TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25313	76162;76163;76164	chr2:178570195;178570194;178570193	chr2:179434922;179434921;179434920
N2AB	23672	71239;71240;71241	chr2:178570195;178570194;178570193	chr2:179434922;179434921;179434920
N2A	22745	68458;68459;68460	chr2:178570195;178570194;178570193	chr2:179434922;179434921;179434920
N2B	16248	48967;48968;48969	chr2:178570195;178570194;178570193	chr2:179434922;179434921;179434920
Novex-1	16373	49342;49343;49344	chr2:178570195;178570194;178570193	chr2:179434922;179434921;179434920
Novex-2	16440	49543;49544;49545	chr2:178570195;178570194;178570193	chr2:179434922;179434921;179434920
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-72
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.3069
• 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/F	None	None	0.638	N	0.788	0.231	0.619865016221	gnomAD-4.0.0	1.36867E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79915E-06	0	0
V/I	None	None	0.002	N	0.223	0.079	0.31291088546	gnomAD-4.0.0	6.84335E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99577E-07	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	0.4126	ambiguous	0.4247	ambiguous	-1.8	Destabilizing	0.334	N	0.514	neutral	N	0.496220805	None	None	N
V/C	0.7927	likely_pathogenic	0.822	pathogenic	-1.3	Destabilizing	0.982	D	0.762	deleterious	None	None	None	None	N
V/D	0.9371	likely_pathogenic	0.9253	pathogenic	-1.768	Destabilizing	0.781	D	0.813	deleterious	N	0.519714657	None	None	N
V/E	0.8938	likely_pathogenic	0.8811	pathogenic	-1.673	Destabilizing	0.826	D	0.801	deleterious	None	None	None	None	N
V/F	0.4217	ambiguous	0.4443	ambiguous	-1.215	Destabilizing	0.638	D	0.788	deleterious	N	0.495806597	None	None	N
V/G	0.6313	likely_pathogenic	0.6294	pathogenic	-2.233	Highly Destabilizing	0.781	D	0.793	deleterious	D	0.53384244	None	None	N
V/H	0.9547	likely_pathogenic	0.9582	pathogenic	-1.889	Destabilizing	0.982	D	0.818	deleterious	None	None	None	None	N
V/I	0.0656	likely_benign	0.0707	benign	-0.662	Destabilizing	0.002	N	0.223	neutral	N	0.485563881	None	None	N
V/K	0.9149	likely_pathogenic	0.9111	pathogenic	-1.519	Destabilizing	0.826	D	0.801	deleterious	None	None	None	None	N
V/L	0.3189	likely_benign	0.3488	ambiguous	-0.662	Destabilizing	0.034	N	0.399	neutral	N	0.474841959	None	None	N
V/M	0.2813	likely_benign	0.3205	benign	-0.564	Destabilizing	0.7	D	0.707	prob.neutral	None	None	None	None	N
V/N	0.7882	likely_pathogenic	0.8016	pathogenic	-1.457	Destabilizing	0.935	D	0.827	deleterious	None	None	None	None	N
V/P	0.7037	likely_pathogenic	0.7257	pathogenic	-1.009	Destabilizing	0.935	D	0.812	deleterious	None	None	None	None	N
V/Q	0.8977	likely_pathogenic	0.8982	pathogenic	-1.482	Destabilizing	0.935	D	0.822	deleterious	None	None	None	None	N
V/R	0.8866	likely_pathogenic	0.8844	pathogenic	-1.172	Destabilizing	0.826	D	0.826	deleterious	None	None	None	None	N
V/S	0.6639	likely_pathogenic	0.6926	pathogenic	-2.065	Highly Destabilizing	0.826	D	0.779	deleterious	None	None	None	None	N
V/T	0.5494	ambiguous	0.5809	pathogenic	-1.84	Destabilizing	0.399	N	0.619	neutral	None	None	None	None	N
V/W	0.9607	likely_pathogenic	0.9639	pathogenic	-1.543	Destabilizing	0.982	D	0.78	deleterious	None	None	None	None	N
V/Y	0.8502	likely_pathogenic	0.8579	pathogenic	-1.209	Destabilizing	0.826	D	0.797	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.