TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26268	79027;79028;79029	chr2:178567330;178567329;178567328	chr2:179432057;179432056;179432055
N2AB	24627	74104;74105;74106	chr2:178567330;178567329;178567328	chr2:179432057;179432056;179432055
N2A	23700	71323;71324;71325	chr2:178567330;178567329;178567328	chr2:179432057;179432056;179432055
N2B	17203	51832;51833;51834	chr2:178567330;178567329;178567328	chr2:179432057;179432056;179432055
Novex-1	17328	52207;52208;52209	chr2:178567330;178567329;178567328	chr2:179432057;179432056;179432055
Novex-2	17395	52408;52409;52410	chr2:178567330;178567329;178567328	chr2:179432057;179432056;179432055
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-137
• Domain position: 76
• Structural Position: 158
• Q(SASA): 0.1059
• 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
A/T	rs1023398113	None	0.92	D	0.72	0.63	0.53600533864	gnomAD-4.0.0	2.75416E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.60819E-06	0	0
A/V	None	None	0.061	N	0.281	0.384	0.440498838766	gnomAD-4.0.0	1.6141E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88339E-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
A/C	0.6478	likely_pathogenic	0.6329	pathogenic	-1.63	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
A/D	0.9979	likely_pathogenic	0.9973	pathogenic	-1.978	Destabilizing	0.996	D	0.812	deleterious	D	0.628321048	None	None	N
A/E	0.9928	likely_pathogenic	0.9911	pathogenic	-1.939	Destabilizing	0.997	D	0.79	deleterious	None	None	None	None	N
A/F	0.9375	likely_pathogenic	0.9274	pathogenic	-1.204	Destabilizing	0.982	D	0.808	deleterious	None	None	None	None	N
A/G	0.4788	ambiguous	0.4428	ambiguous	-1.537	Destabilizing	0.986	D	0.725	prob.delet.	D	0.559661032	None	None	N
A/H	0.9967	likely_pathogenic	0.996	pathogenic	-1.63	Destabilizing	0.999	D	0.808	deleterious	None	None	None	None	N
A/I	0.4905	ambiguous	0.451	ambiguous	-0.444	Destabilizing	0.759	D	0.713	prob.delet.	None	None	None	None	N
A/K	0.9981	likely_pathogenic	0.9977	pathogenic	-1.418	Destabilizing	0.997	D	0.79	deleterious	None	None	None	None	N
A/L	0.3398	likely_benign	0.3177	benign	-0.444	Destabilizing	0.02	N	0.433	neutral	None	None	None	None	N
A/M	0.6834	likely_pathogenic	0.6451	pathogenic	-0.596	Destabilizing	0.982	D	0.769	deleterious	None	None	None	None	N
A/N	0.9914	likely_pathogenic	0.9893	pathogenic	-1.401	Destabilizing	0.997	D	0.812	deleterious	None	None	None	None	N
A/P	0.9937	likely_pathogenic	0.9911	pathogenic	-0.659	Destabilizing	0.996	D	0.791	deleterious	D	0.602581132	None	None	N
A/Q	0.9876	likely_pathogenic	0.9855	pathogenic	-1.505	Destabilizing	0.997	D	0.777	deleterious	None	None	None	None	N
A/R	0.9944	likely_pathogenic	0.9936	pathogenic	-1.144	Destabilizing	0.997	D	0.791	deleterious	None	None	None	None	N
A/S	0.5541	ambiguous	0.5165	ambiguous	-1.821	Destabilizing	0.959	D	0.707	prob.neutral	D	0.579425387	None	None	N
A/T	0.512	ambiguous	0.4477	ambiguous	-1.673	Destabilizing	0.92	D	0.72	prob.delet.	D	0.576669772	None	None	N
A/V	0.2233	likely_benign	0.1921	benign	-0.659	Destabilizing	0.061	N	0.281	neutral	N	0.505283871	None	None	N
A/W	0.9982	likely_pathogenic	0.9976	pathogenic	-1.597	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
A/Y	0.9888	likely_pathogenic	0.9868	pathogenic	-1.171	Destabilizing	0.997	D	0.811	deleterious	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.