TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32252	96979;96980;96981	chr2:178543219;178543218;178543217	chr2:179407946;179407945;179407944
N2AB	30611	92056;92057;92058	chr2:178543219;178543218;178543217	chr2:179407946;179407945;179407944
N2A	29684	89275;89276;89277	chr2:178543219;178543218;178543217	chr2:179407946;179407945;179407944
N2B	23187	69784;69785;69786	chr2:178543219;178543218;178543217	chr2:179407946;179407945;179407944
Novex-1	23312	70159;70160;70161	chr2:178543219;178543218;178543217	chr2:179407946;179407945;179407944
Novex-2	23379	70360;70361;70362	chr2:178543219;178543218;178543217	chr2:179407946;179407945;179407944
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: Fn3-123
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.2508
• 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
V/A	None	None	0.02	N	0.239	0.1	0.570859980718	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/F	rs766999420	-1.269	0.991	N	0.758	0.369	0.799625754913	gnomAD-2.1.1	8.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
V/F	rs766999420	-1.269	0.991	N	0.758	0.369	0.799625754913	gnomAD-4.0.0	4.77356E-06	None	None	None	None	I	None	0	2.28634E-05	None	0	0	None	0	0	0	2.86541E-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	0.2283	likely_benign	0.2123	benign	-1.168	Destabilizing	0.02	N	0.239	neutral	N	0.451640521	None	None	I
V/C	0.8163	likely_pathogenic	0.8194	pathogenic	-0.947	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	I
V/D	0.8635	likely_pathogenic	0.8523	pathogenic	-1.03	Destabilizing	0.991	D	0.79	deleterious	N	0.491852896	None	None	I
V/E	0.7849	likely_pathogenic	0.7598	pathogenic	-1.033	Destabilizing	0.986	D	0.705	prob.neutral	None	None	None	None	I
V/F	0.3775	ambiguous	0.3626	ambiguous	-0.876	Destabilizing	0.991	D	0.758	deleterious	N	0.471395238	None	None	I
V/G	0.4365	ambiguous	0.4299	ambiguous	-1.459	Destabilizing	0.885	D	0.676	prob.neutral	N	0.486029999	None	None	I
V/H	0.8992	likely_pathogenic	0.8924	pathogenic	-0.886	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	I
V/I	0.0981	likely_benign	0.0931	benign	-0.48	Destabilizing	0.863	D	0.502	neutral	N	0.479885915	None	None	I
V/K	0.8447	likely_pathogenic	0.8362	pathogenic	-1.143	Destabilizing	0.986	D	0.726	prob.delet.	None	None	None	None	I
V/L	0.3473	ambiguous	0.3361	benign	-0.48	Destabilizing	0.863	D	0.505	neutral	N	0.49739424	None	None	I
V/M	0.2398	likely_benign	0.2197	benign	-0.494	Destabilizing	0.998	D	0.62	neutral	None	None	None	None	I
V/N	0.746	likely_pathogenic	0.7226	pathogenic	-1.026	Destabilizing	0.993	D	0.811	deleterious	None	None	None	None	I
V/P	0.8955	likely_pathogenic	0.8944	pathogenic	-0.674	Destabilizing	0.993	D	0.756	deleterious	None	None	None	None	I
V/Q	0.7962	likely_pathogenic	0.7802	pathogenic	-1.153	Destabilizing	0.993	D	0.783	deleterious	None	None	None	None	I
V/R	0.7938	likely_pathogenic	0.7888	pathogenic	-0.62	Destabilizing	0.993	D	0.811	deleterious	None	None	None	None	I
V/S	0.5019	ambiguous	0.4737	ambiguous	-1.49	Destabilizing	0.91	D	0.621	neutral	None	None	None	None	I
V/T	0.2801	likely_benign	0.2625	benign	-1.373	Destabilizing	0.953	D	0.49	neutral	None	None	None	None	I
V/W	0.9379	likely_pathogenic	0.9386	pathogenic	-1.056	Destabilizing	0.999	D	0.724	prob.delet.	None	None	None	None	I
V/Y	0.7902	likely_pathogenic	0.7853	pathogenic	-0.758	Destabilizing	0.998	D	0.762	deleterious	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.