TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2197	6814;6815;6816	chr2:178775122;178775121;178775120	chr2:179639849;179639848;179639847
N2AB	2197	6814;6815;6816	chr2:178775122;178775121;178775120	chr2:179639849;179639848;179639847
N2A	2197	6814;6815;6816	chr2:178775122;178775121;178775120	chr2:179639849;179639848;179639847
N2B	2151	6676;6677;6678	chr2:178775122;178775121;178775120	chr2:179639849;179639848;179639847
Novex-1	2151	6676;6677;6678	chr2:178775122;178775121;178775120	chr2:179639849;179639848;179639847
Novex-2	2151	6676;6677;6678	chr2:178775122;178775121;178775120	chr2:179639849;179639848;179639847
Novex-3	2197	6814;6815;6816	chr2:178775122;178775121;178775120	chr2:179639849;179639848;179639847

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-11
• Domain position: 24
• Structural Position: 34
• Q(SASA): 0.227
• Predicted PPI site: N

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	rs139329751	-0.752	0.999	D	0.527	0.476	0.494433119893	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs139329751	-0.752	0.999	D	0.527	0.476	0.494433119893	gnomAD-4.0.0	3.18157E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86541E-05	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	0.4036	ambiguous	0.4435	ambiguous	-0.56	Destabilizing	0.999	D	0.641	neutral	D	0.583699543	None	None	N
E/C	0.976	likely_pathogenic	0.9782	pathogenic	-0.471	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/D	0.6655	likely_pathogenic	0.7077	pathogenic	-1.3	Destabilizing	0.999	D	0.463	neutral	D	0.570494592	None	None	N
E/F	0.9583	likely_pathogenic	0.9668	pathogenic	-0.961	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/G	0.6235	likely_pathogenic	0.658	pathogenic	-0.857	Destabilizing	1.0	D	0.723	prob.delet.	D	0.730268537	None	None	N
E/H	0.8861	likely_pathogenic	0.9077	pathogenic	-1.21	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
E/I	0.6863	likely_pathogenic	0.7264	pathogenic	0.225	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/K	0.5221	ambiguous	0.575	pathogenic	-0.689	Destabilizing	0.999	D	0.527	neutral	D	0.573401957	None	None	N
E/L	0.8198	likely_pathogenic	0.8462	pathogenic	0.225	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/M	0.7853	likely_pathogenic	0.8058	pathogenic	0.675	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/N	0.8022	likely_pathogenic	0.8345	pathogenic	-0.881	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/P	0.9961	likely_pathogenic	0.9966	pathogenic	-0.015	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/Q	0.2994	likely_benign	0.3293	benign	-0.778	Destabilizing	1.0	D	0.603	neutral	D	0.560152803	None	None	N
E/R	0.695	likely_pathogenic	0.7371	pathogenic	-0.719	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/S	0.5482	ambiguous	0.5889	pathogenic	-1.273	Destabilizing	0.999	D	0.578	neutral	None	None	None	None	N
E/T	0.5806	likely_pathogenic	0.6154	pathogenic	-1.015	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
E/V	0.482	ambiguous	0.521	ambiguous	-0.015	Destabilizing	1.0	D	0.757	deleterious	D	0.58616413	None	None	N
E/W	0.9938	likely_pathogenic	0.9948	pathogenic	-1.156	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/Y	0.9531	likely_pathogenic	0.9622	pathogenic	-0.797	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N

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.