TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21354	64285;64286;64287	chr2:178587151;178587150;178587149	chr2:179451878;179451877;179451876
N2AB	19713	59362;59363;59364	chr2:178587151;178587150;178587149	chr2:179451878;179451877;179451876
N2A	18786	56581;56582;56583	chr2:178587151;178587150;178587149	chr2:179451878;179451877;179451876
N2B	12289	37090;37091;37092	chr2:178587151;178587150;178587149	chr2:179451878;179451877;179451876
Novex-1	12414	37465;37466;37467	chr2:178587151;178587150;178587149	chr2:179451878;179451877;179451876
Novex-2	12481	37666;37667;37668	chr2:178587151;178587150;178587149	chr2:179451878;179451877;179451876
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-42
• Domain position: 89
• Structural Position: 123
• Q(SASA): 0.1467
• 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
V/I	None	None	None	N	0.219	0.128	0.119812018005	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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
V/A	0.1173	likely_benign	0.1503	benign	-1.605	Destabilizing	0.002	N	0.532	neutral	N	0.419680031	None	None	N
V/C	0.4455	ambiguous	0.5087	ambiguous	-0.903	Destabilizing	0.439	N	0.641	neutral	None	None	None	None	N
V/D	0.3574	ambiguous	0.4344	ambiguous	-2.22	Highly Destabilizing	0.026	N	0.705	prob.delet.	N	0.489310688	None	None	N
V/E	0.3602	ambiguous	0.4267	ambiguous	-2.054	Highly Destabilizing	0.035	N	0.688	prob.delet.	None	None	None	None	N
V/F	0.1196	likely_benign	0.1508	benign	-0.95	Destabilizing	0.087	N	0.774	deleterious	N	0.459161139	None	None	N
V/G	0.1645	likely_benign	0.2085	benign	-2.069	Highly Destabilizing	0.026	N	0.647	neutral	N	0.518940162	None	None	N
V/H	0.451	ambiguous	0.5173	ambiguous	-1.917	Destabilizing	0.439	N	0.739	deleterious	None	None	None	None	N
V/I	0.0607	likely_benign	0.0644	benign	-0.345	Destabilizing	None	N	0.219	neutral	N	0.421584186	None	None	N
V/K	0.4346	ambiguous	0.4809	ambiguous	-1.462	Destabilizing	0.035	N	0.683	prob.neutral	None	None	None	None	N
V/L	0.0954	likely_benign	0.1086	benign	-0.345	Destabilizing	0.001	N	0.529	neutral	N	0.369405927	None	None	N
V/M	0.0946	likely_benign	0.1114	benign	-0.224	Destabilizing	0.112	N	0.599	neutral	None	None	None	None	N
V/N	0.1741	likely_benign	0.224	benign	-1.612	Destabilizing	0.035	N	0.725	deleterious	None	None	None	None	N
V/P	0.6117	likely_pathogenic	0.7333	pathogenic	-0.736	Destabilizing	0.068	N	0.735	deleterious	None	None	None	None	N
V/Q	0.3477	ambiguous	0.3989	ambiguous	-1.539	Destabilizing	0.204	N	0.737	deleterious	None	None	None	None	N
V/R	0.4151	ambiguous	0.4405	ambiguous	-1.223	Destabilizing	0.112	N	0.783	deleterious	None	None	None	None	N
V/S	0.117	likely_benign	0.1459	benign	-2.118	Highly Destabilizing	0.001	N	0.566	neutral	None	None	None	None	N
V/T	0.1076	likely_benign	0.1248	benign	-1.833	Destabilizing	None	N	0.267	neutral	None	None	None	None	N
V/W	0.7043	likely_pathogenic	0.7639	pathogenic	-1.51	Destabilizing	0.747	D	0.757	deleterious	None	None	None	None	N
V/Y	0.4098	ambiguous	0.4747	ambiguous	-1.063	Destabilizing	0.204	N	0.731	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.