TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27931	84016;84017;84018	chr2:178562341;178562340;178562339	chr2:179427068;179427067;179427066
N2AB	26290	79093;79094;79095	chr2:178562341;178562340;178562339	chr2:179427068;179427067;179427066
N2A	25363	76312;76313;76314	chr2:178562341;178562340;178562339	chr2:179427068;179427067;179427066
N2B	18866	56821;56822;56823	chr2:178562341;178562340;178562339	chr2:179427068;179427067;179427066
Novex-1	18991	57196;57197;57198	chr2:178562341;178562340;178562339	chr2:179427068;179427067;179427066
Novex-2	19058	57397;57398;57399	chr2:178562341;178562340;178562339	chr2:179427068;179427067;179427066
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-91
• Domain position: 69
• Structural Position: 103
• Q(SASA): 0.3793
• 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
E/A	None	None	0.972	N	0.617	0.358	0.365317461125	gnomAD-4.0.0	1.02782E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.35009E-05	0	0
E/D	rs767740501	-1.058	0.815	N	0.446	0.157	0.294206760003	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.73E-05	0	0
E/K	rs752902445	-0.639	0.969	N	0.512	0.293	0.279776271856	gnomAD-2.1.1	1.81E-05	None	None	None	None	N	None	0	5.72E-05	None	0	0	None	0	None	0	2.36E-05	0
E/K	rs752902445	-0.639	0.969	N	0.512	0.293	0.279776271856	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs752902445	-0.639	0.969	N	0.512	0.293	0.279776271856	gnomAD-4.0.0	1.79975E-05	None	None	None	None	N	None	0	6.69703E-05	None	0	0	None	0	0	2.1205E-05	0	0
E/V	None	None	0.987	N	0.787	0.391	0.458101713262	gnomAD-4.0.0	6.85213E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00061E-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
E/A	0.2439	likely_benign	0.2645	benign	-0.811	Destabilizing	0.972	D	0.617	neutral	N	0.475865463	None	None	N
E/C	0.9498	likely_pathogenic	0.9519	pathogenic	-0.517	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
E/D	0.3392	likely_benign	0.4081	ambiguous	-1.088	Destabilizing	0.815	D	0.446	neutral	N	0.50868867	None	None	N
E/F	0.935	likely_pathogenic	0.9455	pathogenic	-0.04	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
E/G	0.4264	ambiguous	0.4498	ambiguous	-1.219	Destabilizing	0.998	D	0.737	prob.delet.	N	0.481398871	None	None	N
E/H	0.8366	likely_pathogenic	0.851	pathogenic	-0.379	Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
E/I	0.5538	ambiguous	0.5945	pathogenic	0.317	Stabilizing	0.996	D	0.79	deleterious	None	None	None	None	N
E/K	0.4798	ambiguous	0.4849	ambiguous	-0.809	Destabilizing	0.969	D	0.512	neutral	N	0.507917878	None	None	N
E/L	0.6851	likely_pathogenic	0.7107	pathogenic	0.317	Stabilizing	0.993	D	0.786	deleterious	None	None	None	None	N
E/M	0.6299	likely_pathogenic	0.666	pathogenic	0.747	Stabilizing	0.995	D	0.759	deleterious	None	None	None	None	N
E/N	0.5067	ambiguous	0.5828	pathogenic	-1.313	Destabilizing	0.985	D	0.706	prob.neutral	None	None	None	None	N
E/P	0.7513	likely_pathogenic	0.7618	pathogenic	-0.038	Destabilizing	0.977	D	0.804	deleterious	None	None	None	None	N
E/Q	0.3009	likely_benign	0.2955	benign	-1.116	Destabilizing	0.585	D	0.255	neutral	N	0.506187082	None	None	N
E/R	0.6818	likely_pathogenic	0.6814	pathogenic	-0.509	Destabilizing	0.993	D	0.714	prob.delet.	None	None	None	None	N
E/S	0.3795	ambiguous	0.4295	ambiguous	-1.676	Destabilizing	0.978	D	0.595	neutral	None	None	None	None	N
E/T	0.3263	likely_benign	0.372	ambiguous	-1.333	Destabilizing	0.995	D	0.768	deleterious	None	None	None	None	N
E/V	0.3479	ambiguous	0.3766	ambiguous	-0.038	Destabilizing	0.987	D	0.787	deleterious	N	0.514577279	None	None	N
E/W	0.9829	likely_pathogenic	0.9841	pathogenic	0.211	Stabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
E/Y	0.8756	likely_pathogenic	0.8932	pathogenic	0.203	Stabilizing	1.0	D	0.781	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.