TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21130	63613;63614;63615	chr2:178588019;178588018;178588017	chr2:179452746;179452745;179452744
N2AB	19489	58690;58691;58692	chr2:178588019;178588018;178588017	chr2:179452746;179452745;179452744
N2A	18562	55909;55910;55911	chr2:178588019;178588018;178588017	chr2:179452746;179452745;179452744
N2B	12065	36418;36419;36420	chr2:178588019;178588018;178588017	chr2:179452746;179452745;179452744
Novex-1	12190	36793;36794;36795	chr2:178588019;178588018;178588017	chr2:179452746;179452745;179452744
Novex-2	12257	36994;36995;36996	chr2:178588019;178588018;178588017	chr2:179452746;179452745;179452744
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: Fn3-41
• Domain position: 67
• Structural Position: 91
• Q(SASA): 0.171
• 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	rs1389556175	None	0.885	N	0.493	0.321	0.276898752692	gnomAD-4.0.0	2.05369E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69928E-06	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	0.9431	likely_pathogenic	0.9445	pathogenic	-2.373	Highly Destabilizing	0.953	D	0.533	neutral	None	None	None	None	I
F/C	0.6928	likely_pathogenic	0.7038	pathogenic	-1.457	Destabilizing	0.999	D	0.699	prob.neutral	N	0.491815062	None	None	I
F/D	0.9766	likely_pathogenic	0.9793	pathogenic	-1.971	Destabilizing	0.998	D	0.744	deleterious	None	None	None	None	I
F/E	0.9791	likely_pathogenic	0.9798	pathogenic	-1.812	Destabilizing	0.993	D	0.715	prob.delet.	None	None	None	None	I
F/G	0.9647	likely_pathogenic	0.9693	pathogenic	-2.777	Highly Destabilizing	0.993	D	0.661	neutral	None	None	None	None	I
F/H	0.8682	likely_pathogenic	0.8685	pathogenic	-1.113	Destabilizing	0.986	D	0.621	neutral	None	None	None	None	I
F/I	0.6495	likely_pathogenic	0.6535	pathogenic	-1.105	Destabilizing	0.982	D	0.483	neutral	N	0.517788155	None	None	I
F/K	0.978	likely_pathogenic	0.9792	pathogenic	-1.743	Destabilizing	0.993	D	0.721	prob.delet.	None	None	None	None	I
F/L	0.9608	likely_pathogenic	0.9601	pathogenic	-1.105	Destabilizing	0.885	D	0.493	neutral	N	0.491620274	None	None	I
F/M	0.7926	likely_pathogenic	0.7799	pathogenic	-0.79	Destabilizing	0.999	D	0.525	neutral	None	None	None	None	I
F/N	0.9376	likely_pathogenic	0.9431	pathogenic	-2.059	Highly Destabilizing	0.998	D	0.762	deleterious	None	None	None	None	I
F/P	0.9996	likely_pathogenic	0.9997	pathogenic	-1.529	Destabilizing	0.998	D	0.768	deleterious	None	None	None	None	I
F/Q	0.9662	likely_pathogenic	0.967	pathogenic	-2.033	Highly Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	I
F/R	0.9613	likely_pathogenic	0.963	pathogenic	-1.194	Destabilizing	0.993	D	0.762	deleterious	None	None	None	None	I
F/S	0.9331	likely_pathogenic	0.936	pathogenic	-2.783	Highly Destabilizing	0.991	D	0.619	neutral	N	0.484753006	None	None	I
F/T	0.9486	likely_pathogenic	0.9495	pathogenic	-2.517	Highly Destabilizing	0.993	D	0.64	neutral	None	None	None	None	I
F/V	0.6747	likely_pathogenic	0.6807	pathogenic	-1.529	Destabilizing	0.939	D	0.482	neutral	N	0.502930559	None	None	I
F/W	0.6459	likely_pathogenic	0.6911	pathogenic	-0.254	Destabilizing	0.998	D	0.517	neutral	None	None	None	None	I
F/Y	0.1573	likely_benign	0.1709	benign	-0.548	Destabilizing	0.02	N	0.235	neutral	N	0.411060548	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.