TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6839	20740;20741;20742	chr2:178725807;178725806;178725805	chr2:179590534;179590533;179590532
N2AB	6522	19789;19790;19791	chr2:178725807;178725806;178725805	chr2:179590534;179590533;179590532
N2A	5595	17008;17009;17010	chr2:178725807;178725806;178725805	chr2:179590534;179590533;179590532
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: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-52
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.8407
• 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	0.673	N	0.567	0.294	0.398727352345	gnomAD-4.0.0	1.60088E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.03638E-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	0.2829	likely_benign	0.2485	benign	-0.398	Destabilizing	0.301	N	0.409	neutral	N	0.499906976	None	None	I
V/C	0.9371	likely_pathogenic	0.9325	pathogenic	-0.864	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	I
V/D	0.938	likely_pathogenic	0.9523	pathogenic	-0.456	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	I
V/E	0.8643	likely_pathogenic	0.8958	pathogenic	-0.575	Destabilizing	0.989	D	0.659	neutral	N	0.489406221	None	None	I
V/F	0.39	ambiguous	0.444	ambiguous	-0.808	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	I
V/G	0.622	likely_pathogenic	0.5632	ambiguous	-0.436	Destabilizing	0.997	D	0.62	neutral	N	0.496786053	None	None	I
V/H	0.9435	likely_pathogenic	0.9574	pathogenic	-0.042	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
V/I	0.1591	likely_benign	0.1609	benign	-0.431	Destabilizing	0.847	D	0.525	neutral	None	None	None	None	I
V/K	0.954	likely_pathogenic	0.9615	pathogenic	-0.447	Destabilizing	0.996	D	0.661	neutral	None	None	None	None	I
V/L	0.6691	likely_pathogenic	0.7194	pathogenic	-0.431	Destabilizing	0.673	D	0.567	neutral	N	0.512086839	None	None	I
V/M	0.4953	ambiguous	0.527	ambiguous	-0.656	Destabilizing	0.999	D	0.664	neutral	N	0.499775021	None	None	I
V/N	0.8466	likely_pathogenic	0.8651	pathogenic	-0.25	Destabilizing	0.992	D	0.699	prob.neutral	None	None	None	None	I
V/P	0.9819	likely_pathogenic	0.9831	pathogenic	-0.395	Destabilizing	0.975	D	0.673	neutral	None	None	None	None	I
V/Q	0.9078	likely_pathogenic	0.9302	pathogenic	-0.466	Destabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	I
V/R	0.9027	likely_pathogenic	0.9202	pathogenic	0.005	Stabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	I
V/S	0.5798	likely_pathogenic	0.5658	pathogenic	-0.546	Destabilizing	0.987	D	0.587	neutral	None	None	None	None	I
V/T	0.4079	ambiguous	0.3817	ambiguous	-0.58	Destabilizing	0.945	D	0.617	neutral	None	None	None	None	I
V/W	0.9633	likely_pathogenic	0.9735	pathogenic	-0.845	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
V/Y	0.842	likely_pathogenic	0.876	pathogenic	-0.592	Destabilizing	0.999	D	0.66	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.