TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28009	84250;84251;84252	chr2:178562107;178562106;178562105	chr2:179426834;179426833;179426832
N2AB	26368	79327;79328;79329	chr2:178562107;178562106;178562105	chr2:179426834;179426833;179426832
N2A	25441	76546;76547;76548	chr2:178562107;178562106;178562105	chr2:179426834;179426833;179426832
N2B	18944	57055;57056;57057	chr2:178562107;178562106;178562105	chr2:179426834;179426833;179426832
Novex-1	19069	57430;57431;57432	chr2:178562107;178562106;178562105	chr2:179426834;179426833;179426832
Novex-2	19136	57631;57632;57633	chr2:178562107;178562106;178562105	chr2:179426834;179426833;179426832
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-142
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1642
• 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
V/A	rs1337839201	-1.793	0.999	N	0.539	0.477	0.69600953434	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
V/A	rs1337839201	-1.793	0.999	N	0.539	0.477	0.69600953434	gnomAD-4.0.0	1.85981E-06	None	None	None	None	N	None	1.33583E-05	0	None	0	0	None	0	0	0	1.09856E-05	1.60185E-05
V/D	None	-1.397	1.0	N	0.81	0.671	0.890010646008	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	5.64E-05	None	0	None	0	0	0
V/D	None	-1.397	1.0	N	0.81	0.671	0.890010646008	gnomAD-4.0.0	1.36892E-06	None	None	None	None	N	None	0	0	None	0	2.52832E-05	None	0	0	8.99643E-07	0	0
V/F	rs770470074	-1.411	1.0	D	0.786	0.441	0.85955502653	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
V/F	rs770470074	-1.411	1.0	D	0.786	0.441	0.85955502653	gnomAD-4.0.0	6.84472E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16034E-05	0
V/G	rs1337839201	None	1.0	D	0.78	0.66	0.920757238843	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
V/G	rs1337839201	None	1.0	D	0.78	0.66	0.920757238843	gnomAD-4.0.0	6.57626E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47046E-05	0	0
V/I	None	None	0.997	N	0.551	0.297	0.595871345579	gnomAD-4.0.0	6.84472E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99628E-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
V/A	0.5508	ambiguous	0.5238	ambiguous	-1.983	Destabilizing	0.999	D	0.539	neutral	N	0.491532588	None	None	N
V/C	0.7985	likely_pathogenic	0.7923	pathogenic	-1.767	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
V/D	0.909	likely_pathogenic	0.9243	pathogenic	-2.121	Highly Destabilizing	1.0	D	0.81	deleterious	N	0.517500882	None	None	N
V/E	0.7731	likely_pathogenic	0.7992	pathogenic	-2.037	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
V/F	0.2747	likely_benign	0.2663	benign	-1.431	Destabilizing	1.0	D	0.786	deleterious	D	0.530037882	None	None	N
V/G	0.5724	likely_pathogenic	0.6042	pathogenic	-2.395	Highly Destabilizing	1.0	D	0.78	deleterious	D	0.523234874	None	None	N
V/H	0.8832	likely_pathogenic	0.8919	pathogenic	-1.936	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
V/I	0.0766	likely_benign	0.0763	benign	-0.903	Destabilizing	0.997	D	0.551	neutral	N	0.502024561	None	None	N
V/K	0.7809	likely_pathogenic	0.7998	pathogenic	-1.672	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
V/L	0.2361	likely_benign	0.2483	benign	-0.903	Destabilizing	0.997	D	0.571	neutral	N	0.49538659	None	None	N
V/M	0.2086	likely_benign	0.2001	benign	-0.921	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
V/N	0.766	likely_pathogenic	0.7805	pathogenic	-1.679	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
V/P	0.9875	likely_pathogenic	0.989	pathogenic	-1.232	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
V/Q	0.7246	likely_pathogenic	0.7445	pathogenic	-1.755	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/R	0.7283	likely_pathogenic	0.7608	pathogenic	-1.247	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
V/S	0.6772	likely_pathogenic	0.6727	pathogenic	-2.303	Highly Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
V/T	0.4634	ambiguous	0.4622	ambiguous	-2.092	Highly Destabilizing	0.999	D	0.549	neutral	None	None	None	None	N
V/W	0.8953	likely_pathogenic	0.9008	pathogenic	-1.695	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
V/Y	0.7174	likely_pathogenic	0.719	pathogenic	-1.39	Destabilizing	1.0	D	0.793	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.