TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32678	98257;98258;98259	chr2:178540134;178540133;178540132	chr2:179404861;179404860;179404859
N2AB	31037	93334;93335;93336	chr2:178540134;178540133;178540132	chr2:179404861;179404860;179404859
N2A	30110	90553;90554;90555	chr2:178540134;178540133;178540132	chr2:179404861;179404860;179404859
N2B	23613	71062;71063;71064	chr2:178540134;178540133;178540132	chr2:179404861;179404860;179404859
Novex-1	23738	71437;71438;71439	chr2:178540134;178540133;178540132	chr2:179404861;179404860;179404859
Novex-2	23805	71638;71639;71640	chr2:178540134;178540133;178540132	chr2:179404861;179404860;179404859
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-126
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.1608
• 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
C/G	rs368160975	-1.764	0.999	N	0.701	0.463	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
C/S	None	None	0.99	N	0.632	0.474	0.642663040669	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
C/A	0.6075	likely_pathogenic	0.6195	pathogenic	-1.009	Destabilizing	0.964	D	0.447	neutral	None	None	None	None	N
C/D	0.939	likely_pathogenic	0.9515	pathogenic	-1.557	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
C/E	0.9179	likely_pathogenic	0.9282	pathogenic	-1.405	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
C/F	0.3193	likely_benign	0.3382	benign	-0.93	Destabilizing	0.997	D	0.719	prob.delet.	N	0.46926349	None	None	N
C/G	0.5513	ambiguous	0.5669	pathogenic	-1.273	Destabilizing	0.999	D	0.701	prob.neutral	N	0.488542684	None	None	N
C/H	0.7408	likely_pathogenic	0.774	pathogenic	-1.866	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
C/I	0.4962	ambiguous	0.4984	ambiguous	-0.352	Destabilizing	0.971	D	0.551	neutral	None	None	None	None	N
C/K	0.9229	likely_pathogenic	0.9363	pathogenic	-0.707	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
C/L	0.5751	likely_pathogenic	0.5758	pathogenic	-0.352	Destabilizing	0.931	D	0.559	neutral	None	None	None	None	N
C/M	0.6508	likely_pathogenic	0.6576	pathogenic	-0.005	Destabilizing	0.998	D	0.696	prob.neutral	None	None	None	None	N
C/N	0.7915	likely_pathogenic	0.8019	pathogenic	-1.099	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
C/P	0.9954	likely_pathogenic	0.9962	pathogenic	-0.546	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
C/Q	0.7729	likely_pathogenic	0.7955	pathogenic	-0.899	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
C/R	0.7029	likely_pathogenic	0.7468	pathogenic	-1.012	Destabilizing	0.999	D	0.786	deleterious	N	0.414812929	None	None	N
C/S	0.4882	ambiguous	0.5078	ambiguous	-1.25	Destabilizing	0.99	D	0.632	neutral	N	0.452197882	None	None	N
C/T	0.5386	ambiguous	0.552	ambiguous	-0.949	Destabilizing	0.985	D	0.609	neutral	None	None	None	None	N
C/V	0.3661	ambiguous	0.3569	ambiguous	-0.546	Destabilizing	0.469	N	0.332	neutral	None	None	None	None	N
C/W	0.6974	likely_pathogenic	0.7237	pathogenic	-1.391	Destabilizing	1.0	D	0.731	prob.delet.	N	0.469874301	None	None	N
C/Y	0.4756	ambiguous	0.5023	ambiguous	-1.02	Destabilizing	0.999	D	0.731	prob.delet.	N	0.442076888	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.