TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5462	16609;16610;16611	chr2:178732677;178732676;178732675	chr2:179597404;179597403;179597402
N2AB	5145	15658;15659;15660	chr2:178732677;178732676;178732675	chr2:179597404;179597403;179597402
N2A	4218	12877;12878;12879	chr2:178732677;178732676;178732675	chr2:179597404;179597403;179597402
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-38
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.8625
• 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
L/P	None	None	0.995	N	0.638	0.477	0.864942860777	gnomAD-4.0.0	1.37563E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.35211E-05	0
L/Q	rs778031659	-0.257	0.995	N	0.613	0.269	0.833684530568	gnomAD-2.1.1	4.16E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.12E-06	0
L/Q	rs778031659	-0.257	0.995	N	0.613	0.269	0.833684530568	gnomAD-4.0.0	6.87817E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.02433E-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
L/A	0.1852	likely_benign	0.2081	benign	-0.741	Destabilizing	0.851	D	0.548	neutral	None	None	None	None	I
L/C	0.4954	ambiguous	0.5434	ambiguous	-0.785	Destabilizing	0.999	D	0.537	neutral	None	None	None	None	I
L/D	0.5264	ambiguous	0.6129	pathogenic	-0.061	Destabilizing	0.996	D	0.639	neutral	None	None	None	None	I
L/E	0.2701	likely_benign	0.3155	benign	-0.115	Destabilizing	0.988	D	0.639	neutral	None	None	None	None	I
L/F	0.128	likely_benign	0.155	benign	-0.526	Destabilizing	0.976	D	0.473	neutral	None	None	None	None	I
L/G	0.4279	ambiguous	0.479	ambiguous	-0.947	Destabilizing	0.988	D	0.635	neutral	None	None	None	None	I
L/H	0.2023	likely_benign	0.2342	benign	-0.113	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	I
L/I	0.089	likely_benign	0.097	benign	-0.305	Destabilizing	0.015	N	0.232	neutral	None	None	None	None	I
L/K	0.2234	likely_benign	0.2409	benign	-0.484	Destabilizing	0.988	D	0.609	neutral	None	None	None	None	I
L/M	0.1292	likely_benign	0.1354	benign	-0.472	Destabilizing	0.984	D	0.457	neutral	D	0.532019394	None	None	I
L/N	0.2882	likely_benign	0.3389	benign	-0.385	Destabilizing	0.996	D	0.64	neutral	None	None	None	None	I
L/P	0.1478	likely_benign	0.1715	benign	-0.417	Destabilizing	0.995	D	0.638	neutral	N	0.520167605	None	None	I
L/Q	0.1329	likely_benign	0.1428	benign	-0.539	Destabilizing	0.995	D	0.613	neutral	N	0.505870156	None	None	I
L/R	0.1733	likely_benign	0.1895	benign	0.038	Stabilizing	0.984	D	0.609	neutral	N	0.519588815	None	None	I
L/S	0.1808	likely_benign	0.2132	benign	-0.904	Destabilizing	0.988	D	0.575	neutral	None	None	None	None	I
L/T	0.1814	likely_benign	0.2004	benign	-0.842	Destabilizing	0.919	D	0.527	neutral	None	None	None	None	I
L/V	0.0953	likely_benign	0.1008	benign	-0.417	Destabilizing	0.026	N	0.273	neutral	D	0.528979089	None	None	I
L/W	0.2632	likely_benign	0.3229	benign	-0.553	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	I
L/Y	0.3035	likely_benign	0.3592	ambiguous	-0.32	Destabilizing	0.988	D	0.496	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.