TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5184	15775;15776;15777	chr2:178733839;178733838;178733837	chr2:179598566;179598565;179598564
N2AB	4867	14824;14825;14826	chr2:178733839;178733838;178733837	chr2:179598566;179598565;179598564
N2A	3940	12043;12044;12045	chr2:178733839;178733838;178733837	chr2:179598566;179598565;179598564
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-35
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.3808
• 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/A	None	None	0.022	N	0.111	0.079	0.110078149338	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
T/I	None	None	0.966	D	0.412	0.286	0.348764635752	gnomAD-4.0.0	6.84379E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99685E-07	0	0
T/N	None	None	0.005	N	0.106	0.055	0.202086224978	gnomAD-4.0.0	6.84379E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99685E-07	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	0.0674	likely_benign	0.071	benign	-0.526	Destabilizing	0.022	N	0.111	neutral	N	0.456848273	None	None	I
T/C	0.3513	ambiguous	0.434	ambiguous	-0.38	Destabilizing	0.998	D	0.389	neutral	None	None	None	None	I
T/D	0.2244	likely_benign	0.2762	benign	0.201	Stabilizing	0.728	D	0.351	neutral	None	None	None	None	I
T/E	0.1762	likely_benign	0.202	benign	0.178	Stabilizing	0.842	D	0.349	neutral	None	None	None	None	I
T/F	0.1914	likely_benign	0.2315	benign	-0.741	Destabilizing	0.991	D	0.394	neutral	None	None	None	None	I
T/G	0.1919	likely_benign	0.2308	benign	-0.745	Destabilizing	0.525	D	0.357	neutral	None	None	None	None	I
T/H	0.1854	likely_benign	0.2205	benign	-1.037	Destabilizing	0.974	D	0.375	neutral	None	None	None	None	I
T/I	0.126	likely_benign	0.1469	benign	-0.052	Destabilizing	0.966	D	0.412	neutral	D	0.541294959	None	None	I
T/K	0.1393	likely_benign	0.1587	benign	-0.514	Destabilizing	0.842	D	0.351	neutral	None	None	None	None	I
T/L	0.086	likely_benign	0.0929	benign	-0.052	Destabilizing	0.842	D	0.343	neutral	None	None	None	None	I
T/M	0.0708	likely_benign	0.0716	benign	0.065	Stabilizing	0.991	D	0.393	neutral	None	None	None	None	I
T/N	0.0841	likely_benign	0.0966	benign	-0.413	Destabilizing	0.005	N	0.106	neutral	N	0.451375931	None	None	I
T/P	0.0807	likely_benign	0.084	benign	-0.178	Destabilizing	0.012	N	0.248	neutral	N	0.448027187	None	None	I
T/Q	0.1542	likely_benign	0.1724	benign	-0.555	Destabilizing	0.974	D	0.432	neutral	None	None	None	None	I
T/R	0.1171	likely_benign	0.1294	benign	-0.317	Destabilizing	0.842	D	0.405	neutral	None	None	None	None	I
T/S	0.0852	likely_benign	0.0955	benign	-0.678	Destabilizing	0.136	N	0.133	neutral	N	0.447308652	None	None	I
T/V	0.1037	likely_benign	0.1164	benign	-0.178	Destabilizing	0.842	D	0.231	neutral	None	None	None	None	I
T/W	0.4915	ambiguous	0.5501	ambiguous	-0.719	Destabilizing	0.998	D	0.474	neutral	None	None	None	None	I
T/Y	0.2043	likely_benign	0.2499	benign	-0.455	Destabilizing	0.991	D	0.392	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.