TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18751	56476;56477;56478	chr2:178599650;178599649;178599648	chr2:179464377;179464376;179464375
N2AB	17110	51553;51554;51555	chr2:178599650;178599649;178599648	chr2:179464377;179464376;179464375
N2A	16183	48772;48773;48774	chr2:178599650;178599649;178599648	chr2:179464377;179464376;179464375
N2B	9686	29281;29282;29283	chr2:178599650;178599649;178599648	chr2:179464377;179464376;179464375
Novex-1	9811	29656;29657;29658	chr2:178599650;178599649;178599648	chr2:179464377;179464376;179464375
Novex-2	9878	29857;29858;29859	chr2:178599650;178599649;178599648	chr2:179464377;179464376;179464375
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-116
• Domain position: 64
• Structural Position: 140
• Q(SASA): 0.0977
• 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/F	None	None	0.998	D	0.721	0.836	0.816700955439	gnomAD-4.0.0	2.05369E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73792E-04	0	2.32213E-05	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	0.9697	likely_pathogenic	0.9507	pathogenic	-2.927	Highly Destabilizing	0.992	D	0.695	prob.neutral	None	None	None	None	N
I/C	0.9613	likely_pathogenic	0.9294	pathogenic	-2.491	Highly Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
I/D	0.9935	likely_pathogenic	0.9909	pathogenic	-3.793	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
I/E	0.9904	likely_pathogenic	0.9854	pathogenic	-3.592	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
I/F	0.4372	ambiguous	0.3283	benign	-1.794	Destabilizing	0.998	D	0.721	prob.delet.	D	0.572953343	None	None	N
I/G	0.9935	likely_pathogenic	0.9884	pathogenic	-3.446	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
I/H	0.9656	likely_pathogenic	0.9401	pathogenic	-2.95	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
I/K	0.9734	likely_pathogenic	0.9501	pathogenic	-2.58	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
I/L	0.2394	likely_benign	0.1992	benign	-1.416	Destabilizing	0.889	D	0.376	neutral	D	0.572240189	None	None	N
I/M	0.3259	likely_benign	0.2542	benign	-1.401	Destabilizing	0.998	D	0.689	prob.neutral	D	0.59228373	None	None	N
I/N	0.9033	likely_pathogenic	0.8585	pathogenic	-2.961	Highly Destabilizing	0.999	D	0.882	deleterious	D	0.619234471	None	None	N
I/P	0.9921	likely_pathogenic	0.9878	pathogenic	-1.903	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
I/Q	0.972	likely_pathogenic	0.9532	pathogenic	-2.845	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
I/R	0.9626	likely_pathogenic	0.9322	pathogenic	-2.135	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
I/S	0.9462	likely_pathogenic	0.9159	pathogenic	-3.55	Highly Destabilizing	0.998	D	0.843	deleterious	D	0.60971572	None	None	N
I/T	0.9567	likely_pathogenic	0.9306	pathogenic	-3.219	Highly Destabilizing	0.989	D	0.753	deleterious	D	0.618830863	None	None	N
I/V	0.2463	likely_benign	0.1941	benign	-1.903	Destabilizing	0.333	N	0.259	neutral	D	0.547113422	None	None	N
I/W	0.9725	likely_pathogenic	0.9523	pathogenic	-2.297	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
I/Y	0.9142	likely_pathogenic	0.8546	pathogenic	-2.09	Highly Destabilizing	1.0	D	0.77	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.