TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16938	51037;51038;51039	chr2:178611417;178611416;178611415	chr2:179476144;179476143;179476142
N2AB	15297	46114;46115;46116	chr2:178611417;178611416;178611415	chr2:179476144;179476143;179476142
N2A	14370	43333;43334;43335	chr2:178611417;178611416;178611415	chr2:179476144;179476143;179476142
N2B	7873	23842;23843;23844	chr2:178611417;178611416;178611415	chr2:179476144;179476143;179476142
Novex-1	7998	24217;24218;24219	chr2:178611417;178611416;178611415	chr2:179476144;179476143;179476142
Novex-2	8065	24418;24419;24420	chr2:178611417;178611416;178611415	chr2:179476144;179476143;179476142
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: Fn3-11
• Domain position: 87
• Structural Position: 119
• Q(SASA): 0.5249
• 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/D	rs779893350	-0.342	0.006	N	0.205	0.046	0.0611884634855	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
E/D	rs779893350	-0.342	0.006	N	0.205	0.046	0.0611884634855	gnomAD-4.0.0	1.59317E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86139E-06	0	0
E/K	rs72677250	0.315	0.963	N	0.592	0.244	0.355865052028	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs72677250	0.315	0.963	N	0.592	0.244	0.355865052028	gnomAD-4.0.0	1.23223E-05	None	None	None	None	I	None	0	2.23794E-05	None	3.83083E-05	0	None	0	0	1.16973E-05	3.47891E-05	0
E/Q	rs72677250	-0.084	0.976	N	0.655	0.248	0.280987212366	gnomAD-2.1.1	2.87E-05	None	None	None	None	I	None	0	2.83E-05	None	0	0	None	0	None	0	5.5E-05	0
E/Q	rs72677250	-0.084	0.976	N	0.655	0.248	0.280987212366	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	4.42E-05	0	0
E/Q	rs72677250	-0.084	0.976	N	0.655	0.248	0.280987212366	gnomAD-4.0.0	1.61216E-05	None	None	None	None	I	None	0	1.66828E-05	None	0	0	None	0	0	2.1199E-05	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
E/A	0.1817	likely_benign	0.3668	ambiguous	-0.644	Destabilizing	0.822	D	0.639	neutral	N	0.481693036	None	None	I
E/C	0.8522	likely_pathogenic	0.964	pathogenic	-0.248	Destabilizing	0.998	D	0.768	deleterious	None	None	None	None	I
E/D	0.0675	likely_benign	0.1203	benign	-0.582	Destabilizing	0.006	N	0.205	neutral	N	0.459938237	None	None	I
E/F	0.768	likely_pathogenic	0.9299	pathogenic	-0.411	Destabilizing	0.998	D	0.725	prob.delet.	None	None	None	None	I
E/G	0.2237	likely_benign	0.4698	ambiguous	-0.873	Destabilizing	0.822	D	0.631	neutral	D	0.546621772	None	None	I
E/H	0.5321	ambiguous	0.8121	pathogenic	-0.229	Destabilizing	0.998	D	0.606	neutral	None	None	None	None	I
E/I	0.4073	ambiguous	0.7113	pathogenic	-0.061	Destabilizing	0.978	D	0.745	deleterious	None	None	None	None	I
E/K	0.234	likely_benign	0.4373	ambiguous	None	Stabilizing	0.963	D	0.592	neutral	N	0.482816403	None	None	I
E/L	0.3714	ambiguous	0.6878	pathogenic	-0.061	Destabilizing	0.978	D	0.733	prob.delet.	None	None	None	None	I
E/M	0.5198	ambiguous	0.7646	pathogenic	0.11	Stabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	I
E/N	0.2262	likely_benign	0.503	ambiguous	-0.373	Destabilizing	0.915	D	0.649	neutral	None	None	None	None	I
E/P	0.3774	ambiguous	0.7247	pathogenic	-0.235	Destabilizing	0.978	D	0.703	prob.neutral	None	None	None	None	I
E/Q	0.1931	likely_benign	0.3613	ambiguous	-0.331	Destabilizing	0.976	D	0.655	neutral	N	0.482818545	None	None	I
E/R	0.3848	ambiguous	0.6434	pathogenic	0.29	Stabilizing	0.978	D	0.654	neutral	None	None	None	None	I
E/S	0.2075	likely_benign	0.4381	ambiguous	-0.548	Destabilizing	0.86	D	0.593	neutral	None	None	None	None	I
E/T	0.2916	likely_benign	0.5653	pathogenic	-0.363	Destabilizing	0.956	D	0.661	neutral	None	None	None	None	I
E/V	0.2563	likely_benign	0.4912	ambiguous	-0.235	Destabilizing	0.971	D	0.716	prob.delet.	N	0.481864881	None	None	I
E/W	0.9163	likely_pathogenic	0.9809	pathogenic	-0.199	Destabilizing	0.998	D	0.756	deleterious	None	None	None	None	I
E/Y	0.6247	likely_pathogenic	0.8684	pathogenic	-0.165	Destabilizing	0.998	D	0.726	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.