TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27877	83854;83855;83856	chr2:178562503;178562502;178562501	chr2:179427230;179427229;179427228
N2AB	26236	78931;78932;78933	chr2:178562503;178562502;178562501	chr2:179427230;179427229;179427228
N2A	25309	76150;76151;76152	chr2:178562503;178562502;178562501	chr2:179427230;179427229;179427228
N2B	18812	56659;56660;56661	chr2:178562503;178562502;178562501	chr2:179427230;179427229;179427228
Novex-1	18937	57034;57035;57036	chr2:178562503;178562502;178562501	chr2:179427230;179427229;179427228
Novex-2	19004	57235;57236;57237	chr2:178562503;178562502;178562501	chr2:179427230;179427229;179427228
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-91
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.5648
• 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
R/C	rs527624888	-0.423	0.036	N	0.536	0.139	0.343101102393	gnomAD-2.1.1	3.59E-05	None	None	None	None	N	None	4.14E-05	8.57E-05	None	0	5.17E-05	None	1.66301E-04	None	0	0	0
R/C	rs527624888	-0.423	0.036	N	0.536	0.139	0.343101102393	gnomAD-3.1.2	3.95E-05	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	1.03648E-03	0
R/C	rs527624888	-0.423	0.036	N	0.536	0.139	0.343101102393	1000 genomes	3.99361E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	2E-03	None
R/C	rs527624888	-0.423	0.036	N	0.536	0.139	0.343101102393	gnomAD-4.0.0	1.92252E-05	None	None	None	None	N	None	2.67094E-05	6.68606E-05	None	0	6.69792E-05	None	1.5647E-05	3.30469E-04	2.54351E-06	1.76495E-04	0
R/G	None	None	0.697	N	0.628	0.131	0.341934017632	gnomAD-4.0.0	1.36955E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7994E-06	0	0
R/H	rs371345921	-1.15	0.979	N	0.489	0.215	0.218112801441	gnomAD-2.1.1	5.03E-05	None	None	None	None	N	None	1.65577E-04	1.14155E-04	None	0	0	None	9.97E-05	None	0	2.35E-05	0
R/H	rs371345921	-1.15	0.979	N	0.489	0.215	0.218112801441	gnomAD-3.1.2	4.6E-05	None	None	None	None	N	None	1.20744E-04	6.56E-05	0	0	0	None	0	0	1.47E-05	0	0
R/H	rs371345921	-1.15	0.979	N	0.489	0.215	0.218112801441	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
R/H	rs371345921	-1.15	0.979	N	0.489	0.215	0.218112801441	gnomAD-4.0.0	2.29462E-05	None	None	None	None	N	None	1.06775E-04	8.36037E-05	None	0	0	None	0	0	9.32632E-06	1.3238E-04	1.60179E-05
R/L	rs371345921	None	0.324	N	0.629	0.201	0.289474373501	gnomAD-4.0.0	2.05442E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69917E-05	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
R/A	0.388	ambiguous	0.3917	ambiguous	-0.295	Destabilizing	0.199	N	0.611	neutral	None	None	None	None	N
R/C	0.187	likely_benign	0.1906	benign	-0.179	Destabilizing	0.036	N	0.536	neutral	N	0.470470185	None	None	N
R/D	0.7676	likely_pathogenic	0.783	pathogenic	-0.169	Destabilizing	0.895	D	0.64	neutral	None	None	None	None	N
R/E	0.4141	ambiguous	0.4381	ambiguous	-0.114	Destabilizing	0.265	N	0.509	neutral	None	None	None	None	N
R/F	0.7431	likely_pathogenic	0.7506	pathogenic	-0.548	Destabilizing	0.773	D	0.708	prob.delet.	None	None	None	None	N
R/G	0.2448	likely_benign	0.2482	benign	-0.504	Destabilizing	0.697	D	0.628	neutral	N	0.46972485	None	None	N
R/H	0.1425	likely_benign	0.1451	benign	-0.977	Destabilizing	0.979	D	0.489	neutral	N	0.512784981	None	None	N
R/I	0.4723	ambiguous	0.4964	ambiguous	0.228	Stabilizing	0.636	D	0.709	prob.delet.	None	None	None	None	N
R/K	0.1067	likely_benign	0.1083	benign	-0.29	Destabilizing	0.002	N	0.18	neutral	None	None	None	None	N
R/L	0.3604	ambiguous	0.373	ambiguous	0.228	Stabilizing	0.324	N	0.629	neutral	N	0.476293082	None	None	N
R/M	0.3949	ambiguous	0.4101	ambiguous	0.076	Stabilizing	0.976	D	0.591	neutral	None	None	None	None	N
R/N	0.6174	likely_pathogenic	0.6288	pathogenic	0.18	Stabilizing	0.895	D	0.507	neutral	None	None	None	None	N
R/P	0.6915	likely_pathogenic	0.7103	pathogenic	0.074	Stabilizing	0.98	D	0.691	prob.neutral	N	0.483038077	None	None	N
R/Q	0.1049	likely_benign	0.1065	benign	-0.063	Destabilizing	0.757	D	0.569	neutral	None	None	None	None	N
R/S	0.4977	ambiguous	0.5077	ambiguous	-0.323	Destabilizing	0.697	D	0.627	neutral	N	0.439033796	None	None	N
R/T	0.362	ambiguous	0.3858	ambiguous	-0.134	Destabilizing	0.546	D	0.611	neutral	None	None	None	None	N
R/V	0.5151	ambiguous	0.5389	ambiguous	0.074	Stabilizing	0.388	N	0.645	neutral	None	None	None	None	N
R/W	0.2749	likely_benign	0.2931	benign	-0.475	Destabilizing	0.993	D	0.793	deleterious	None	None	None	None	N
R/Y	0.5187	ambiguous	0.5298	ambiguous	-0.084	Destabilizing	0.912	D	0.683	prob.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.