TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16842	50749;50750;50751	chr2:178611785;178611784;178611783	chr2:179476512;179476511;179476510
N2AB	15201	45826;45827;45828	chr2:178611785;178611784;178611783	chr2:179476512;179476511;179476510
N2A	14274	43045;43046;43047	chr2:178611785;178611784;178611783	chr2:179476512;179476511;179476510
N2B	7777	23554;23555;23556	chr2:178611785;178611784;178611783	chr2:179476512;179476511;179476510
Novex-1	7902	23929;23930;23931	chr2:178611785;178611784;178611783	chr2:179476512;179476511;179476510
Novex-2	7969	24130;24131;24132	chr2:178611785;178611784;178611783	chr2:179476512;179476511;179476510
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: Fn3-10
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.4887
• 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	None	None	0.799	N	0.571	0.221	0.292062946507	gnomAD-4.0.0	1.59391E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86229E-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	0.2504	likely_benign	0.2078	benign	-0.116	Destabilizing	0.799	D	0.596	neutral	N	0.470490728	None	None	I
E/C	0.9248	likely_pathogenic	0.8994	pathogenic	-0.309	Destabilizing	0.998	D	0.82	deleterious	None	None	None	None	I
E/D	0.0717	likely_benign	0.0717	benign	-0.304	Destabilizing	0.002	N	0.169	neutral	N	0.455392981	None	None	I
E/F	0.919	likely_pathogenic	0.8807	pathogenic	-0.034	Destabilizing	0.991	D	0.789	deleterious	None	None	None	None	I
E/G	0.2534	likely_benign	0.2084	benign	-0.261	Destabilizing	0.799	D	0.587	neutral	N	0.473923389	None	None	I
E/H	0.7066	likely_pathogenic	0.6192	pathogenic	0.604	Stabilizing	0.991	D	0.55	neutral	None	None	None	None	I
E/I	0.6387	likely_pathogenic	0.5696	pathogenic	0.217	Stabilizing	0.974	D	0.798	deleterious	None	None	None	None	I
E/K	0.3485	ambiguous	0.2443	benign	0.328	Stabilizing	0.799	D	0.571	neutral	N	0.471862583	None	None	I
E/L	0.6343	likely_pathogenic	0.5807	pathogenic	0.217	Stabilizing	0.974	D	0.745	deleterious	None	None	None	None	I
E/M	0.7169	likely_pathogenic	0.6407	pathogenic	-0.045	Destabilizing	0.998	D	0.761	deleterious	None	None	None	None	I
E/N	0.2709	likely_benign	0.2269	benign	-0.002	Destabilizing	0.725	D	0.582	neutral	None	None	None	None	I
E/P	0.5304	ambiguous	0.4868	ambiguous	0.125	Stabilizing	0.974	D	0.589	neutral	None	None	None	None	I
E/Q	0.2788	likely_benign	0.2239	benign	0.03	Stabilizing	0.89	D	0.546	neutral	N	0.47138682	None	None	I
E/R	0.5437	ambiguous	0.4191	ambiguous	0.658	Stabilizing	0.974	D	0.538	neutral	None	None	None	None	I
E/S	0.2561	likely_benign	0.2151	benign	-0.15	Destabilizing	0.841	D	0.568	neutral	None	None	None	None	I
E/T	0.3655	ambiguous	0.3041	benign	-0.021	Destabilizing	0.841	D	0.638	neutral	None	None	None	None	I
E/V	0.4019	ambiguous	0.341	ambiguous	0.125	Stabilizing	0.966	D	0.649	prob.neutral	N	0.466674818	None	None	I
E/W	0.9756	likely_pathogenic	0.9581	pathogenic	0.061	Stabilizing	0.998	D	0.815	deleterious	None	None	None	None	I
E/Y	0.8375	likely_pathogenic	0.7708	pathogenic	0.201	Stabilizing	0.991	D	0.775	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.