TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29098	87517;87518;87519	chr2:178558062;178558061;178558060	chr2:179422789;179422788;179422787
N2AB	27457	82594;82595;82596	chr2:178558062;178558061;178558060	chr2:179422789;179422788;179422787
N2A	26530	79813;79814;79815	chr2:178558062;178558061;178558060	chr2:179422789;179422788;179422787
N2B	20033	60322;60323;60324	chr2:178558062;178558061;178558060	chr2:179422789;179422788;179422787
Novex-1	20158	60697;60698;60699	chr2:178558062;178558061;178558060	chr2:179422789;179422788;179422787
Novex-2	20225	60898;60899;60900	chr2:178558062;178558061;178558060	chr2:179422789;179422788;179422787
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-145
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.5675
• 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	rs755499990	-0.207	0.011	N	0.178	0.054	0.187945064343	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/D	rs755499990	-0.207	0.011	N	0.178	0.054	0.187945064343	gnomAD-4.0.0	1.59102E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02352E-05
E/K	rs369063299	0.478	0.961	N	0.578	0.378	None	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
E/K	rs369063299	0.478	0.961	N	0.578	0.378	None	gnomAD-4.0.0	4.10502E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39656E-06	0	0
E/Q	rs369063299	-0.04	0.98	D	0.535	0.231	0.361958692863	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/Q	rs369063299	-0.04	0.98	D	0.535	0.231	0.361958692863	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/Q	rs369063299	-0.04	0.98	D	0.535	0.231	0.361958692863	gnomAD-4.0.0	1.23929E-06	None	None	None	None	N	None	2.6688E-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	0.1691	likely_benign	0.1662	benign	-0.224	Destabilizing	0.98	D	0.611	neutral	N	0.514278995	None	None	N
E/C	0.8458	likely_pathogenic	0.8336	pathogenic	0.067	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/D	0.0957	likely_benign	0.0968	benign	-0.235	Destabilizing	0.011	N	0.178	neutral	N	0.420523472	None	None	N
E/F	0.825	likely_pathogenic	0.8105	pathogenic	-0.234	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
E/G	0.1141	likely_benign	0.1119	benign	-0.382	Destabilizing	0.961	D	0.649	neutral	N	0.466237119	None	None	N
E/H	0.4543	ambiguous	0.4176	ambiguous	0.092	Stabilizing	0.999	D	0.606	neutral	None	None	None	None	N
E/I	0.4945	ambiguous	0.4774	ambiguous	0.146	Stabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	N
E/K	0.1418	likely_benign	0.1242	benign	0.487	Stabilizing	0.961	D	0.578	neutral	N	0.496039951	None	None	N
E/L	0.5095	ambiguous	0.4916	ambiguous	0.146	Stabilizing	0.996	D	0.701	prob.neutral	None	None	None	None	N
E/M	0.5554	ambiguous	0.5374	ambiguous	0.185	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/N	0.1789	likely_benign	0.1862	benign	0.229	Stabilizing	0.97	D	0.585	neutral	None	None	None	None	N
E/P	0.7734	likely_pathogenic	0.7568	pathogenic	0.042	Stabilizing	0.999	D	0.619	neutral	None	None	None	None	N
E/Q	0.1396	likely_benign	0.1282	benign	0.246	Stabilizing	0.98	D	0.535	neutral	D	0.534174265	None	None	N
E/R	0.2608	likely_benign	0.2275	benign	0.636	Stabilizing	0.996	D	0.604	neutral	None	None	None	None	N
E/S	0.1689	likely_benign	0.1697	benign	0.081	Stabilizing	0.97	D	0.571	neutral	None	None	None	None	N
E/T	0.2023	likely_benign	0.1999	benign	0.211	Stabilizing	0.985	D	0.603	neutral	None	None	None	None	N
E/V	0.3083	likely_benign	0.2898	benign	0.042	Stabilizing	0.998	D	0.656	neutral	N	0.486999181	None	None	N
E/W	0.8986	likely_pathogenic	0.8797	pathogenic	-0.142	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
E/Y	0.6637	likely_pathogenic	0.6428	pathogenic	None	Stabilizing	0.999	D	0.713	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.