TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27798	83617;83618;83619	chr2:178562740;178562739;178562738	chr2:179427467;179427466;179427465
N2AB	26157	78694;78695;78696	chr2:178562740;178562739;178562738	chr2:179427467;179427466;179427465
N2A	25230	75913;75914;75915	chr2:178562740;178562739;178562738	chr2:179427467;179427466;179427465
N2B	18733	56422;56423;56424	chr2:178562740;178562739;178562738	chr2:179427467;179427466;179427465
Novex-1	18858	56797;56798;56799	chr2:178562740;178562739;178562738	chr2:179427467;179427466;179427465
Novex-2	18925	56998;56999;57000	chr2:178562740;178562739;178562738	chr2:179427467;179427466;179427465
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: Fn3-90
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.2083
• 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
I/N	None	None	0.999	D	0.815	0.634	0.886518283301	gnomAD-4.0.0	1.60035E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87358E-06	0	0
I/T	None	None	0.925	N	0.75	0.573	0.767795433346	gnomAD-4.0.0	1.60035E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87358E-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	0.9782	likely_pathogenic	0.9721	pathogenic	-2.318	Highly Destabilizing	0.965	D	0.649	neutral	None	None	None	None	I
I/C	0.9811	likely_pathogenic	0.9762	pathogenic	-1.436	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	I
I/D	0.9984	likely_pathogenic	0.9984	pathogenic	-2.22	Highly Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	I
I/E	0.9957	likely_pathogenic	0.9951	pathogenic	-2.153	Highly Destabilizing	0.997	D	0.807	deleterious	None	None	None	None	I
I/F	0.9471	likely_pathogenic	0.9284	pathogenic	-1.686	Destabilizing	0.992	D	0.749	deleterious	D	0.527334753	None	None	I
I/G	0.9962	likely_pathogenic	0.9949	pathogenic	-2.729	Highly Destabilizing	0.997	D	0.808	deleterious	None	None	None	None	I
I/H	0.9971	likely_pathogenic	0.9966	pathogenic	-2.047	Highly Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	I
I/K	0.9924	likely_pathogenic	0.9905	pathogenic	-1.639	Destabilizing	0.92	D	0.808	deleterious	None	None	None	None	I
I/L	0.4582	ambiguous	0.4273	ambiguous	-1.197	Destabilizing	0.099	N	0.419	neutral	N	0.491935937	None	None	I
I/M	0.5675	likely_pathogenic	0.518	ambiguous	-0.83	Destabilizing	0.972	D	0.721	prob.delet.	D	0.541225954	None	None	I
I/N	0.9483	likely_pathogenic	0.9473	pathogenic	-1.558	Destabilizing	0.999	D	0.815	deleterious	D	0.535491962	None	None	I
I/P	0.9712	likely_pathogenic	0.9624	pathogenic	-1.544	Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	I
I/Q	0.9945	likely_pathogenic	0.9928	pathogenic	-1.684	Destabilizing	0.998	D	0.808	deleterious	None	None	None	None	I
I/R	0.992	likely_pathogenic	0.9902	pathogenic	-1.063	Destabilizing	0.998	D	0.814	deleterious	None	None	None	None	I
I/S	0.9818	likely_pathogenic	0.9777	pathogenic	-2.202	Highly Destabilizing	0.997	D	0.787	deleterious	D	0.552835749	None	None	I
I/T	0.9543	likely_pathogenic	0.9407	pathogenic	-2.011	Highly Destabilizing	0.925	D	0.75	deleterious	N	0.516627239	None	None	I
I/V	0.1161	likely_benign	0.1112	benign	-1.544	Destabilizing	0.002	N	0.228	neutral	N	0.461380299	None	None	I
I/W	0.9988	likely_pathogenic	0.9986	pathogenic	-1.888	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
I/Y	0.9915	likely_pathogenic	0.9894	pathogenic	-1.669	Destabilizing	0.982	D	0.775	deleterious	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.