TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17232	51919;51920;51921	chr2:178609729;178609728;178609727	chr2:179474456;179474455;179474454
N2AB	15591	46996;46997;46998	chr2:178609729;178609728;178609727	chr2:179474456;179474455;179474454
N2A	14664	44215;44216;44217	chr2:178609729;178609728;178609727	chr2:179474456;179474455;179474454
N2B	8167	24724;24725;24726	chr2:178609729;178609728;178609727	chr2:179474456;179474455;179474454
Novex-1	8292	25099;25100;25101	chr2:178609729;178609728;178609727	chr2:179474456;179474455;179474454
Novex-2	8359	25300;25301;25302	chr2:178609729;178609728;178609727	chr2:179474456;179474455;179474454
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-13
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.5301
• Predicted PPI site: I

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
E/K	rs765280689	0.013	0.565	N	0.598	0.157	0.231231049324	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
E/K	rs765280689	0.013	0.565	N	0.598	0.157	0.231231049324	gnomAD-4.0.0	6.85872E-07	None	None	None	None	I	None	0	0	None	0	2.52564E-05	None	0	0	0	0	0
E/V	None	None	0.901	N	0.653	0.309	0.434497104326	gnomAD-4.0.0	1.59989E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87829E-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
E/A	0.3118	likely_benign	0.2554	benign	-0.613	Destabilizing	0.565	D	0.587	neutral	N	0.466102092	None	None	I
E/C	0.9496	likely_pathogenic	0.9299	pathogenic	-0.249	Destabilizing	0.996	D	0.771	deleterious	None	None	None	None	I
E/D	0.1097	likely_benign	0.1157	benign	-0.555	Destabilizing	0.003	N	0.083	neutral	N	0.467130049	None	None	I
E/F	0.8903	likely_pathogenic	0.8485	pathogenic	-0.373	Destabilizing	0.987	D	0.715	prob.delet.	None	None	None	None	I
E/G	0.373	ambiguous	0.3343	benign	-0.834	Destabilizing	0.008	N	0.412	neutral	N	0.49291608	None	None	I
E/H	0.7766	likely_pathogenic	0.7111	pathogenic	-0.135	Destabilizing	0.961	D	0.556	neutral	None	None	None	None	I
E/I	0.6199	likely_pathogenic	0.5148	ambiguous	-0.053	Destabilizing	0.961	D	0.716	prob.delet.	None	None	None	None	I
E/K	0.4029	ambiguous	0.3207	benign	0.076	Stabilizing	0.565	D	0.598	neutral	N	0.518326873	None	None	I
E/L	0.5805	likely_pathogenic	0.4978	ambiguous	-0.053	Destabilizing	0.923	D	0.677	prob.neutral	None	None	None	None	I
E/M	0.6917	likely_pathogenic	0.617	pathogenic	0.079	Stabilizing	0.989	D	0.689	prob.neutral	None	None	None	None	I
E/N	0.4243	ambiguous	0.3865	ambiguous	-0.337	Destabilizing	0.633	D	0.587	neutral	None	None	None	None	I
E/P	0.605	likely_pathogenic	0.5309	ambiguous	-0.22	Destabilizing	0.961	D	0.685	prob.neutral	None	None	None	None	I
E/Q	0.3254	likely_benign	0.2712	benign	-0.294	Destabilizing	0.075	N	0.232	neutral	N	0.468001423	None	None	I
E/R	0.6009	likely_pathogenic	0.508	ambiguous	0.37	Stabilizing	0.858	D	0.589	neutral	None	None	None	None	I
E/S	0.3608	ambiguous	0.322	benign	-0.495	Destabilizing	0.633	D	0.543	neutral	None	None	None	None	I
E/T	0.4785	ambiguous	0.414	ambiguous	-0.314	Destabilizing	0.775	D	0.657	neutral	None	None	None	None	I
E/V	0.4225	ambiguous	0.3335	benign	-0.22	Destabilizing	0.901	D	0.653	neutral	N	0.480625176	None	None	I
E/W	0.9714	likely_pathogenic	0.9571	pathogenic	-0.159	Destabilizing	0.996	D	0.78	deleterious	None	None	None	None	I
E/Y	0.812	likely_pathogenic	0.7566	pathogenic	-0.124	Destabilizing	0.961	D	0.709	prob.delet.	None	None	None	None	I

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.