TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29037	87334;87335;87336	chr2:178558350;178558349;178558348	chr2:179423077;179423076;179423075
N2AB	27396	82411;82412;82413	chr2:178558350;178558349;178558348	chr2:179423077;179423076;179423075
N2A	26469	79630;79631;79632	chr2:178558350;178558349;178558348	chr2:179423077;179423076;179423075
N2B	19972	60139;60140;60141	chr2:178558350;178558349;178558348	chr2:179423077;179423076;179423075
Novex-1	20097	60514;60515;60516	chr2:178558350;178558349;178558348	chr2:179423077;179423076;179423075
Novex-2	20164	60715;60716;60717	chr2:178558350;178558349;178558348	chr2:179423077;179423076;179423075
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-99
• Domain position: 96
• Structural Position: 132
• Q(SASA): 0.937
• 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	0.115	N	0.649	0.305	0.39798585902	gnomAD-4.0.0	1.59821E-06	None	None	None	None	N	None	0	0	None	0	2.78474E-05	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	0.2173	likely_benign	0.2224	benign	-0.228	Destabilizing	0.115	N	0.694	prob.delet.	N	0.486014959	None	None	N
E/C	0.8957	likely_pathogenic	0.8916	pathogenic	-0.092	Destabilizing	0.934	D	0.843	deleterious	None	None	None	None	N
E/D	0.0753	likely_benign	0.0739	benign	-0.256	Destabilizing	None	N	0.248	neutral	N	0.392987367	None	None	N
E/F	0.8848	likely_pathogenic	0.8802	pathogenic	-0.123	Destabilizing	0.789	D	0.721	deleterious	None	None	None	None	N
E/G	0.1895	likely_benign	0.1968	benign	-0.403	Destabilizing	0.115	N	0.649	prob.neutral	N	0.491453228	None	None	N
E/H	0.6139	likely_pathogenic	0.6046	pathogenic	0.243	Stabilizing	0.552	D	0.588	neutral	None	None	None	None	N
E/I	0.6342	likely_pathogenic	0.6406	pathogenic	0.192	Stabilizing	0.552	D	0.763	deleterious	None	None	None	None	N
E/K	0.3677	ambiguous	0.3582	ambiguous	0.383	Stabilizing	0.115	N	0.677	prob.neutral	N	0.489932291	None	None	N
E/L	0.5824	likely_pathogenic	0.5784	pathogenic	0.192	Stabilizing	0.378	N	0.743	deleterious	None	None	None	None	N
E/M	0.6552	likely_pathogenic	0.666	pathogenic	0.142	Stabilizing	0.934	D	0.745	deleterious	None	None	None	None	N
E/N	0.2355	likely_benign	0.2285	benign	0.091	Stabilizing	0.08	N	0.692	prob.delet.	None	None	None	None	N
E/P	0.5011	ambiguous	0.4773	ambiguous	0.072	Stabilizing	0.552	D	0.687	prob.delet.	None	None	None	None	N
E/Q	0.2116	likely_benign	0.2191	benign	0.118	Stabilizing	0.115	N	0.602	neutral	N	0.484109394	None	None	N
E/R	0.5329	ambiguous	0.5169	ambiguous	0.616	Stabilizing	0.378	N	0.679	prob.neutral	None	None	None	None	N
E/S	0.2339	likely_benign	0.2381	benign	-0.075	Destabilizing	0.08	N	0.682	prob.neutral	None	None	None	None	N
E/T	0.3727	ambiguous	0.3789	ambiguous	0.071	Stabilizing	0.147	N	0.695	prob.delet.	None	None	None	None	N
E/V	0.398	ambiguous	0.3963	ambiguous	0.072	Stabilizing	0.481	N	0.637	neutral	N	0.503316512	None	None	N
E/W	0.9429	likely_pathogenic	0.9429	pathogenic	0.003	Stabilizing	0.934	D	0.868	deleterious	None	None	None	None	N
E/Y	0.7293	likely_pathogenic	0.7125	pathogenic	0.119	Stabilizing	0.789	D	0.719	prob.delet.	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.