TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23776	71551;71552;71553	chr2:178574806;178574805;178574804	chr2:179439533;179439532;179439531
N2AB	22135	66628;66629;66630	chr2:178574806;178574805;178574804	chr2:179439533;179439532;179439531
N2A	21208	63847;63848;63849	chr2:178574806;178574805;178574804	chr2:179439533;179439532;179439531
N2B	14711	44356;44357;44358	chr2:178574806;178574805;178574804	chr2:179439533;179439532;179439531
Novex-1	14836	44731;44732;44733	chr2:178574806;178574805;178574804	chr2:179439533;179439532;179439531
Novex-2	14903	44932;44933;44934	chr2:178574806;178574805;178574804	chr2:179439533;179439532;179439531
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-60
• Domain position: 51
• Structural Position: 67
• Q(SASA): 0.6426
• 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
E/K	rs746336948	0.43	0.999	N	0.664	0.354	None	gnomAD-2.1.1	1.22E-05	None	None	None	None	I	None	1.29618E-04	0	None	0	0	None	0	None	0	8.99E-06	0
E/K	rs746336948	0.43	0.999	N	0.664	0.354	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs746336948	0.43	0.999	N	0.664	0.354	None	gnomAD-4.0.0	8.98673E-06	None	None	None	None	I	None	5.07752E-05	1.69681E-05	None	0	0	None	0	0	4.79683E-06	0	2.85144E-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
E/A	0.2189	likely_benign	0.2361	benign	-0.667	Destabilizing	0.999	D	0.715	prob.delet.	N	0.470634501	None	None	I
E/C	0.8605	likely_pathogenic	0.8856	pathogenic	-0.287	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
E/D	0.2798	likely_benign	0.2971	benign	-0.645	Destabilizing	0.999	D	0.515	neutral	N	0.495858232	None	None	I
E/F	0.9126	likely_pathogenic	0.922	pathogenic	-0.277	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
E/G	0.3714	ambiguous	0.4115	ambiguous	-0.94	Destabilizing	1.0	D	0.72	prob.delet.	N	0.513078556	None	None	I
E/H	0.7372	likely_pathogenic	0.7677	pathogenic	-0.202	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
E/I	0.4414	ambiguous	0.4784	ambiguous	0.046	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
E/K	0.4074	ambiguous	0.4263	ambiguous	-0.035	Destabilizing	0.999	D	0.664	neutral	N	0.448643075	None	None	I
E/L	0.5172	ambiguous	0.5608	ambiguous	0.046	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
E/M	0.5345	ambiguous	0.5636	ambiguous	0.242	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
E/N	0.4277	ambiguous	0.4541	ambiguous	-0.506	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
E/P	0.4195	ambiguous	0.4286	ambiguous	-0.171	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
E/Q	0.2124	likely_benign	0.2237	benign	-0.439	Destabilizing	1.0	D	0.661	neutral	N	0.455203688	None	None	I
E/R	0.5982	likely_pathogenic	0.6119	pathogenic	0.265	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
E/S	0.3255	likely_benign	0.3553	ambiguous	-0.707	Destabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	I
E/T	0.2753	likely_benign	0.3058	benign	-0.483	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
E/V	0.2597	likely_benign	0.2819	benign	-0.171	Destabilizing	1.0	D	0.773	deleterious	N	0.436887286	None	None	I
E/W	0.98	likely_pathogenic	0.9829	pathogenic	-0.023	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	I
E/Y	0.855	likely_pathogenic	0.8776	pathogenic	-0.015	Destabilizing	1.0	D	0.755	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.