TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26715	80368;80369;80370	chr2:178565989;178565988;178565987	chr2:179430716;179430715;179430714
N2AB	25074	75445;75446;75447	chr2:178565989;178565988;178565987	chr2:179430716;179430715;179430714
N2A	24147	72664;72665;72666	chr2:178565989;178565988;178565987	chr2:179430716;179430715;179430714
N2B	17650	53173;53174;53175	chr2:178565989;178565988;178565987	chr2:179430716;179430715;179430714
Novex-1	17775	53548;53549;53550	chr2:178565989;178565988;178565987	chr2:179430716;179430715;179430714
Novex-2	17842	53749;53750;53751	chr2:178565989;178565988;178565987	chr2:179430716;179430715;179430714
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: Fn3-82
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.3632
• 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/F	rs1705694653	None	0.317	N	0.733	0.289	0.511503663882	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	1.93349E-04	None	0	0	0	0	0
V/F	rs1705694653	None	0.317	N	0.733	0.289	0.511503663882	gnomAD-4.0.0	2.56306E-06	None	None	None	None	I	None	0	0	None	0	2.42624E-05	None	0	0	0	0	2.84576E-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	0.9033	likely_pathogenic	0.9078	pathogenic	-2.049	Highly Destabilizing	0.052	N	0.569	neutral	N	0.491767672	None	None	I
V/C	0.943	likely_pathogenic	0.9525	pathogenic	-1.226	Destabilizing	0.935	D	0.695	prob.neutral	None	None	None	None	I
V/D	0.9933	likely_pathogenic	0.9926	pathogenic	-2.463	Highly Destabilizing	0.484	N	0.785	deleterious	N	0.477017552	None	None	I
V/E	0.9761	likely_pathogenic	0.9769	pathogenic	-2.386	Highly Destabilizing	0.555	D	0.753	deleterious	None	None	None	None	I
V/F	0.8406	likely_pathogenic	0.8354	pathogenic	-1.475	Destabilizing	0.317	N	0.733	prob.delet.	N	0.507844011	None	None	I
V/G	0.9167	likely_pathogenic	0.9145	pathogenic	-2.452	Highly Destabilizing	0.484	N	0.788	deleterious	N	0.510885885	None	None	I
V/H	0.9934	likely_pathogenic	0.9934	pathogenic	-2.152	Highly Destabilizing	0.935	D	0.765	deleterious	None	None	None	None	I
V/I	0.0678	likely_benign	0.0652	benign	-0.976	Destabilizing	None	N	0.15	neutral	N	0.3585915	None	None	I
V/K	0.9848	likely_pathogenic	0.9848	pathogenic	-1.773	Destabilizing	0.555	D	0.751	deleterious	None	None	None	None	I
V/L	0.4542	ambiguous	0.4393	ambiguous	-0.976	Destabilizing	0.004	N	0.319	neutral	N	0.50280006	None	None	I
V/M	0.5736	likely_pathogenic	0.5759	pathogenic	-0.61	Destabilizing	0.38	N	0.665	neutral	None	None	None	None	I
V/N	0.9621	likely_pathogenic	0.9561	pathogenic	-1.671	Destabilizing	0.791	D	0.8	deleterious	None	None	None	None	I
V/P	0.8793	likely_pathogenic	0.8854	pathogenic	-1.305	Destabilizing	0.791	D	0.763	deleterious	None	None	None	None	I
V/Q	0.977	likely_pathogenic	0.9777	pathogenic	-1.754	Destabilizing	0.791	D	0.764	deleterious	None	None	None	None	I
V/R	0.9788	likely_pathogenic	0.9784	pathogenic	-1.285	Destabilizing	0.555	D	0.795	deleterious	None	None	None	None	I
V/S	0.9538	likely_pathogenic	0.9487	pathogenic	-2.166	Highly Destabilizing	0.555	D	0.763	deleterious	None	None	None	None	I
V/T	0.8949	likely_pathogenic	0.8951	pathogenic	-1.984	Destabilizing	0.149	N	0.603	neutral	None	None	None	None	I
V/W	0.9926	likely_pathogenic	0.993	pathogenic	-1.867	Destabilizing	0.935	D	0.773	deleterious	None	None	None	None	I
V/Y	0.9737	likely_pathogenic	0.9747	pathogenic	-1.582	Destabilizing	0.555	D	0.721	prob.delet.	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.