TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5772	17539;17540;17541	chr2:178731452;178731451;178731450	chr2:179596179;179596178;179596177
N2AB	5455	16588;16589;16590	chr2:178731452;178731451;178731450	chr2:179596179;179596178;179596177
N2A	4528	13807;13808;13809	chr2:178731452;178731451;178731450	chr2:179596179;179596178;179596177
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-41
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.8959
• 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	rs763931240	0.833	0.994	D	0.49	0.32	0.483816155017	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/K	rs763931240	0.833	0.994	D	0.49	0.32	0.483816155017	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/K	rs763931240	0.833	0.994	D	0.49	0.32	0.483816155017	gnomAD-4.0.0	2.56244E-06	None	None	None	None	I	None	0	3.39098E-05	None	0	0	None	0	0	0	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
E/A	0.1365	likely_benign	0.1443	benign	-0.523	Destabilizing	0.989	D	0.494	neutral	N	0.497696177	None	None	I
E/C	0.9035	likely_pathogenic	0.909	pathogenic	-0.137	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	I
E/D	0.1936	likely_benign	0.2074	benign	-0.584	Destabilizing	0.217	N	0.315	neutral	N	0.481420002	None	None	I
E/F	0.846	likely_pathogenic	0.8718	pathogenic	-0.265	Destabilizing	1.0	D	0.592	neutral	None	None	None	None	I
E/G	0.1459	likely_benign	0.1598	benign	-0.784	Destabilizing	0.994	D	0.445	neutral	D	0.522882623	None	None	I
E/H	0.5883	likely_pathogenic	0.6248	pathogenic	-0.235	Destabilizing	1.0	D	0.463	neutral	None	None	None	None	I
E/I	0.4798	ambiguous	0.5319	ambiguous	0.154	Stabilizing	0.998	D	0.593	neutral	None	None	None	None	I
E/K	0.1279	likely_benign	0.1476	benign	0.003	Stabilizing	0.994	D	0.49	neutral	D	0.525709497	None	None	I
E/L	0.4894	ambiguous	0.5336	ambiguous	0.154	Stabilizing	0.998	D	0.533	neutral	None	None	None	None	I
E/M	0.5299	ambiguous	0.5722	pathogenic	0.355	Stabilizing	1.0	D	0.559	neutral	None	None	None	None	I
E/N	0.3484	ambiguous	0.3597	ambiguous	-0.356	Destabilizing	0.998	D	0.436	neutral	None	None	None	None	I
E/P	0.4364	ambiguous	0.454	ambiguous	-0.05	Destabilizing	1.0	D	0.498	neutral	None	None	None	None	I
E/Q	0.1622	likely_benign	0.1761	benign	-0.281	Destabilizing	0.998	D	0.443	neutral	N	0.499581689	None	None	I
E/R	0.2529	likely_benign	0.2797	benign	0.248	Stabilizing	0.999	D	0.472	neutral	None	None	None	None	I
E/S	0.224	likely_benign	0.2367	benign	-0.55	Destabilizing	0.983	D	0.473	neutral	None	None	None	None	I
E/T	0.2635	likely_benign	0.2871	benign	-0.34	Destabilizing	0.784	D	0.353	neutral	None	None	None	None	I
E/V	0.27	likely_benign	0.2986	benign	-0.05	Destabilizing	0.997	D	0.439	neutral	N	0.515975293	None	None	I
E/W	0.9281	likely_pathogenic	0.9403	pathogenic	-0.081	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	I
E/Y	0.7408	likely_pathogenic	0.7739	pathogenic	-0.023	Destabilizing	1.0	D	0.556	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.