TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6837	20734;20735;20736	chr2:178725813;178725812;178725811	chr2:179590540;179590539;179590538
N2AB	6520	19783;19784;19785	chr2:178725813;178725812;178725811	chr2:179590540;179590539;179590538
N2A	5593	17002;17003;17004	chr2:178725813;178725812;178725811	chr2:179590540;179590539;179590538
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-52
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.1596
• 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
N/K	None	None	1.0	D	0.743	0.669	0.40528724903	gnomAD-4.0.0	1.59745E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87071E-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
N/A	0.9956	likely_pathogenic	0.9965	pathogenic	-0.993	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
N/C	0.989	likely_pathogenic	0.9888	pathogenic	-0.238	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
N/D	0.9681	likely_pathogenic	0.9739	pathogenic	-1.083	Destabilizing	0.999	D	0.615	neutral	D	0.64649774	None	None	N
N/E	0.9971	likely_pathogenic	0.9975	pathogenic	-0.959	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
N/F	0.9994	likely_pathogenic	0.9995	pathogenic	-0.633	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
N/G	0.9832	likely_pathogenic	0.9854	pathogenic	-1.345	Destabilizing	1.0	D	0.559	neutral	None	None	None	None	N
N/H	0.9804	likely_pathogenic	0.9826	pathogenic	-1.05	Destabilizing	1.0	D	0.749	deleterious	D	0.647304957	None	None	N
N/I	0.9944	likely_pathogenic	0.9956	pathogenic	-0.083	Destabilizing	1.0	D	0.717	prob.delet.	D	0.663929731	None	None	N
N/K	0.9976	likely_pathogenic	0.998	pathogenic	-0.397	Destabilizing	1.0	D	0.743	deleterious	D	0.663324318	None	None	N
N/L	0.9863	likely_pathogenic	0.987	pathogenic	-0.083	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
N/M	0.9911	likely_pathogenic	0.9916	pathogenic	0.323	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
N/P	0.9987	likely_pathogenic	0.999	pathogenic	-0.358	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
N/Q	0.9976	likely_pathogenic	0.998	pathogenic	-1.01	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
N/R	0.9974	likely_pathogenic	0.9976	pathogenic	-0.437	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
N/S	0.8523	likely_pathogenic	0.875	pathogenic	-1.052	Destabilizing	0.999	D	0.579	neutral	D	0.594412495	None	None	N
N/T	0.957	likely_pathogenic	0.9668	pathogenic	-0.747	Destabilizing	0.999	D	0.718	prob.delet.	D	0.617446798	None	None	N
N/V	0.9928	likely_pathogenic	0.9942	pathogenic	-0.358	Destabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	N
N/W	0.9996	likely_pathogenic	0.9996	pathogenic	-0.39	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
N/Y	0.9911	likely_pathogenic	0.9922	pathogenic	-0.168	Destabilizing	1.0	D	0.744	deleterious	D	0.663929731	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.