TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31173	93742;93743;93744	chr2:178548109;178548108;178548107	chr2:179412836;179412835;179412834
N2AB	29532	88819;88820;88821	chr2:178548109;178548108;178548107	chr2:179412836;179412835;179412834
N2A	28605	86038;86039;86040	chr2:178548109;178548108;178548107	chr2:179412836;179412835;179412834
N2B	22108	66547;66548;66549	chr2:178548109;178548108;178548107	chr2:179412836;179412835;179412834
Novex-1	22233	66922;66923;66924	chr2:178548109;178548108;178548107	chr2:179412836;179412835;179412834
Novex-2	22300	67123;67124;67125	chr2:178548109;178548108;178548107	chr2:179412836;179412835;179412834
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-115
• Domain position: 61
• Structural Position: 93
• Q(SASA): 0.1085
• 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	rs1440743167	0.027	0.026	N	0.275	0.07	0.361758802978	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	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
V/A	0.1893	likely_benign	0.2619	benign	-1.795	Destabilizing	0.896	D	0.663	neutral	D	0.52639457	None	None	N
V/C	0.7954	likely_pathogenic	0.8513	pathogenic	-1.368	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
V/D	0.9439	likely_pathogenic	0.9582	pathogenic	-1.716	Destabilizing	0.996	D	0.819	deleterious	None	None	None	None	N
V/E	0.8705	likely_pathogenic	0.9022	pathogenic	-1.504	Destabilizing	0.995	D	0.783	deleterious	D	0.542124553	None	None	N
V/F	0.4549	ambiguous	0.548	ambiguous	-1.01	Destabilizing	0.976	D	0.749	deleterious	None	None	None	None	N
V/G	0.6221	likely_pathogenic	0.6853	pathogenic	-2.334	Highly Destabilizing	0.995	D	0.815	deleterious	D	0.542124553	None	None	N
V/H	0.9418	likely_pathogenic	0.9599	pathogenic	-1.932	Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
V/I	0.0844	likely_benign	0.0912	benign	-0.309	Destabilizing	0.026	N	0.275	neutral	N	0.504072284	None	None	N
V/K	0.8864	likely_pathogenic	0.9115	pathogenic	-1.371	Destabilizing	0.988	D	0.785	deleterious	None	None	None	None	N
V/L	0.2495	likely_benign	0.3067	benign	-0.309	Destabilizing	0.011	N	0.297	neutral	N	0.512456907	None	None	N
V/M	0.2244	likely_benign	0.2755	benign	-0.408	Destabilizing	0.976	D	0.669	neutral	None	None	None	None	N
V/N	0.8623	likely_pathogenic	0.9082	pathogenic	-1.607	Destabilizing	0.996	D	0.828	deleterious	None	None	None	None	N
V/P	0.9083	likely_pathogenic	0.9345	pathogenic	-0.775	Destabilizing	0.996	D	0.775	deleterious	None	None	None	None	N
V/Q	0.8503	likely_pathogenic	0.8893	pathogenic	-1.431	Destabilizing	0.996	D	0.791	deleterious	None	None	None	None	N
V/R	0.8479	likely_pathogenic	0.8723	pathogenic	-1.294	Destabilizing	0.996	D	0.817	deleterious	None	None	None	None	N
V/S	0.5602	ambiguous	0.6653	pathogenic	-2.33	Highly Destabilizing	0.988	D	0.783	deleterious	None	None	None	None	N
V/T	0.3209	likely_benign	0.4096	ambiguous	-1.951	Destabilizing	0.919	D	0.656	neutral	None	None	None	None	N
V/W	0.9575	likely_pathogenic	0.9711	pathogenic	-1.391	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
V/Y	0.8842	likely_pathogenic	0.9195	pathogenic	-1.0	Destabilizing	0.996	D	0.727	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.