TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32373	97342;97343;97344	chr2:178542737;178542736;178542735	chr2:179407464;179407463;179407462
N2AB	30732	92419;92420;92421	chr2:178542737;178542736;178542735	chr2:179407464;179407463;179407462
N2A	29805	89638;89639;89640	chr2:178542737;178542736;178542735	chr2:179407464;179407463;179407462
N2B	23308	70147;70148;70149	chr2:178542737;178542736;178542735	chr2:179407464;179407463;179407462
Novex-1	23433	70522;70523;70524	chr2:178542737;178542736;178542735	chr2:179407464;179407463;179407462
Novex-2	23500	70723;70724;70725	chr2:178542737;178542736;178542735	chr2:179407464;179407463;179407462
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-154
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.1423
• 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
D/N	None	None	1.0	D	0.783	0.768	0.605542551707	gnomAD-4.0.0	1.59125E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85834E-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
D/A	0.9946	likely_pathogenic	0.992	pathogenic	0.071	Stabilizing	1.0	D	0.849	deleterious	D	0.618566543	None	None	N
D/C	0.997	likely_pathogenic	0.9951	pathogenic	0.292	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
D/E	0.97	likely_pathogenic	0.9568	pathogenic	-0.288	Destabilizing	1.0	D	0.584	neutral	D	0.591817606	None	None	N
D/F	0.9981	likely_pathogenic	0.9971	pathogenic	0.82	Stabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
D/G	0.99	likely_pathogenic	0.9862	pathogenic	-0.37	Destabilizing	1.0	D	0.786	deleterious	D	0.618768347	None	None	N
D/H	0.982	likely_pathogenic	0.9723	pathogenic	0.595	Stabilizing	1.0	D	0.836	deleterious	D	0.557678683	None	None	N
D/I	0.9987	likely_pathogenic	0.9977	pathogenic	1.262	Stabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
D/K	0.9975	likely_pathogenic	0.9964	pathogenic	0.45	Stabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
D/L	0.9968	likely_pathogenic	0.9948	pathogenic	1.262	Stabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
D/M	0.9989	likely_pathogenic	0.9983	pathogenic	1.647	Stabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
D/N	0.9454	likely_pathogenic	0.92	pathogenic	-0.408	Destabilizing	1.0	D	0.783	deleterious	D	0.5795736	None	None	N
D/P	0.9996	likely_pathogenic	0.9994	pathogenic	0.893	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
D/Q	0.9962	likely_pathogenic	0.9946	pathogenic	-0.118	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
D/R	0.9979	likely_pathogenic	0.997	pathogenic	0.495	Stabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
D/S	0.9878	likely_pathogenic	0.9821	pathogenic	-0.694	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
D/T	0.9978	likely_pathogenic	0.9965	pathogenic	-0.277	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
D/V	0.996	likely_pathogenic	0.9931	pathogenic	0.893	Stabilizing	1.0	D	0.854	deleterious	D	0.619171956	None	None	N
D/W	0.9994	likely_pathogenic	0.9991	pathogenic	1.026	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
D/Y	0.9817	likely_pathogenic	0.9723	pathogenic	1.153	Stabilizing	1.0	D	0.853	deleterious	D	0.618970151	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.