TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8330	25213;25214;25215	chr2:178718018;178718017;178718016	chr2:179582745;179582744;179582743
N2AB	8013	24262;24263;24264	chr2:178718018;178718017;178718016	chr2:179582745;179582744;179582743
N2A	7086	21481;21482;21483	chr2:178718018;178718017;178718016	chr2:179582745;179582744;179582743
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-68
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.1418
• 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/H	None	None	1.0	D	0.845	0.644	0.661693444866	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
D/A	0.8285	likely_pathogenic	0.9014	pathogenic	0.388	Stabilizing	1.0	D	0.847	deleterious	D	0.633425081	None	None	N
D/C	0.9628	likely_pathogenic	0.9826	pathogenic	0.303	Stabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
D/E	0.7922	likely_pathogenic	0.8603	pathogenic	-0.475	Destabilizing	0.965	D	0.625	neutral	D	0.606676143	None	None	N
D/F	0.9709	likely_pathogenic	0.9846	pathogenic	1.142	Stabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
D/G	0.9104	likely_pathogenic	0.9583	pathogenic	-0.06	Destabilizing	0.996	D	0.736	prob.delet.	D	0.665665607	None	None	N
D/H	0.8203	likely_pathogenic	0.8728	pathogenic	0.841	Stabilizing	1.0	D	0.845	deleterious	D	0.591342558	None	None	N
D/I	0.9564	likely_pathogenic	0.9793	pathogenic	1.589	Stabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
D/K	0.9736	likely_pathogenic	0.983	pathogenic	0.385	Stabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
D/L	0.9492	likely_pathogenic	0.9724	pathogenic	1.589	Stabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
D/M	0.974	likely_pathogenic	0.9854	pathogenic	1.867	Stabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
D/N	0.5535	ambiguous	0.6929	pathogenic	-0.505	Destabilizing	0.668	D	0.373	neutral	D	0.608362017	None	None	N
D/P	0.9959	likely_pathogenic	0.9974	pathogenic	1.219	Stabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
D/Q	0.9423	likely_pathogenic	0.9611	pathogenic	-0.173	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
D/R	0.9762	likely_pathogenic	0.9846	pathogenic	0.425	Stabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
D/S	0.6961	likely_pathogenic	0.8119	pathogenic	-0.727	Destabilizing	0.998	D	0.655	neutral	None	None	None	None	N
D/T	0.9181	likely_pathogenic	0.9579	pathogenic	-0.307	Destabilizing	0.999	D	0.83	deleterious	None	None	None	None	N
D/V	0.8878	likely_pathogenic	0.943	pathogenic	1.219	Stabilizing	1.0	D	0.882	deleterious	D	0.666069215	None	None	N
D/W	0.9949	likely_pathogenic	0.9971	pathogenic	1.255	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
D/Y	0.8636	likely_pathogenic	0.9205	pathogenic	1.435	Stabilizing	1.0	D	0.889	deleterious	D	0.64984805	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.