TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24293	73102;73103;73104	chr2:178573255;178573254;178573253	chr2:179437982;179437981;179437980
N2AB	22652	68179;68180;68181	chr2:178573255;178573254;178573253	chr2:179437982;179437981;179437980
N2A	21725	65398;65399;65400	chr2:178573255;178573254;178573253	chr2:179437982;179437981;179437980
N2B	15228	45907;45908;45909	chr2:178573255;178573254;178573253	chr2:179437982;179437981;179437980
Novex-1	15353	46282;46283;46284	chr2:178573255;178573254;178573253	chr2:179437982;179437981;179437980
Novex-2	15420	46483;46484;46485	chr2:178573255;178573254;178573253	chr2:179437982;179437981;179437980
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-64
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.0772
• 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	None	None	1.0	D	0.869	0.784	0.924592780308	gnomAD-4.0.0	2.75087E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.61167E-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	0.9912	likely_pathogenic	0.987	pathogenic	-3.62	Highly Destabilizing	0.991	D	0.822	deleterious	None	None	None	None	N
Y/C	0.9122	likely_pathogenic	0.8752	pathogenic	-1.907	Destabilizing	1.0	D	0.869	deleterious	D	0.670846413	None	None	N
Y/D	0.9925	likely_pathogenic	0.9888	pathogenic	-3.918	Highly Destabilizing	0.999	D	0.873	deleterious	D	0.69615236	None	None	N
Y/E	0.9969	likely_pathogenic	0.9957	pathogenic	-3.721	Highly Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
Y/F	0.3086	likely_benign	0.2543	benign	-1.618	Destabilizing	0.117	N	0.5	neutral	D	0.656957612	None	None	N
Y/G	0.9828	likely_pathogenic	0.9773	pathogenic	-3.986	Highly Destabilizing	0.998	D	0.867	deleterious	None	None	None	None	N
Y/H	0.9716	likely_pathogenic	0.9634	pathogenic	-2.663	Highly Destabilizing	0.999	D	0.779	deleterious	D	0.69615236	None	None	N
Y/I	0.9357	likely_pathogenic	0.914	pathogenic	-2.361	Highly Destabilizing	0.99	D	0.799	deleterious	None	None	None	None	N
Y/K	0.9977	likely_pathogenic	0.9968	pathogenic	-2.633	Highly Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
Y/L	0.9325	likely_pathogenic	0.9156	pathogenic	-2.361	Highly Destabilizing	0.966	D	0.767	deleterious	None	None	None	None	N
Y/M	0.9531	likely_pathogenic	0.939	pathogenic	-1.948	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
Y/N	0.9471	likely_pathogenic	0.9317	pathogenic	-3.381	Highly Destabilizing	0.999	D	0.861	deleterious	D	0.695950556	None	None	N
Y/P	0.9993	likely_pathogenic	0.9989	pathogenic	-2.801	Highly Destabilizing	0.999	D	0.883	deleterious	None	None	None	None	N
Y/Q	0.9959	likely_pathogenic	0.9942	pathogenic	-3.158	Highly Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
Y/R	0.9944	likely_pathogenic	0.9921	pathogenic	-2.307	Highly Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
Y/S	0.9815	likely_pathogenic	0.9726	pathogenic	-3.647	Highly Destabilizing	0.997	D	0.861	deleterious	D	0.670846413	None	None	N
Y/T	0.9877	likely_pathogenic	0.9819	pathogenic	-3.348	Highly Destabilizing	0.998	D	0.859	deleterious	None	None	None	None	N
Y/V	0.8794	likely_pathogenic	0.8452	pathogenic	-2.801	Highly Destabilizing	0.983	D	0.775	deleterious	None	None	None	None	N
Y/W	0.8712	likely_pathogenic	0.8529	pathogenic	-0.914	Destabilizing	1.0	D	0.767	deleterious	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.