TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35747	107464;107465;107466	chr2:178528412;178528411;178528410	chr2:179393139;179393138;179393137
N2AB	34106	102541;102542;102543	chr2:178528412;178528411;178528410	chr2:179393139;179393138;179393137
N2A	33179	99760;99761;99762	chr2:178528412;178528411;178528410	chr2:179393139;179393138;179393137
N2B	26682	80269;80270;80271	chr2:178528412;178528411;178528410	chr2:179393139;179393138;179393137
Novex-1	26807	80644;80645;80646	chr2:178528412;178528411;178528410	chr2:179393139;179393138;179393137
Novex-2	26874	80845;80846;80847	chr2:178528412;178528411;178528410	chr2:179393139;179393138;179393137
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-168
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.6309
• 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
N/D	None	None	0.117	N	0.358	0.094	0.0482279557977	gnomAD-4.0.0	1.59264E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85883E-06	0	0
N/H	None	None	None	N	0.143	0.098	0.0401082797425	gnomAD-4.0.0	1.59264E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85883E-06	0	0
N/S	rs903505453	None	0.027	N	0.355	0.181	0.0762999501168	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
N/S	rs903505453	None	0.027	N	0.355	0.181	0.0762999501168	gnomAD-4.0.0	3.09948E-06	None	None	None	None	N	None	1.33511E-05	0	None	0	0	None	0	0	3.39064E-06	0	0
N/Y	rs1687478590	None	0.188	N	0.363	0.054	0.234412748748	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
N/Y	rs1687478590	None	0.188	N	0.363	0.054	0.234412748748	gnomAD-4.0.0	6.57039E-06	None	None	None	None	N	None	2.41173E-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
N/A	0.2137	likely_benign	0.2044	benign	-0.561	Destabilizing	0.081	N	0.317	neutral	None	None	None	None	N
N/C	0.4489	ambiguous	0.4171	ambiguous	0.25	Stabilizing	0.935	D	0.441	neutral	None	None	None	None	N
N/D	0.135	likely_benign	0.1302	benign	0.087	Stabilizing	0.117	N	0.358	neutral	N	0.400912551	None	None	N
N/E	0.3825	ambiguous	0.353	ambiguous	0.051	Stabilizing	0.081	N	0.301	neutral	None	None	None	None	N
N/F	0.5837	likely_pathogenic	0.5679	pathogenic	-0.954	Destabilizing	0.38	N	0.391	neutral	None	None	None	None	N
N/G	0.2564	likely_benign	0.2527	benign	-0.724	Destabilizing	0.149	N	0.301	neutral	None	None	None	None	N
N/H	0.1074	likely_benign	0.1018	benign	-0.799	Destabilizing	None	N	0.143	neutral	N	0.419941029	None	None	N
N/I	0.3188	likely_benign	0.3127	benign	-0.217	Destabilizing	0.484	N	0.396	neutral	N	0.467060186	None	None	N
N/K	0.25	likely_benign	0.2037	benign	0.136	Stabilizing	None	N	0.145	neutral	N	0.372435084	None	None	N
N/L	0.2976	likely_benign	0.2874	benign	-0.217	Destabilizing	0.149	N	0.393	neutral	None	None	None	None	N
N/M	0.4112	ambiguous	0.4013	ambiguous	0.301	Stabilizing	0.935	D	0.352	neutral	None	None	None	None	N
N/P	0.6504	likely_pathogenic	0.6299	pathogenic	-0.307	Destabilizing	0.555	D	0.359	neutral	None	None	None	None	N
N/Q	0.3352	likely_benign	0.3094	benign	-0.432	Destabilizing	0.235	N	0.334	neutral	None	None	None	None	N
N/R	0.2731	likely_benign	0.2329	benign	0.195	Stabilizing	0.081	N	0.3	neutral	None	None	None	None	N
N/S	0.0758	likely_benign	0.0783	benign	-0.188	Destabilizing	0.027	N	0.355	neutral	N	0.419228953	None	None	N
N/T	0.1299	likely_benign	0.1254	benign	-0.076	Destabilizing	0.117	N	0.306	neutral	N	0.430984742	None	None	N
N/V	0.3003	likely_benign	0.2976	benign	-0.307	Destabilizing	0.38	N	0.397	neutral	None	None	None	None	N
N/W	0.8309	likely_pathogenic	0.8225	pathogenic	-0.866	Destabilizing	0.935	D	0.505	neutral	None	None	None	None	N
N/Y	0.2055	likely_benign	0.2006	benign	-0.617	Destabilizing	0.188	N	0.363	neutral	N	0.448474425	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.