TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29012	87259;87260;87261	chr2:178558425;178558424;178558423	chr2:179423152;179423151;179423150
N2AB	27371	82336;82337;82338	chr2:178558425;178558424;178558423	chr2:179423152;179423151;179423150
N2A	26444	79555;79556;79557	chr2:178558425;178558424;178558423	chr2:179423152;179423151;179423150
N2B	19947	60064;60065;60066	chr2:178558425;178558424;178558423	chr2:179423152;179423151;179423150
Novex-1	20072	60439;60440;60441	chr2:178558425;178558424;178558423	chr2:179423152;179423151;179423150
Novex-2	20139	60640;60641;60642	chr2:178558425;178558424;178558423	chr2:179423152;179423151;179423150
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: Fn3-99
• Domain position: 71
• Structural Position: 105
• Q(SASA): 0.2166
• 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	0.477	N	0.579	0.326	0.468168183122	gnomAD-4.0.0	1.5914E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85799E-06	0	0
F/V	None	None	0.645	N	0.584	0.419	0.623909720503	gnomAD-4.0.0	1.5914E-06	None	None	None	None	N	None	0	0	None	0	2.77948E-05	None	0	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	0.3928	ambiguous	0.3933	ambiguous	-2.393	Highly Destabilizing	0.707	D	0.618	neutral	None	None	None	None	N
F/C	0.187	likely_benign	0.1895	benign	-0.863	Destabilizing	0.993	D	0.699	prob.neutral	N	0.490870913	None	None	N
F/D	0.6831	likely_pathogenic	0.6692	pathogenic	-3.198	Highly Destabilizing	0.945	D	0.749	deleterious	None	None	None	None	N
F/E	0.7034	likely_pathogenic	0.6856	pathogenic	-2.99	Highly Destabilizing	0.945	D	0.726	prob.delet.	None	None	None	None	N
F/G	0.6682	likely_pathogenic	0.6812	pathogenic	-2.796	Highly Destabilizing	0.945	D	0.684	prob.neutral	None	None	None	None	N
F/H	0.3081	likely_benign	0.291	benign	-1.667	Destabilizing	0.894	D	0.667	neutral	None	None	None	None	N
F/I	0.1512	likely_benign	0.1527	benign	-1.067	Destabilizing	0.864	D	0.572	neutral	N	0.441962245	None	None	N
F/K	0.7274	likely_pathogenic	0.6867	pathogenic	-1.674	Destabilizing	0.894	D	0.729	prob.delet.	None	None	None	None	N
F/L	0.6366	likely_pathogenic	0.6079	pathogenic	-1.067	Destabilizing	0.477	N	0.579	neutral	N	0.430206456	None	None	N
F/M	0.3816	ambiguous	0.3685	ambiguous	-0.571	Destabilizing	0.995	D	0.604	neutral	None	None	None	None	N
F/N	0.4155	ambiguous	0.3919	ambiguous	-2.26	Highly Destabilizing	0.945	D	0.765	deleterious	None	None	None	None	N
F/P	0.9934	likely_pathogenic	0.9936	pathogenic	-1.522	Destabilizing	0.981	D	0.763	deleterious	None	None	None	None	N
F/Q	0.5174	ambiguous	0.4904	ambiguous	-2.166	Highly Destabilizing	0.945	D	0.768	deleterious	None	None	None	None	N
F/R	0.522	ambiguous	0.5046	ambiguous	-1.393	Destabilizing	0.945	D	0.764	deleterious	None	None	None	None	N
F/S	0.2322	likely_benign	0.2274	benign	-2.666	Highly Destabilizing	0.864	D	0.667	neutral	N	0.427395438	None	None	N
F/T	0.2902	likely_benign	0.286	benign	-2.358	Highly Destabilizing	0.945	D	0.68	prob.neutral	None	None	None	None	N
F/V	0.137	likely_benign	0.1375	benign	-1.522	Destabilizing	0.645	D	0.584	neutral	N	0.388762479	None	None	N
F/W	0.4912	ambiguous	0.4999	ambiguous	-0.394	Destabilizing	0.985	D	0.605	neutral	None	None	None	None	N
F/Y	0.0825	likely_benign	0.082	benign	-0.679	Destabilizing	0.002	N	0.295	neutral	N	0.409100465	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.