TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8295	25108;25109;25110	chr2:178718123;178718122;178718121	chr2:179582850;179582849;179582848
N2AB	7978	24157;24158;24159	chr2:178718123;178718122;178718121	chr2:179582850;179582849;179582848
N2A	7051	21376;21377;21378	chr2:178718123;178718122;178718121	chr2:179582850;179582849;179582848
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-68
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.1745
• 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
I/N	rs752786293	-1.373	0.965	D	0.845	0.658	0.899350334792	gnomAD-2.1.1	8.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
I/N	rs752786293	-1.373	0.965	D	0.845	0.658	0.899350334792	gnomAD-4.0.0	6.38857E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.73197E-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
I/A	0.9335	likely_pathogenic	0.9474	pathogenic	-2.056	Highly Destabilizing	0.513	D	0.585	neutral	None	None	None	None	N
I/C	0.9439	likely_pathogenic	0.9473	pathogenic	-1.27	Destabilizing	0.993	D	0.749	deleterious	None	None	None	None	N
I/D	0.9937	likely_pathogenic	0.997	pathogenic	-1.693	Destabilizing	0.973	D	0.821	deleterious	None	None	None	None	N
I/E	0.9879	likely_pathogenic	0.9934	pathogenic	-1.555	Destabilizing	0.964	D	0.823	deleterious	None	None	None	None	N
I/F	0.5361	ambiguous	0.5375	ambiguous	-1.203	Destabilizing	0.843	D	0.688	prob.neutral	N	0.498692746	None	None	N
I/G	0.9841	likely_pathogenic	0.9893	pathogenic	-2.527	Highly Destabilizing	0.912	D	0.819	deleterious	None	None	None	None	N
I/H	0.9814	likely_pathogenic	0.9878	pathogenic	-1.831	Destabilizing	0.994	D	0.846	deleterious	None	None	None	None	N
I/K	0.9701	likely_pathogenic	0.9827	pathogenic	-1.452	Destabilizing	0.345	N	0.823	deleterious	None	None	None	None	N
I/L	0.3039	likely_benign	0.3223	benign	-0.754	Destabilizing	0.01	N	0.488	neutral	D	0.540105734	None	None	N
I/M	0.3689	ambiguous	0.3811	ambiguous	-0.62	Destabilizing	0.618	D	0.649	neutral	N	0.496415022	None	None	N
I/N	0.9307	likely_pathogenic	0.9586	pathogenic	-1.502	Destabilizing	0.965	D	0.845	deleterious	D	0.530990917	None	None	N
I/P	0.9565	likely_pathogenic	0.9799	pathogenic	-1.162	Destabilizing	0.991	D	0.841	deleterious	None	None	None	None	N
I/Q	0.978	likely_pathogenic	0.986	pathogenic	-1.485	Destabilizing	0.979	D	0.844	deleterious	None	None	None	None	N
I/R	0.963	likely_pathogenic	0.978	pathogenic	-1.069	Destabilizing	0.935	D	0.848	deleterious	None	None	None	None	N
I/S	0.9378	likely_pathogenic	0.9595	pathogenic	-2.227	Highly Destabilizing	0.659	D	0.791	deleterious	D	0.542093733	None	None	N
I/T	0.8835	likely_pathogenic	0.9076	pathogenic	-1.949	Destabilizing	0.015	N	0.471	neutral	N	0.517152623	None	None	N
I/V	0.1015	likely_benign	0.1051	benign	-1.162	Destabilizing	None	N	0.227	neutral	N	0.425363571	None	None	N
I/W	0.9799	likely_pathogenic	0.9845	pathogenic	-1.453	Destabilizing	0.998	D	0.848	deleterious	None	None	None	None	N
I/Y	0.9204	likely_pathogenic	0.9352	pathogenic	-1.172	Destabilizing	0.629	D	0.775	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.