TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5759	17500;17501;17502	chr2:178731491;178731490;178731489	chr2:179596218;179596217;179596216
N2AB	5442	16549;16550;16551	chr2:178731491;178731490;178731489	chr2:179596218;179596217;179596216
N2A	4515	13768;13769;13770	chr2:178731491;178731490;178731489	chr2:179596218;179596217;179596216
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-41
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.2046
• 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
I/V	rs1365586736	-1.275	0.267	N	0.395	0.093	0.388174495139	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/V	rs1365586736	-1.275	0.267	N	0.395	0.093	0.388174495139	gnomAD-4.0.0	2.73715E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	1.73551E-04	1.79901E-06	1.15939E-05	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
I/A	0.7963	likely_pathogenic	0.7901	pathogenic	-2.489	Highly Destabilizing	0.688	D	0.429	neutral	None	None	None	None	I
I/C	0.9351	likely_pathogenic	0.9299	pathogenic	-1.781	Destabilizing	0.998	D	0.545	neutral	None	None	None	None	I
I/D	0.9904	likely_pathogenic	0.9902	pathogenic	-2.331	Highly Destabilizing	0.974	D	0.613	neutral	None	None	None	None	I
I/E	0.9756	likely_pathogenic	0.9747	pathogenic	-2.156	Highly Destabilizing	0.974	D	0.619	neutral	None	None	None	None	I
I/F	0.4517	ambiguous	0.4465	ambiguous	-1.52	Destabilizing	0.934	D	0.533	neutral	D	0.536059777	None	None	I
I/G	0.9701	likely_pathogenic	0.9685	pathogenic	-3.006	Highly Destabilizing	0.974	D	0.618	neutral	None	None	None	None	I
I/H	0.9704	likely_pathogenic	0.9703	pathogenic	-2.342	Highly Destabilizing	0.998	D	0.589	neutral	None	None	None	None	I
I/K	0.9429	likely_pathogenic	0.9471	pathogenic	-1.868	Destabilizing	0.974	D	0.621	neutral	None	None	None	None	I
I/L	0.1664	likely_benign	0.1587	benign	-1.026	Destabilizing	0.005	N	0.108	neutral	N	0.458500283	None	None	I
I/M	0.1551	likely_benign	0.1469	benign	-0.93	Destabilizing	0.136	N	0.294	neutral	N	0.48380416	None	None	I
I/N	0.9035	likely_pathogenic	0.8989	pathogenic	-2.014	Highly Destabilizing	0.989	D	0.631	neutral	N	0.500949882	None	None	I
I/P	0.9255	likely_pathogenic	0.9352	pathogenic	-1.491	Destabilizing	0.016	N	0.363	neutral	None	None	None	None	I
I/Q	0.946	likely_pathogenic	0.9446	pathogenic	-1.957	Destabilizing	0.974	D	0.629	neutral	None	None	None	None	I
I/R	0.919	likely_pathogenic	0.9248	pathogenic	-1.496	Destabilizing	0.974	D	0.631	neutral	None	None	None	None	I
I/S	0.8893	likely_pathogenic	0.8854	pathogenic	-2.774	Highly Destabilizing	0.891	D	0.528	neutral	N	0.500442903	None	None	I
I/T	0.86	likely_pathogenic	0.8609	pathogenic	-2.452	Highly Destabilizing	0.891	D	0.526	neutral	N	0.489086598	None	None	I
I/V	0.088	likely_benign	0.0872	benign	-1.491	Destabilizing	0.267	N	0.395	neutral	N	0.5127402	None	None	I
I/W	0.9686	likely_pathogenic	0.971	pathogenic	-1.803	Destabilizing	0.998	D	0.611	neutral	None	None	None	None	I
I/Y	0.887	likely_pathogenic	0.8897	pathogenic	-1.545	Destabilizing	0.974	D	0.593	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.