TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28924	86995;86996;86997	chr2:178559362;178559361;178559360	chr2:179424089;179424088;179424087
N2AB	27283	82072;82073;82074	chr2:178559362;178559361;178559360	chr2:179424089;179424088;179424087
N2A	26356	79291;79292;79293	chr2:178559362;178559361;178559360	chr2:179424089;179424088;179424087
N2B	19859	59800;59801;59802	chr2:178559362;178559361;178559360	chr2:179424089;179424088;179424087
Novex-1	19984	60175;60176;60177	chr2:178559362;178559361;178559360	chr2:179424089;179424088;179424087
Novex-2	20051	60376;60377;60378	chr2:178559362;178559361;178559360	chr2:179424089;179424088;179424087
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-98
• Domain position: 80
• Structural Position: 113
• Q(SASA): 0.4687
• 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
E/D	None	None	0.941	N	0.376	0.222	0.166414681773	gnomAD-4.0.0	6.84865E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.0014E-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
E/A	0.3094	likely_benign	0.3271	benign	-0.549	Destabilizing	0.992	D	0.58	neutral	N	0.479499126	None	None	I
E/C	0.9462	likely_pathogenic	0.9501	pathogenic	-0.334	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
E/D	0.2507	likely_benign	0.2306	benign	-0.495	Destabilizing	0.941	D	0.376	neutral	N	0.490428196	None	None	I
E/F	0.9566	likely_pathogenic	0.9522	pathogenic	-0.136	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	I
E/G	0.5707	likely_pathogenic	0.5654	pathogenic	-0.785	Destabilizing	0.999	D	0.564	neutral	N	0.515454352	None	None	I
E/H	0.8209	likely_pathogenic	0.8126	pathogenic	0.229	Stabilizing	1.0	D	0.621	neutral	None	None	None	None	I
E/I	0.528	ambiguous	0.5174	ambiguous	0.059	Stabilizing	0.998	D	0.635	neutral	None	None	None	None	I
E/K	0.4309	ambiguous	0.3961	ambiguous	0.175	Stabilizing	0.996	D	0.565	neutral	N	0.452813957	None	None	I
E/L	0.7561	likely_pathogenic	0.7467	pathogenic	0.059	Stabilizing	0.998	D	0.612	neutral	None	None	None	None	I
E/M	0.7179	likely_pathogenic	0.6979	pathogenic	0.072	Stabilizing	0.997	D	0.608	neutral	None	None	None	None	I
E/N	0.5552	ambiguous	0.5307	ambiguous	-0.403	Destabilizing	0.996	D	0.667	neutral	None	None	None	None	I
E/P	0.8391	likely_pathogenic	0.8201	pathogenic	-0.124	Destabilizing	0.987	D	0.605	neutral	None	None	None	None	I
E/Q	0.2989	likely_benign	0.2866	benign	-0.32	Destabilizing	0.998	D	0.554	neutral	N	0.501375908	None	None	I
E/R	0.5942	likely_pathogenic	0.5785	pathogenic	0.544	Stabilizing	0.999	D	0.665	neutral	None	None	None	None	I
E/S	0.4524	ambiguous	0.4437	ambiguous	-0.544	Destabilizing	0.994	D	0.607	neutral	None	None	None	None	I
E/T	0.4743	ambiguous	0.4554	ambiguous	-0.335	Destabilizing	0.999	D	0.618	neutral	None	None	None	None	I
E/V	0.3925	ambiguous	0.3842	ambiguous	-0.124	Destabilizing	0.996	D	0.607	neutral	N	0.503069419	None	None	I
E/W	0.9904	likely_pathogenic	0.9894	pathogenic	0.125	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
E/Y	0.8755	likely_pathogenic	0.8774	pathogenic	0.134	Stabilizing	1.0	D	0.612	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.