TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5846	17761;17762;17763	chr2:178731129;178731128;178731127	chr2:179595856;179595855;179595854
N2AB	5529	16810;16811;16812	chr2:178731129;178731128;178731127	chr2:179595856;179595855;179595854
N2A	4602	14029;14030;14031	chr2:178731129;178731128;178731127	chr2:179595856;179595855;179595854
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: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-42
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1141
• 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
F/L	None	None	0.978	N	0.635	0.277	0.405012372841	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.9619	likely_pathogenic	0.9518	pathogenic	-3.245	Highly Destabilizing	0.992	D	0.751	deleterious	None	None	None	None	N
F/C	0.7495	likely_pathogenic	0.7297	pathogenic	-2.227	Highly Destabilizing	1.0	D	0.805	deleterious	N	0.494024122	None	None	N
F/D	0.9976	likely_pathogenic	0.9972	pathogenic	-3.448	Highly Destabilizing	0.999	D	0.846	deleterious	None	None	None	None	N
F/E	0.9968	likely_pathogenic	0.9962	pathogenic	-3.254	Highly Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
F/G	0.9881	likely_pathogenic	0.9844	pathogenic	-3.64	Highly Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
F/H	0.9576	likely_pathogenic	0.9509	pathogenic	-2.207	Highly Destabilizing	0.995	D	0.771	deleterious	None	None	None	None	N
F/I	0.5797	likely_pathogenic	0.4775	ambiguous	-1.94	Destabilizing	0.997	D	0.716	prob.delet.	N	0.459844291	None	None	N
F/K	0.9957	likely_pathogenic	0.9945	pathogenic	-2.189	Highly Destabilizing	0.998	D	0.846	deleterious	None	None	None	None	N
F/L	0.9798	likely_pathogenic	0.9702	pathogenic	-1.94	Destabilizing	0.978	D	0.635	neutral	N	0.486553676	None	None	N
F/M	0.8906	likely_pathogenic	0.8601	pathogenic	-1.851	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
F/N	0.9853	likely_pathogenic	0.9836	pathogenic	-2.594	Highly Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
F/P	0.9994	likely_pathogenic	0.9992	pathogenic	-2.388	Highly Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
F/Q	0.992	likely_pathogenic	0.9909	pathogenic	-2.596	Highly Destabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
F/R	0.9879	likely_pathogenic	0.9863	pathogenic	-1.674	Destabilizing	0.998	D	0.843	deleterious	None	None	None	None	N
F/S	0.9668	likely_pathogenic	0.9609	pathogenic	-3.203	Highly Destabilizing	0.997	D	0.814	deleterious	N	0.483726802	None	None	N
F/T	0.9685	likely_pathogenic	0.9595	pathogenic	-2.904	Highly Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	N
F/V	0.5351	ambiguous	0.4805	ambiguous	-2.388	Highly Destabilizing	0.978	D	0.732	prob.delet.	N	0.394459087	None	None	N
F/W	0.846	likely_pathogenic	0.7931	pathogenic	-0.719	Destabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	N
F/Y	0.2611	likely_benign	0.2203	benign	-1.162	Destabilizing	0.37	N	0.249	neutral	N	0.487940543	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.