TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4880	14863;14864;14865	chr2:178735808;178735807;178735806	chr2:179600535;179600534;179600533
N2AB	4563	13912;13913;13914	chr2:178735808;178735807;178735806	chr2:179600535;179600534;179600533
N2A	3636	11131;11132;11133	chr2:178735808;178735807;178735806	chr2:179600535;179600534;179600533
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-31
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.119
• 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
A/V	rs373683445	0.056	0.669	N	0.609	0.372	None	gnomAD-2.1.1	4.29E-05	None	None	None	None	I	None	4.96032E-04	0	None	0	0	None	0	None	0	0	0
A/V	rs373683445	0.056	0.669	N	0.609	0.372	None	gnomAD-3.1.2	1.31427E-04	None	None	None	None	I	None	4.58494E-04	6.55E-05	0	0	0	None	0	0	0	0	0
A/V	rs373683445	0.056	0.669	N	0.609	0.372	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	8E-04	0	None	None	0	0	None	None	None	0	None
A/V	rs373683445	0.056	0.669	N	0.609	0.372	None	gnomAD-4.0.0	2.54071E-05	None	None	None	None	I	None	4.79744E-04	3.33344E-05	None	0	0	None	0	0	0	0	4.80307E-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
A/C	0.7833	likely_pathogenic	0.7054	pathogenic	-1.013	Destabilizing	0.998	D	0.673	neutral	None	None	None	None	I
A/D	0.8312	likely_pathogenic	0.8216	pathogenic	-1.533	Destabilizing	0.949	D	0.766	deleterious	None	None	None	None	I
A/E	0.8267	likely_pathogenic	0.8182	pathogenic	-1.459	Destabilizing	0.801	D	0.73	prob.delet.	D	0.704471673	None	None	I
A/F	0.8967	likely_pathogenic	0.8477	pathogenic	-0.868	Destabilizing	0.949	D	0.77	deleterious	None	None	None	None	I
A/G	0.1687	likely_benign	0.1547	benign	-1.384	Destabilizing	0.669	D	0.616	neutral	N	0.521381682	None	None	I
A/H	0.9511	likely_pathogenic	0.942	pathogenic	-1.692	Destabilizing	0.998	D	0.727	prob.delet.	None	None	None	None	I
A/I	0.8204	likely_pathogenic	0.7313	pathogenic	-0.058	Destabilizing	0.728	D	0.742	deleterious	None	None	None	None	I
A/K	0.9582	likely_pathogenic	0.9553	pathogenic	-1.195	Destabilizing	0.842	D	0.721	prob.delet.	None	None	None	None	I
A/L	0.7334	likely_pathogenic	0.6483	pathogenic	-0.058	Destabilizing	0.525	D	0.632	neutral	None	None	None	None	I
A/M	0.6752	likely_pathogenic	0.5724	pathogenic	-0.111	Destabilizing	0.525	D	0.565	neutral	None	None	None	None	I
A/N	0.8107	likely_pathogenic	0.7669	pathogenic	-1.114	Destabilizing	0.949	D	0.772	deleterious	None	None	None	None	I
A/P	0.9752	likely_pathogenic	0.9768	pathogenic	-0.328	Destabilizing	0.966	D	0.765	deleterious	D	0.704928236	None	None	I
A/Q	0.8823	likely_pathogenic	0.8708	pathogenic	-1.113	Destabilizing	0.974	D	0.753	deleterious	None	None	None	None	I
A/R	0.922	likely_pathogenic	0.9253	pathogenic	-1.072	Destabilizing	0.949	D	0.761	deleterious	None	None	None	None	I
A/S	0.1607	likely_benign	0.145	benign	-1.557	Destabilizing	0.051	N	0.267	neutral	N	0.521893759	None	None	I
A/T	0.202	likely_benign	0.1485	benign	-1.365	Destabilizing	0.022	N	0.173	neutral	N	0.520384463	None	None	I
A/V	0.4409	ambiguous	0.3601	ambiguous	-0.328	Destabilizing	0.669	D	0.609	neutral	N	0.51015592	None	None	I
A/W	0.981	likely_pathogenic	0.975	pathogenic	-1.41	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	I
A/Y	0.9361	likely_pathogenic	0.9172	pathogenic	-0.916	Destabilizing	0.991	D	0.744	deleterious	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.