TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15410	46453;46454;46455	chr2:178620293;178620292;178620291	chr2:179485020;179485019;179485018
N2AB	13769	41530;41531;41532	chr2:178620293;178620292;178620291	chr2:179485020;179485019;179485018
N2A	12842	38749;38750;38751	chr2:178620293;178620292;178620291	chr2:179485020;179485019;179485018
N2B	6345	19258;19259;19260	chr2:178620293;178620292;178620291	chr2:179485020;179485019;179485018
Novex-1	6470	19633;19634;19635	chr2:178620293;178620292;178620291	chr2:179485020;179485019;179485018
Novex-2	6537	19834;19835;19836	chr2:178620293;178620292;178620291	chr2:179485020;179485019;179485018
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-106
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1283
• 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	rs1450114008	None	0.014	N	0.337	0.382	0.388970301349	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.95E-05	0	0
F/L	rs1450114008	None	0.014	N	0.337	0.382	0.388970301349	gnomAD-4.0.0	1.31643E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.94516E-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	0.9983	likely_pathogenic	0.9986	pathogenic	-2.274	Highly Destabilizing	0.86	D	0.773	deleterious	None	None	None	None	N
F/C	0.9928	likely_pathogenic	0.9959	pathogenic	-0.984	Destabilizing	0.997	D	0.827	deleterious	D	0.747976259	None	None	N
F/D	0.9998	likely_pathogenic	0.9998	pathogenic	-2.992	Highly Destabilizing	0.993	D	0.855	deleterious	None	None	None	None	N
F/E	0.9998	likely_pathogenic	0.9998	pathogenic	-2.732	Highly Destabilizing	0.978	D	0.855	deleterious	None	None	None	None	N
F/G	0.9992	likely_pathogenic	0.9994	pathogenic	-2.753	Highly Destabilizing	0.978	D	0.849	deleterious	None	None	None	None	N
F/H	0.9974	likely_pathogenic	0.9982	pathogenic	-1.864	Destabilizing	0.998	D	0.749	deleterious	None	None	None	None	N
F/I	0.939	likely_pathogenic	0.9619	pathogenic	-0.701	Destabilizing	0.698	D	0.646	neutral	D	0.607812486	None	None	N
F/K	0.9996	likely_pathogenic	0.9997	pathogenic	-1.616	Destabilizing	0.978	D	0.852	deleterious	None	None	None	None	N
F/L	0.9774	likely_pathogenic	0.9806	pathogenic	-0.701	Destabilizing	0.014	N	0.337	neutral	N	0.495802874	None	None	N
F/M	0.9501	likely_pathogenic	0.9652	pathogenic	-0.477	Destabilizing	0.956	D	0.697	prob.neutral	None	None	None	None	N
F/N	0.9993	likely_pathogenic	0.9995	pathogenic	-2.306	Highly Destabilizing	0.993	D	0.852	deleterious	None	None	None	None	N
F/P	1.0	likely_pathogenic	1.0	pathogenic	-1.24	Destabilizing	0.993	D	0.86	deleterious	None	None	None	None	N
F/Q	0.9993	likely_pathogenic	0.9995	pathogenic	-2.051	Highly Destabilizing	0.993	D	0.859	deleterious	None	None	None	None	N
F/R	0.9989	likely_pathogenic	0.999	pathogenic	-1.653	Destabilizing	0.978	D	0.848	deleterious	None	None	None	None	N
F/S	0.9989	likely_pathogenic	0.9993	pathogenic	-2.745	Highly Destabilizing	0.971	D	0.828	deleterious	D	0.747976259	None	None	N
F/T	0.9991	likely_pathogenic	0.9994	pathogenic	-2.354	Highly Destabilizing	0.956	D	0.819	deleterious	None	None	None	None	N
F/V	0.9649	likely_pathogenic	0.9788	pathogenic	-1.24	Destabilizing	0.698	D	0.688	prob.neutral	D	0.632957411	None	None	N
F/W	0.9761	likely_pathogenic	0.9826	pathogenic	0.031	Stabilizing	0.998	D	0.676	prob.neutral	None	None	None	None	N
F/Y	0.8279	likely_pathogenic	0.8593	pathogenic	-0.386	Destabilizing	0.904	D	0.602	neutral	D	0.710398604	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.