TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17692	53299;53300;53301	chr2:178607614;178607613;178607612	chr2:179472341;179472340;179472339
N2AB	16051	48376;48377;48378	chr2:178607614;178607613;178607612	chr2:179472341;179472340;179472339
N2A	15124	45595;45596;45597	chr2:178607614;178607613;178607612	chr2:179472341;179472340;179472339
N2B	8627	26104;26105;26106	chr2:178607614;178607613;178607612	chr2:179472341;179472340;179472339
Novex-1	8752	26479;26480;26481	chr2:178607614;178607613;178607612	chr2:179472341;179472340;179472339
Novex-2	8819	26680;26681;26682	chr2:178607614;178607613;178607612	chr2:179472341;179472340;179472339
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-113
• Domain position: 16
• Structural Position: 30
• Q(SASA): 0.1764
• 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
I/V	rs753698005	-0.988	0.103	N	0.261	0.126	0.455357065977	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.96E-06	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
I/A	0.9919	likely_pathogenic	0.9942	pathogenic	-2.507	Highly Destabilizing	0.919	D	0.732	prob.delet.	None	None	None	None	N
I/C	0.9877	likely_pathogenic	0.9913	pathogenic	-1.722	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
I/D	0.998	likely_pathogenic	0.9987	pathogenic	-3.214	Highly Destabilizing	0.996	D	0.867	deleterious	None	None	None	None	N
I/E	0.9962	likely_pathogenic	0.9976	pathogenic	-2.937	Highly Destabilizing	0.996	D	0.871	deleterious	None	None	None	None	N
I/F	0.6092	likely_pathogenic	0.6174	pathogenic	-1.587	Destabilizing	0.968	D	0.727	prob.delet.	N	0.448525645	None	None	N
I/G	0.9972	likely_pathogenic	0.998	pathogenic	-3.037	Highly Destabilizing	0.996	D	0.863	deleterious	None	None	None	None	N
I/H	0.9924	likely_pathogenic	0.9942	pathogenic	-2.486	Highly Destabilizing	0.999	D	0.85	deleterious	None	None	None	None	N
I/K	0.9898	likely_pathogenic	0.9923	pathogenic	-2.067	Highly Destabilizing	0.988	D	0.868	deleterious	None	None	None	None	N
I/L	0.1862	likely_benign	0.1977	benign	-0.932	Destabilizing	0.011	N	0.251	neutral	N	0.365157687	None	None	N
I/M	0.4132	ambiguous	0.4487	ambiguous	-0.909	Destabilizing	0.968	D	0.708	prob.delet.	N	0.481110571	None	None	N
I/N	0.9769	likely_pathogenic	0.9838	pathogenic	-2.651	Highly Destabilizing	0.995	D	0.856	deleterious	N	0.515295155	None	None	N
I/P	0.997	likely_pathogenic	0.9976	pathogenic	-1.446	Destabilizing	0.996	D	0.864	deleterious	None	None	None	None	N
I/Q	0.9923	likely_pathogenic	0.9946	pathogenic	-2.417	Highly Destabilizing	0.996	D	0.868	deleterious	None	None	None	None	N
I/R	0.9886	likely_pathogenic	0.9913	pathogenic	-1.981	Destabilizing	0.988	D	0.856	deleterious	None	None	None	None	N
I/S	0.9901	likely_pathogenic	0.9932	pathogenic	-3.215	Highly Destabilizing	0.984	D	0.833	deleterious	N	0.515295155	None	None	N
I/T	0.9934	likely_pathogenic	0.9953	pathogenic	-2.784	Highly Destabilizing	0.896	D	0.783	deleterious	N	0.503685361	None	None	N
I/V	0.3558	ambiguous	0.3841	ambiguous	-1.446	Destabilizing	0.103	N	0.261	neutral	N	0.502928638	None	None	N
I/W	0.9874	likely_pathogenic	0.9898	pathogenic	-1.921	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
I/Y	0.9531	likely_pathogenic	0.9618	pathogenic	-1.643	Destabilizing	0.988	D	0.779	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.