TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19814	59665;59666;59667	chr2:178592565;178592564;178592563	chr2:179457292;179457291;179457290
N2AB	18173	54742;54743;54744	chr2:178592565;178592564;178592563	chr2:179457292;179457291;179457290
N2A	17246	51961;51962;51963	chr2:178592565;178592564;178592563	chr2:179457292;179457291;179457290
N2B	10749	32470;32471;32472	chr2:178592565;178592564;178592563	chr2:179457292;179457291;179457290
Novex-1	10874	32845;32846;32847	chr2:178592565;178592564;178592563	chr2:179457292;179457291;179457290
Novex-2	10941	33046;33047;33048	chr2:178592565;178592564;178592563	chr2:179457292;179457291;179457290
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-119
• Domain position: 25
• Structural Position: 42
• Q(SASA): 0.5517
• 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
P/S	None	None	1.0	D	0.698	0.697	0.648632380062	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
P/A	0.9725	likely_pathogenic	0.9794	pathogenic	-0.724	Destabilizing	1.0	D	0.693	prob.neutral	D	0.572647611	None	None	I
P/C	0.9972	likely_pathogenic	0.9974	pathogenic	-0.611	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
P/D	0.995	likely_pathogenic	0.9962	pathogenic	-0.627	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
P/E	0.9959	likely_pathogenic	0.9967	pathogenic	-0.728	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	I
P/F	0.9991	likely_pathogenic	0.9993	pathogenic	-0.863	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
P/G	0.9868	likely_pathogenic	0.9911	pathogenic	-0.882	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
P/H	0.9926	likely_pathogenic	0.9943	pathogenic	-0.452	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
P/I	0.9936	likely_pathogenic	0.9943	pathogenic	-0.444	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
P/K	0.996	likely_pathogenic	0.9969	pathogenic	-0.709	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
P/L	0.9779	likely_pathogenic	0.9841	pathogenic	-0.444	Destabilizing	1.0	D	0.685	prob.neutral	D	0.620600688	None	None	I
P/M	0.9969	likely_pathogenic	0.9975	pathogenic	-0.43	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
P/N	0.9937	likely_pathogenic	0.9956	pathogenic	-0.416	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
P/Q	0.9936	likely_pathogenic	0.9953	pathogenic	-0.664	Destabilizing	1.0	D	0.691	prob.neutral	D	0.561291306	None	None	I
P/R	0.987	likely_pathogenic	0.9903	pathogenic	-0.138	Destabilizing	1.0	D	0.695	prob.neutral	D	0.62019708	None	None	I
P/S	0.9894	likely_pathogenic	0.9929	pathogenic	-0.747	Destabilizing	1.0	D	0.698	prob.neutral	D	0.549428021	None	None	I
P/T	0.9814	likely_pathogenic	0.9857	pathogenic	-0.752	Destabilizing	1.0	D	0.691	prob.neutral	D	0.610910494	None	None	I
P/V	0.9876	likely_pathogenic	0.9886	pathogenic	-0.503	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
P/W	0.9994	likely_pathogenic	0.9995	pathogenic	-0.963	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
P/Y	0.9981	likely_pathogenic	0.9984	pathogenic	-0.684	Destabilizing	1.0	D	0.733	prob.delet.	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.