TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6850	20773;20774;20775	chr2:178725774;178725773;178725772	chr2:179590501;179590500;179590499
N2AB	6533	19822;19823;19824	chr2:178725774;178725773;178725772	chr2:179590501;179590500;179590499
N2A	5606	17041;17042;17043	chr2:178725774;178725773;178725772	chr2:179590501;179590500;179590499
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: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-52
• Domain position: 90
• Structural Position: 177
• Q(SASA): 1.0369
• 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
L/F	None	None	1.0	N	0.671	0.393	0.32714864917	gnomAD-4.0.0	1.66516E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.98836E-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
L/A	0.3749	ambiguous	0.3731	ambiguous	-1.321	Destabilizing	1.0	D	0.608	neutral	None	None	None	None	I
L/C	0.5662	likely_pathogenic	0.5806	pathogenic	-0.844	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
L/D	0.8287	likely_pathogenic	0.8338	pathogenic	-0.643	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
L/E	0.4546	ambiguous	0.4672	ambiguous	-0.642	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
L/F	0.1324	likely_benign	0.1344	benign	-0.814	Destabilizing	1.0	D	0.671	neutral	N	0.491989287	None	None	I
L/G	0.6401	likely_pathogenic	0.6221	pathogenic	-1.626	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
L/H	0.3056	likely_benign	0.3189	benign	-0.739	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
L/I	0.1139	likely_benign	0.1119	benign	-0.57	Destabilizing	0.563	D	0.329	neutral	None	None	None	None	I
L/K	0.325	likely_benign	0.3562	ambiguous	-0.955	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	I
L/M	0.0928	likely_benign	0.0974	benign	-0.532	Destabilizing	0.999	D	0.656	neutral	D	0.535876137	None	None	I
L/N	0.5406	ambiguous	0.5392	ambiguous	-0.795	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
L/P	0.4325	ambiguous	0.421	ambiguous	-0.788	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
L/Q	0.1679	likely_benign	0.1735	benign	-0.932	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	I
L/R	0.2564	likely_benign	0.2825	benign	-0.388	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	I
L/S	0.4623	ambiguous	0.4548	ambiguous	-1.39	Destabilizing	1.0	D	0.659	neutral	N	0.511431858	None	None	I
L/T	0.3745	ambiguous	0.3643	ambiguous	-1.269	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	I
L/V	0.1223	likely_benign	0.1201	benign	-0.788	Destabilizing	0.895	D	0.577	neutral	N	0.451262093	None	None	I
L/W	0.2061	likely_benign	0.2047	benign	-0.879	Destabilizing	1.0	D	0.748	deleterious	N	0.511938837	None	None	I
L/Y	0.3147	likely_benign	0.3168	benign	-0.66	Destabilizing	0.999	D	0.692	prob.neutral	None	None	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.