TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14254	42985;42986;42987	chr2:178633599;178633598;178633597	chr2:179498326;179498325;179498324
N2AB	12613	38062;38063;38064	chr2:178633599;178633598;178633597	chr2:179498326;179498325;179498324
N2A	11686	35281;35282;35283	chr2:178633599;178633598;178633597	chr2:179498326;179498325;179498324
N2B	5189	15790;15791;15792	chr2:178633599;178633598;178633597	chr2:179498326;179498325;179498324
Novex-1	5314	16165;16166;16167	chr2:178633599;178633598;178633597	chr2:179498326;179498325;179498324
Novex-2	5381	16366;16367;16368	chr2:178633599;178633598;178633597	chr2:179498326;179498325;179498324
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-93
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1136
• 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/E	rs1342186371	None	0.896	D	0.77	0.664	0.874471701311	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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	0.5749	likely_pathogenic	0.5945	pathogenic	-2.414	Highly Destabilizing	0.334	N	0.568	neutral	D	0.530560139	None	None	N
V/C	0.8897	likely_pathogenic	0.9098	pathogenic	-1.825	Destabilizing	0.992	D	0.752	deleterious	None	None	None	None	N
V/D	0.9585	likely_pathogenic	0.9673	pathogenic	-3.087	Highly Destabilizing	0.972	D	0.811	deleterious	None	None	None	None	N
V/E	0.9139	likely_pathogenic	0.9329	pathogenic	-2.845	Highly Destabilizing	0.896	D	0.77	deleterious	D	0.760087314	None	None	N
V/F	0.5832	likely_pathogenic	0.6833	pathogenic	-1.305	Destabilizing	0.447	N	0.737	prob.delet.	None	None	None	None	N
V/G	0.6352	likely_pathogenic	0.6682	pathogenic	-2.923	Highly Destabilizing	0.896	D	0.769	deleterious	D	0.684974353	None	None	N
V/H	0.9729	likely_pathogenic	0.9805	pathogenic	-2.59	Highly Destabilizing	0.992	D	0.793	deleterious	None	None	None	None	N
V/I	0.1016	likely_benign	0.1105	benign	-0.956	Destabilizing	0.127	N	0.491	neutral	None	None	None	None	N
V/K	0.9282	likely_pathogenic	0.9467	pathogenic	-1.794	Destabilizing	0.766	D	0.748	deleterious	None	None	None	None	N
V/L	0.1397	likely_benign	0.1791	benign	-0.956	Destabilizing	0.001	N	0.23	neutral	N	0.456430665	None	None	N
V/M	0.3471	ambiguous	0.3865	ambiguous	-1.157	Destabilizing	0.81	D	0.665	neutral	D	0.646780689	None	None	N
V/N	0.8568	likely_pathogenic	0.8854	pathogenic	-2.217	Highly Destabilizing	0.972	D	0.811	deleterious	None	None	None	None	N
V/P	0.9512	likely_pathogenic	0.9642	pathogenic	-1.423	Destabilizing	0.972	D	0.786	deleterious	None	None	None	None	N
V/Q	0.9136	likely_pathogenic	0.9353	pathogenic	-2.004	Highly Destabilizing	0.972	D	0.789	deleterious	None	None	None	None	N
V/R	0.8953	likely_pathogenic	0.9292	pathogenic	-1.679	Destabilizing	0.92	D	0.809	deleterious	None	None	None	None	N
V/S	0.8137	likely_pathogenic	0.8329	pathogenic	-2.758	Highly Destabilizing	0.766	D	0.72	prob.delet.	None	None	None	None	N
V/T	0.5394	ambiguous	0.5814	pathogenic	-2.389	Highly Destabilizing	0.617	D	0.613	neutral	None	None	None	None	N
V/W	0.9789	likely_pathogenic	0.9871	pathogenic	-1.813	Destabilizing	0.992	D	0.795	deleterious	None	None	None	None	N
V/Y	0.9145	likely_pathogenic	0.9458	pathogenic	-1.553	Destabilizing	0.92	D	0.773	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.