TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6179	18760;18761;18762	chr2:178729718;178729717;178729716	chr2:179594445;179594444;179594443
N2AB	5862	17809;17810;17811	chr2:178729718;178729717;178729716	chr2:179594445;179594444;179594443
N2A	4935	15028;15029;15030	chr2:178729718;178729717;178729716	chr2:179594445;179594444;179594443
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-45
• Domain position: 75
• Structural Position: 157
• Q(SASA): 0.2221
• 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/K	None	None	0.999	N	0.635	0.323	0.397540356873	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/V	None	None	1.0	N	0.852	0.465	0.539478914628	gnomAD-4.0.0	1.5914E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85869E-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
E/A	0.3759	ambiguous	0.3659	ambiguous	-1.127	Destabilizing	0.999	D	0.719	prob.delet.	N	0.503076249	None	None	N
E/C	0.9593	likely_pathogenic	0.9581	pathogenic	-0.618	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
E/D	0.4576	ambiguous	0.437	ambiguous	-1.302	Destabilizing	0.999	D	0.586	neutral	D	0.540045228	None	None	N
E/F	0.8705	likely_pathogenic	0.8627	pathogenic	-0.796	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
E/G	0.5699	likely_pathogenic	0.5394	ambiguous	-1.504	Destabilizing	1.0	D	0.809	deleterious	D	0.540552207	None	None	N
E/H	0.639	likely_pathogenic	0.6125	pathogenic	-1.136	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/I	0.4787	ambiguous	0.4748	ambiguous	-0.087	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
E/K	0.2012	likely_benign	0.1944	benign	-0.9	Destabilizing	0.999	D	0.635	neutral	N	0.501291055	None	None	N
E/L	0.603	likely_pathogenic	0.593	pathogenic	-0.087	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
E/M	0.6094	likely_pathogenic	0.6114	pathogenic	0.533	Stabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
E/N	0.6255	likely_pathogenic	0.6154	pathogenic	-1.273	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/P	0.9952	likely_pathogenic	0.9929	pathogenic	-0.414	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
E/Q	0.2026	likely_benign	0.1904	benign	-1.131	Destabilizing	1.0	D	0.693	prob.neutral	D	0.524533274	None	None	N
E/R	0.3784	ambiguous	0.3571	ambiguous	-0.739	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
E/S	0.4945	ambiguous	0.476	ambiguous	-1.704	Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	N
E/T	0.4169	ambiguous	0.4034	ambiguous	-1.379	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
E/V	0.3022	likely_benign	0.2955	benign	-0.414	Destabilizing	1.0	D	0.852	deleterious	N	0.473875168	None	None	N
E/W	0.9629	likely_pathogenic	0.9567	pathogenic	-0.623	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
E/Y	0.8208	likely_pathogenic	0.8021	pathogenic	-0.551	Destabilizing	1.0	D	0.871	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.