TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20068	60427;60428;60429	chr2:178591617;178591616;178591615	chr2:179456344;179456343;179456342
N2AB	18427	55504;55505;55506	chr2:178591617;178591616;178591615	chr2:179456344;179456343;179456342
N2A	17500	52723;52724;52725	chr2:178591617;178591616;178591615	chr2:179456344;179456343;179456342
N2B	11003	33232;33233;33234	chr2:178591617;178591616;178591615	chr2:179456344;179456343;179456342
Novex-1	11128	33607;33608;33609	chr2:178591617;178591616;178591615	chr2:179456344;179456343;179456342
Novex-2	11195	33808;33809;33810	chr2:178591617;178591616;178591615	chr2:179456344;179456343;179456342
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: Fn3-33
• Domain position: 92
• Structural Position: 129
• Q(SASA): 0.5391
• 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	rs774629592	-0.297	0.971	N	0.451	0.164	0.267299060538	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
E/D	rs774629592	-0.297	0.971	N	0.451	0.164	0.267299060538	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs774629592	-0.297	0.971	N	0.451	0.164	0.267299060538	gnomAD-4.0.0	6.57471E-06	None	None	None	None	N	None	2.41278E-05	0	None	0	0	None	0	0	0	0	0
E/K	rs759291854	0.469	0.971	N	0.427	0.276	0.28722502521	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.31E-05	None	0	0	0
E/K	rs759291854	0.469	0.971	N	0.427	0.276	0.28722502521	gnomAD-4.0.0	2.05446E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79957E-06	1.16705E-05	0
E/Q	rs759291854	0.059	0.971	N	0.511	0.243	0.329282125956	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
E/Q	rs759291854	0.059	0.971	N	0.511	0.243	0.329282125956	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
E/Q	rs759291854	0.059	0.971	N	0.511	0.243	0.329282125956	gnomAD-4.0.0	2.6303E-05	None	None	None	None	N	None	9.65298E-05	0	None	0	0	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	0.1251	likely_benign	0.1411	benign	-0.609	Destabilizing	0.817	D	0.461	neutral	N	0.37012915	None	None	N
E/C	0.7953	likely_pathogenic	0.8534	pathogenic	-0.079	Destabilizing	0.998	D	0.588	neutral	None	None	None	None	N
E/D	0.2617	likely_benign	0.2767	benign	-0.531	Destabilizing	0.971	D	0.451	neutral	N	0.426675867	None	None	N
E/F	0.6811	likely_pathogenic	0.7492	pathogenic	-0.487	Destabilizing	0.961	D	0.543	neutral	None	None	None	None	N
E/G	0.2998	likely_benign	0.3455	ambiguous	-0.843	Destabilizing	0.971	D	0.492	neutral	N	0.427542658	None	None	N
E/H	0.4402	ambiguous	0.5144	ambiguous	-0.469	Destabilizing	0.998	D	0.41	neutral	None	None	None	None	N
E/I	0.1733	likely_benign	0.2055	benign	-0.015	Destabilizing	0.78	D	0.521	neutral	None	None	None	None	N
E/K	0.1345	likely_benign	0.1612	benign	0.122	Stabilizing	0.971	D	0.427	neutral	N	0.425462358	None	None	N
E/L	0.2413	likely_benign	0.2855	benign	-0.015	Destabilizing	0.003	N	0.372	neutral	None	None	None	None	N
E/M	0.3413	ambiguous	0.3817	ambiguous	0.268	Stabilizing	0.961	D	0.541	neutral	None	None	None	None	N
E/N	0.3123	likely_benign	0.3467	ambiguous	-0.206	Destabilizing	0.994	D	0.421	neutral	None	None	None	None	N
E/P	0.5377	ambiguous	0.5916	pathogenic	-0.193	Destabilizing	0.994	D	0.487	neutral	None	None	None	None	N
E/Q	0.1124	likely_benign	0.1279	benign	-0.172	Destabilizing	0.971	D	0.511	neutral	N	0.42632915	None	None	N
E/R	0.2378	likely_benign	0.2904	benign	0.289	Stabilizing	0.994	D	0.403	neutral	None	None	None	None	N
E/S	0.227	likely_benign	0.255	benign	-0.401	Destabilizing	0.978	D	0.325	neutral	None	None	None	None	N
E/T	0.1354	likely_benign	0.1554	benign	-0.212	Destabilizing	0.935	D	0.503	neutral	None	None	None	None	N
E/V	0.1127	likely_benign	0.1319	benign	-0.193	Destabilizing	0.728	D	0.471	neutral	N	0.426675867	None	None	N
E/W	0.9204	likely_pathogenic	0.9438	pathogenic	-0.309	Destabilizing	0.998	D	0.656	prob.neutral	None	None	None	None	N
E/Y	0.6175	likely_pathogenic	0.6999	pathogenic	-0.24	Destabilizing	0.994	D	0.555	neutral	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.