TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15404	46435;46436;46437	chr2:178620311;178620310;178620309	chr2:179485038;179485037;179485036
N2AB	13763	41512;41513;41514	chr2:178620311;178620310;178620309	chr2:179485038;179485037;179485036
N2A	12836	38731;38732;38733	chr2:178620311;178620310;178620309	chr2:179485038;179485037;179485036
N2B	6339	19240;19241;19242	chr2:178620311;178620310;178620309	chr2:179485038;179485037;179485036
Novex-1	6464	19615;19616;19617	chr2:178620311;178620310;178620309	chr2:179485038;179485037;179485036
Novex-2	6531	19816;19817;19818	chr2:178620311;178620310;178620309	chr2:179485038;179485037;179485036
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: Ig-106
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.6121
• 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	rs878854311	None	1.0	D	0.672	0.729	0.665719803998	gnomAD-4.0.0	1.68363E-06	None	None	None	None	N	None	6.01106E-05	0	None	0	0	None	0	0	0	0	0
E/K	None	None	0.999	D	0.63	0.521	0.503002171853	gnomAD-4.0.0	1.67923E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.00589E-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	0.5165	ambiguous	0.6221	pathogenic	-0.991	Destabilizing	0.999	D	0.657	neutral	D	0.558775783	None	None	N
E/C	0.9852	likely_pathogenic	0.9909	pathogenic	-0.443	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/D	0.905	likely_pathogenic	0.9471	pathogenic	-0.789	Destabilizing	0.999	D	0.463	neutral	D	0.594233147	None	None	N
E/F	0.9921	likely_pathogenic	0.9963	pathogenic	-0.455	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/G	0.8245	likely_pathogenic	0.8902	pathogenic	-1.298	Destabilizing	1.0	D	0.672	neutral	D	0.724769076	None	None	N
E/H	0.9814	likely_pathogenic	0.9902	pathogenic	-0.445	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/I	0.8854	likely_pathogenic	0.9154	pathogenic	-0.166	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
E/K	0.8392	likely_pathogenic	0.8931	pathogenic	-0.296	Destabilizing	0.999	D	0.63	neutral	D	0.586941346	None	None	N
E/L	0.9319	likely_pathogenic	0.959	pathogenic	-0.166	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/M	0.9078	likely_pathogenic	0.9467	pathogenic	0.189	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/N	0.9464	likely_pathogenic	0.9723	pathogenic	-0.847	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/P	0.9286	likely_pathogenic	0.9463	pathogenic	-0.421	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
E/Q	0.5739	likely_pathogenic	0.7004	pathogenic	-0.746	Destabilizing	1.0	D	0.645	neutral	D	0.623769681	None	None	N
E/R	0.8909	likely_pathogenic	0.9292	pathogenic	0.04	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/S	0.8348	likely_pathogenic	0.9051	pathogenic	-1.078	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
E/T	0.8715	likely_pathogenic	0.9198	pathogenic	-0.815	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/V	0.7534	likely_pathogenic	0.8111	pathogenic	-0.421	Destabilizing	1.0	D	0.727	prob.delet.	D	0.532847594	None	None	N
E/W	0.9985	likely_pathogenic	0.9993	pathogenic	-0.117	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
E/Y	0.9859	likely_pathogenic	0.9933	pathogenic	-0.179	Destabilizing	1.0	D	0.711	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.