TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32905	98938;98939;98940	chr2:178539222;178539221;178539220	chr2:179403949;179403948;179403947
N2AB	31264	94015;94016;94017	chr2:178539222;178539221;178539220	chr2:179403949;179403948;179403947
N2A	30337	91234;91235;91236	chr2:178539222;178539221;178539220	chr2:179403949;179403948;179403947
N2B	23840	71743;71744;71745	chr2:178539222;178539221;178539220	chr2:179403949;179403948;179403947
Novex-1	23965	72118;72119;72120	chr2:178539222;178539221;178539220	chr2:179403949;179403948;179403947
Novex-2	24032	72319;72320;72321	chr2:178539222;178539221;178539220	chr2:179403949;179403948;179403947
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: Fn3-128
• Domain position: 10
• Structural Position: 11
• Q(SASA): 0.8179
• 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
E/D	rs768468641	-0.164	0.999	N	0.523	0.136	0.401185642668	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
E/D	rs768468641	-0.164	0.999	N	0.523	0.136	0.401185642668	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.41E-05	0	0	0	0
E/D	rs768468641	-0.164	0.999	N	0.523	0.136	0.401185642668	gnomAD-4.0.0	6.84273E-07	None	None	None	None	N	None	0	0	None	0	2.51953E-05	None	0	0	0	0	0
E/G	None	None	1.0	N	0.713	0.342	0.451599300725	gnomAD-4.0.0	1.59159E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85922E-06	0	0
E/K	None	0.546	0.999	N	0.649	0.327	0.332386209738	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.66E-05	0
E/K	None	0.546	0.999	N	0.649	0.327	0.332386209738	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	7.35E-05	0	0
E/K	None	0.546	0.999	N	0.649	0.327	0.332386209738	gnomAD-4.0.0	1.42541E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.86493E-05	0	1.60138E-05
E/Q	rs763344306	0.126	1.0	N	0.685	0.244	0.340992353424	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	4.13E-05	0	None	0	0	None	0	None	0	1.56E-05	1.4041E-04
E/Q	rs763344306	0.126	1.0	N	0.685	0.244	0.340992353424	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
E/Q	rs763344306	0.126	1.0	N	0.685	0.244	0.340992353424	gnomAD-4.0.0	2.47897E-06	None	None	None	None	N	None	2.66951E-05	0	None	0	0	None	0	0	8.47693E-07	0	1.60138E-05

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	0.4987	ambiguous	0.4776	ambiguous	-0.54	Destabilizing	0.999	D	0.701	prob.neutral	N	0.466836108	None	None	N
E/C	0.9701	likely_pathogenic	0.959	pathogenic	-0.24	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
E/D	0.3201	likely_benign	0.2963	benign	-0.511	Destabilizing	0.999	D	0.523	neutral	N	0.466266676	None	None	N
E/F	0.95	likely_pathogenic	0.9311	pathogenic	-0.201	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/G	0.6925	likely_pathogenic	0.6883	pathogenic	-0.782	Destabilizing	1.0	D	0.713	prob.delet.	N	0.476319535	None	None	N
E/H	0.8366	likely_pathogenic	0.7928	pathogenic	-0.01	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/I	0.6876	likely_pathogenic	0.6094	pathogenic	0.082	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/K	0.5139	ambiguous	0.4859	ambiguous	0.133	Stabilizing	0.999	D	0.649	neutral	N	0.45889178	None	None	N
E/L	0.7547	likely_pathogenic	0.7056	pathogenic	0.082	Stabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
E/M	0.7901	likely_pathogenic	0.7443	pathogenic	0.171	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/N	0.6821	likely_pathogenic	0.6621	pathogenic	-0.342	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/P	0.9871	likely_pathogenic	0.9891	pathogenic	-0.105	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/Q	0.3524	ambiguous	0.3205	benign	-0.275	Destabilizing	1.0	D	0.685	prob.neutral	N	0.498988964	None	None	N
E/R	0.6613	likely_pathogenic	0.628	pathogenic	0.421	Stabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
E/S	0.5682	likely_pathogenic	0.546	ambiguous	-0.501	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
E/T	0.5742	likely_pathogenic	0.5355	ambiguous	-0.299	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/V	0.4549	ambiguous	0.3967	ambiguous	-0.105	Destabilizing	1.0	D	0.777	deleterious	N	0.497604884	None	None	N
E/W	0.987	likely_pathogenic	0.9816	pathogenic	0.03	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/Y	0.9232	likely_pathogenic	0.8952	pathogenic	0.057	Stabilizing	1.0	D	0.783	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.