TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2445	7558;7559;7560	chr2:178773723;178773722;178773721	chr2:179638450;179638449;179638448
N2AB	2445	7558;7559;7560	chr2:178773723;178773722;178773721	chr2:179638450;179638449;179638448
N2A	2445	7558;7559;7560	chr2:178773723;178773722;178773721	chr2:179638450;179638449;179638448
N2B	2399	7420;7421;7422	chr2:178773723;178773722;178773721	chr2:179638450;179638449;179638448
Novex-1	2399	7420;7421;7422	chr2:178773723;178773722;178773721	chr2:179638450;179638449;179638448
Novex-2	2399	7420;7421;7422	chr2:178773723;178773722;178773721	chr2:179638450;179638449;179638448
Novex-3	2445	7558;7559;7560	chr2:178773723;178773722;178773721	chr2:179638450;179638449;179638448

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-14
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.9469
• 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
V/G	None	None	0.999	D	0.585	0.658	0.838309375149	gnomAD-4.0.0	3.60349E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.94021E-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
V/A	0.2728	likely_benign	0.2746	benign	-0.915	Destabilizing	0.948	D	0.543	neutral	N	0.506035732	None	None	I
V/C	0.8747	likely_pathogenic	0.8712	pathogenic	-0.881	Destabilizing	1.0	D	0.494	neutral	None	None	None	None	I
V/D	0.9412	likely_pathogenic	0.9478	pathogenic	-0.512	Destabilizing	0.999	D	0.583	neutral	None	None	None	None	I
V/E	0.8844	likely_pathogenic	0.8958	pathogenic	-0.556	Destabilizing	0.999	D	0.533	neutral	D	0.541237069	None	None	I
V/F	0.5731	likely_pathogenic	0.5838	pathogenic	-0.782	Destabilizing	0.998	D	0.464	neutral	None	None	None	None	I
V/G	0.6079	likely_pathogenic	0.6124	pathogenic	-1.163	Destabilizing	0.999	D	0.585	neutral	D	0.541795808	None	None	I
V/H	0.9676	likely_pathogenic	0.9713	pathogenic	-0.707	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	I
V/I	0.1057	likely_benign	0.1048	benign	-0.371	Destabilizing	0.246	N	0.301	neutral	None	None	None	None	I
V/K	0.928	likely_pathogenic	0.9362	pathogenic	-0.87	Destabilizing	0.999	D	0.533	neutral	None	None	None	None	I
V/L	0.4703	ambiguous	0.468	ambiguous	-0.371	Destabilizing	0.9	D	0.488	neutral	N	0.497866407	None	None	I
V/M	0.3249	likely_benign	0.3308	benign	-0.433	Destabilizing	0.997	D	0.463	neutral	N	0.506413469	None	None	I
V/N	0.8677	likely_pathogenic	0.874	pathogenic	-0.659	Destabilizing	0.999	D	0.583	neutral	None	None	None	None	I
V/P	0.7944	likely_pathogenic	0.7979	pathogenic	-0.516	Destabilizing	0.999	D	0.523	neutral	None	None	None	None	I
V/Q	0.9023	likely_pathogenic	0.9097	pathogenic	-0.81	Destabilizing	0.999	D	0.523	neutral	None	None	None	None	I
V/R	0.903	likely_pathogenic	0.9114	pathogenic	-0.403	Destabilizing	0.999	D	0.578	neutral	None	None	None	None	I
V/S	0.5917	likely_pathogenic	0.5974	pathogenic	-1.135	Destabilizing	0.999	D	0.502	neutral	None	None	None	None	I
V/T	0.3484	ambiguous	0.338	benign	-1.06	Destabilizing	0.992	D	0.467	neutral	None	None	None	None	I
V/W	0.9819	likely_pathogenic	0.984	pathogenic	-0.919	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
V/Y	0.9366	likely_pathogenic	0.9419	pathogenic	-0.621	Destabilizing	0.999	D	0.452	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.