TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18204	54835;54836;54837	chr2:178604077;178604076;178604075	chr2:179468804;179468803;179468802
N2AB	16563	49912;49913;49914	chr2:178604077;178604076;178604075	chr2:179468804;179468803;179468802
N2A	15636	47131;47132;47133	chr2:178604077;178604076;178604075	chr2:179468804;179468803;179468802
N2B	9139	27640;27641;27642	chr2:178604077;178604076;178604075	chr2:179468804;179468803;179468802
Novex-1	9264	28015;28016;28017	chr2:178604077;178604076;178604075	chr2:179468804;179468803;179468802
Novex-2	9331	28216;28217;28218	chr2:178604077;178604076;178604075	chr2:179468804;179468803;179468802
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: Fn3-20
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1601
• 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/G	rs778173480	-1.901	0.946	N	0.761	0.415	None	gnomAD-4.0.0	1.5949E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.14025E-04	0	5.7262E-06	0	6.06796E-05
E/Q	rs749849370	-1.274	0.716	N	0.725	0.32	0.260249123532	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
E/Q	rs749849370	-1.274	0.716	N	0.725	0.32	0.260249123532	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/Q	rs749849370	-1.274	0.716	N	0.725	0.32	0.260249123532	gnomAD-4.0.0	6.82064E-06	None	None	None	None	N	None	0	1.66817E-05	None	0	0	None	0	0	7.63237E-06	1.09888E-05	0
E/V	rs778173480	None	0.946	N	0.793	0.532	0.539970339866	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
E/V	rs778173480	None	0.946	N	0.793	0.532	0.539970339866	gnomAD-4.0.0	1.59476E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86303E-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
E/A	0.9518	likely_pathogenic	0.9363	pathogenic	-1.283	Destabilizing	0.716	D	0.661	neutral	D	0.524164293	None	None	N
E/C	0.9879	likely_pathogenic	0.9888	pathogenic	-0.584	Destabilizing	0.998	D	0.802	deleterious	None	None	None	None	N
E/D	0.8749	likely_pathogenic	0.8579	pathogenic	-1.642	Destabilizing	0.834	D	0.634	neutral	N	0.473890453	None	None	N
E/F	0.995	likely_pathogenic	0.995	pathogenic	-0.878	Destabilizing	0.998	D	0.82	deleterious	None	None	None	None	N
E/G	0.9509	likely_pathogenic	0.9398	pathogenic	-1.696	Destabilizing	0.946	D	0.761	deleterious	N	0.519190771	None	None	N
E/H	0.9845	likely_pathogenic	0.9837	pathogenic	-0.856	Destabilizing	0.994	D	0.822	deleterious	None	None	None	None	N
E/I	0.9858	likely_pathogenic	0.9829	pathogenic	-0.099	Destabilizing	0.979	D	0.836	deleterious	None	None	None	None	N
E/K	0.9722	likely_pathogenic	0.966	pathogenic	-1.358	Destabilizing	0.016	N	0.463	neutral	N	0.516148896	None	None	N
E/L	0.9766	likely_pathogenic	0.9748	pathogenic	-0.099	Destabilizing	0.959	D	0.801	deleterious	None	None	None	None	N
E/M	0.9793	likely_pathogenic	0.978	pathogenic	0.597	Stabilizing	0.998	D	0.814	deleterious	None	None	None	None	N
E/N	0.9878	likely_pathogenic	0.9858	pathogenic	-1.629	Destabilizing	0.959	D	0.8	deleterious	None	None	None	None	N
E/P	0.9994	likely_pathogenic	0.9992	pathogenic	-0.479	Destabilizing	0.979	D	0.815	deleterious	None	None	None	None	N
E/Q	0.7583	likely_pathogenic	0.7385	pathogenic	-1.302	Destabilizing	0.716	D	0.725	prob.delet.	N	0.51465185	None	None	N
E/R	0.9688	likely_pathogenic	0.9652	pathogenic	-1.234	Destabilizing	0.921	D	0.787	deleterious	None	None	None	None	N
E/S	0.9601	likely_pathogenic	0.9521	pathogenic	-2.262	Highly Destabilizing	0.769	D	0.685	prob.neutral	None	None	None	None	N
E/T	0.979	likely_pathogenic	0.9754	pathogenic	-1.871	Destabilizing	0.959	D	0.772	deleterious	None	None	None	None	N
E/V	0.96	likely_pathogenic	0.9548	pathogenic	-0.479	Destabilizing	0.946	D	0.793	deleterious	N	0.513568457	None	None	N
E/W	0.996	likely_pathogenic	0.9964	pathogenic	-0.986	Destabilizing	0.998	D	0.81	deleterious	None	None	None	None	N
E/Y	0.9911	likely_pathogenic	0.9916	pathogenic	-0.699	Destabilizing	0.993	D	0.821	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.