TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19717	59374;59375;59376	chr2:178592970;178592969;178592968	chr2:179457697;179457696;179457695
N2AB	18076	54451;54452;54453	chr2:178592970;178592969;178592968	chr2:179457697;179457696;179457695
N2A	17149	51670;51671;51672	chr2:178592970;178592969;178592968	chr2:179457697;179457696;179457695
N2B	10652	32179;32180;32181	chr2:178592970;178592969;178592968	chr2:179457697;179457696;179457695
Novex-1	10777	32554;32555;32556	chr2:178592970;178592969;178592968	chr2:179457697;179457696;179457695
Novex-2	10844	32755;32756;32757	chr2:178592970;178592969;178592968	chr2:179457697;179457696;179457695
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: Fn3-31
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.1139
• 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/A	None	None	0.625	D	0.597	0.508	0.734413240494	gnomAD-4.0.0	2.73722E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59831E-06	0	0
V/I	rs1308382519	-0.661	0.012	N	0.243	0.146	0.387689773709	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/I	rs1308382519	-0.661	0.012	N	0.243	0.146	0.387689773709	gnomAD-4.0.0	3.18353E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86599E-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
V/A	0.881	likely_pathogenic	0.8562	pathogenic	-2.453	Highly Destabilizing	0.625	D	0.597	neutral	D	0.537362656	None	None	N
V/C	0.976	likely_pathogenic	0.976	pathogenic	-1.704	Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
V/D	0.9989	likely_pathogenic	0.9985	pathogenic	-3.472	Highly Destabilizing	0.989	D	0.867	deleterious	D	0.54947943	None	None	N
V/E	0.9963	likely_pathogenic	0.9942	pathogenic	-3.149	Highly Destabilizing	0.991	D	0.83	deleterious	None	None	None	None	N
V/F	0.9174	likely_pathogenic	0.9025	pathogenic	-1.454	Destabilizing	0.934	D	0.738	prob.delet.	D	0.549225941	None	None	N
V/G	0.9752	likely_pathogenic	0.9678	pathogenic	-3.047	Highly Destabilizing	0.989	D	0.825	deleterious	D	0.54947943	None	None	N
V/H	0.9989	likely_pathogenic	0.9985	pathogenic	-2.956	Highly Destabilizing	0.998	D	0.872	deleterious	None	None	None	None	N
V/I	0.0779	likely_benign	0.0826	benign	-0.708	Destabilizing	0.012	N	0.243	neutral	N	0.445104125	None	None	N
V/K	0.9966	likely_pathogenic	0.9948	pathogenic	-2.091	Highly Destabilizing	0.974	D	0.805	deleterious	None	None	None	None	N
V/L	0.513	ambiguous	0.5143	ambiguous	-0.708	Destabilizing	0.002	N	0.321	neutral	N	0.483742658	None	None	N
V/M	0.7557	likely_pathogenic	0.7099	pathogenic	-0.868	Destabilizing	0.949	D	0.606	neutral	None	None	None	None	N
V/N	0.9966	likely_pathogenic	0.9955	pathogenic	-2.817	Highly Destabilizing	0.991	D	0.877	deleterious	None	None	None	None	N
V/P	0.9892	likely_pathogenic	0.9872	pathogenic	-1.274	Destabilizing	0.991	D	0.847	deleterious	None	None	None	None	N
V/Q	0.9958	likely_pathogenic	0.9934	pathogenic	-2.444	Highly Destabilizing	0.991	D	0.863	deleterious	None	None	None	None	N
V/R	0.993	likely_pathogenic	0.9894	pathogenic	-2.187	Highly Destabilizing	0.991	D	0.871	deleterious	None	None	None	None	N
V/S	0.9834	likely_pathogenic	0.9772	pathogenic	-3.269	Highly Destabilizing	0.974	D	0.795	deleterious	None	None	None	None	N
V/T	0.9002	likely_pathogenic	0.88	pathogenic	-2.792	Highly Destabilizing	0.842	D	0.589	neutral	None	None	None	None	N
V/W	0.9985	likely_pathogenic	0.998	pathogenic	-2.02	Highly Destabilizing	0.998	D	0.86	deleterious	None	None	None	None	N
V/Y	0.9955	likely_pathogenic	0.994	pathogenic	-1.718	Destabilizing	0.991	D	0.763	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.