TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28028	84307;84308;84309	chr2:178562050;178562049;178562048	chr2:179426777;179426776;179426775
N2AB	26387	79384;79385;79386	chr2:178562050;178562049;178562048	chr2:179426777;179426776;179426775
N2A	25460	76603;76604;76605	chr2:178562050;178562049;178562048	chr2:179426777;179426776;179426775
N2B	18963	57112;57113;57114	chr2:178562050;178562049;178562048	chr2:179426777;179426776;179426775
Novex-1	19088	57487;57488;57489	chr2:178562050;178562049;178562048	chr2:179426777;179426776;179426775
Novex-2	19155	57688;57689;57690	chr2:178562050;178562049;178562048	chr2:179426777;179426776;179426775
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: Ig-142
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.4029
• 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	None	None	0.822	N	0.462	0.329	0.323886383625	gnomAD-4.0.0	5.47518E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19651E-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	0.1539	likely_benign	0.1438	benign	-0.277	Destabilizing	0.822	D	0.468	neutral	N	0.461354108	None	None	N
E/C	0.8324	likely_pathogenic	0.8235	pathogenic	0.135	Stabilizing	0.998	D	0.705	prob.neutral	None	None	None	None	N
E/D	0.0872	likely_benign	0.0811	benign	-0.164	Destabilizing	0.006	N	0.187	neutral	N	0.442415244	None	None	N
E/F	0.7708	likely_pathogenic	0.7399	pathogenic	-0.311	Destabilizing	0.993	D	0.656	neutral	None	None	None	None	N
E/G	0.1542	likely_benign	0.1488	benign	-0.439	Destabilizing	0.822	D	0.462	neutral	N	0.510256389	None	None	N
E/H	0.539	ambiguous	0.5114	ambiguous	-0.054	Destabilizing	0.978	D	0.47	neutral	None	None	None	None	N
E/I	0.4218	ambiguous	0.3917	ambiguous	0.103	Stabilizing	0.978	D	0.658	neutral	None	None	None	None	N
E/K	0.2136	likely_benign	0.2052	benign	0.454	Stabilizing	0.698	D	0.475	neutral	N	0.513488696	None	None	N
E/L	0.4503	ambiguous	0.4182	ambiguous	0.103	Stabilizing	0.956	D	0.575	neutral	None	None	None	None	N
E/M	0.498	ambiguous	0.473	ambiguous	0.243	Stabilizing	0.998	D	0.622	neutral	None	None	None	None	N
E/N	0.233	likely_benign	0.2109	benign	0.249	Stabilizing	0.754	D	0.441	neutral	None	None	None	None	N
E/P	0.6908	likely_pathogenic	0.6733	pathogenic	-0.004	Destabilizing	0.978	D	0.525	neutral	None	None	None	None	N
E/Q	0.203	likely_benign	0.1906	benign	0.268	Stabilizing	0.822	D	0.45	neutral	N	0.475699381	None	None	N
E/R	0.3472	ambiguous	0.3328	benign	0.576	Stabilizing	0.043	N	0.257	neutral	None	None	None	None	N
E/S	0.2053	likely_benign	0.1872	benign	0.075	Stabilizing	0.86	D	0.445	neutral	None	None	None	None	N
E/T	0.2251	likely_benign	0.2068	benign	0.208	Stabilizing	0.956	D	0.479	neutral	None	None	None	None	N
E/V	0.2474	likely_benign	0.232	benign	-0.004	Destabilizing	0.97	D	0.576	neutral	N	0.476966829	None	None	N
E/W	0.8719	likely_pathogenic	0.8592	pathogenic	-0.221	Destabilizing	0.998	D	0.698	prob.neutral	None	None	None	None	N
E/Y	0.5985	likely_pathogenic	0.5632	ambiguous	-0.08	Destabilizing	0.993	D	0.62	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.