TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16587	49984;49985;49986	chr2:178612962;178612961;178612960	chr2:179477689;179477688;179477687
N2AB	14946	45061;45062;45063	chr2:178612962;178612961;178612960	chr2:179477689;179477688;179477687
N2A	14019	42280;42281;42282	chr2:178612962;178612961;178612960	chr2:179477689;179477688;179477687
N2B	7522	22789;22790;22791	chr2:178612962;178612961;178612960	chr2:179477689;179477688;179477687
Novex-1	7647	23164;23165;23166	chr2:178612962;178612961;178612960	chr2:179477689;179477688;179477687
Novex-2	7714	23365;23366;23367	chr2:178612962;178612961;178612960	chr2:179477689;179477688;179477687
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: Fn3-8
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.153
• 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	0.334	N	0.616	0.233	0.531581166724	gnomAD-4.0.0	1.59351E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86172E-06	0	0
V/G	None	None	0.781	N	0.759	0.338	0.626364337782	gnomAD-4.0.0	1.59351E-06	None	None	None	None	N	None	0	0	None	0	2.78909E-05	None	0	0	0	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	0.4506	ambiguous	0.4118	ambiguous	-2.524	Highly Destabilizing	0.334	N	0.616	neutral	N	0.473466138	None	None	N
V/C	0.7874	likely_pathogenic	0.7229	pathogenic	-2.161	Highly Destabilizing	0.982	D	0.747	deleterious	None	None	None	None	N
V/D	0.7693	likely_pathogenic	0.8128	pathogenic	-3.366	Highly Destabilizing	0.781	D	0.801	deleterious	N	0.517932922	None	None	N
V/E	0.6263	likely_pathogenic	0.6633	pathogenic	-3.156	Highly Destabilizing	0.826	D	0.719	prob.delet.	None	None	None	None	N
V/F	0.2864	likely_benign	0.2757	benign	-1.403	Destabilizing	0.638	D	0.726	prob.delet.	N	0.480356617	None	None	N
V/G	0.6085	likely_pathogenic	0.6242	pathogenic	-3.01	Highly Destabilizing	0.781	D	0.759	deleterious	N	0.505940723	None	None	N
V/H	0.7704	likely_pathogenic	0.7599	pathogenic	-2.573	Highly Destabilizing	0.982	D	0.772	deleterious	None	None	None	None	N
V/I	0.0709	likely_benign	0.0596	benign	-1.152	Destabilizing	0.002	N	0.243	neutral	N	0.402655687	None	None	N
V/K	0.6909	likely_pathogenic	0.7254	pathogenic	-2.131	Highly Destabilizing	0.826	D	0.731	prob.delet.	None	None	None	None	N
V/L	0.2412	likely_benign	0.2156	benign	-1.152	Destabilizing	0.034	N	0.515	neutral	N	0.475391686	None	None	N
V/M	0.2244	likely_benign	0.1877	benign	-1.401	Destabilizing	0.7	D	0.733	prob.delet.	None	None	None	None	N
V/N	0.5888	likely_pathogenic	0.5594	ambiguous	-2.483	Highly Destabilizing	0.935	D	0.801	deleterious	None	None	None	None	N
V/P	0.9854	likely_pathogenic	0.9896	pathogenic	-1.588	Destabilizing	0.935	D	0.782	deleterious	None	None	None	None	N
V/Q	0.6261	likely_pathogenic	0.6354	pathogenic	-2.346	Highly Destabilizing	0.935	D	0.769	deleterious	None	None	None	None	N
V/R	0.6026	likely_pathogenic	0.6579	pathogenic	-1.845	Destabilizing	0.826	D	0.799	deleterious	None	None	None	None	N
V/S	0.4914	ambiguous	0.4535	ambiguous	-3.015	Highly Destabilizing	0.826	D	0.73	prob.delet.	None	None	None	None	N
V/T	0.3567	ambiguous	0.2551	benign	-2.685	Highly Destabilizing	0.399	N	0.687	prob.neutral	None	None	None	None	N
V/W	0.892	likely_pathogenic	0.8844	pathogenic	-1.883	Destabilizing	0.982	D	0.759	deleterious	None	None	None	None	N
V/Y	0.6986	likely_pathogenic	0.6898	pathogenic	-1.628	Destabilizing	0.826	D	0.765	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.