TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27777	83554;83555;83556	chr2:178562803;178562802;178562801	chr2:179427530;179427529;179427528
N2AB	26136	78631;78632;78633	chr2:178562803;178562802;178562801	chr2:179427530;179427529;179427528
N2A	25209	75850;75851;75852	chr2:178562803;178562802;178562801	chr2:179427530;179427529;179427528
N2B	18712	56359;56360;56361	chr2:178562803;178562802;178562801	chr2:179427530;179427529;179427528
Novex-1	18837	56734;56735;56736	chr2:178562803;178562802;178562801	chr2:179427530;179427529;179427528
Novex-2	18904	56935;56936;56937	chr2:178562803;178562802;178562801	chr2:179427530;179427529;179427528
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: Fn3-90
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.2109
• 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/A	None	None	0.367	N	0.387	0.295	0.338110398507	gnomAD-4.0.0	1.59268E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85981E-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	0.2559	likely_benign	0.2765	benign	-0.593	Destabilizing	0.367	N	0.387	neutral	N	0.469900754	None	None	N
E/C	0.9	likely_pathogenic	0.9045	pathogenic	-0.274	Destabilizing	0.984	D	0.551	neutral	None	None	None	None	N
E/D	0.0816	likely_benign	0.0849	benign	-0.576	Destabilizing	None	N	0.069	neutral	N	0.436364424	None	None	N
E/F	0.8696	likely_pathogenic	0.8662	pathogenic	-0.208	Destabilizing	0.969	D	0.515	neutral	None	None	None	None	N
E/G	0.2952	likely_benign	0.32	benign	-0.861	Destabilizing	0.491	N	0.432	neutral	N	0.477902925	None	None	N
E/H	0.6417	likely_pathogenic	0.6529	pathogenic	-0.157	Destabilizing	0.879	D	0.418	neutral	None	None	None	None	N
E/I	0.6494	likely_pathogenic	0.6476	pathogenic	0.107	Stabilizing	0.826	D	0.528	neutral	None	None	None	None	N
E/K	0.4616	ambiguous	0.4933	ambiguous	-0.005	Destabilizing	0.518	D	0.427	neutral	N	0.484183575	None	None	N
E/L	0.6631	likely_pathogenic	0.6763	pathogenic	0.107	Stabilizing	0.826	D	0.487	neutral	None	None	None	None	N
E/M	0.6929	likely_pathogenic	0.7	pathogenic	0.259	Stabilizing	0.907	D	0.483	neutral	None	None	None	None	N
E/N	0.2885	likely_benign	0.3173	benign	-0.464	Destabilizing	0.001	N	0.17	neutral	None	None	None	None	N
E/P	0.959	likely_pathogenic	0.9698	pathogenic	-0.105	Destabilizing	0.682	D	0.444	neutral	None	None	None	None	N
E/Q	0.2987	likely_benign	0.3106	benign	-0.387	Destabilizing	0.434	N	0.433	neutral	N	0.471839765	None	None	N
E/R	0.6177	likely_pathogenic	0.6415	pathogenic	0.269	Stabilizing	0.833	D	0.423	neutral	None	None	None	None	N
E/S	0.2921	likely_benign	0.3075	benign	-0.654	Destabilizing	0.278	N	0.387	neutral	None	None	None	None	N
E/T	0.3773	ambiguous	0.3839	ambiguous	-0.433	Destabilizing	0.515	D	0.418	neutral	None	None	None	None	N
E/V	0.4316	ambiguous	0.4433	ambiguous	-0.105	Destabilizing	0.717	D	0.476	neutral	N	0.478916883	None	None	N
E/W	0.9485	likely_pathogenic	0.9501	pathogenic	0.03	Stabilizing	0.997	D	0.616	neutral	None	None	None	None	N
E/Y	0.7507	likely_pathogenic	0.7555	pathogenic	0.046	Stabilizing	0.988	D	0.508	neutral	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.