TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27875	83848;83849;83850	chr2:178562509;178562508;178562507	chr2:179427236;179427235;179427234
N2AB	26234	78925;78926;78927	chr2:178562509;178562508;178562507	chr2:179427236;179427235;179427234
N2A	25307	76144;76145;76146	chr2:178562509;178562508;178562507	chr2:179427236;179427235;179427234
N2B	18810	56653;56654;56655	chr2:178562509;178562508;178562507	chr2:179427236;179427235;179427234
Novex-1	18935	57028;57029;57030	chr2:178562509;178562508;178562507	chr2:179427236;179427235;179427234
Novex-2	19002	57229;57230;57231	chr2:178562509;178562508;178562507	chr2:179427236;179427235;179427234
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-91
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.2948
• 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
V/L	None	None	0.867	N	0.4	0.218	0.44318313171	gnomAD-4.0.0	1.59558E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.03012E-05

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
V/A	0.6142	likely_pathogenic	0.6154	pathogenic	-1.561	Destabilizing	0.998	D	0.481	neutral	N	0.479690578	None	None	N
V/C	0.9184	likely_pathogenic	0.9215	pathogenic	-1.792	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
V/D	0.951	likely_pathogenic	0.9607	pathogenic	-2.089	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
V/E	0.8884	likely_pathogenic	0.9038	pathogenic	-2.055	Highly Destabilizing	0.999	D	0.827	deleterious	N	0.510556717	None	None	N
V/F	0.6316	likely_pathogenic	0.6713	pathogenic	-1.394	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/G	0.7532	likely_pathogenic	0.7769	pathogenic	-1.873	Destabilizing	1.0	D	0.84	deleterious	N	0.512077654	None	None	N
V/H	0.9646	likely_pathogenic	0.9674	pathogenic	-1.418	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/I	0.0963	likely_benign	0.0995	benign	-0.781	Destabilizing	0.359	N	0.286	neutral	None	None	None	None	N
V/K	0.8947	likely_pathogenic	0.8995	pathogenic	-1.26	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
V/L	0.6451	likely_pathogenic	0.6533	pathogenic	-0.781	Destabilizing	0.867	D	0.4	neutral	N	0.483778728	None	None	N
V/M	0.3814	ambiguous	0.4066	ambiguous	-0.915	Destabilizing	0.999	D	0.708	prob.delet.	N	0.517166535	None	None	N
V/N	0.8546	likely_pathogenic	0.878	pathogenic	-1.31	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
V/P	0.9914	likely_pathogenic	0.9899	pathogenic	-1.01	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
V/Q	0.8641	likely_pathogenic	0.8748	pathogenic	-1.5	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
V/R	0.858	likely_pathogenic	0.864	pathogenic	-0.838	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
V/S	0.7201	likely_pathogenic	0.7453	pathogenic	-1.837	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
V/T	0.4979	ambiguous	0.5028	ambiguous	-1.69	Destabilizing	0.995	D	0.601	neutral	None	None	None	None	N
V/W	0.9864	likely_pathogenic	0.989	pathogenic	-1.587	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/Y	0.9309	likely_pathogenic	0.9386	pathogenic	-1.231	Destabilizing	1.0	D	0.833	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.