TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24609	74050;74051;74052	chr2:178572307;178572306;178572305	chr2:179437034;179437033;179437032
N2AB	22968	69127;69128;69129	chr2:178572307;178572306;178572305	chr2:179437034;179437033;179437032
N2A	22041	66346;66347;66348	chr2:178572307;178572306;178572305	chr2:179437034;179437033;179437032
N2B	15544	46855;46856;46857	chr2:178572307;178572306;178572305	chr2:179437034;179437033;179437032
Novex-1	15669	47230;47231;47232	chr2:178572307;178572306;178572305	chr2:179437034;179437033;179437032
Novex-2	15736	47431;47432;47433	chr2:178572307;178572306;178572305	chr2:179437034;179437033;179437032
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-66
• Domain position: 91
• Structural Position: 125
• Q(SASA): 0.5308
• 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/D	rs754097967	0.024	None	N	0.22	0.064	0.185906805712	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
E/D	rs754097967	0.024	None	N	0.22	0.064	0.185906805712	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.93573E-04	None	0	0	0	0	0
E/D	rs754097967	0.024	None	N	0.22	0.064	0.185906805712	gnomAD-4.0.0	6.57376E-06	None	None	None	None	N	None	0	0	None	0	1.93573E-04	None	0	0	0	0	0
E/K	rs55762754	0.693	0.519	N	0.605	0.234	0.327686398923	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	5.61E-05	None	0	None	0	8.92E-06	0
E/K	rs55762754	0.693	0.519	N	0.605	0.234	0.327686398923	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.93573E-04	None	0	0	0	0	0
E/K	rs55762754	0.693	0.519	N	0.605	0.234	0.327686398923	gnomAD-4.0.0	1.86143E-06	None	None	None	None	N	None	0	0	None	0	2.23684E-05	None	0	0	1.69765E-06	0	0
E/Q	rs55762754	0.351	0.846	N	0.66	0.209	None	gnomAD-2.1.1	3.33679E-03	None	None	None	None	N	None	3.30743E-04	1.21924E-03	None	5.81734E-04	0	None	2.61746E-04	None	1.30187E-02	3.99837E-03	4.50958E-03
E/Q	rs55762754	0.351	0.846	N	0.66	0.209	None	gnomAD-3.1.2	3.02413E-03	None	None	None	None	N	None	5.30837E-04	7.8637E-04	1.09649E-03	8.64553E-04	0	None	1.23329E-02	0	4.13223E-03	8.285E-04	2.87081E-03
E/Q	rs55762754	0.351	0.846	N	0.66	0.209	None	1000 genomes	1.59744E-03	None	None	None	None	N	None	0	0	None	None	0	8E-03	None	None	None	0	None
E/Q	rs55762754	0.351	0.846	N	0.66	0.209	None	gnomAD-4.0.0	2.94478E-03	None	None	None	None	N	None	4.13355E-04	1.11756E-03	None	6.08643E-04	0	None	1.32229E-02	8.27267E-04	3.02862E-03	3.95491E-04	2.78945E-03
E/V	None	None	0.718	N	0.725	0.384	0.344017737713	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
E/A	0.1624	likely_benign	0.141	benign	-0.095	Destabilizing	0.368	N	0.635	neutral	N	0.48019974	None	None	N
E/C	0.7983	likely_pathogenic	0.772	pathogenic	-0.334	Destabilizing	0.984	D	0.727	deleterious	None	None	None	None	N
E/D	0.0732	likely_benign	0.0758	benign	-0.309	Destabilizing	None	N	0.22	neutral	N	0.452541811	None	None	N
E/F	0.7001	likely_pathogenic	0.6446	pathogenic	-0.04	Destabilizing	0.992	D	0.682	prob.neutral	None	None	None	None	N
E/G	0.1816	likely_benign	0.1554	benign	-0.218	Destabilizing	0.66	D	0.538	neutral	N	0.462210844	None	None	N
E/H	0.4962	ambiguous	0.447	ambiguous	0.622	Stabilizing	0.988	D	0.651	prob.neutral	None	None	None	None	N
E/I	0.3306	likely_benign	0.295	benign	0.177	Stabilizing	0.826	D	0.741	deleterious	None	None	None	None	N
E/K	0.2636	likely_benign	0.2144	benign	0.343	Stabilizing	0.519	D	0.605	neutral	N	0.474528201	None	None	N
E/L	0.4042	ambiguous	0.3632	ambiguous	0.177	Stabilizing	0.826	D	0.74	deleterious	None	None	None	None	N
E/M	0.4822	ambiguous	0.4272	ambiguous	-0.09	Destabilizing	0.907	D	0.728	deleterious	None	None	None	None	N
E/N	0.1895	likely_benign	0.1802	benign	0.002	Stabilizing	0.353	N	0.649	prob.neutral	None	None	None	None	N
E/P	0.7668	likely_pathogenic	0.6944	pathogenic	0.104	Stabilizing	0.414	N	0.717	prob.delet.	None	None	None	None	N
E/Q	0.1874	likely_benign	0.1664	benign	0.031	Stabilizing	0.846	D	0.66	prob.neutral	N	0.468705304	None	None	N
E/R	0.4237	ambiguous	0.3588	ambiguous	0.638	Stabilizing	0.91	D	0.692	prob.delet.	None	None	None	None	N
E/S	0.1747	likely_benign	0.1575	benign	-0.126	Destabilizing	0.435	N	0.585	neutral	None	None	None	None	N
E/T	0.1981	likely_benign	0.1714	benign	-0.012	Destabilizing	0.789	D	0.661	prob.neutral	None	None	None	None	N
E/V	0.2062	likely_benign	0.1776	benign	0.104	Stabilizing	0.718	D	0.725	deleterious	N	0.490795577	None	None	N
E/W	0.9132	likely_pathogenic	0.8841	pathogenic	0.04	Stabilizing	0.997	D	0.707	prob.delet.	None	None	None	None	N
E/Y	0.5891	likely_pathogenic	0.5361	ambiguous	0.186	Stabilizing	0.997	D	0.703	prob.delet.	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.