TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27950	84073;84074;84075	chr2:178562284;178562283;178562282	chr2:179427011;179427010;179427009
N2AB	26309	79150;79151;79152	chr2:178562284;178562283;178562282	chr2:179427011;179427010;179427009
N2A	25382	76369;76370;76371	chr2:178562284;178562283;178562282	chr2:179427011;179427010;179427009
N2B	18885	56878;56879;56880	chr2:178562284;178562283;178562282	chr2:179427011;179427010;179427009
Novex-1	19010	57253;57254;57255	chr2:178562284;178562283;178562282	chr2:179427011;179427010;179427009
Novex-2	19077	57454;57455;57456	chr2:178562284;178562283;178562282	chr2:179427011;179427010;179427009
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-91
• Domain position: 88
• Structural Position: 123
• Q(SASA): 0.2173
• 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
L/F	None	None	0.998	N	0.815	0.221	0.370424759081	gnomAD-4.0.0	1.59216E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85927E-06	0	0
L/I	None	None	0.811	N	0.663	0.077	0.237489013734	gnomAD-4.0.0	1.59216E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43382E-05	0
L/P	None	None	0.999	N	0.849	0.423	0.667319264289	gnomAD-4.0.0	2.05312E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.6987E-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
L/A	0.6088	likely_pathogenic	0.6779	pathogenic	-2.196	Highly Destabilizing	0.99	D	0.703	prob.delet.	None	None	None	None	N
L/C	0.8565	likely_pathogenic	0.8708	pathogenic	-1.444	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
L/D	0.9905	likely_pathogenic	0.9912	pathogenic	-2.263	Highly Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
L/E	0.9601	likely_pathogenic	0.9648	pathogenic	-2.104	Highly Destabilizing	0.998	D	0.836	deleterious	None	None	None	None	N
L/F	0.7014	likely_pathogenic	0.7365	pathogenic	-1.273	Destabilizing	0.998	D	0.815	deleterious	N	0.489456132	None	None	N
L/G	0.9232	likely_pathogenic	0.9342	pathogenic	-2.683	Highly Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
L/H	0.9448	likely_pathogenic	0.9506	pathogenic	-2.064	Highly Destabilizing	1.0	D	0.897	deleterious	N	0.49498954	None	None	N
L/I	0.2209	likely_benign	0.2604	benign	-0.833	Destabilizing	0.811	D	0.663	prob.neutral	N	0.468279268	None	None	N
L/K	0.9606	likely_pathogenic	0.9627	pathogenic	-1.785	Destabilizing	0.952	D	0.831	deleterious	None	None	None	None	N
L/M	0.2735	likely_benign	0.3109	benign	-0.705	Destabilizing	0.998	D	0.752	deleterious	None	None	None	None	N
L/N	0.9501	likely_pathogenic	0.9585	pathogenic	-1.936	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
L/P	0.85	likely_pathogenic	0.8851	pathogenic	-1.263	Destabilizing	0.999	D	0.849	deleterious	N	0.428643444	None	None	N
L/Q	0.8997	likely_pathogenic	0.9152	pathogenic	-1.896	Destabilizing	0.998	D	0.869	deleterious	None	None	None	None	N
L/R	0.929	likely_pathogenic	0.9353	pathogenic	-1.378	Destabilizing	0.995	D	0.847	deleterious	N	0.485835281	None	None	N
L/S	0.8626	likely_pathogenic	0.8919	pathogenic	-2.597	Highly Destabilizing	0.997	D	0.772	deleterious	None	None	None	None	N
L/T	0.4803	ambiguous	0.5485	ambiguous	-2.303	Highly Destabilizing	0.296	N	0.485	neutral	None	None	None	None	N
L/V	0.25	likely_benign	0.2949	benign	-1.263	Destabilizing	0.739	D	0.705	prob.delet.	N	0.493444284	None	None	N
L/W	0.8806	likely_pathogenic	0.8837	pathogenic	-1.606	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
L/Y	0.9405	likely_pathogenic	0.9437	pathogenic	-1.31	Destabilizing	0.995	D	0.785	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.