TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20015	60268;60269;60270	chr2:178591776;178591775;178591774	chr2:179456503;179456502;179456501
N2AB	18374	55345;55346;55347	chr2:178591776;178591775;178591774	chr2:179456503;179456502;179456501
N2A	17447	52564;52565;52566	chr2:178591776;178591775;178591774	chr2:179456503;179456502;179456501
N2B	10950	33073;33074;33075	chr2:178591776;178591775;178591774	chr2:179456503;179456502;179456501
Novex-1	11075	33448;33449;33450	chr2:178591776;178591775;178591774	chr2:179456503;179456502;179456501
Novex-2	11142	33649;33650;33651	chr2:178591776;178591775;178591774	chr2:179456503;179456502;179456501
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: Fn3-33
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1034
• 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
E/D	rs575796706	-2.174	0.117	N	0.358	0.066	0.154104182512	gnomAD-2.1.1	2.5E-05	None	None	None	None	N	None	0	1.70116E-04	None	0	0	None	0	None	0	7.84E-06	0
E/D	rs575796706	-2.174	0.117	N	0.358	0.066	0.154104182512	gnomAD-3.1.2	3.95E-05	None	None	None	None	N	None	0	3.93494E-04	0	0	0	None	0	0	0	0	0
E/D	rs575796706	-2.174	0.117	N	0.358	0.066	0.154104182512	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
E/D	rs575796706	-2.174	0.117	N	0.358	0.066	0.154104182512	gnomAD-4.0.0	1.9215E-05	None	None	None	None	N	None	0	2.8356E-04	None	0	0	None	0	0	1.18687E-05	0	0
E/Q	None	None	0.997	N	0.805	0.321	0.243972157842	gnomAD-4.0.0	3.18462E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71935E-06	0	0
E/V	rs2050261843	None	0.997	N	0.789	0.548	0.677432480161	gnomAD-4.0.0	2.05317E-06	None	None	None	None	N	None	8.96807E-05	0	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	0.8026	likely_pathogenic	0.8267	pathogenic	-1.495	Destabilizing	0.977	D	0.724	prob.delet.	N	0.516922592	None	None	N
E/C	0.9724	likely_pathogenic	0.9745	pathogenic	-0.638	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
E/D	0.6294	likely_pathogenic	0.694	pathogenic	-1.946	Destabilizing	0.117	N	0.358	neutral	N	0.497991673	None	None	N
E/F	0.9876	likely_pathogenic	0.9902	pathogenic	-1.219	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
E/G	0.8989	likely_pathogenic	0.9143	pathogenic	-1.858	Destabilizing	0.993	D	0.755	deleterious	D	0.525444968	None	None	N
E/H	0.964	likely_pathogenic	0.9705	pathogenic	-1.023	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
E/I	0.9555	likely_pathogenic	0.9683	pathogenic	-0.448	Destabilizing	0.998	D	0.852	deleterious	None	None	None	None	N
E/K	0.9522	likely_pathogenic	0.9627	pathogenic	-1.449	Destabilizing	0.977	D	0.681	prob.neutral	N	0.510882204	None	None	N
E/L	0.9661	likely_pathogenic	0.9727	pathogenic	-0.448	Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	N
E/M	0.938	likely_pathogenic	0.9488	pathogenic	0.228	Stabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
E/N	0.9397	likely_pathogenic	0.9536	pathogenic	-1.694	Destabilizing	0.99	D	0.819	deleterious	None	None	None	None	N
E/P	0.9996	likely_pathogenic	0.9997	pathogenic	-0.785	Destabilizing	0.998	D	0.813	deleterious	None	None	None	None	N
E/Q	0.6731	likely_pathogenic	0.7014	pathogenic	-1.398	Destabilizing	0.997	D	0.805	deleterious	N	0.508456596	None	None	N
E/R	0.961	likely_pathogenic	0.9704	pathogenic	-1.318	Destabilizing	0.998	D	0.834	deleterious	None	None	None	None	N
E/S	0.7845	likely_pathogenic	0.8191	pathogenic	-2.246	Highly Destabilizing	0.983	D	0.701	prob.neutral	None	None	None	None	N
E/T	0.9078	likely_pathogenic	0.9316	pathogenic	-1.892	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
E/V	0.9087	likely_pathogenic	0.9312	pathogenic	-0.785	Destabilizing	0.997	D	0.789	deleterious	N	0.51291012	None	None	N
E/W	0.9932	likely_pathogenic	0.9945	pathogenic	-1.361	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
E/Y	0.9719	likely_pathogenic	0.9789	pathogenic	-1.055	Destabilizing	1.0	D	0.857	deleterious	None	None	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.