TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8257	24994;24995;24996	chr2:178718337;178718336;178718335	chr2:179583064;179583063;179583062
N2AB	7940	24043;24044;24045	chr2:178718337;178718336;178718335	chr2:179583064;179583063;179583062
N2A	7013	21262;21263;21264	chr2:178718337;178718336;178718335	chr2:179583064;179583063;179583062
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-67
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.3241
• 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
L/V	rs371322658	-0.799	None	N	0.181	0.083	None	gnomAD-2.1.1	2.86E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.27E-05	0
L/V	rs371322658	-0.799	None	N	0.181	0.083	None	gnomAD-3.1.2	3.94E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	8.82E-05	0	0
L/V	rs371322658	-0.799	None	N	0.181	0.083	None	gnomAD-4.0.0	3.09921E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.2389E-05	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
L/A	0.1337	likely_benign	0.1497	benign	-1.784	Destabilizing	0.035	N	0.479	neutral	None	None	None	None	N
L/C	0.5096	ambiguous	0.5469	ambiguous	-1.123	Destabilizing	0.824	D	0.587	neutral	None	None	None	None	N
L/D	0.3938	ambiguous	0.4564	ambiguous	-1.033	Destabilizing	0.081	N	0.635	neutral	None	None	None	None	N
L/E	0.1748	likely_benign	0.196	benign	-1.007	Destabilizing	0.002	N	0.403	neutral	None	None	None	None	N
L/F	0.1087	likely_benign	0.1177	benign	-1.274	Destabilizing	0.38	N	0.591	neutral	None	None	None	None	N
L/G	0.3976	ambiguous	0.4347	ambiguous	-2.129	Highly Destabilizing	0.262	N	0.643	neutral	None	None	None	None	N
L/H	0.1419	likely_benign	0.1499	benign	-1.276	Destabilizing	0.555	D	0.635	neutral	None	None	None	None	N
L/I	0.077	likely_benign	0.089	benign	-0.897	Destabilizing	0.029	N	0.463	neutral	None	None	None	None	N
L/K	0.1196	likely_benign	0.1455	benign	-1.05	Destabilizing	0.081	N	0.645	neutral	None	None	None	None	N
L/M	0.0953	likely_benign	0.0981	benign	-0.698	Destabilizing	0.317	N	0.583	neutral	N	0.498961646	None	None	N
L/N	0.1845	likely_benign	0.2274	benign	-0.908	Destabilizing	0.555	D	0.67	neutral	None	None	None	None	N
L/P	0.5291	ambiguous	0.5765	pathogenic	-1.162	Destabilizing	None	N	0.423	neutral	N	0.498708157	None	None	N
L/Q	0.0916	likely_benign	0.0996	benign	-1.075	Destabilizing	0.012	N	0.381	neutral	N	0.453326537	None	None	N
L/R	0.1057	likely_benign	0.1154	benign	-0.481	Destabilizing	0.317	N	0.667	neutral	N	0.450440948	None	None	N
L/S	0.1367	likely_benign	0.1595	benign	-1.618	Destabilizing	0.081	N	0.613	neutral	None	None	None	None	N
L/T	0.1086	likely_benign	0.1236	benign	-1.471	Destabilizing	0.002	N	0.225	neutral	None	None	None	None	N
L/V	0.0744	likely_benign	0.0793	benign	-1.162	Destabilizing	None	N	0.181	neutral	N	0.498098822	None	None	N
L/W	0.204	likely_benign	0.201	benign	-1.329	Destabilizing	0.935	D	0.623	neutral	None	None	None	None	N
L/Y	0.2529	likely_benign	0.275	benign	-1.096	Destabilizing	0.555	D	0.641	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.