TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24382	73369;73370;73371	chr2:178572988;178572987;178572986	chr2:179437715;179437714;179437713
N2AB	22741	68446;68447;68448	chr2:178572988;178572987;178572986	chr2:179437715;179437714;179437713
N2A	21814	65665;65666;65667	chr2:178572988;178572987;178572986	chr2:179437715;179437714;179437713
N2B	15317	46174;46175;46176	chr2:178572988;178572987;178572986	chr2:179437715;179437714;179437713
Novex-1	15442	46549;46550;46551	chr2:178572988;178572987;178572986	chr2:179437715;179437714;179437713
Novex-2	15509	46750;46751;46752	chr2:178572988;178572987;178572986	chr2:179437715;179437714;179437713
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-65
• Domain position: 60
• Structural Position: 89
• Q(SASA): 0.3185
• 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
T/N	None	None	0.999	N	0.579	0.351	0.342168650903	gnomAD-4.0.0	1.59273E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88352E-05	0	0	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
T/A	0.0984	likely_benign	0.092	benign	-0.998	Destabilizing	0.996	D	0.507	neutral	N	0.50811291	None	None	I
T/C	0.3768	ambiguous	0.4051	ambiguous	-0.568	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
T/D	0.6903	likely_pathogenic	0.6857	pathogenic	-0.044	Destabilizing	0.999	D	0.636	neutral	None	None	None	None	I
T/E	0.6234	likely_pathogenic	0.6094	pathogenic	0.033	Stabilizing	0.994	D	0.561	neutral	None	None	None	None	I
T/F	0.5443	ambiguous	0.5352	ambiguous	-1.022	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
T/G	0.2938	likely_benign	0.2927	benign	-1.309	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	I
T/H	0.4256	ambiguous	0.4617	ambiguous	-1.353	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
T/I	0.3916	ambiguous	0.398	ambiguous	-0.236	Destabilizing	1.0	D	0.689	prob.neutral	N	0.50161845	None	None	I
T/K	0.2668	likely_benign	0.3234	benign	-0.442	Destabilizing	0.994	D	0.596	neutral	None	None	None	None	I
T/L	0.1352	likely_benign	0.1413	benign	-0.236	Destabilizing	0.998	D	0.561	neutral	None	None	None	None	I
T/M	0.1351	likely_benign	0.1352	benign	-0.155	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
T/N	0.1586	likely_benign	0.1622	benign	-0.676	Destabilizing	0.999	D	0.579	neutral	N	0.476321719	None	None	I
T/P	0.1228	likely_benign	0.1404	benign	-0.458	Destabilizing	1.0	D	0.689	prob.neutral	N	0.476019004	None	None	I
T/Q	0.3031	likely_benign	0.3243	benign	-0.642	Destabilizing	0.967	D	0.421	neutral	None	None	None	None	I
T/R	0.2326	likely_benign	0.2763	benign	-0.357	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	I
T/S	0.1543	likely_benign	0.1462	benign	-1.043	Destabilizing	0.996	D	0.474	neutral	N	0.471966852	None	None	I
T/V	0.2273	likely_benign	0.2348	benign	-0.458	Destabilizing	0.998	D	0.505	neutral	None	None	None	None	I
T/W	0.857	likely_pathogenic	0.8704	pathogenic	-0.991	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
T/Y	0.5591	ambiguous	0.5766	pathogenic	-0.701	Destabilizing	1.0	D	0.759	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.