benign	0.2762	benign	-0.528	Destabilizing	0.939	D	0.607	neutral	N	0.511227542	None	None	N
E/C	0.8949	likely_pathogenic	0.8757	pathogenic	-0.35	Destabilizing	0.999	D	0.738	prob.delet.	None	None	None	None	N
E/D	0.1893	likely_benign	0.1548	benign	-0.79	Destabilizing	0.02	N	0.14	neutral	N	0.454758184	None	None	N
E/F	0.9265	likely_pathogenic	0.897	pathogenic	0.029	Stabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
E/G	0.3396	likely_benign	0.2773	benign	-0.846	Destabilizing	0.939	D	0.604	neutral	N	0.493508573	None	None	N
E/H	0.6276	likely_pathogenic	0.5592	ambiguous	0.015	Stabilizing	0.999	D	0.573	neutral	None	None	None	None	N
E/I	0.6457	likely_pathogenic	0.5748	pathogenic	0.319	Stabilizing	0.993	D	0.761	deleterious	None	None	None	None	N
E/K	0.3269	likely_benign	0.2738	benign	-0.208	Destabilizing	0.939	D	0.503	neutral	N	0.486753172	None	None	N
E/L	0.671	likely_pathogenic	0.5958	pathogenic	0.319	Stabilizing	0.993	D	0.75	deleterious	None	None	None	None	N
E/M	0.6824	likely_pathogenic	0.6265	pathogenic	0.458	Stabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
E/N	0.4621	ambiguous	0.3808	ambiguous	-0.737	Destabilizing	0.973	D	0.584	neutral	None	None	None	None	N
E/P	0.9646	likely_pathogenic	0.9451	pathogenic	0.059	Stabilizing	0.993	D	0.723	prob.delet.	None	None	None	None	N
E/Q	0.2114	likely_benign	0.1856	benign	-0.612	Destabilizing	0.991	D	0.561	neutral	N	0.507803235	None	None	N
E/R	0.4912	ambiguous	0.4261	ambiguous	0.136	Stabilizing	0.993	D	0.619	neutral	None	None	None	None	N
E/S	0.2884	likely_benign	0.2485	benign	-0.943	Destabilizing	0.953	D	0.516	neutral	None	None	None	None	N
E/T	0.309	likely_benign	0.2749	benign	-0.68	Destabilizing	0.993	D	0.663	neutral	None	None	None	None	N
E/V	0.4253	ambiguous	0.366	ambiguous	0.059	Stabilizing	0.991	D	0.718	prob.delet.	N	0.474690739	None	None	N
E/W	0.949	likely_pathogenic	0.9332	pathogenic	0.272	Stabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
E/Y	0.8356	likely_pathogenic	0.7857	pathogenic	0.281	Stabilizing	0.999	D	0.722	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.