TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8179	24760;24761;24762	chr2:178718571;178718570;178718569	chr2:179583298;179583297;179583296
N2AB	7862	23809;23810;23811	chr2:178718571;178718570;178718569	chr2:179583298;179583297;179583296
N2A	6935	21028;21029;21030	chr2:178718571;178718570;178718569	chr2:179583298;179583297;179583296
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-67
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.4619
• 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	rs756975386	-0.094	0.999	N	0.505	0.256	0.146414634003	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	8.92E-06	0
D/N	rs756975386	-0.094	0.999	N	0.505	0.256	0.146414634003	gnomAD-4.0.0	1.3695E-05	None	None	None	None	N	None	0	0	None	0	2.52143E-05	None	0	0	1.71021E-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
D/A	0.3896	ambiguous	0.3538	ambiguous	-0.177	Destabilizing	0.989	D	0.487	neutral	N	0.47487646	None	None	N
D/C	0.9173	likely_pathogenic	0.8788	pathogenic	0.081	Stabilizing	1.0	D	0.622	neutral	None	None	None	None	N
D/E	0.46	ambiguous	0.4447	ambiguous	-0.256	Destabilizing	0.996	D	0.401	neutral	N	0.458062425	None	None	N
D/F	0.9086	likely_pathogenic	0.8879	pathogenic	-0.125	Destabilizing	0.99	D	0.62	neutral	None	None	None	None	N
D/G	0.335	likely_benign	0.2984	benign	-0.363	Destabilizing	0.996	D	0.502	neutral	N	0.482345199	None	None	N
D/H	0.6358	likely_pathogenic	0.5597	ambiguous	0.096	Stabilizing	0.994	D	0.579	neutral	N	0.47728277	None	None	N
D/I	0.8031	likely_pathogenic	0.7776	pathogenic	0.261	Stabilizing	0.998	D	0.641	neutral	None	None	None	None	N
D/K	0.7751	likely_pathogenic	0.75	pathogenic	0.488	Stabilizing	0.998	D	0.573	neutral	None	None	None	None	N
D/L	0.7823	likely_pathogenic	0.7628	pathogenic	0.261	Stabilizing	0.995	D	0.583	neutral	None	None	None	None	N
D/M	0.9207	likely_pathogenic	0.9034	pathogenic	0.321	Stabilizing	1.0	D	0.597	neutral	None	None	None	None	N
D/N	0.1185	likely_benign	0.1134	benign	0.129	Stabilizing	0.999	D	0.505	neutral	N	0.501250117	None	None	N
D/P	0.7032	likely_pathogenic	0.6031	pathogenic	0.137	Stabilizing	0.999	D	0.6	neutral	None	None	None	None	N
D/Q	0.7516	likely_pathogenic	0.7192	pathogenic	0.167	Stabilizing	0.999	D	0.556	neutral	None	None	None	None	N
D/R	0.7796	likely_pathogenic	0.7566	pathogenic	0.628	Stabilizing	0.998	D	0.583	neutral	None	None	None	None	N
D/S	0.2136	likely_benign	0.1949	benign	0.051	Stabilizing	0.992	D	0.459	neutral	None	None	None	None	N
D/T	0.5074	ambiguous	0.4926	ambiguous	0.202	Stabilizing	0.998	D	0.569	neutral	None	None	None	None	N
D/V	0.6123	likely_pathogenic	0.5912	pathogenic	0.137	Stabilizing	0.994	D	0.591	neutral	N	0.494626557	None	None	N
D/W	0.9837	likely_pathogenic	0.9759	pathogenic	-0.004	Destabilizing	0.999	D	0.608	neutral	None	None	None	None	N
D/Y	0.562	ambiguous	0.5081	ambiguous	0.119	Stabilizing	0.576	D	0.392	neutral	N	0.513326696	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.