TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7005	21238;21239;21240	chr2:178724362;178724361;178724360	chr2:179589089;179589088;179589087
N2AB	6688	20287;20288;20289	chr2:178724362;178724361;178724360	chr2:179589089;179589088;179589087
N2A	5761	17506;17507;17508	chr2:178724362;178724361;178724360	chr2:179589089;179589088;179589087
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: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-54
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0758
• 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
L/F	None	None	0.982	N	0.691	0.533	0.605722390383	gnomAD-4.0.0	1.59181E-06	None	None	None	None	N	None	0	0	None	0	2.77362E-05	None	0	0	0	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
L/A	0.9149	likely_pathogenic	0.9177	pathogenic	-2.415	Highly Destabilizing	0.953	D	0.717	prob.delet.	None	None	None	None	N
L/C	0.8834	likely_pathogenic	0.8785	pathogenic	-1.559	Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	N
L/D	0.9991	likely_pathogenic	0.9993	pathogenic	-3.097	Highly Destabilizing	0.998	D	0.881	deleterious	None	None	None	None	N
L/E	0.9918	likely_pathogenic	0.9942	pathogenic	-2.767	Highly Destabilizing	0.998	D	0.874	deleterious	None	None	None	None	N
L/F	0.4327	ambiguous	0.4636	ambiguous	-1.472	Destabilizing	0.982	D	0.691	prob.neutral	N	0.521698527	None	None	N
L/G	0.982	likely_pathogenic	0.9844	pathogenic	-3.016	Highly Destabilizing	0.998	D	0.872	deleterious	None	None	None	None	N
L/H	0.9681	likely_pathogenic	0.9747	pathogenic	-2.961	Highly Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
L/I	0.2027	likely_benign	0.2135	benign	-0.593	Destabilizing	0.046	N	0.409	neutral	N	0.515088708	None	None	N
L/K	0.9834	likely_pathogenic	0.9886	pathogenic	-1.675	Destabilizing	0.993	D	0.849	deleterious	None	None	None	None	N
L/M	0.2998	likely_benign	0.2943	benign	-0.885	Destabilizing	0.986	D	0.681	prob.neutral	None	None	None	None	N
L/N	0.9919	likely_pathogenic	0.9942	pathogenic	-2.443	Highly Destabilizing	0.998	D	0.883	deleterious	None	None	None	None	N
L/P	0.9948	likely_pathogenic	0.9959	pathogenic	-1.194	Destabilizing	0.998	D	0.882	deleterious	None	None	None	None	N
L/Q	0.9517	likely_pathogenic	0.962	pathogenic	-2.016	Highly Destabilizing	0.998	D	0.863	deleterious	None	None	None	None	N
L/R	0.9623	likely_pathogenic	0.971	pathogenic	-1.987	Destabilizing	0.998	D	0.86	deleterious	None	None	None	None	N
L/S	0.9839	likely_pathogenic	0.9861	pathogenic	-2.901	Highly Destabilizing	0.991	D	0.845	deleterious	D	0.568328744	None	None	N
L/T	0.9603	likely_pathogenic	0.964	pathogenic	-2.4	Highly Destabilizing	0.986	D	0.762	deleterious	None	None	None	None	N
L/V	0.2653	likely_benign	0.2534	benign	-1.194	Destabilizing	0.17	N	0.415	neutral	N	0.512899889	None	None	N
L/W	0.8977	likely_pathogenic	0.9191	pathogenic	-1.845	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
L/Y	0.9202	likely_pathogenic	0.9337	pathogenic	-1.653	Destabilizing	0.998	D	0.761	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.