TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9495	28708;28709;28710	chr2:178709836;178709835;178709834	chr2:179574563;179574562;179574561
N2AB	9178	27757;27758;27759	chr2:178709836;178709835;178709834	chr2:179574563;179574562;179574561
N2A	8251	24976;24977;24978	chr2:178709836;178709835;178709834	chr2:179574563;179574562;179574561
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: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-81
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.5918
• Predicted PPI site: I

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
F/L	None	None	0.999	None	0.568	0.709	0.558774299873	gnomAD-4.0.0	1.59569E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.90244E-05	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
F/A	0.9944	likely_pathogenic	0.9961	pathogenic	-2.54	Highly Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
F/C	0.9774	likely_pathogenic	0.9825	pathogenic	-1.586	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
F/D	0.9989	likely_pathogenic	0.9994	pathogenic	-1.436	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	I
F/E	0.9991	likely_pathogenic	0.9995	pathogenic	-1.336	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
F/G	0.9983	likely_pathogenic	0.9987	pathogenic	-2.901	Highly Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	I
F/H	0.9904	likely_pathogenic	0.9952	pathogenic	-1.19	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
F/I	0.7661	likely_pathogenic	0.8088	pathogenic	-1.431	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
F/K	0.9988	likely_pathogenic	0.9995	pathogenic	-1.389	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
F/L	0.9844	likely_pathogenic	0.9879	pathogenic	-1.431	Destabilizing	0.999	D	0.568	neutral	None	None	None	None	I
F/M	0.9358	likely_pathogenic	0.9566	pathogenic	-1.198	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
F/N	0.9964	likely_pathogenic	0.9979	pathogenic	-1.406	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
F/P	0.9989	likely_pathogenic	0.9993	pathogenic	-1.798	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
F/Q	0.9981	likely_pathogenic	0.999	pathogenic	-1.53	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
F/R	0.9968	likely_pathogenic	0.9983	pathogenic	-0.7	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
F/S	0.995	likely_pathogenic	0.9966	pathogenic	-2.28	Highly Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
F/T	0.9949	likely_pathogenic	0.997	pathogenic	-2.081	Highly Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
F/V	0.8269	likely_pathogenic	0.8512	pathogenic	-1.798	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
F/W	0.9225	likely_pathogenic	0.9379	pathogenic	-0.575	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	I
F/Y	0.7083	likely_pathogenic	0.7632	pathogenic	-0.793	Destabilizing	0.999	D	0.606	neutral	None	None	None	None	I

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.