TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2230	6913;6914;6915	chr2:178775023;178775022;178775021	chr2:179639750;179639749;179639748
N2AB	2230	6913;6914;6915	chr2:178775023;178775022;178775021	chr2:179639750;179639749;179639748
N2A	2230	6913;6914;6915	chr2:178775023;178775022;178775021	chr2:179639750;179639749;179639748
N2B	2184	6775;6776;6777	chr2:178775023;178775022;178775021	chr2:179639750;179639749;179639748
Novex-1	2184	6775;6776;6777	chr2:178775023;178775022;178775021	chr2:179639750;179639749;179639748
Novex-2	2184	6775;6776;6777	chr2:178775023;178775022;178775021	chr2:179639750;179639749;179639748
Novex-3	2230	6913;6914;6915	chr2:178775023;178775022;178775021	chr2:179639750;179639749;179639748

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-11
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.2401
• 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/C	None	None	0.997	N	0.732	0.536	0.781051952282	gnomAD-4.0.0	6.84128E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99336E-07	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	0.9504	likely_pathogenic	0.959	pathogenic	-2.665	Highly Destabilizing	0.86	D	0.625	neutral	None	None	None	None	N
F/C	0.8051	likely_pathogenic	0.8419	pathogenic	-1.347	Destabilizing	0.997	D	0.732	prob.delet.	N	0.510755985	None	None	N
F/D	0.9903	likely_pathogenic	0.9922	pathogenic	-2.488	Highly Destabilizing	0.993	D	0.767	deleterious	None	None	None	None	N
F/E	0.9861	likely_pathogenic	0.9888	pathogenic	-2.394	Highly Destabilizing	0.978	D	0.757	deleterious	None	None	None	None	N
F/G	0.9822	likely_pathogenic	0.9855	pathogenic	-3.011	Highly Destabilizing	0.978	D	0.703	prob.neutral	None	None	None	None	N
F/H	0.8235	likely_pathogenic	0.84	pathogenic	-1.392	Destabilizing	0.956	D	0.702	prob.neutral	None	None	None	None	N
F/I	0.657	likely_pathogenic	0.6979	pathogenic	-1.577	Destabilizing	0.698	D	0.559	neutral	N	0.477229867	None	None	N
F/K	0.9754	likely_pathogenic	0.9784	pathogenic	-1.376	Destabilizing	0.978	D	0.748	deleterious	None	None	None	None	N
F/L	0.9667	likely_pathogenic	0.9725	pathogenic	-1.577	Destabilizing	0.489	N	0.591	neutral	N	0.508601651	None	None	N
F/M	0.8578	likely_pathogenic	0.8734	pathogenic	-1.19	Destabilizing	0.559	D	0.461	neutral	None	None	None	None	N
F/N	0.9409	likely_pathogenic	0.9525	pathogenic	-1.482	Destabilizing	0.978	D	0.769	deleterious	None	None	None	None	N
F/P	0.9999	likely_pathogenic	0.9999	pathogenic	-1.941	Destabilizing	0.993	D	0.773	deleterious	None	None	None	None	N
F/Q	0.954	likely_pathogenic	0.9601	pathogenic	-1.654	Destabilizing	0.978	D	0.769	deleterious	None	None	None	None	N
F/R	0.9331	likely_pathogenic	0.94	pathogenic	-0.648	Destabilizing	0.978	D	0.771	deleterious	None	None	None	None	N
F/S	0.8857	likely_pathogenic	0.9099	pathogenic	-2.151	Highly Destabilizing	0.97	D	0.678	prob.neutral	N	0.471083069	None	None	N
F/T	0.9189	likely_pathogenic	0.9329	pathogenic	-1.966	Destabilizing	0.978	D	0.679	prob.neutral	None	None	None	None	N
F/V	0.6668	likely_pathogenic	0.7129	pathogenic	-1.941	Destabilizing	0.698	D	0.576	neutral	N	0.504987561	None	None	N
F/W	0.8625	likely_pathogenic	0.8722	pathogenic	-0.688	Destabilizing	0.994	D	0.621	neutral	None	None	None	None	N
F/Y	0.2825	likely_benign	0.3004	benign	-0.925	Destabilizing	0.014	N	0.429	neutral	N	0.505370739	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.