TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23822	71689;71690;71691	chr2:178574668;178574667;178574666	chr2:179439395;179439394;179439393
N2AB	22181	66766;66767;66768	chr2:178574668;178574667;178574666	chr2:179439395;179439394;179439393
N2A	21254	63985;63986;63987	chr2:178574668;178574667;178574666	chr2:179439395;179439394;179439393
N2B	14757	44494;44495;44496	chr2:178574668;178574667;178574666	chr2:179439395;179439394;179439393
Novex-1	14882	44869;44870;44871	chr2:178574668;178574667;178574666	chr2:179439395;179439394;179439393
Novex-2	14949	45070;45071;45072	chr2:178574668;178574667;178574666	chr2:179439395;179439394;179439393
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-60
• Domain position: 97
• Structural Position: 132
• Q(SASA): 1.1245
• Predicted PPI site: I

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
Y/N	None	None	0.994	N	0.684	0.444	0.673276159487	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62501E-06	0	0
Y/S	rs1709438613	None	0.981	N	0.671	0.297	0.612832922585	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/S	rs1709438613	None	0.981	N	0.671	0.297	0.612832922585	gnomAD-4.0.0	2.47971E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.39126E-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
Y/A	0.8674	likely_pathogenic	0.8564	pathogenic	-0.635	Destabilizing	0.95	D	0.482	neutral	None	None	None	None	I
Y/C	0.5348	ambiguous	0.5358	ambiguous	0.11	Stabilizing	0.998	D	0.753	deleterious	N	0.475186538	None	None	I
Y/D	0.731	likely_pathogenic	0.7146	pathogenic	1.06	Stabilizing	0.994	D	0.731	deleterious	N	0.461910656	None	None	I
Y/E	0.9541	likely_pathogenic	0.9546	pathogenic	1.038	Stabilizing	0.995	D	0.705	prob.delet.	None	None	None	None	I
Y/F	0.1685	likely_benign	0.1616	benign	-0.354	Destabilizing	0.022	N	0.385	neutral	N	0.466032278	None	None	I
Y/G	0.8748	likely_pathogenic	0.8741	pathogenic	-0.817	Destabilizing	0.985	D	0.705	prob.delet.	None	None	None	None	I
Y/H	0.3273	likely_benign	0.3536	ambiguous	0.195	Stabilizing	0.994	D	0.527	neutral	N	0.476629392	None	None	I
Y/I	0.8526	likely_pathogenic	0.8496	pathogenic	-0.189	Destabilizing	0.943	D	0.567	neutral	None	None	None	None	I
Y/K	0.9179	likely_pathogenic	0.9286	pathogenic	0.294	Stabilizing	0.995	D	0.699	prob.delet.	None	None	None	None	I
Y/L	0.644	likely_pathogenic	0.6507	pathogenic	-0.189	Destabilizing	0.825	D	0.641	neutral	None	None	None	None	I
Y/M	0.8712	likely_pathogenic	0.8676	pathogenic	0.003	Stabilizing	0.996	D	0.503	neutral	None	None	None	None	I
Y/N	0.4925	ambiguous	0.4992	ambiguous	0.153	Stabilizing	0.994	D	0.684	prob.delet.	N	0.494041717	None	None	I
Y/P	0.8985	likely_pathogenic	0.8972	pathogenic	-0.317	Destabilizing	0.995	D	0.707	prob.delet.	None	None	None	None	I
Y/Q	0.8952	likely_pathogenic	0.9038	pathogenic	0.18	Stabilizing	0.995	D	0.517	neutral	None	None	None	None	I
Y/R	0.851	likely_pathogenic	0.871	pathogenic	0.55	Stabilizing	0.995	D	0.682	prob.neutral	None	None	None	None	I
Y/S	0.5678	likely_pathogenic	0.565	pathogenic	-0.331	Destabilizing	0.981	D	0.671	prob.neutral	N	0.491001412	None	None	I
Y/T	0.8518	likely_pathogenic	0.8591	pathogenic	-0.26	Destabilizing	0.985	D	0.697	prob.delet.	None	None	None	None	I
Y/V	0.795	likely_pathogenic	0.787	pathogenic	-0.317	Destabilizing	0.904	D	0.611	neutral	None	None	None	None	I
Y/W	0.657	likely_pathogenic	0.652	pathogenic	-0.479	Destabilizing	0.999	D	0.508	neutral	None	None	None	None	I

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.