TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19902	59929;59930;59931	chr2:178592200;178592199;178592198	chr2:179456927;179456926;179456925
N2AB	18261	55006;55007;55008	chr2:178592200;178592199;178592198	chr2:179456927;179456926;179456925
N2A	17334	52225;52226;52227	chr2:178592200;178592199;178592198	chr2:179456927;179456926;179456925
N2B	10837	32734;32735;32736	chr2:178592200;178592199;178592198	chr2:179456927;179456926;179456925
Novex-1	10962	33109;33110;33111	chr2:178592200;178592199;178592198	chr2:179456927;179456926;179456925
Novex-2	11029	33310;33311;33312	chr2:178592200;178592199;178592198	chr2:179456927;179456926;179456925
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-32
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.6691
• 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
L/V	None	None	0.771	N	0.375	0.08	0.241078983079	gnomAD-4.0.0	1.59503E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.863E-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
L/A	0.0786	likely_benign	0.0711	benign	-0.451	Destabilizing	0.688	D	0.327	neutral	None	None	None	None	I
L/C	0.4121	ambiguous	0.3538	ambiguous	-0.689	Destabilizing	0.998	D	0.33	neutral	None	None	None	None	I
L/D	0.2201	likely_benign	0.224	benign	-0.295	Destabilizing	0.525	D	0.353	neutral	None	None	None	None	I
L/E	0.1179	likely_benign	0.1139	benign	-0.394	Destabilizing	0.002	N	0.211	neutral	None	None	None	None	I
L/F	0.1191	likely_benign	0.1097	benign	-0.583	Destabilizing	0.991	D	0.324	neutral	None	None	None	None	I
L/G	0.2299	likely_benign	0.206	benign	-0.569	Destabilizing	0.842	D	0.377	neutral	None	None	None	None	I
L/H	0.1484	likely_benign	0.1364	benign	0.116	Stabilizing	0.974	D	0.349	neutral	None	None	None	None	I
L/I	0.0751	likely_benign	0.0719	benign	-0.268	Destabilizing	0.915	D	0.347	neutral	None	None	None	None	I
L/K	0.1314	likely_benign	0.1288	benign	-0.311	Destabilizing	0.525	D	0.333	neutral	None	None	None	None	I
L/M	0.095	likely_benign	0.0845	benign	-0.503	Destabilizing	0.989	D	0.332	neutral	N	0.480251275	None	None	I
L/N	0.1402	likely_benign	0.1353	benign	-0.144	Destabilizing	0.842	D	0.377	neutral	None	None	None	None	I
L/P	0.1349	likely_benign	0.1183	benign	-0.299	Destabilizing	0.966	D	0.369	neutral	N	0.439460658	None	None	I
L/Q	0.0859	likely_benign	0.0757	benign	-0.36	Destabilizing	0.669	D	0.365	neutral	N	0.455680904	None	None	I
L/R	0.1349	likely_benign	0.1291	benign	0.214	Stabilizing	0.801	D	0.373	neutral	N	0.432457328	None	None	I
L/S	0.0935	likely_benign	0.0897	benign	-0.524	Destabilizing	0.842	D	0.345	neutral	None	None	None	None	I
L/T	0.0875	likely_benign	0.0794	benign	-0.521	Destabilizing	0.842	D	0.355	neutral	None	None	None	None	I
L/V	0.0686	likely_benign	0.062	benign	-0.299	Destabilizing	0.771	D	0.375	neutral	N	0.435825707	None	None	I
L/W	0.2105	likely_benign	0.1995	benign	-0.598	Destabilizing	0.998	D	0.389	neutral	None	None	None	None	I
L/Y	0.2402	likely_benign	0.2331	benign	-0.354	Destabilizing	0.991	D	0.321	neutral	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.