TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2892	8899;8900;8901	chr2:178769907;178769906;178769905	chr2:179634634;179634633;179634632
N2AB	2892	8899;8900;8901	chr2:178769907;178769906;178769905	chr2:179634634;179634633;179634632
N2A	2892	8899;8900;8901	chr2:178769907;178769906;178769905	chr2:179634634;179634633;179634632
N2B	2846	8761;8762;8763	chr2:178769907;178769906;178769905	chr2:179634634;179634633;179634632
Novex-1	2846	8761;8762;8763	chr2:178769907;178769906;178769905	chr2:179634634;179634633;179634632
Novex-2	2846	8761;8762;8763	chr2:178769907;178769906;178769905	chr2:179634634;179634633;179634632
Novex-3	2892	8899;8900;8901	chr2:178769907;178769906;178769905	chr2:179634634;179634633;179634632

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-19
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.3459
• 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	rs763393324	0.367	0.742	N	0.575	0.122	0.345175991111	gnomAD-2.1.1	1.2E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.65E-05	0
E/K	rs763393324	0.367	0.742	N	0.575	0.122	0.345175991111	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/K	rs763393324	0.367	0.742	N	0.575	0.122	0.345175991111	gnomAD-4.0.0	1.30129E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69493E-05	0	1.60041E-05
E/Q	rs763393324	-0.045	0.008	N	0.228	0.107	0.252681307341	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.63559E-04
E/Q	rs763393324	-0.045	0.008	N	0.228	0.107	0.252681307341	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
E/Q	rs763393324	-0.045	0.008	N	0.228	0.107	0.252681307341	gnomAD-4.0.0	1.23933E-06	None	None	None	None	N	None	1.33601E-05	0	None	0	0	None	0	0	8.47463E-07	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	0.1429	likely_benign	0.1375	benign	-0.437	Destabilizing	0.338	N	0.544	neutral	N	0.512344528	None	None	N
E/C	0.7777	likely_pathogenic	0.8134	pathogenic	-0.213	Destabilizing	0.991	D	0.682	prob.neutral	None	None	None	None	N
E/D	0.2023	likely_benign	0.1904	benign	-0.481	Destabilizing	0.505	D	0.552	neutral	D	0.53678514	None	None	N
E/F	0.7385	likely_pathogenic	0.7381	pathogenic	-0.147	Destabilizing	0.967	D	0.614	neutral	None	None	None	None	N
E/G	0.2961	likely_benign	0.3115	benign	-0.67	Destabilizing	0.505	D	0.497	neutral	D	0.587372217	None	None	N
E/H	0.3634	ambiguous	0.3847	ambiguous	0.092	Stabilizing	0.826	D	0.52	neutral	None	None	None	None	N
E/I	0.2783	likely_benign	0.2576	benign	0.155	Stabilizing	0.906	D	0.621	neutral	None	None	None	None	N
E/K	0.1184	likely_benign	0.1299	benign	0.205	Stabilizing	0.742	D	0.575	neutral	N	0.508308856	None	None	N
E/L	0.3535	ambiguous	0.3236	benign	0.155	Stabilizing	0.826	D	0.525	neutral	None	None	None	None	N
E/M	0.3601	ambiguous	0.351	ambiguous	0.183	Stabilizing	0.973	D	0.566	neutral	None	None	None	None	N
E/N	0.2751	likely_benign	0.2487	benign	-0.257	Destabilizing	0.826	D	0.518	neutral	None	None	None	None	N
E/P	0.8074	likely_pathogenic	0.8248	pathogenic	-0.021	Destabilizing	0.906	D	0.535	neutral	None	None	None	None	N
E/Q	0.1126	likely_benign	0.1085	benign	-0.193	Destabilizing	0.008	N	0.228	neutral	N	0.514709059	None	None	N
E/R	0.2075	likely_benign	0.2449	benign	0.494	Stabilizing	0.704	D	0.515	neutral	None	None	None	None	N
E/S	0.1854	likely_benign	0.1758	benign	-0.41	Destabilizing	0.05	N	0.273	neutral	None	None	None	None	N
E/T	0.1457	likely_benign	0.135	benign	-0.215	Destabilizing	0.404	N	0.519	neutral	None	None	None	None	N
E/V	0.1556	likely_benign	0.1442	benign	-0.021	Destabilizing	0.782	D	0.491	neutral	N	0.492117271	None	None	N
E/W	0.9011	likely_pathogenic	0.9178	pathogenic	0.054	Stabilizing	0.991	D	0.695	prob.neutral	None	None	None	None	N
E/Y	0.6333	likely_pathogenic	0.6536	pathogenic	0.106	Stabilizing	0.906	D	0.581	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.