TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9312	28159;28160;28161	chr2:178711302;178711301;178711300	chr2:179576029;179576028;179576027
N2AB	8995	27208;27209;27210	chr2:178711302;178711301;178711300	chr2:179576029;179576028;179576027
N2A	8068	24427;24428;24429	chr2:178711302;178711301;178711300	chr2:179576029;179576028;179576027
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-79
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.0969
• 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	None	None	0.071	N	0.425	0.229	0.3349148499	gnomAD-4.0.0	1.59332E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86251E-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	0.2279	likely_benign	0.2762	benign	-0.799	Destabilizing	0.961	D	0.486	neutral	N	0.439605091	None	None	N
E/C	0.9538	likely_pathogenic	0.9636	pathogenic	-0.403	Destabilizing	1.0	D	0.634	neutral	None	None	None	None	N
E/D	0.4429	ambiguous	0.4813	ambiguous	-1.214	Destabilizing	0.961	D	0.492	neutral	D	0.534192908	None	None	N
E/F	0.932	likely_pathogenic	0.9479	pathogenic	-0.266	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
E/G	0.2582	likely_benign	0.3094	benign	-1.188	Destabilizing	0.071	N	0.425	neutral	N	0.444688411	None	None	N
E/H	0.7834	likely_pathogenic	0.8135	pathogenic	-0.576	Destabilizing	0.996	D	0.571	neutral	None	None	None	None	N
E/I	0.6813	likely_pathogenic	0.7411	pathogenic	0.266	Stabilizing	0.999	D	0.671	neutral	None	None	None	None	N
E/K	0.3062	likely_benign	0.3894	ambiguous	-0.542	Destabilizing	0.925	D	0.527	neutral	D	0.528363013	None	None	N
E/L	0.7245	likely_pathogenic	0.7763	pathogenic	0.266	Stabilizing	0.991	D	0.656	neutral	None	None	None	None	N
E/M	0.7024	likely_pathogenic	0.7503	pathogenic	0.721	Stabilizing	1.0	D	0.595	neutral	None	None	None	None	N
E/N	0.5788	likely_pathogenic	0.6371	pathogenic	-1.068	Destabilizing	0.996	D	0.59	neutral	None	None	None	None	N
E/P	0.9682	likely_pathogenic	0.9844	pathogenic	-0.067	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
E/Q	0.1902	likely_benign	0.2299	benign	-0.904	Destabilizing	0.489	N	0.299	neutral	N	0.504659435	None	None	N
E/R	0.4896	ambiguous	0.5886	pathogenic	-0.324	Destabilizing	0.991	D	0.601	neutral	None	None	None	None	N
E/S	0.4193	ambiguous	0.4863	ambiguous	-1.393	Destabilizing	0.97	D	0.543	neutral	None	None	None	None	N
E/T	0.4456	ambiguous	0.5185	ambiguous	-1.062	Destabilizing	0.996	D	0.605	neutral	None	None	None	None	N
E/V	0.3785	ambiguous	0.4436	ambiguous	-0.067	Destabilizing	0.994	D	0.601	neutral	N	0.410202117	None	None	N
E/W	0.986	likely_pathogenic	0.9903	pathogenic	-0.043	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
E/Y	0.8694	likely_pathogenic	0.8963	pathogenic	-0.002	Destabilizing	0.999	D	0.605	neutral	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.