TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32237	96934;96935;96936	chr2:178543264;178543263;178543262	chr2:179407991;179407990;179407989
N2AB	30596	92011;92012;92013	chr2:178543264;178543263;178543262	chr2:179407991;179407990;179407989
N2A	29669	89230;89231;89232	chr2:178543264;178543263;178543262	chr2:179407991;179407990;179407989
N2B	23172	69739;69740;69741	chr2:178543264;178543263;178543262	chr2:179407991;179407990;179407989
Novex-1	23297	70114;70115;70116	chr2:178543264;178543263;178543262	chr2:179407991;179407990;179407989
Novex-2	23364	70315;70316;70317	chr2:178543264;178543263;178543262	chr2:179407991;179407990;179407989
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: Fn3-123
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.0891
• 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/H	None	None	1.0	D	0.71	0.865	0.740777020696	gnomAD-4.0.0	1.59113E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85814E-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	0.9844	likely_pathogenic	0.9885	pathogenic	-3.609	Highly Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
Y/C	0.7809	likely_pathogenic	0.8151	pathogenic	-1.786	Destabilizing	1.0	D	0.827	deleterious	D	0.64794073	None	None	N
Y/D	0.9874	likely_pathogenic	0.9916	pathogenic	-3.746	Highly Destabilizing	1.0	D	0.878	deleterious	D	0.648142535	None	None	N
Y/E	0.9962	likely_pathogenic	0.9974	pathogenic	-3.538	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
Y/F	0.1431	likely_benign	0.1541	benign	-1.695	Destabilizing	0.184	N	0.328	neutral	D	0.547000904	None	None	N
Y/G	0.9722	likely_pathogenic	0.979	pathogenic	-3.978	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Y/H	0.9328	likely_pathogenic	0.9509	pathogenic	-2.872	Highly Destabilizing	1.0	D	0.71	prob.delet.	D	0.631517761	None	None	N
Y/I	0.9064	likely_pathogenic	0.9249	pathogenic	-2.337	Highly Destabilizing	0.991	D	0.728	prob.delet.	None	None	None	None	N
Y/K	0.9955	likely_pathogenic	0.997	pathogenic	-2.64	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Y/L	0.8452	likely_pathogenic	0.8622	pathogenic	-2.337	Highly Destabilizing	0.939	D	0.727	prob.delet.	None	None	None	None	N
Y/M	0.9323	likely_pathogenic	0.9445	pathogenic	-1.956	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
Y/N	0.9431	likely_pathogenic	0.9538	pathogenic	-3.392	Highly Destabilizing	1.0	D	0.86	deleterious	D	0.64794073	None	None	N
Y/P	0.9972	likely_pathogenic	0.9983	pathogenic	-2.782	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
Y/Q	0.9938	likely_pathogenic	0.9959	pathogenic	-3.114	Highly Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
Y/R	0.9867	likely_pathogenic	0.9914	pathogenic	-2.476	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
Y/S	0.96	likely_pathogenic	0.9685	pathogenic	-3.628	Highly Destabilizing	1.0	D	0.838	deleterious	D	0.64794073	None	None	N
Y/T	0.9802	likely_pathogenic	0.9858	pathogenic	-3.31	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
Y/V	0.8685	likely_pathogenic	0.8884	pathogenic	-2.782	Highly Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
Y/W	0.6619	likely_pathogenic	0.7147	pathogenic	-0.928	Destabilizing	1.0	D	0.707	prob.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.