TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7797	23614;23615;23616	chr2:178720253;178720252;178720251	chr2:179584980;179584979;179584978
N2AB	7480	22663;22664;22665	chr2:178720253;178720252;178720251	chr2:179584980;179584979;179584978
N2A	6553	19882;19883;19884	chr2:178720253;178720252;178720251	chr2:179584980;179584979;179584978
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-63
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.125
• 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	rs754815317	None	0.987	D	0.663	0.716	0.374255764437	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
F/L	rs754815317	None	0.987	D	0.663	0.716	0.374255764437	gnomAD-4.0.0	7.45733E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.01957E-05	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	0.9899	likely_pathogenic	0.989	pathogenic	-2.716	Highly Destabilizing	0.996	D	0.76	deleterious	None	None	None	None	I
F/C	0.9719	likely_pathogenic	0.9683	pathogenic	-1.369	Destabilizing	0.571	D	0.673	neutral	D	0.569049532	None	None	I
F/D	0.9985	likely_pathogenic	0.9982	pathogenic	-2.409	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
F/E	0.9985	likely_pathogenic	0.9984	pathogenic	-2.268	Highly Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	I
F/G	0.9971	likely_pathogenic	0.9968	pathogenic	-3.101	Highly Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	I
F/H	0.9912	likely_pathogenic	0.991	pathogenic	-1.374	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
F/I	0.6896	likely_pathogenic	0.687	pathogenic	-1.494	Destabilizing	0.994	D	0.701	prob.neutral	N	0.489988878	None	None	I
F/K	0.999	likely_pathogenic	0.9989	pathogenic	-1.563	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
F/L	0.9822	likely_pathogenic	0.9814	pathogenic	-1.494	Destabilizing	0.987	D	0.663	neutral	D	0.531013689	None	None	I
F/M	0.9149	likely_pathogenic	0.9156	pathogenic	-1.103	Destabilizing	0.995	D	0.709	prob.delet.	None	None	None	None	I
F/N	0.994	likely_pathogenic	0.9935	pathogenic	-1.766	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
F/P	0.9986	likely_pathogenic	0.9982	pathogenic	-1.905	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
F/Q	0.9979	likely_pathogenic	0.9979	pathogenic	-1.856	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	I
F/R	0.9972	likely_pathogenic	0.9971	pathogenic	-0.9	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
F/S	0.9924	likely_pathogenic	0.9913	pathogenic	-2.483	Highly Destabilizing	0.999	D	0.833	deleterious	D	0.557021664	None	None	I
F/T	0.9912	likely_pathogenic	0.9902	pathogenic	-2.249	Highly Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	I
F/V	0.8069	likely_pathogenic	0.8033	pathogenic	-1.905	Destabilizing	0.982	D	0.762	deleterious	D	0.546382466	None	None	I
F/W	0.919	likely_pathogenic	0.9166	pathogenic	-0.419	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	I
F/Y	0.6682	likely_pathogenic	0.6616	pathogenic	-0.734	Destabilizing	0.995	D	0.639	neutral	D	0.545918848	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.