TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7289	22090;22091;22092	chr2:178723142;178723141;178723140	chr2:179587869;179587868;179587867
N2AB	6972	21139;21140;21141	chr2:178723142;178723141;178723140	chr2:179587869;179587868;179587867
N2A	6045	18358;18359;18360	chr2:178723142;178723141;178723140	chr2:179587869;179587868;179587867
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-57
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.097
• 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/M	None	None	0.81	D	0.642	0.616	0.709904841857	gnomAD-4.0.0	6.84322E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99564E-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
I/A	0.9252	likely_pathogenic	0.9185	pathogenic	-2.684	Highly Destabilizing	0.25	N	0.565	neutral	None	None	None	None	N
I/C	0.9179	likely_pathogenic	0.9056	pathogenic	-2.21	Highly Destabilizing	0.005	N	0.493	neutral	None	None	None	None	N
I/D	0.9794	likely_pathogenic	0.9775	pathogenic	-2.812	Highly Destabilizing	0.972	D	0.809	deleterious	None	None	None	None	N
I/E	0.9688	likely_pathogenic	0.9636	pathogenic	-2.656	Highly Destabilizing	0.92	D	0.799	deleterious	None	None	None	None	N
I/F	0.2689	likely_benign	0.2497	benign	-1.71	Destabilizing	0.004	N	0.362	neutral	D	0.563202427	None	None	N
I/G	0.9757	likely_pathogenic	0.9737	pathogenic	-3.179	Highly Destabilizing	0.766	D	0.784	deleterious	None	None	None	None	N
I/H	0.9122	likely_pathogenic	0.8961	pathogenic	-2.393	Highly Destabilizing	0.992	D	0.831	deleterious	None	None	None	None	N
I/K	0.9233	likely_pathogenic	0.9094	pathogenic	-2.073	Highly Destabilizing	0.92	D	0.795	deleterious	None	None	None	None	N
I/L	0.2283	likely_benign	0.2304	benign	-1.281	Destabilizing	0.099	N	0.382	neutral	D	0.549371216	None	None	N
I/M	0.2185	likely_benign	0.2176	benign	-1.258	Destabilizing	0.81	D	0.642	neutral	D	0.604588456	None	None	N
I/N	0.7844	likely_pathogenic	0.7674	pathogenic	-2.256	Highly Destabilizing	0.963	D	0.831	deleterious	D	0.638039808	None	None	N
I/P	0.9943	likely_pathogenic	0.9929	pathogenic	-1.727	Destabilizing	0.972	D	0.831	deleterious	None	None	None	None	N
I/Q	0.9353	likely_pathogenic	0.927	pathogenic	-2.261	Highly Destabilizing	0.972	D	0.834	deleterious	None	None	None	None	N
I/R	0.8917	likely_pathogenic	0.8799	pathogenic	-1.568	Destabilizing	0.92	D	0.832	deleterious	None	None	None	None	N
I/S	0.8851	likely_pathogenic	0.8824	pathogenic	-2.999	Highly Destabilizing	0.549	D	0.731	prob.delet.	D	0.638039808	None	None	N
I/T	0.9033	likely_pathogenic	0.8918	pathogenic	-2.703	Highly Destabilizing	0.549	D	0.651	neutral	D	0.605597477	None	None	N
I/V	0.1652	likely_benign	0.1479	benign	-1.727	Destabilizing	0.002	N	0.265	neutral	D	0.57046665	None	None	N
I/W	0.9313	likely_pathogenic	0.9196	pathogenic	-1.957	Destabilizing	0.992	D	0.827	deleterious	None	None	None	None	N
I/Y	0.6981	likely_pathogenic	0.6828	pathogenic	-1.745	Destabilizing	0.739	D	0.742	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.