TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22518	67777;67778;67779	chr2:178579645;178579644;178579643	chr2:179444372;179444371;179444370
N2AB	20877	62854;62855;62856	chr2:178579645;178579644;178579643	chr2:179444372;179444371;179444370
N2A	19950	60073;60074;60075	chr2:178579645;178579644;178579643	chr2:179444372;179444371;179444370
N2B	13453	40582;40583;40584	chr2:178579645;178579644;178579643	chr2:179444372;179444371;179444370
Novex-1	13578	40957;40958;40959	chr2:178579645;178579644;178579643	chr2:179444372;179444371;179444370
Novex-2	13645	41158;41159;41160	chr2:178579645;178579644;178579643	chr2:179444372;179444371;179444370
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: Fn3-51
• Domain position: 68
• Structural Position: 103
• Q(SASA): 0.5403
• 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/K	rs371063328	0.119	0.865	N	0.528	0.235	None	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	1.29216E-04	0	None	0	0	None	0	None	0	0	0
E/K	rs371063328	0.119	0.865	N	0.528	0.235	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs371063328	0.119	0.865	N	0.528	0.235	None	gnomAD-4.0.0	1.31543E-05	None	None	None	None	N	None	4.82812E-05	0	None	0	0	None	0	0	0	0	0
E/Q	None	None	0.284	N	0.244	0.165	0.248417906384	gnomAD-4.0.0	2.40078E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62517E-06	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	0.1105	likely_benign	0.1091	benign	-0.507	Destabilizing	0.865	D	0.601	neutral	N	0.472738364	None	None	N
E/C	0.7618	likely_pathogenic	0.7658	pathogenic	-0.332	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
E/D	0.1902	likely_benign	0.17	benign	-0.571	Destabilizing	0.928	D	0.451	neutral	N	0.468610534	None	None	N
E/F	0.7092	likely_pathogenic	0.7201	pathogenic	0.029	Stabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
E/G	0.1607	likely_benign	0.1659	benign	-0.784	Destabilizing	0.978	D	0.676	prob.neutral	N	0.489628078	None	None	N
E/H	0.443	ambiguous	0.4552	ambiguous	0.272	Stabilizing	0.996	D	0.727	prob.delet.	None	None	None	None	N
E/I	0.2489	likely_benign	0.2441	benign	0.218	Stabilizing	0.992	D	0.787	deleterious	None	None	None	None	N
E/K	0.132	likely_benign	0.1445	benign	0.133	Stabilizing	0.865	D	0.528	neutral	N	0.517884156	None	None	N
E/L	0.3177	likely_benign	0.3147	benign	0.218	Stabilizing	0.983	D	0.775	deleterious	None	None	None	None	N
E/M	0.3506	ambiguous	0.3456	ambiguous	0.243	Stabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	N
E/N	0.243	likely_benign	0.229	benign	-0.491	Destabilizing	0.983	D	0.706	prob.neutral	None	None	None	None	N
E/P	0.3425	ambiguous	0.3219	benign	-0.003	Destabilizing	0.992	D	0.785	deleterious	None	None	None	None	N
E/Q	0.1178	likely_benign	0.1234	benign	-0.385	Destabilizing	0.284	N	0.244	neutral	N	0.515075924	None	None	N
E/R	0.2216	likely_benign	0.245	benign	0.505	Stabilizing	0.968	D	0.71	prob.delet.	None	None	None	None	N
E/S	0.1764	likely_benign	0.1695	benign	-0.655	Destabilizing	0.895	D	0.605	neutral	None	None	None	None	N
E/T	0.1422	likely_benign	0.1411	benign	-0.413	Destabilizing	0.983	D	0.718	prob.delet.	None	None	None	None	N
E/V	0.1385	likely_benign	0.1384	benign	-0.003	Destabilizing	0.978	D	0.779	deleterious	N	0.471777313	None	None	N
E/W	0.875	likely_pathogenic	0.8859	pathogenic	0.311	Stabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
E/Y	0.5983	likely_pathogenic	0.6036	pathogenic	0.309	Stabilizing	0.992	D	0.781	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.