TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32778	98557;98558;98559	chr2:178539733;178539732;178539731	chr2:179404460;179404459;179404458
N2AB	31137	93634;93635;93636	chr2:178539733;178539732;178539731	chr2:179404460;179404459;179404458
N2A	30210	90853;90854;90855	chr2:178539733;178539732;178539731	chr2:179404460;179404459;179404458
N2B	23713	71362;71363;71364	chr2:178539733;178539732;178539731	chr2:179404460;179404459;179404458
Novex-1	23838	71737;71738;71739	chr2:178539733;178539732;178539731	chr2:179404460;179404459;179404458
Novex-2	23905	71938;71939;71940	chr2:178539733;178539732;178539731	chr2:179404460;179404459;179404458
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: Ig-155
• Domain position: 71
• Structural Position: 159
• Q(SASA): 0.2802
• 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	rs771233778	-0.416	0.067	N	0.328	0.264	0.245660935333	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs771233778	-0.416	0.067	N	0.328	0.264	0.245660935333	gnomAD-4.0.0	4.77374E-06	None	None	None	None	I	None	0	2.28666E-05	None	0	0	None	0	0	0	2.86541E-05	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	0.5463	ambiguous	0.5892	pathogenic	-0.869	Destabilizing	0.919	D	0.589	neutral	D	0.534963699	None	None	I
E/C	0.9591	likely_pathogenic	0.9662	pathogenic	-0.275	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
E/D	0.5768	likely_pathogenic	0.5997	pathogenic	-0.8	Destabilizing	0.958	D	0.457	neutral	N	0.484606827	None	None	I
E/F	0.9646	likely_pathogenic	0.9708	pathogenic	-0.571	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
E/G	0.6407	likely_pathogenic	0.7039	pathogenic	-1.158	Destabilizing	0.988	D	0.707	prob.neutral	N	0.48553188	None	None	I
E/H	0.8533	likely_pathogenic	0.8713	pathogenic	-0.713	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	I
E/I	0.7939	likely_pathogenic	0.8158	pathogenic	-0.105	Destabilizing	0.995	D	0.805	deleterious	None	None	None	None	I
E/K	0.5833	likely_pathogenic	0.6307	pathogenic	-0.165	Destabilizing	0.067	N	0.328	neutral	N	0.500176335	None	None	I
E/L	0.8621	likely_pathogenic	0.8808	pathogenic	-0.105	Destabilizing	0.991	D	0.769	deleterious	None	None	None	None	I
E/M	0.8273	likely_pathogenic	0.8477	pathogenic	0.297	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
E/N	0.7816	likely_pathogenic	0.8047	pathogenic	-0.6	Destabilizing	0.991	D	0.697	prob.neutral	None	None	None	None	I
E/P	0.9972	likely_pathogenic	0.9977	pathogenic	-0.339	Destabilizing	0.995	D	0.731	prob.delet.	None	None	None	None	I
E/Q	0.2904	likely_benign	0.3076	benign	-0.534	Destabilizing	0.958	D	0.619	neutral	N	0.52032232	None	None	I
E/R	0.7237	likely_pathogenic	0.7602	pathogenic	0.011	Stabilizing	0.982	D	0.703	prob.neutral	None	None	None	None	I
E/S	0.5884	likely_pathogenic	0.6245	pathogenic	-0.83	Destabilizing	0.968	D	0.623	neutral	None	None	None	None	I
E/T	0.5725	likely_pathogenic	0.6111	pathogenic	-0.587	Destabilizing	0.991	D	0.673	neutral	None	None	None	None	I
E/V	0.6033	likely_pathogenic	0.6395	pathogenic	-0.339	Destabilizing	0.988	D	0.763	deleterious	N	0.516628654	None	None	I
E/W	0.9818	likely_pathogenic	0.9857	pathogenic	-0.321	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
E/Y	0.9388	likely_pathogenic	0.9503	pathogenic	-0.307	Destabilizing	0.998	D	0.784	deleterious	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.