TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29033	87322;87323;87324	chr2:178558362;178558361;178558360	chr2:179423089;179423088;179423087
N2AB	27392	82399;82400;82401	chr2:178558362;178558361;178558360	chr2:179423089;179423088;179423087
N2A	26465	79618;79619;79620	chr2:178558362;178558361;178558360	chr2:179423089;179423088;179423087
N2B	19968	60127;60128;60129	chr2:178558362;178558361;178558360	chr2:179423089;179423088;179423087
Novex-1	20093	60502;60503;60504	chr2:178558362;178558361;178558360	chr2:179423089;179423088;179423087
Novex-2	20160	60703;60704;60705	chr2:178558362;178558361;178558360	chr2:179423089;179423088;179423087
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-99
• Domain position: 92
• Structural Position: 127
• Q(SASA): 0.1373
• 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/F	None	None	1.0	N	0.817	0.419	0.749804721492	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.4773	ambiguous	0.4355	ambiguous	-1.857	Destabilizing	0.999	D	0.613	neutral	D	0.533907693	None	None	N
V/C	0.846	likely_pathogenic	0.8217	pathogenic	-1.195	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/D	0.959	likely_pathogenic	0.9347	pathogenic	-2.75	Highly Destabilizing	1.0	D	0.894	deleterious	D	0.524110701	None	None	N
V/E	0.8542	likely_pathogenic	0.8137	pathogenic	-2.482	Highly Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
V/F	0.3136	likely_benign	0.2919	benign	-1.22	Destabilizing	1.0	D	0.817	deleterious	N	0.511829343	None	None	N
V/G	0.7718	likely_pathogenic	0.7165	pathogenic	-2.372	Highly Destabilizing	1.0	D	0.894	deleterious	D	0.524110701	None	None	N
V/H	0.8997	likely_pathogenic	0.8715	pathogenic	-2.131	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
V/I	0.0795	likely_benign	0.0795	benign	-0.386	Destabilizing	0.984	D	0.538	neutral	N	0.488977906	None	None	N
V/K	0.8603	likely_pathogenic	0.8229	pathogenic	-1.576	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/L	0.2743	likely_benign	0.2601	benign	-0.386	Destabilizing	0.984	D	0.6	neutral	N	0.516185937	None	None	N
V/M	0.2338	likely_benign	0.2198	benign	-0.403	Destabilizing	1.0	D	0.655	prob.neutral	None	None	None	None	N
V/N	0.8574	likely_pathogenic	0.8043	pathogenic	-2.144	Highly Destabilizing	0.998	D	0.906	deleterious	None	None	None	None	N
V/P	0.9784	likely_pathogenic	0.9659	pathogenic	-0.856	Destabilizing	0.998	D	0.872	deleterious	None	None	None	None	N
V/Q	0.7922	likely_pathogenic	0.7508	pathogenic	-1.887	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
V/R	0.831	likely_pathogenic	0.7928	pathogenic	-1.626	Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
V/S	0.7181	likely_pathogenic	0.6484	pathogenic	-2.635	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/T	0.473	ambiguous	0.4377	ambiguous	-2.215	Highly Destabilizing	0.998	D	0.506	neutral	None	None	None	None	N
V/W	0.9576	likely_pathogenic	0.9512	pathogenic	-1.707	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
V/Y	0.7943	likely_pathogenic	0.7592	pathogenic	-1.285	Destabilizing	1.0	D	0.803	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.