TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6557	19894;19895;19896	chr2:178728155;178728154;178728153	chr2:179592882;179592881;179592880
N2AB	6240	18943;18944;18945	chr2:178728155;178728154;178728153	chr2:179592882;179592881;179592880
N2A	5313	16162;16163;16164	chr2:178728155;178728154;178728153	chr2:179592882;179592881;179592880
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-49
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.1619
• 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	rs764245160	-0.839	0.999	N	0.589	0.544	None	gnomAD-2.1.1	4.1E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.05E-06	0
N/S	rs764245160	-0.839	0.999	N	0.589	0.544	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/S	rs764245160	-0.839	0.999	N	0.589	0.544	None	gnomAD-4.0.0	6.45303E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.2061E-05	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
N/A	0.9768	likely_pathogenic	0.9481	pathogenic	-0.787	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
N/C	0.9339	likely_pathogenic	0.9052	pathogenic	-0.086	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
N/D	0.9493	likely_pathogenic	0.9157	pathogenic	-0.956	Destabilizing	0.999	D	0.623	neutral	D	0.542548491	None	None	I
N/E	0.9958	likely_pathogenic	0.992	pathogenic	-0.923	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	I
N/F	0.997	likely_pathogenic	0.9937	pathogenic	-0.943	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
N/G	0.9433	likely_pathogenic	0.9097	pathogenic	-1.031	Destabilizing	0.999	D	0.563	neutral	None	None	None	None	I
N/H	0.9217	likely_pathogenic	0.8826	pathogenic	-0.974	Destabilizing	1.0	D	0.741	deleterious	D	0.537232573	None	None	I
N/I	0.9819	likely_pathogenic	0.9617	pathogenic	-0.197	Destabilizing	1.0	D	0.729	prob.delet.	D	0.544069428	None	None	I
N/K	0.9955	likely_pathogenic	0.9915	pathogenic	-0.144	Destabilizing	1.0	D	0.737	prob.delet.	D	0.554665265	None	None	I
N/L	0.9547	likely_pathogenic	0.9222	pathogenic	-0.197	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
N/M	0.9835	likely_pathogenic	0.9708	pathogenic	0.43	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
N/P	0.988	likely_pathogenic	0.9769	pathogenic	-0.367	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
N/Q	0.9945	likely_pathogenic	0.9893	pathogenic	-0.966	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
N/R	0.9906	likely_pathogenic	0.9829	pathogenic	0.002	Stabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
N/S	0.469	ambiguous	0.3568	ambiguous	-0.671	Destabilizing	0.999	D	0.589	neutral	N	0.508453122	None	None	I
N/T	0.8585	likely_pathogenic	0.786	pathogenic	-0.481	Destabilizing	0.999	D	0.709	prob.delet.	D	0.531445675	None	None	I
N/V	0.971	likely_pathogenic	0.9398	pathogenic	-0.367	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
N/W	0.9991	likely_pathogenic	0.9978	pathogenic	-0.741	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	I
N/Y	0.9796	likely_pathogenic	0.9597	pathogenic	-0.486	Destabilizing	1.0	D	0.748	deleterious	D	0.543815939	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.