TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22033	66322;66323;66324	chr2:178582359;178582358;178582357	chr2:179447086;179447085;179447084
N2AB	20392	61399;61400;61401	chr2:178582359;178582358;178582357	chr2:179447086;179447085;179447084
N2A	19465	58618;58619;58620	chr2:178582359;178582358;178582357	chr2:179447086;179447085;179447084
N2B	12968	39127;39128;39129	chr2:178582359;178582358;178582357	chr2:179447086;179447085;179447084
Novex-1	13093	39502;39503;39504	chr2:178582359;178582358;178582357	chr2:179447086;179447085;179447084
Novex-2	13160	39703;39704;39705	chr2:178582359;178582358;178582357	chr2:179447086;179447085;179447084
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: Fn3-47
• Domain position: 78
• Structural Position: 111
• Q(SASA): 0.2756
• 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	rs768277403	-1.395	0.998	N	0.413	0.294	0.250039746154	gnomAD-2.1.1	3.24E-05	None	None	None	None	I	None	0	0	None	0	0	None	2.65869E-04	None	0	0	0
E/D	rs768277403	-1.395	0.998	N	0.413	0.294	0.250039746154	gnomAD-4.0.0	1.30303E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.09952E-04	1.66107E-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	0.5682	likely_pathogenic	0.5334	ambiguous	-0.724	Destabilizing	0.996	D	0.554	neutral	N	0.467201275	None	None	I
E/C	0.9634	likely_pathogenic	0.9575	pathogenic	-0.632	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
E/D	0.9496	likely_pathogenic	0.9447	pathogenic	-1.454	Destabilizing	0.998	D	0.413	neutral	N	0.492764722	None	None	I
E/F	0.9864	likely_pathogenic	0.9853	pathogenic	-1.032	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
E/G	0.8449	likely_pathogenic	0.833	pathogenic	-1.057	Destabilizing	0.999	D	0.72	prob.delet.	N	0.501158513	None	None	I
E/H	0.9627	likely_pathogenic	0.9574	pathogenic	-1.303	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	I
E/I	0.726	likely_pathogenic	0.7021	pathogenic	0.175	Stabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
E/K	0.6197	likely_pathogenic	0.6022	pathogenic	-0.917	Destabilizing	0.767	D	0.309	neutral	N	0.472659004	None	None	I
E/L	0.9298	likely_pathogenic	0.9176	pathogenic	0.175	Stabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
E/M	0.8162	likely_pathogenic	0.7896	pathogenic	0.665	Stabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
E/N	0.9427	likely_pathogenic	0.9446	pathogenic	-1.157	Destabilizing	1.0	D	0.62	neutral	None	None	None	None	I
E/P	0.999	likely_pathogenic	0.9987	pathogenic	-0.103	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
E/Q	0.2231	likely_benign	0.2209	benign	-0.977	Destabilizing	0.996	D	0.531	neutral	N	0.49970104	None	None	I
E/R	0.751	likely_pathogenic	0.7317	pathogenic	-0.954	Destabilizing	0.998	D	0.623	neutral	None	None	None	None	I
E/S	0.7603	likely_pathogenic	0.7581	pathogenic	-1.602	Destabilizing	0.997	D	0.459	neutral	None	None	None	None	I
E/T	0.7505	likely_pathogenic	0.7415	pathogenic	-1.302	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
E/V	0.4045	ambiguous	0.3917	ambiguous	-0.103	Destabilizing	0.999	D	0.779	deleterious	N	0.415172715	None	None	I
E/W	0.9975	likely_pathogenic	0.9973	pathogenic	-1.242	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
E/Y	0.9863	likely_pathogenic	0.9834	pathogenic	-0.878	Destabilizing	1.0	D	0.815	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.