TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9679	29260;29261;29262	chr2:178707532;178707531;178707530	chr2:179572259;179572258;179572257
N2AB	9362	28309;28310;28311	chr2:178707532;178707531;178707530	chr2:179572259;179572258;179572257
N2A	8435	25528;25529;25530	chr2:178707532;178707531;178707530	chr2:179572259;179572258;179572257
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-82
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.3619
• 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
I/T	rs749610242	-1.232	0.051	None	0.519	0.539	0.655038028955	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
I/T	rs749610242	-1.232	0.051	None	0.519	0.539	0.655038028955	gnomAD-4.0.0	4.79419E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.3023E-06	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
I/A	0.7543	likely_pathogenic	0.7014	pathogenic	-2.015	Highly Destabilizing	0.525	D	0.567	neutral	None	None	None	None	N
I/C	0.8971	likely_pathogenic	0.8892	pathogenic	-1.662	Destabilizing	0.998	D	0.628	neutral	None	None	None	None	N
I/D	0.9912	likely_pathogenic	0.9862	pathogenic	-2.237	Highly Destabilizing	0.974	D	0.662	neutral	None	None	None	None	N
I/E	0.9788	likely_pathogenic	0.9664	pathogenic	-2.198	Highly Destabilizing	0.974	D	0.663	neutral	None	None	None	None	N
I/F	0.4432	ambiguous	0.4324	ambiguous	-1.512	Destabilizing	0.966	D	0.473	neutral	None	None	None	None	N
I/G	0.9461	likely_pathogenic	0.93	pathogenic	-2.362	Highly Destabilizing	0.915	D	0.667	neutral	None	None	None	None	N
I/H	0.9672	likely_pathogenic	0.9544	pathogenic	-1.568	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
I/K	0.9555	likely_pathogenic	0.9269	pathogenic	-1.381	Destabilizing	0.974	D	0.661	neutral	None	None	None	None	N
I/L	0.2504	likely_benign	0.2306	benign	-1.098	Destabilizing	0.267	N	0.463	neutral	None	None	None	None	N
I/M	0.2773	likely_benign	0.2482	benign	-1.044	Destabilizing	0.966	D	0.531	neutral	None	None	None	None	N
I/N	0.9022	likely_pathogenic	0.8616	pathogenic	-1.38	Destabilizing	0.966	D	0.683	prob.neutral	None	None	None	None	N
I/P	0.9465	likely_pathogenic	0.9403	pathogenic	-1.377	Destabilizing	0.991	D	0.68	prob.neutral	None	None	None	None	N
I/Q	0.9574	likely_pathogenic	0.935	pathogenic	-1.589	Destabilizing	0.991	D	0.7	prob.neutral	None	None	None	None	N
I/R	0.9249	likely_pathogenic	0.8826	pathogenic	-0.817	Destabilizing	0.974	D	0.701	prob.neutral	None	None	None	None	N
I/S	0.8384	likely_pathogenic	0.7847	pathogenic	-1.981	Destabilizing	0.669	D	0.587	neutral	None	None	None	None	N
I/T	0.7602	likely_pathogenic	0.7045	pathogenic	-1.828	Destabilizing	0.051	N	0.519	neutral	None	None	None	None	N
I/V	0.0692	likely_benign	0.0733	benign	-1.377	Destabilizing	0.005	N	0.337	neutral	None	None	None	None	N
I/W	0.9714	likely_pathogenic	0.9651	pathogenic	-1.621	Destabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	N
I/Y	0.9003	likely_pathogenic	0.8823	pathogenic	-1.367	Destabilizing	0.991	D	0.617	neutral	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.