TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25968	78127;78128;78129	chr2:178568230;178568229;178568228	chr2:179432957;179432956;179432955
N2AB	24327	73204;73205;73206	chr2:178568230;178568229;178568228	chr2:179432957;179432956;179432955
N2A	23400	70423;70424;70425	chr2:178568230;178568229;178568228	chr2:179432957;179432956;179432955
N2B	16903	50932;50933;50934	chr2:178568230;178568229;178568228	chr2:179432957;179432956;179432955
Novex-1	17028	51307;51308;51309	chr2:178568230;178568229;178568228	chr2:179432957;179432956;179432955
Novex-2	17095	51508;51509;51510	chr2:178568230;178568229;178568228	chr2:179432957;179432956;179432955
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-76
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.2294
• 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	rs756933390	-0.181	1.0	N	0.548	0.327	None	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	0	0	None	0	1.67168E-04	None	0	None	0	8.88E-06	0
E/K	rs756933390	-0.181	1.0	N	0.548	0.327	None	gnomAD-4.0.0	1.98445E-05	None	None	None	None	I	None	0	0	None	0	7.56048E-05	None	0	0	2.33892E-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	0.4115	ambiguous	0.396	ambiguous	-0.646	Destabilizing	0.999	D	0.679	prob.neutral	N	0.482343015	None	None	I
E/C	0.9474	likely_pathogenic	0.9379	pathogenic	-0.505	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	I
E/D	0.8532	likely_pathogenic	0.8629	pathogenic	-1.428	Destabilizing	0.999	D	0.465	neutral	N	0.503298107	None	None	I
E/F	0.9691	likely_pathogenic	0.9707	pathogenic	-0.933	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	I
E/G	0.6151	likely_pathogenic	0.6189	pathogenic	-0.965	Destabilizing	1.0	D	0.773	deleterious	D	0.532758667	None	None	I
E/H	0.8972	likely_pathogenic	0.9061	pathogenic	-1.194	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
E/I	0.7383	likely_pathogenic	0.6616	pathogenic	0.206	Stabilizing	1.0	D	0.891	deleterious	None	None	None	None	I
E/K	0.4354	ambiguous	0.4574	ambiguous	-0.653	Destabilizing	1.0	D	0.548	neutral	N	0.480888211	None	None	I
E/L	0.8574	likely_pathogenic	0.8439	pathogenic	0.206	Stabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
E/M	0.7562	likely_pathogenic	0.7123	pathogenic	0.677	Stabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
E/N	0.8365	likely_pathogenic	0.8426	pathogenic	-0.929	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
E/P	0.9984	likely_pathogenic	0.9981	pathogenic	-0.056	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
E/Q	0.1989	likely_benign	0.1944	benign	-0.812	Destabilizing	1.0	D	0.63	neutral	N	0.473050625	None	None	I
E/R	0.6125	likely_pathogenic	0.6313	pathogenic	-0.68	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
E/S	0.5618	ambiguous	0.5512	ambiguous	-1.321	Destabilizing	0.999	D	0.608	neutral	None	None	None	None	I
E/T	0.5998	likely_pathogenic	0.5434	ambiguous	-1.037	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
E/V	0.4935	ambiguous	0.4104	ambiguous	-0.056	Destabilizing	1.0	D	0.841	deleterious	N	0.477125251	None	None	I
E/W	0.993	likely_pathogenic	0.993	pathogenic	-1.065	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
E/Y	0.9642	likely_pathogenic	0.9644	pathogenic	-0.74	Destabilizing	1.0	D	0.862	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.