TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29551	88876;88877;88878	chr2:178554696;178554695;178554694	chr2:179419423;179419422;179419421
N2AB	27910	83953;83954;83955	chr2:178554696;178554695;178554694	chr2:179419423;179419422;179419421
N2A	26983	81172;81173;81174	chr2:178554696;178554695;178554694	chr2:179419423;179419422;179419421
N2B	20486	61681;61682;61683	chr2:178554696;178554695;178554694	chr2:179419423;179419422;179419421
Novex-1	20611	62056;62057;62058	chr2:178554696;178554695;178554694	chr2:179419423;179419422;179419421
Novex-2	20678	62257;62258;62259	chr2:178554696;178554695;178554694	chr2:179419423;179419422;179419421
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-103
• Domain position: 19
• Structural Position: 20
• Q(SASA): 0.0536
• 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
I/T	None	None	0.549	D	0.789	0.391	0.726905758573	gnomAD-4.0.0	2.73664E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59769E-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
I/A	0.8231	likely_pathogenic	0.8613	pathogenic	-2.856	Highly Destabilizing	0.25	N	0.684	prob.neutral	None	None	None	None	N
I/C	0.8061	likely_pathogenic	0.8149	pathogenic	-2.599	Highly Destabilizing	0.992	D	0.793	deleterious	None	None	None	None	N
I/D	0.9976	likely_pathogenic	0.9978	pathogenic	-3.077	Highly Destabilizing	0.972	D	0.823	deleterious	None	None	None	None	N
I/E	0.993	likely_pathogenic	0.9936	pathogenic	-2.772	Highly Destabilizing	0.92	D	0.812	deleterious	None	None	None	None	N
I/F	0.4944	ambiguous	0.5472	ambiguous	-1.747	Destabilizing	0.81	D	0.727	prob.delet.	N	0.507824665	None	None	N
I/G	0.9777	likely_pathogenic	0.9831	pathogenic	-3.474	Highly Destabilizing	0.92	D	0.802	deleterious	None	None	None	None	N
I/H	0.9886	likely_pathogenic	0.9895	pathogenic	-2.982	Highly Destabilizing	0.992	D	0.793	deleterious	None	None	None	None	N
I/K	0.9885	likely_pathogenic	0.9887	pathogenic	-2.104	Highly Destabilizing	0.85	D	0.813	deleterious	None	None	None	None	N
I/L	0.1982	likely_benign	0.2291	benign	-1.016	Destabilizing	0.036	N	0.505	neutral	N	0.432398613	None	None	N
I/M	0.1315	likely_benign	0.1376	benign	-1.392	Destabilizing	0.016	N	0.417	neutral	N	0.479715344	None	None	N
I/N	0.9553	likely_pathogenic	0.9594	pathogenic	-2.679	Highly Destabilizing	0.896	D	0.827	deleterious	N	0.494783093	None	None	N
I/P	0.9971	likely_pathogenic	0.9978	pathogenic	-1.617	Destabilizing	0.972	D	0.827	deleterious	None	None	None	None	N
I/Q	0.9822	likely_pathogenic	0.9836	pathogenic	-2.388	Highly Destabilizing	0.92	D	0.826	deleterious	None	None	None	None	N
I/R	0.9822	likely_pathogenic	0.9836	pathogenic	-2.062	Highly Destabilizing	0.85	D	0.826	deleterious	None	None	None	None	N
I/S	0.9347	likely_pathogenic	0.949	pathogenic	-3.441	Highly Destabilizing	0.549	D	0.784	deleterious	N	0.471816993	None	None	N
I/T	0.8889	likely_pathogenic	0.9119	pathogenic	-2.958	Highly Destabilizing	0.549	D	0.789	deleterious	D	0.524063554	None	None	N
I/V	0.106	likely_benign	0.1142	benign	-1.617	Destabilizing	0.002	N	0.215	neutral	N	0.382121721	None	None	N
I/W	0.9865	likely_pathogenic	0.9876	pathogenic	-2.022	Highly Destabilizing	0.992	D	0.788	deleterious	None	None	None	None	N
I/Y	0.9277	likely_pathogenic	0.9312	pathogenic	-1.823	Destabilizing	0.92	D	0.836	deleterious	None	None	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.