TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9473	28642;28643;28644	chr2:178710680;178710679;178710678	chr2:179575407;179575406;179575405
N2AB	9156	27691;27692;27693	chr2:178710680;178710679;178710678	chr2:179575407;179575406;179575405
N2A	8229	24910;24911;24912	chr2:178710680;178710679;178710678	chr2:179575407;179575406;179575405
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-80
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.1398
• 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
N/H	None	None	1.0	None	0.721	0.634	0.398133443147	gnomAD-4.0.0	3.18585E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.7171E-06	0	0
N/S	rs2076526398	None	0.999	None	0.582	0.553	0.262175524916	gnomAD-4.0.0	1.59291E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43345E-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
N/A	0.9815	likely_pathogenic	0.9903	pathogenic	-0.782	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
N/C	0.9598	likely_pathogenic	0.9781	pathogenic	-0.139	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
N/D	0.9091	likely_pathogenic	0.9586	pathogenic	-1.185	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	I
N/E	0.9936	likely_pathogenic	0.9961	pathogenic	-1.083	Destabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	I
N/F	0.9992	likely_pathogenic	0.9994	pathogenic	-0.517	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
N/G	0.9312	likely_pathogenic	0.9656	pathogenic	-1.117	Destabilizing	0.999	D	0.554	neutral	None	None	None	None	I
N/H	0.9421	likely_pathogenic	0.9704	pathogenic	-0.928	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
N/I	0.9933	likely_pathogenic	0.9956	pathogenic	0.073	Stabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
N/K	0.9961	likely_pathogenic	0.9974	pathogenic	-0.411	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
N/L	0.9772	likely_pathogenic	0.9814	pathogenic	0.073	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
N/M	0.9884	likely_pathogenic	0.9918	pathogenic	0.511	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
N/P	0.9946	likely_pathogenic	0.9954	pathogenic	-0.183	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
N/Q	0.9925	likely_pathogenic	0.9969	pathogenic	-1.087	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
N/R	0.9943	likely_pathogenic	0.9962	pathogenic	-0.423	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
N/S	0.4165	ambiguous	0.5927	pathogenic	-0.996	Destabilizing	0.999	D	0.582	neutral	None	None	None	None	I
N/T	0.8285	likely_pathogenic	0.911	pathogenic	-0.723	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	I
N/V	0.9907	likely_pathogenic	0.9937	pathogenic	-0.183	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
N/W	0.9995	likely_pathogenic	0.9996	pathogenic	-0.321	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
N/Y	0.9896	likely_pathogenic	0.993	pathogenic	-0.078	Destabilizing	1.0	D	0.739	prob.delet.	None	None	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.