TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8271	25036;25037;25038	chr2:178718195;178718194;178718193	chr2:179582922;179582921;179582920
N2AB	7954	24085;24086;24087	chr2:178718195;178718194;178718193	chr2:179582922;179582921;179582920
N2A	7027	21304;21305;21306	chr2:178718195;178718194;178718193	chr2:179582922;179582921;179582920
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-68
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.7731
• 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
E/K	None	None	0.002	N	0.192	0.174	0.260249123532	gnomAD-4.0.0	4.13603E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	4.65452E-05	3.32303E-05
E/Q	None	None	None	N	0.173	0.106	0.264547087235	gnomAD-4.0.0	6.89338E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.16363E-05	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
E/A	0.1181	likely_benign	0.1225	benign	-0.393	Destabilizing	None	N	0.128	neutral	N	0.504448791	None	None	I
E/C	0.7403	likely_pathogenic	0.7675	pathogenic	-0.313	Destabilizing	0.685	D	0.31	neutral	None	None	None	None	I
E/D	0.1486	likely_benign	0.1432	benign	-0.334	Destabilizing	None	N	0.187	neutral	N	0.520340963	None	None	I
E/F	0.6634	likely_pathogenic	0.6838	pathogenic	-0.18	Destabilizing	0.516	D	0.326	neutral	None	None	None	None	I
E/G	0.108	likely_benign	0.1193	benign	-0.599	Destabilizing	0.001	N	0.213	neutral	D	0.523727985	None	None	I
E/H	0.3	likely_benign	0.3192	benign	0.144	Stabilizing	0.273	N	0.367	neutral	None	None	None	None	I
E/I	0.3167	likely_benign	0.3088	benign	0.123	Stabilizing	0.198	N	0.351	neutral	None	None	None	None	I
E/K	0.0827	likely_benign	0.0927	benign	0.012	Stabilizing	0.002	N	0.192	neutral	N	0.469005279	None	None	I
E/L	0.2769	likely_benign	0.2945	benign	0.123	Stabilizing	0.034	N	0.381	neutral	None	None	None	None	I
E/M	0.3971	ambiguous	0.4014	ambiguous	0.048	Stabilizing	0.252	N	0.32	neutral	None	None	None	None	I
E/N	0.1981	likely_benign	0.1952	benign	-0.232	Destabilizing	0.016	N	0.341	neutral	None	None	None	None	I
E/P	0.4257	ambiguous	0.5286	ambiguous	-0.03	Destabilizing	0.069	N	0.362	neutral	None	None	None	None	I
E/Q	0.0795	likely_benign	0.0853	benign	-0.185	Destabilizing	None	N	0.173	neutral	N	0.471258937	None	None	I
E/R	0.1395	likely_benign	0.1609	benign	0.353	Stabilizing	0.07	N	0.339	neutral	None	None	None	None	I
E/S	0.1457	likely_benign	0.146	benign	-0.439	Destabilizing	0.016	N	0.319	neutral	None	None	None	None	I
E/T	0.1719	likely_benign	0.1717	benign	-0.275	Destabilizing	0.053	N	0.343	neutral	None	None	None	None	I
E/V	0.1795	likely_benign	0.1752	benign	-0.03	Destabilizing	0.018	N	0.366	neutral	D	0.522207832	None	None	I
E/W	0.8093	likely_pathogenic	0.8434	pathogenic	-0.026	Destabilizing	0.97	D	0.439	neutral	None	None	None	None	I
E/Y	0.5044	ambiguous	0.53	ambiguous	0.048	Stabilizing	0.74	D	0.335	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.