TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26394	79405;79406;79407	chr2:178566952;178566951;178566950	chr2:179431679;179431678;179431677
N2AB	24753	74482;74483;74484	chr2:178566952;178566951;178566950	chr2:179431679;179431678;179431677
N2A	23826	71701;71702;71703	chr2:178566952;178566951;178566950	chr2:179431679;179431678;179431677
N2B	17329	52210;52211;52212	chr2:178566952;178566951;178566950	chr2:179431679;179431678;179431677
Novex-1	17454	52585;52586;52587	chr2:178566952;178566951;178566950	chr2:179431679;179431678;179431677
Novex-2	17521	52786;52787;52788	chr2:178566952;178566951;178566950	chr2:179431679;179431678;179431677
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: Fn3-80
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5894
• 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
E/Q	rs144788732	-0.139	1.0	N	0.659	0.199	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	1.93424E-04	None	0	0	0	0	0
E/Q	rs144788732	-0.139	1.0	N	0.659	0.199	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	1E-03	0	None	None	None	0	None
E/Q	rs144788732	-0.139	1.0	N	0.659	0.199	None	gnomAD-4.0.0	1.02504E-05	None	None	None	None	I	None	0	0	None	0	1.94156E-04	None	0	0	0	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	0.3101	likely_benign	0.3614	ambiguous	-0.498	Destabilizing	0.999	D	0.745	deleterious	N	0.475394483	None	None	I
E/C	0.904	likely_pathogenic	0.9198	pathogenic	-0.065	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
E/D	0.212	likely_benign	0.2239	benign	-0.492	Destabilizing	0.999	D	0.512	neutral	N	0.484370931	None	None	I
E/F	0.8767	likely_pathogenic	0.8974	pathogenic	-0.265	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
E/G	0.5303	ambiguous	0.567	pathogenic	-0.741	Destabilizing	1.0	D	0.779	deleterious	N	0.500513403	None	None	I
E/H	0.6414	likely_pathogenic	0.7195	pathogenic	-0.184	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
E/I	0.483	ambiguous	0.5331	ambiguous	0.123	Stabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
E/K	0.4366	ambiguous	0.5314	ambiguous	0.219	Stabilizing	0.999	D	0.633	neutral	N	0.486635742	None	None	I
E/L	0.5775	likely_pathogenic	0.6359	pathogenic	0.123	Stabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
E/M	0.6097	likely_pathogenic	0.6508	pathogenic	0.31	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
E/N	0.5035	ambiguous	0.5445	ambiguous	-0.187	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
E/P	0.9718	likely_pathogenic	0.9794	pathogenic	-0.063	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	I
E/Q	0.2214	likely_benign	0.2717	benign	-0.122	Destabilizing	1.0	D	0.659	neutral	N	0.517036007	None	None	I
E/R	0.5594	ambiguous	0.6471	pathogenic	0.42	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
E/S	0.3916	ambiguous	0.4344	ambiguous	-0.355	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	I
E/T	0.3206	likely_benign	0.3767	ambiguous	-0.153	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
E/V	0.2771	likely_benign	0.3269	benign	-0.063	Destabilizing	1.0	D	0.843	deleterious	N	0.497604884	None	None	I
E/W	0.9589	likely_pathogenic	0.9687	pathogenic	-0.069	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	I
E/Y	0.8168	likely_pathogenic	0.8441	pathogenic	-0.008	Destabilizing	1.0	D	0.839	deleterious	None	None	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.