TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7090	21493;21494;21495	chr2:178723991;178723990;178723989	chr2:179588718;179588717;179588716
N2AB	6773	20542;20543;20544	chr2:178723991;178723990;178723989	chr2:179588718;179588717;179588716
N2A	5846	17761;17762;17763	chr2:178723991;178723990;178723989	chr2:179588718;179588717;179588716
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-55
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1992
• 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
Y/C	rs1560711168	None	0.999	N	0.697	0.561	0.754557078919	gnomAD-4.0.0	1.59189E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43299E-05	0
Y/N	None	None	0.896	D	0.573	0.534	0.76754552583	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
Y/A	0.6651	likely_pathogenic	0.6493	pathogenic	-2.854	Highly Destabilizing	0.919	D	0.553	neutral	None	None	None	None	N
Y/C	0.2081	likely_benign	0.1795	benign	-1.883	Destabilizing	0.999	D	0.697	prob.neutral	N	0.500611168	None	None	N
Y/D	0.6294	likely_pathogenic	0.6392	pathogenic	-2.308	Highly Destabilizing	0.968	D	0.652	neutral	D	0.539960004	None	None	N
Y/E	0.7861	likely_pathogenic	0.785	pathogenic	-2.146	Highly Destabilizing	0.919	D	0.568	neutral	None	None	None	None	N
Y/F	0.137	likely_benign	0.1322	benign	-1.176	Destabilizing	0.946	D	0.528	neutral	D	0.529229805	None	None	N
Y/G	0.5461	ambiguous	0.5702	pathogenic	-3.262	Highly Destabilizing	0.919	D	0.611	neutral	None	None	None	None	N
Y/H	0.2387	likely_benign	0.2172	benign	-1.771	Destabilizing	0.011	N	0.144	neutral	D	0.523709342	None	None	N
Y/I	0.5229	ambiguous	0.5094	ambiguous	-1.544	Destabilizing	0.988	D	0.607	neutral	None	None	None	None	N
Y/K	0.7128	likely_pathogenic	0.7186	pathogenic	-1.937	Destabilizing	0.976	D	0.593	neutral	None	None	None	None	N
Y/L	0.5168	ambiguous	0.502	ambiguous	-1.544	Destabilizing	0.919	D	0.517	neutral	None	None	None	None	N
Y/M	0.7092	likely_pathogenic	0.692	pathogenic	-1.349	Destabilizing	0.999	D	0.622	neutral	None	None	None	None	N
Y/N	0.2865	likely_benign	0.2936	benign	-2.504	Highly Destabilizing	0.896	D	0.573	neutral	D	0.523577269	None	None	N
Y/P	0.9329	likely_pathogenic	0.9365	pathogenic	-1.987	Destabilizing	0.996	D	0.723	prob.delet.	None	None	None	None	N
Y/Q	0.6055	likely_pathogenic	0.5847	pathogenic	-2.311	Highly Destabilizing	0.976	D	0.611	neutral	None	None	None	None	N
Y/R	0.5424	ambiguous	0.5358	ambiguous	-1.619	Destabilizing	0.976	D	0.616	neutral	None	None	None	None	N
Y/S	0.3738	ambiguous	0.3764	ambiguous	-3.03	Highly Destabilizing	0.896	D	0.572	neutral	N	0.512448	None	None	N
Y/T	0.5785	likely_pathogenic	0.5766	pathogenic	-2.747	Highly Destabilizing	0.988	D	0.611	neutral	None	None	None	None	N
Y/V	0.4486	ambiguous	0.4365	ambiguous	-1.987	Destabilizing	0.959	D	0.531	neutral	None	None	None	None	N
Y/W	0.5108	ambiguous	0.4903	ambiguous	-0.603	Destabilizing	0.999	D	0.577	neutral	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.