TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9220	27883;27884;27885	chr2:178712172;178712171;178712170	chr2:179576899;179576898;179576897
N2AB	8903	26932;26933;26934	chr2:178712172;178712171;178712170	chr2:179576899;179576898;179576897
N2A	7976	24151;24152;24153	chr2:178712172;178712171;178712170	chr2:179576899;179576898;179576897
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-78
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.7336
• 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
D/N	rs758435347	0.432	0.991	N	0.456	0.236	0.151104730317	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
D/N	rs758435347	0.432	0.991	N	0.456	0.236	0.151104730317	gnomAD-4.0.0	4.78952E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.29641E-06	0	0
D/V	None	None	0.982	N	0.632	0.45	0.465721554213	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.2018	likely_benign	0.2847	benign	-0.387	Destabilizing	0.939	D	0.469	neutral	N	0.506253292	None	None	I
D/C	0.7114	likely_pathogenic	0.7952	pathogenic	0.149	Stabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	I
D/E	0.1781	likely_benign	0.1829	benign	-0.311	Destabilizing	0.17	N	0.269	neutral	N	0.436003773	None	None	I
D/F	0.5722	likely_pathogenic	0.6757	pathogenic	-0.407	Destabilizing	0.973	D	0.638	neutral	None	None	None	None	I
D/G	0.2287	likely_benign	0.3048	benign	-0.58	Destabilizing	0.969	D	0.475	neutral	N	0.475853027	None	None	I
D/H	0.3405	ambiguous	0.3923	ambiguous	-0.36	Destabilizing	0.982	D	0.482	neutral	N	0.458138104	None	None	I
D/I	0.4231	ambiguous	0.546	ambiguous	0.072	Stabilizing	0.986	D	0.645	neutral	None	None	None	None	I
D/K	0.397	ambiguous	0.3831	ambiguous	0.404	Stabilizing	0.986	D	0.451	neutral	None	None	None	None	I
D/L	0.462	ambiguous	0.571	pathogenic	0.072	Stabilizing	0.973	D	0.63	neutral	None	None	None	None	I
D/M	0.6297	likely_pathogenic	0.7054	pathogenic	0.345	Stabilizing	0.999	D	0.633	neutral	None	None	None	None	I
D/N	0.1038	likely_benign	0.1223	benign	0.092	Stabilizing	0.991	D	0.456	neutral	N	0.508600164	None	None	I
D/P	0.946	likely_pathogenic	0.9712	pathogenic	-0.059	Destabilizing	0.998	D	0.48	neutral	None	None	None	None	I
D/Q	0.3384	likely_benign	0.3415	ambiguous	0.111	Stabilizing	0.986	D	0.465	neutral	None	None	None	None	I
D/R	0.4616	ambiguous	0.4978	ambiguous	0.46	Stabilizing	0.986	D	0.566	neutral	None	None	None	None	I
D/S	0.1351	likely_benign	0.1677	benign	-0.007	Destabilizing	0.953	D	0.44	neutral	None	None	None	None	I
D/T	0.2996	likely_benign	0.3702	ambiguous	0.147	Stabilizing	0.993	D	0.457	neutral	None	None	None	None	I
D/V	0.2569	likely_benign	0.3562	ambiguous	-0.059	Destabilizing	0.982	D	0.632	neutral	N	0.478977837	None	None	I
D/W	0.9219	likely_pathogenic	0.9468	pathogenic	-0.273	Destabilizing	0.998	D	0.688	prob.neutral	None	None	None	None	I
D/Y	0.2435	likely_benign	0.314	benign	-0.165	Destabilizing	0.1	N	0.461	neutral	N	0.464405528	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.