TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19861	59806;59807;59808	chr2:178592424;178592423;178592422	chr2:179457151;179457150;179457149
N2AB	18220	54883;54884;54885	chr2:178592424;178592423;178592422	chr2:179457151;179457150;179457149
N2A	17293	52102;52103;52104	chr2:178592424;178592423;178592422	chr2:179457151;179457150;179457149
N2B	10796	32611;32612;32613	chr2:178592424;178592423;178592422	chr2:179457151;179457150;179457149
Novex-1	10921	32986;32987;32988	chr2:178592424;178592423;178592422	chr2:179457151;179457150;179457149
Novex-2	10988	33187;33188;33189	chr2:178592424;178592423;178592422	chr2:179457151;179457150;179457149
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-119
• Domain position: 72
• Structural Position: 161
• Q(SASA): 0.1761
• 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
N/S	None	None	0.999	N	0.558	0.619	0.292062946507	gnomAD-4.0.0	1.59214E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02572E-05

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
N/A	0.9984	likely_pathogenic	0.9982	pathogenic	-0.615	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
N/C	0.9881	likely_pathogenic	0.9857	pathogenic	0.144	Stabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	I
N/D	0.9952	likely_pathogenic	0.9952	pathogenic	-0.96	Destabilizing	0.999	D	0.593	neutral	D	0.524773405	None	None	I
N/E	0.9988	likely_pathogenic	0.999	pathogenic	-0.924	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	I
N/F	0.9995	likely_pathogenic	0.9995	pathogenic	-0.719	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
N/G	0.9917	likely_pathogenic	0.9917	pathogenic	-0.886	Destabilizing	0.999	D	0.539	neutral	None	None	None	None	I
N/H	0.9889	likely_pathogenic	0.9887	pathogenic	-0.945	Destabilizing	1.0	D	0.739	prob.delet.	D	0.543980523	None	None	I
N/I	0.9934	likely_pathogenic	0.9931	pathogenic	0.043	Stabilizing	1.0	D	0.703	prob.neutral	D	0.544234013	None	None	I
N/K	0.9992	likely_pathogenic	0.9992	pathogenic	-0.232	Destabilizing	1.0	D	0.737	prob.delet.	D	0.543473544	None	None	I
N/L	0.9915	likely_pathogenic	0.992	pathogenic	0.043	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
N/M	0.9935	likely_pathogenic	0.9936	pathogenic	0.684	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
N/P	0.9992	likely_pathogenic	0.9994	pathogenic	-0.148	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
N/Q	0.9992	likely_pathogenic	0.9993	pathogenic	-0.956	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
N/R	0.9994	likely_pathogenic	0.9995	pathogenic	-0.175	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
N/S	0.9313	likely_pathogenic	0.9237	pathogenic	-0.667	Destabilizing	0.999	D	0.558	neutral	N	0.481132155	None	None	I
N/T	0.9779	likely_pathogenic	0.976	pathogenic	-0.474	Destabilizing	0.999	D	0.702	prob.neutral	N	0.511037243	None	None	I
N/V	0.9957	likely_pathogenic	0.9954	pathogenic	-0.148	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
N/W	0.9999	likely_pathogenic	0.9999	pathogenic	-0.586	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	I
N/Y	0.9951	likely_pathogenic	0.9957	pathogenic	-0.326	Destabilizing	1.0	D	0.726	prob.delet.	D	0.543980523	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.