TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32856	98791;98792;98793	chr2:178539499;178539498;178539497	chr2:179404226;179404225;179404224
N2AB	31215	93868;93869;93870	chr2:178539499;178539498;178539497	chr2:179404226;179404225;179404224
N2A	30288	91087;91088;91089	chr2:178539499;178539498;178539497	chr2:179404226;179404225;179404224
N2B	23791	71596;71597;71598	chr2:178539499;178539498;178539497	chr2:179404226;179404225;179404224
Novex-1	23916	71971;71972;71973	chr2:178539499;178539498;178539497	chr2:179404226;179404225;179404224
Novex-2	23983	72172;72173;72174	chr2:178539499;178539498;178539497	chr2:179404226;179404225;179404224
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-127
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.4703
• 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/L	rs1693334476	None	0.997	N	0.491	0.285	0.475971816791	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/L	rs1693334476	None	0.997	N	0.491	0.285	0.475971816791	gnomAD-4.0.0	6.57479E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46998E-05	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	0.3483	ambiguous	0.2624	benign	-1.154	Destabilizing	0.999	D	0.553	neutral	N	0.495258012	None	None	N
V/C	0.8999	likely_pathogenic	0.8553	pathogenic	-0.928	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/D	0.7189	likely_pathogenic	0.6246	pathogenic	-0.663	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
V/E	0.6018	likely_pathogenic	0.5166	ambiguous	-0.704	Destabilizing	1.0	D	0.838	deleterious	N	0.484424943	None	None	N
V/F	0.3596	ambiguous	0.2959	benign	-0.922	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/G	0.5618	ambiguous	0.4565	ambiguous	-1.412	Destabilizing	1.0	D	0.846	deleterious	D	0.523330048	None	None	N
V/H	0.8203	likely_pathogenic	0.7396	pathogenic	-0.794	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/I	0.0902	likely_benign	0.0845	benign	-0.577	Destabilizing	0.998	D	0.459	neutral	None	None	None	None	N
V/K	0.7178	likely_pathogenic	0.626	pathogenic	-0.945	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
V/L	0.2842	likely_benign	0.229	benign	-0.577	Destabilizing	0.997	D	0.491	neutral	N	0.483232865	None	None	N
V/M	0.2669	likely_benign	0.2142	benign	-0.516	Destabilizing	1.0	D	0.691	prob.neutral	N	0.505667007	None	None	N
V/N	0.5646	likely_pathogenic	0.4392	ambiguous	-0.736	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/P	0.7129	likely_pathogenic	0.6134	pathogenic	-0.733	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/Q	0.6133	likely_pathogenic	0.512	ambiguous	-0.938	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/R	0.6462	likely_pathogenic	0.5478	ambiguous	-0.384	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
V/S	0.4589	ambiguous	0.3471	ambiguous	-1.265	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
V/T	0.251	likely_benign	0.1946	benign	-1.196	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	N
V/W	0.9209	likely_pathogenic	0.888	pathogenic	-1.01	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
V/Y	0.787	likely_pathogenic	0.709	pathogenic	-0.739	Destabilizing	1.0	D	0.841	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.