TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6615	20068;20069;20070	chr2:178727735;178727734;178727733	chr2:179592462;179592461;179592460
N2AB	6298	19117;19118;19119	chr2:178727735;178727734;178727733	chr2:179592462;179592461;179592460
N2A	5371	16336;16337;16338	chr2:178727735;178727734;178727733	chr2:179592462;179592461;179592460
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: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-50
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.6976
• Predicted PPI site: I

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/L	None	None	None	N	0.093	0.066	0.443388199986	gnomAD-4.0.0	8.21269E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99698E-06	0	3.31422E-05

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	0.0739	likely_benign	0.0806	benign	-0.334	Destabilizing	None	N	0.078	neutral	N	0.484956166	None	None	I
V/C	0.4922	ambiguous	0.5138	ambiguous	-0.749	Destabilizing	0.356	N	0.318	neutral	None	None	None	None	I
V/D	0.1353	likely_benign	0.1366	benign	-0.225	Destabilizing	0.029	N	0.413	neutral	D	0.527477579	None	None	I
V/E	0.1248	likely_benign	0.127	benign	-0.33	Destabilizing	None	N	0.227	neutral	None	None	None	None	I
V/F	0.1037	likely_benign	0.1022	benign	-0.618	Destabilizing	0.171	N	0.374	neutral	D	0.531576677	None	None	I
V/G	0.0987	likely_benign	0.1055	benign	-0.422	Destabilizing	0.029	N	0.395	neutral	N	0.520012889	None	None	I
V/H	0.2611	likely_benign	0.2722	benign	0.031	Stabilizing	0.356	N	0.328	neutral	None	None	None	None	I
V/I	0.0723	likely_benign	0.0767	benign	-0.244	Destabilizing	0.001	N	0.177	neutral	N	0.520455606	None	None	I
V/K	0.1546	likely_benign	0.1544	benign	-0.368	Destabilizing	0.038	N	0.395	neutral	None	None	None	None	I
V/L	0.096	likely_benign	0.0954	benign	-0.244	Destabilizing	None	N	0.093	neutral	N	0.484457521	None	None	I
V/M	0.1044	likely_benign	0.1161	benign	-0.53	Destabilizing	0.003	N	0.157	neutral	None	None	None	None	I
V/N	0.111	likely_benign	0.1186	benign	-0.178	Destabilizing	0.072	N	0.417	neutral	None	None	None	None	I
V/P	0.1466	likely_benign	0.1546	benign	-0.244	Destabilizing	0.214	N	0.387	neutral	None	None	None	None	I
V/Q	0.1439	likely_benign	0.1438	benign	-0.369	Destabilizing	0.12	N	0.389	neutral	None	None	None	None	I
V/R	0.1445	likely_benign	0.134	benign	0.074	Stabilizing	0.214	N	0.405	neutral	None	None	None	None	I
V/S	0.0846	likely_benign	0.0913	benign	-0.513	Destabilizing	0.003	N	0.191	neutral	None	None	None	None	I
V/T	0.0865	likely_benign	0.0978	benign	-0.52	Destabilizing	None	N	0.139	neutral	None	None	None	None	I
V/W	0.5424	ambiguous	0.5538	ambiguous	-0.689	Destabilizing	0.864	D	0.352	neutral	None	None	None	None	I
V/Y	0.2811	likely_benign	0.2896	benign	-0.408	Destabilizing	0.356	N	0.346	neutral	None	None	None	None	I

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.