TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6570	19933;19934;19935	chr2:178728116;178728115;178728114	chr2:179592843;179592842;179592841
N2AB	6253	18982;18983;18984	chr2:178728116;178728115;178728114	chr2:179592843;179592842;179592841
N2A	5326	16201;16202;16203	chr2:178728116;178728115;178728114	chr2:179592843;179592842;179592841
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-49
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.3957
• 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
V/A	None	None	0.998	D	0.595	0.807	0.819384144463	gnomAD-4.0.0	6.39828E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.28285E-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
V/A	0.7015	likely_pathogenic	0.8054	pathogenic	-2.089	Highly Destabilizing	0.998	D	0.595	neutral	D	0.626411933	None	None	N
V/C	0.9738	likely_pathogenic	0.9804	pathogenic	-1.886	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
V/D	0.9917	likely_pathogenic	0.9949	pathogenic	-2.782	Highly Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
V/E	0.9703	likely_pathogenic	0.9809	pathogenic	-2.661	Highly Destabilizing	1.0	D	0.719	prob.delet.	D	0.643036707	None	None	N
V/F	0.8612	likely_pathogenic	0.8884	pathogenic	-1.387	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	N
V/G	0.8612	likely_pathogenic	0.9084	pathogenic	-2.512	Highly Destabilizing	1.0	D	0.716	prob.delet.	D	0.643036707	None	None	N
V/H	0.9953	likely_pathogenic	0.9971	pathogenic	-2.07	Highly Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
V/I	0.1062	likely_benign	0.1147	benign	-0.952	Destabilizing	0.985	D	0.591	neutral	None	None	None	None	N
V/K	0.9812	likely_pathogenic	0.988	pathogenic	-1.763	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
V/L	0.5938	likely_pathogenic	0.6848	pathogenic	-0.952	Destabilizing	0.434	N	0.491	neutral	D	0.608142365	None	None	N
V/M	0.6122	likely_pathogenic	0.6938	pathogenic	-1.057	Destabilizing	0.999	D	0.745	deleterious	D	0.626613738	None	None	N
V/N	0.9723	likely_pathogenic	0.9827	pathogenic	-1.92	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
V/P	0.9658	likely_pathogenic	0.973	pathogenic	-1.303	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
V/Q	0.9739	likely_pathogenic	0.9838	pathogenic	-1.952	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
V/R	0.9691	likely_pathogenic	0.9792	pathogenic	-1.375	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
V/S	0.9006	likely_pathogenic	0.9392	pathogenic	-2.471	Highly Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
V/T	0.811	likely_pathogenic	0.8738	pathogenic	-2.233	Highly Destabilizing	0.998	D	0.669	neutral	None	None	None	None	N
V/W	0.9969	likely_pathogenic	0.9979	pathogenic	-1.758	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
V/Y	0.9885	likely_pathogenic	0.9916	pathogenic	-1.45	Destabilizing	1.0	D	0.728	prob.delet.	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.