TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26924	80995;80996;80997	chr2:178565362;178565361;178565360	chr2:179430089;179430088;179430087
N2AB	25283	76072;76073;76074	chr2:178565362;178565361;178565360	chr2:179430089;179430088;179430087
N2A	24356	73291;73292;73293	chr2:178565362;178565361;178565360	chr2:179430089;179430088;179430087
N2B	17859	53800;53801;53802	chr2:178565362;178565361;178565360	chr2:179430089;179430088;179430087
Novex-1	17984	54175;54176;54177	chr2:178565362;178565361;178565360	chr2:179430089;179430088;179430087
Novex-2	18051	54376;54377;54378	chr2:178565362;178565361;178565360	chr2:179430089;179430088;179430087
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-139
• Domain position: 45
• Structural Position: 109
• Q(SASA): 0.8026
• 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
T/P	None	None	1.0	N	0.605	0.379	0.267299060538	gnomAD-4.0.0	1.36855E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79909E-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
T/A	0.1719	likely_benign	0.1673	benign	-0.134	Destabilizing	0.999	D	0.481	neutral	N	0.489472899	None	None	N
T/C	0.8621	likely_pathogenic	0.8568	pathogenic	-0.273	Destabilizing	1.0	D	0.628	neutral	None	None	None	None	N
T/D	0.8556	likely_pathogenic	0.819	pathogenic	0.029	Stabilizing	1.0	D	0.602	neutral	None	None	None	None	N
T/E	0.7608	likely_pathogenic	0.7123	pathogenic	-0.061	Destabilizing	1.0	D	0.606	neutral	None	None	None	None	N
T/F	0.7315	likely_pathogenic	0.7156	pathogenic	-0.785	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
T/G	0.4683	ambiguous	0.4478	ambiguous	-0.203	Destabilizing	1.0	D	0.595	neutral	None	None	None	None	N
T/H	0.7273	likely_pathogenic	0.6956	pathogenic	-0.395	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
T/I	0.6085	likely_pathogenic	0.5841	pathogenic	-0.077	Destabilizing	1.0	D	0.597	neutral	N	0.47131438	None	None	N
T/K	0.6183	likely_pathogenic	0.5761	pathogenic	-0.252	Destabilizing	1.0	D	0.605	neutral	N	0.476813033	None	None	N
T/L	0.2491	likely_benign	0.2466	benign	-0.077	Destabilizing	0.999	D	0.533	neutral	None	None	None	None	N
T/M	0.1725	likely_benign	0.1736	benign	-0.081	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	N
T/N	0.421	ambiguous	0.4005	ambiguous	-0.024	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
T/P	0.3515	ambiguous	0.346	ambiguous	-0.071	Destabilizing	1.0	D	0.605	neutral	N	0.484104364	None	None	N
T/Q	0.5365	ambiguous	0.5056	ambiguous	-0.236	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
T/R	0.5685	likely_pathogenic	0.5254	ambiguous	0.032	Stabilizing	1.0	D	0.614	neutral	N	0.470521778	None	None	N
T/S	0.2142	likely_benign	0.2071	benign	-0.183	Destabilizing	0.999	D	0.486	neutral	N	0.420111601	None	None	N
T/V	0.3786	ambiguous	0.3618	ambiguous	-0.071	Destabilizing	0.999	D	0.545	neutral	None	None	None	None	N
T/W	0.9246	likely_pathogenic	0.9173	pathogenic	-0.875	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
T/Y	0.7777	likely_pathogenic	0.7585	pathogenic	-0.549	Destabilizing	1.0	D	0.661	neutral	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.