TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8183	24772;24773;24774	chr2:178718559;178718558;178718557	chr2:179583286;179583285;179583284
N2AB	7866	23821;23822;23823	chr2:178718559;178718558;178718557	chr2:179583286;179583285;179583284
N2A	6939	21040;21041;21042	chr2:178718559;178718558;178718557	chr2:179583286;179583285;179583284
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: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-67
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.5323
• 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/D	None	None	0.979	N	0.327	0.33	0.250039746154	gnomAD-4.0.0	2.05312E-06	None	None	None	None	I	None	5.978E-05	0	None	0	0	None	0	0	8.99633E-07	0	0
E/Q	rs201365398	0.44	0.959	N	0.376	0.261	None	gnomAD-2.1.1	9.66E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	6.81417E-04	5.48E-05	4.23131E-04
E/Q	rs201365398	0.44	0.959	N	0.376	0.261	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	I	None	0	0	0	0	0	None	4.71431E-04	0	0	0	0
E/Q	rs201365398	0.44	0.959	N	0.376	0.261	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	1E-03	None	None	None	0	None
E/Q	rs201365398	0.44	0.959	N	0.376	0.261	None	gnomAD-4.0.0	5.45413E-05	None	None	None	None	I	None	0	1.6665E-05	None	0	0	None	1.25051E-03	0	4.23882E-06	0	3.20205E-05

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	0.198	likely_benign	0.1961	benign	-0.366	Destabilizing	0.906	D	0.394	neutral	D	0.531768678	None	None	I
E/C	0.9392	likely_pathogenic	0.9346	pathogenic	0.024	Stabilizing	1.0	D	0.466	neutral	None	None	None	None	I
E/D	0.2824	likely_benign	0.3011	benign	-0.264	Destabilizing	0.979	D	0.327	neutral	N	0.513876351	None	None	I
E/F	0.8568	likely_pathogenic	0.8624	pathogenic	-0.273	Destabilizing	0.088	N	0.404	neutral	None	None	None	None	I
E/G	0.2601	likely_benign	0.2701	benign	-0.538	Destabilizing	0.979	D	0.467	neutral	N	0.514040934	None	None	I
E/H	0.6487	likely_pathogenic	0.6748	pathogenic	-0.001	Destabilizing	0.999	D	0.355	neutral	None	None	None	None	I
E/I	0.5092	ambiguous	0.5022	ambiguous	0.048	Stabilizing	0.939	D	0.462	neutral	None	None	None	None	I
E/K	0.1582	likely_benign	0.1671	benign	0.495	Stabilizing	0.238	N	0.237	neutral	D	0.523263838	None	None	I
E/L	0.5169	ambiguous	0.5214	ambiguous	0.048	Stabilizing	0.088	N	0.329	neutral	None	None	None	None	I
E/M	0.5707	likely_pathogenic	0.5737	pathogenic	0.146	Stabilizing	0.991	D	0.453	neutral	None	None	None	None	I
E/N	0.4017	ambiguous	0.4287	ambiguous	0.105	Stabilizing	0.995	D	0.361	neutral	None	None	None	None	I
E/P	0.4889	ambiguous	0.4944	ambiguous	-0.07	Destabilizing	0.999	D	0.419	neutral	None	None	None	None	I
E/Q	0.1497	likely_benign	0.1531	benign	0.145	Stabilizing	0.959	D	0.376	neutral	N	0.500002976	None	None	I
E/R	0.2974	likely_benign	0.3196	benign	0.629	Stabilizing	0.939	D	0.367	neutral	None	None	None	None	I
E/S	0.3058	likely_benign	0.3241	benign	-0.012	Destabilizing	0.969	D	0.341	neutral	None	None	None	None	I
E/T	0.3225	likely_benign	0.3282	benign	0.139	Stabilizing	0.984	D	0.426	neutral	None	None	None	None	I
E/V	0.2892	likely_benign	0.2906	benign	-0.07	Destabilizing	0.921	D	0.448	neutral	N	0.506585019	None	None	I
E/W	0.9714	likely_pathogenic	0.9716	pathogenic	-0.127	Destabilizing	1.0	D	0.47	neutral	None	None	None	None	I
E/Y	0.8024	likely_pathogenic	0.8117	pathogenic	-0.029	Destabilizing	0.982	D	0.451	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.