TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2950	9073;9074;9075	chr2:178769733;178769732;178769731	chr2:179634460;179634459;179634458
N2AB	2950	9073;9074;9075	chr2:178769733;178769732;178769731	chr2:179634460;179634459;179634458
N2A	2950	9073;9074;9075	chr2:178769733;178769732;178769731	chr2:179634460;179634459;179634458
N2B	2904	8935;8936;8937	chr2:178769733;178769732;178769731	chr2:179634460;179634459;179634458
Novex-1	2904	8935;8936;8937	chr2:178769733;178769732;178769731	chr2:179634460;179634459;179634458
Novex-2	2904	8935;8936;8937	chr2:178769733;178769732;178769731	chr2:179634460;179634459;179634458
Novex-3	2950	9073;9074;9075	chr2:178769733;178769732;178769731	chr2:179634460;179634459;179634458

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-19
• Domain position: 69
• Structural Position: 153
• Q(SASA): 0.2743
• 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	1.0	D	0.759	0.601	0.662942300025	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.1848	likely_benign	0.1695	benign	-0.898	Destabilizing	0.999	D	0.693	prob.neutral	D	0.649631147	None	None	N
E/C	0.9081	likely_pathogenic	0.9064	pathogenic	-0.31	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/D	0.2079	likely_benign	0.1976	benign	-1.143	Destabilizing	0.999	D	0.539	neutral	N	0.511265133	None	None	N
E/F	0.8802	likely_pathogenic	0.8638	pathogenic	-0.878	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
E/G	0.3599	ambiguous	0.321	benign	-1.207	Destabilizing	1.0	D	0.759	deleterious	D	0.651970533	None	None	N
E/H	0.6042	likely_pathogenic	0.5953	pathogenic	-1.127	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/I	0.3456	ambiguous	0.3429	ambiguous	-0.068	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/K	0.1606	likely_benign	0.1565	benign	-0.372	Destabilizing	0.999	D	0.642	neutral	N	0.502135414	None	None	N
E/L	0.4729	ambiguous	0.4598	ambiguous	-0.068	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/M	0.4849	ambiguous	0.4798	ambiguous	0.484	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/N	0.2904	likely_benign	0.2887	benign	-0.728	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/P	0.7408	likely_pathogenic	0.7266	pathogenic	-0.324	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
E/Q	0.149	likely_benign	0.1547	benign	-0.662	Destabilizing	1.0	D	0.619	neutral	N	0.503871543	None	None	N
E/R	0.3077	likely_benign	0.3102	benign	-0.291	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/S	0.2532	likely_benign	0.2391	benign	-1.037	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	N
E/T	0.212	likely_benign	0.205	benign	-0.773	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/V	0.1918	likely_benign	0.195	benign	-0.324	Destabilizing	1.0	D	0.795	deleterious	N	0.504062077	None	None	N
E/W	0.9684	likely_pathogenic	0.9624	pathogenic	-0.749	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/Y	0.8195	likely_pathogenic	0.7988	pathogenic	-0.624	Destabilizing	1.0	D	0.783	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.