TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25451	76576;76577;76578	chr2:178569781;178569780;178569779	chr2:179434508;179434507;179434506
N2AB	23810	71653;71654;71655	chr2:178569781;178569780;178569779	chr2:179434508;179434507;179434506
N2A	22883	68872;68873;68874	chr2:178569781;178569780;178569779	chr2:179434508;179434507;179434506
N2B	16386	49381;49382;49383	chr2:178569781;178569780;178569779	chr2:179434508;179434507;179434506
Novex-1	16511	49756;49757;49758	chr2:178569781;178569780;178569779	chr2:179434508;179434507;179434506
Novex-2	16578	49957;49958;49959	chr2:178569781;178569780;178569779	chr2:179434508;179434507;179434506
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: Fn3-73
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.7068
• 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/G	None	None	0.822	N	0.483	0.331	0.371344866733	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1761	likely_benign	0.1584	benign	-0.441	Destabilizing	0.822	D	0.545	neutral	N	0.471332786	None	None	I
E/C	0.7719	likely_pathogenic	0.7195	pathogenic	-0.185	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	I
E/D	0.0978	likely_benign	0.0805	benign	-0.283	Destabilizing	0.006	N	0.372	neutral	N	0.503242777	None	None	I
E/F	0.6692	likely_pathogenic	0.6136	pathogenic	-0.251	Destabilizing	0.998	D	0.66	neutral	None	None	None	None	I
E/G	0.1783	likely_benign	0.1651	benign	-0.636	Destabilizing	0.822	D	0.483	neutral	N	0.520116385	None	None	I
E/H	0.4008	ambiguous	0.3576	ambiguous	0.094	Stabilizing	0.998	D	0.561	neutral	None	None	None	None	I
E/I	0.2701	likely_benign	0.2369	benign	0.041	Stabilizing	0.978	D	0.672	neutral	None	None	None	None	I
E/K	0.12	likely_benign	0.1224	benign	0.2	Stabilizing	0.822	D	0.528	neutral	N	0.509592747	None	None	I
E/L	0.3368	likely_benign	0.2965	benign	0.041	Stabilizing	0.978	D	0.653	neutral	None	None	None	None	I
E/M	0.3746	ambiguous	0.3399	benign	0.064	Stabilizing	0.998	D	0.619	neutral	None	None	None	None	I
E/N	0.1701	likely_benign	0.1431	benign	-0.112	Destabilizing	0.915	D	0.512	neutral	None	None	None	None	I
E/P	0.6642	likely_pathogenic	0.5682	pathogenic	-0.1	Destabilizing	0.978	D	0.547	neutral	None	None	None	None	I
E/Q	0.1315	likely_benign	0.1288	benign	-0.065	Destabilizing	0.942	D	0.499	neutral	N	0.489564191	None	None	I
E/R	0.2495	likely_benign	0.2481	benign	0.486	Stabilizing	0.978	D	0.546	neutral	None	None	None	None	I
E/S	0.1793	likely_benign	0.1562	benign	-0.293	Destabilizing	0.754	D	0.526	neutral	None	None	None	None	I
E/T	0.1878	likely_benign	0.172	benign	-0.13	Destabilizing	0.956	D	0.534	neutral	None	None	None	None	I
E/V	0.1781	likely_benign	0.1589	benign	-0.1	Destabilizing	0.971	D	0.598	neutral	N	0.520772532	None	None	I
E/W	0.8772	likely_pathogenic	0.8476	pathogenic	-0.075	Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	I
E/Y	0.5424	ambiguous	0.4821	ambiguous	-0.006	Destabilizing	0.998	D	0.604	neutral	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.