TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19987	60184;60185;60186	chr2:178591860;178591859;178591858	chr2:179456587;179456586;179456585
N2AB	18346	55261;55262;55263	chr2:178591860;178591859;178591858	chr2:179456587;179456586;179456585
N2A	17419	52480;52481;52482	chr2:178591860;178591859;178591858	chr2:179456587;179456586;179456585
N2B	10922	32989;32990;32991	chr2:178591860;178591859;178591858	chr2:179456587;179456586;179456585
Novex-1	11047	33364;33365;33366	chr2:178591860;178591859;178591858	chr2:179456587;179456586;179456585
Novex-2	11114	33565;33566;33567	chr2:178591860;178591859;178591858	chr2:179456587;179456586;179456585
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-33
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.42
• 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/E	rs2050279012	None	0.062	N	0.411	0.174	0.387850303812	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	0.1739	likely_benign	0.1636	benign	-1.069	Destabilizing	0.027	N	0.335	neutral	N	0.488003966	None	None	N
V/C	0.7625	likely_pathogenic	0.7814	pathogenic	-0.43	Destabilizing	0.935	D	0.421	neutral	None	None	None	None	N
V/D	0.4028	ambiguous	0.391	ambiguous	-1.078	Destabilizing	0.001	N	0.338	neutral	None	None	None	None	N
V/E	0.2946	likely_benign	0.2718	benign	-1.157	Destabilizing	0.062	N	0.411	neutral	N	0.458681137	None	None	N
V/F	0.2731	likely_benign	0.2462	benign	-1.085	Destabilizing	0.38	N	0.465	neutral	None	None	None	None	N
V/G	0.2689	likely_benign	0.2534	benign	-1.289	Destabilizing	0.117	N	0.448	neutral	N	0.482944863	None	None	N
V/H	0.5962	likely_pathogenic	0.5624	ambiguous	-0.905	Destabilizing	0.935	D	0.417	neutral	None	None	None	None	N
V/I	0.0854	likely_benign	0.0794	benign	-0.598	Destabilizing	None	N	0.087	neutral	N	0.483886226	None	None	N
V/K	0.2715	likely_benign	0.2467	benign	-0.89	Destabilizing	0.149	N	0.436	neutral	None	None	None	None	N
V/L	0.3005	likely_benign	0.2569	benign	-0.598	Destabilizing	0.009	N	0.327	neutral	N	0.436921785	None	None	N
V/M	0.1726	likely_benign	0.1508	benign	-0.303	Destabilizing	0.38	N	0.426	neutral	None	None	None	None	N
V/N	0.3311	likely_benign	0.3071	benign	-0.477	Destabilizing	0.149	N	0.449	neutral	None	None	None	None	N
V/P	0.9165	likely_pathogenic	0.908	pathogenic	-0.72	Destabilizing	0.555	D	0.448	neutral	None	None	None	None	N
V/Q	0.2906	likely_benign	0.2761	benign	-0.749	Destabilizing	0.555	D	0.451	neutral	None	None	None	None	N
V/R	0.2451	likely_benign	0.2343	benign	-0.28	Destabilizing	0.555	D	0.477	neutral	None	None	None	None	N
V/S	0.2211	likely_benign	0.214	benign	-0.826	Destabilizing	0.007	N	0.322	neutral	None	None	None	None	N
V/T	0.1322	likely_benign	0.1277	benign	-0.815	Destabilizing	0.001	N	0.085	neutral	None	None	None	None	N
V/W	0.8496	likely_pathogenic	0.8302	pathogenic	-1.221	Destabilizing	0.935	D	0.486	neutral	None	None	None	None	N
V/Y	0.6481	likely_pathogenic	0.6253	pathogenic	-0.953	Destabilizing	0.555	D	0.455	neutral	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.