TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28062	84409;84410;84411	chr2:178561948;178561947;178561946	chr2:179426675;179426674;179426673
N2AB	26421	79486;79487;79488	chr2:178561948;178561947;178561946	chr2:179426675;179426674;179426673
N2A	25494	76705;76706;76707	chr2:178561948;178561947;178561946	chr2:179426675;179426674;179426673
N2B	18997	57214;57215;57216	chr2:178561948;178561947;178561946	chr2:179426675;179426674;179426673
Novex-1	19122	57589;57590;57591	chr2:178561948;178561947;178561946	chr2:179426675;179426674;179426673
Novex-2	19189	57790;57791;57792	chr2:178561948;178561947;178561946	chr2:179426675;179426674;179426673
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-92
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.1892
• 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	rs750669319	-2.256	0.062	N	0.71	0.383	0.581692290366	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
I/T	rs750669319	-2.256	0.062	N	0.71	0.383	0.581692290366	gnomAD-4.0.0	4.77742E-06	None	None	None	None	N	None	0	2.2877E-05	None	0	0	None	0	0	2.86038E-06	1.43299E-05	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	0.8078	likely_pathogenic	0.7407	pathogenic	-2.439	Highly Destabilizing	0.035	N	0.629	neutral	None	None	None	None	N
I/C	0.8597	likely_pathogenic	0.8264	pathogenic	-2.05	Highly Destabilizing	0.824	D	0.727	prob.delet.	None	None	None	None	N
I/D	0.9902	likely_pathogenic	0.9797	pathogenic	-2.646	Highly Destabilizing	0.555	D	0.819	deleterious	None	None	None	None	N
I/E	0.9812	likely_pathogenic	0.9596	pathogenic	-2.44	Highly Destabilizing	0.555	D	0.808	deleterious	None	None	None	None	N
I/F	0.3625	ambiguous	0.308	benign	-1.43	Destabilizing	0.38	N	0.704	prob.neutral	None	None	None	None	N
I/G	0.9615	likely_pathogenic	0.9319	pathogenic	-2.955	Highly Destabilizing	0.555	D	0.8	deleterious	None	None	None	None	N
I/H	0.97	likely_pathogenic	0.9428	pathogenic	-2.386	Highly Destabilizing	0.935	D	0.802	deleterious	None	None	None	None	N
I/K	0.9644	likely_pathogenic	0.9281	pathogenic	-1.721	Destabilizing	0.484	N	0.804	deleterious	N	0.513630909	None	None	N
I/L	0.132	likely_benign	0.1129	benign	-0.962	Destabilizing	None	N	0.277	neutral	N	0.417575515	None	None	N
I/M	0.2017	likely_benign	0.1753	benign	-1.215	Destabilizing	0.317	N	0.668	neutral	N	0.486118905	None	None	N
I/N	0.9087	likely_pathogenic	0.8401	pathogenic	-2.012	Highly Destabilizing	0.791	D	0.821	deleterious	None	None	None	None	N
I/P	0.8631	likely_pathogenic	0.84	pathogenic	-1.435	Destabilizing	0.555	D	0.817	deleterious	None	None	None	None	N
I/Q	0.9589	likely_pathogenic	0.9213	pathogenic	-1.908	Destabilizing	0.791	D	0.815	deleterious	None	None	None	None	N
I/R	0.95	likely_pathogenic	0.9022	pathogenic	-1.498	Destabilizing	0.484	N	0.821	deleterious	N	0.502274603	None	None	N
I/S	0.8905	likely_pathogenic	0.8277	pathogenic	-2.724	Highly Destabilizing	0.38	N	0.785	deleterious	None	None	None	None	N
I/T	0.813	likely_pathogenic	0.7499	pathogenic	-2.373	Highly Destabilizing	0.062	N	0.71	prob.delet.	N	0.501767624	None	None	N
I/V	0.0756	likely_benign	0.0743	benign	-1.435	Destabilizing	None	N	0.22	neutral	N	0.396917815	None	None	N
I/W	0.9663	likely_pathogenic	0.9498	pathogenic	-1.733	Destabilizing	0.935	D	0.806	deleterious	None	None	None	None	N
I/Y	0.8891	likely_pathogenic	0.8184	pathogenic	-1.462	Destabilizing	0.555	D	0.762	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.