TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5068	15427;15428;15429	chr2:178734722;178734721;178734720	chr2:179599449;179599448;179599447
N2AB	4751	14476;14477;14478	chr2:178734722;178734721;178734720	chr2:179599449;179599448;179599447
N2A	3824	11695;11696;11697	chr2:178734722;178734721;178734720	chr2:179599449;179599448;179599447
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-33
• Domain position: 88
• Structural Position: 173
• Q(SASA): 0.4956
• 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/G	None	None	0.92	N	0.555	0.404	0.580704020645	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

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	0.221	likely_benign	0.2035	benign	-1.14	Destabilizing	0.134	N	0.201	neutral	N	0.476377625	None	None	N
E/C	0.9171	likely_pathogenic	0.9155	pathogenic	-0.347	Destabilizing	0.999	D	0.575	neutral	None	None	None	None	N
E/D	0.1228	likely_benign	0.1211	benign	-0.843	Destabilizing	0.92	D	0.451	neutral	N	0.510428671	None	None	N
E/F	0.8393	likely_pathogenic	0.838	pathogenic	-0.964	Destabilizing	0.982	D	0.604	neutral	None	None	None	None	N
E/G	0.2599	likely_benign	0.2438	benign	-1.419	Destabilizing	0.92	D	0.555	neutral	N	0.511487369	None	None	N
E/H	0.5114	ambiguous	0.4868	ambiguous	-1.139	Destabilizing	0.991	D	0.566	neutral	None	None	None	None	N
E/I	0.485	ambiguous	0.4936	ambiguous	-0.39	Destabilizing	0.884	D	0.6	neutral	None	None	None	None	N
E/K	0.1743	likely_benign	0.1575	benign	-0.206	Destabilizing	0.852	D	0.479	neutral	N	0.464473899	None	None	N
E/L	0.5517	ambiguous	0.5357	ambiguous	-0.39	Destabilizing	0.02	N	0.328	neutral	None	None	None	None	N
E/M	0.5514	ambiguous	0.5509	ambiguous	0.181	Stabilizing	0.982	D	0.588	neutral	None	None	None	None	N
E/N	0.2415	likely_benign	0.2372	benign	-0.64	Destabilizing	0.991	D	0.559	neutral	None	None	None	None	N
E/P	0.8584	likely_pathogenic	0.8167	pathogenic	-0.622	Destabilizing	0.991	D	0.61	neutral	None	None	None	None	N
E/Q	0.1604	likely_benign	0.1444	benign	-0.585	Destabilizing	0.31	N	0.252	neutral	N	0.48736129	None	None	N
E/R	0.3263	likely_benign	0.2933	benign	-0.132	Destabilizing	0.939	D	0.548	neutral	None	None	None	None	N
E/S	0.2335	likely_benign	0.2251	benign	-0.913	Destabilizing	0.884	D	0.478	neutral	None	None	None	None	N
E/T	0.2534	likely_benign	0.2442	benign	-0.66	Destabilizing	0.939	D	0.554	neutral	None	None	None	None	N
E/V	0.2877	likely_benign	0.283	benign	-0.622	Destabilizing	0.852	D	0.533	neutral	N	0.491967225	None	None	N
E/W	0.939	likely_pathogenic	0.9358	pathogenic	-0.702	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	N
E/Y	0.7188	likely_pathogenic	0.7115	pathogenic	-0.684	Destabilizing	0.997	D	0.599	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.