TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26348	79267;79268;79269	chr2:178567090;178567089;178567088	chr2:179431817;179431816;179431815
N2AB	24707	74344;74345;74346	chr2:178567090;178567089;178567088	chr2:179431817;179431816;179431815
N2A	23780	71563;71564;71565	chr2:178567090;178567089;178567088	chr2:179431817;179431816;179431815
N2B	17283	52072;52073;52074	chr2:178567090;178567089;178567088	chr2:179431817;179431816;179431815
Novex-1	17408	52447;52448;52449	chr2:178567090;178567089;178567088	chr2:179431817;179431816;179431815
Novex-2	17475	52648;52649;52650	chr2:178567090;178567089;178567088	chr2:179431817;179431816;179431815
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-79
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1292
• 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	rs1341655578	-2.228	0.581	D	0.653	0.415	0.564579235405	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
V/A	rs1341655578	-2.228	0.581	D	0.653	0.415	0.564579235405	gnomAD-4.0.0	2.0529E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69876E-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
V/A	0.6734	likely_pathogenic	0.6555	pathogenic	-1.791	Destabilizing	0.581	D	0.653	neutral	D	0.525586493	None	None	N
V/C	0.9148	likely_pathogenic	0.9085	pathogenic	-1.278	Destabilizing	0.993	D	0.842	deleterious	None	None	None	None	N
V/D	0.9936	likely_pathogenic	0.9949	pathogenic	-1.843	Destabilizing	0.908	D	0.833	deleterious	N	0.508776426	None	None	N
V/E	0.9799	likely_pathogenic	0.9846	pathogenic	-1.676	Destabilizing	0.929	D	0.839	deleterious	None	None	None	None	N
V/F	0.7135	likely_pathogenic	0.743	pathogenic	-1.102	Destabilizing	0.83	D	0.814	deleterious	N	0.501126195	None	None	N
V/G	0.8933	likely_pathogenic	0.8963	pathogenic	-2.285	Highly Destabilizing	0.908	D	0.848	deleterious	D	0.550518344	None	None	N
V/H	0.9928	likely_pathogenic	0.9941	pathogenic	-1.887	Destabilizing	0.993	D	0.88	deleterious	None	None	None	None	N
V/I	0.0784	likely_benign	0.0832	benign	-0.452	Destabilizing	0.004	N	0.239	neutral	N	0.473634733	None	None	N
V/K	0.9896	likely_pathogenic	0.9924	pathogenic	-1.463	Destabilizing	0.929	D	0.84	deleterious	None	None	None	None	N
V/L	0.5377	ambiguous	0.5864	pathogenic	-0.452	Destabilizing	0.09	N	0.631	neutral	N	0.470657541	None	None	N
V/M	0.5403	ambiguous	0.5595	ambiguous	-0.42	Destabilizing	0.866	D	0.757	deleterious	None	None	None	None	N
V/N	0.9715	likely_pathogenic	0.977	pathogenic	-1.604	Destabilizing	0.976	D	0.886	deleterious	None	None	None	None	N
V/P	0.9772	likely_pathogenic	0.9831	pathogenic	-0.867	Destabilizing	0.976	D	0.836	deleterious	None	None	None	None	N
V/Q	0.98	likely_pathogenic	0.9838	pathogenic	-1.515	Destabilizing	0.976	D	0.895	deleterious	None	None	None	None	N
V/R	0.9844	likely_pathogenic	0.9879	pathogenic	-1.239	Destabilizing	0.929	D	0.89	deleterious	None	None	None	None	N
V/S	0.9142	likely_pathogenic	0.9146	pathogenic	-2.256	Highly Destabilizing	0.929	D	0.841	deleterious	None	None	None	None	N
V/T	0.8179	likely_pathogenic	0.8201	pathogenic	-1.937	Destabilizing	0.648	D	0.707	prob.neutral	None	None	None	None	N
V/W	0.9941	likely_pathogenic	0.9949	pathogenic	-1.49	Destabilizing	0.993	D	0.868	deleterious	None	None	None	None	N
V/Y	0.9697	likely_pathogenic	0.9711	pathogenic	-1.104	Destabilizing	0.929	D	0.809	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.