TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29035	87328;87329;87330	chr2:178558356;178558355;178558354	chr2:179423083;179423082;179423081
N2AB	27394	82405;82406;82407	chr2:178558356;178558355;178558354	chr2:179423083;179423082;179423081
N2A	26467	79624;79625;79626	chr2:178558356;178558355;178558354	chr2:179423083;179423082;179423081
N2B	19970	60133;60134;60135	chr2:178558356;178558355;178558354	chr2:179423083;179423082;179423081
Novex-1	20095	60508;60509;60510	chr2:178558356;178558355;178558354	chr2:179423083;179423082;179423081
Novex-2	20162	60709;60710;60711	chr2:178558356;178558355;178558354	chr2:179423083;179423082;179423081
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-99
• Domain position: 94
• Structural Position: 130
• Q(SASA): 0.0472
• 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
I/T	rs768635896	-3.338	0.006	N	0.579	0.212	0.642006589361	gnomAD-2.1.1	2.03E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.65937E-04	None	0	0	0
I/T	rs768635896	-3.338	0.006	N	0.579	0.212	0.642006589361	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06868E-04	0
I/T	rs768635896	-3.338	0.006	N	0.579	0.212	0.642006589361	gnomAD-4.0.0	1.41187E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.48444E-04	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
I/A	0.489	ambiguous	0.5338	ambiguous	-3.201	Highly Destabilizing	0.007	N	0.558	neutral	None	None	None	None	N
I/C	0.7222	likely_pathogenic	0.7529	pathogenic	-2.511	Highly Destabilizing	0.204	N	0.577	neutral	None	None	None	None	N
I/D	0.9865	likely_pathogenic	0.9867	pathogenic	-3.598	Highly Destabilizing	0.204	N	0.715	prob.delet.	None	None	None	None	N
I/E	0.9715	likely_pathogenic	0.9723	pathogenic	-3.327	Highly Destabilizing	0.068	N	0.665	prob.neutral	None	None	None	None	N
I/F	0.5683	likely_pathogenic	0.6051	pathogenic	-1.8	Destabilizing	0.026	N	0.584	neutral	N	0.518892594	None	None	N
I/G	0.8833	likely_pathogenic	0.9025	pathogenic	-3.726	Highly Destabilizing	0.068	N	0.671	prob.neutral	None	None	None	None	N
I/H	0.9634	likely_pathogenic	0.9635	pathogenic	-3.034	Highly Destabilizing	0.747	D	0.677	prob.neutral	None	None	None	None	N
I/K	0.957	likely_pathogenic	0.9479	pathogenic	-2.301	Highly Destabilizing	0.035	N	0.675	prob.neutral	None	None	None	None	N
I/L	0.1851	likely_benign	0.1991	benign	-1.625	Destabilizing	None	N	0.316	neutral	N	0.477847835	None	None	N
I/M	0.2278	likely_benign	0.2571	benign	-1.909	Destabilizing	0.001	N	0.328	neutral	N	0.475525819	None	None	N
I/N	0.824	likely_pathogenic	0.8275	pathogenic	-2.836	Highly Destabilizing	0.162	N	0.719	prob.delet.	N	0.478354814	None	None	N
I/P	0.8559	likely_pathogenic	0.8379	pathogenic	-2.142	Highly Destabilizing	0.439	N	0.709	prob.delet.	None	None	None	None	N
I/Q	0.9275	likely_pathogenic	0.9325	pathogenic	-2.599	Highly Destabilizing	0.204	N	0.719	prob.delet.	None	None	None	None	N
I/R	0.9099	likely_pathogenic	0.8998	pathogenic	-2.106	Highly Destabilizing	0.112	N	0.723	deleterious	None	None	None	None	N
I/S	0.7013	likely_pathogenic	0.7211	pathogenic	-3.427	Highly Destabilizing	0.026	N	0.575	neutral	N	0.477087366	None	None	N
I/T	0.5481	ambiguous	0.5857	pathogenic	-3.017	Highly Destabilizing	0.006	N	0.579	neutral	N	0.477275258	None	None	N
I/V	0.0567	likely_benign	0.0615	benign	-2.142	Highly Destabilizing	None	N	0.091	neutral	N	0.375782899	None	None	N
I/W	0.983	likely_pathogenic	0.9838	pathogenic	-2.083	Highly Destabilizing	0.747	D	0.682	prob.neutral	None	None	None	None	N
I/Y	0.9345	likely_pathogenic	0.9388	pathogenic	-2.0	Highly Destabilizing	0.204	N	0.659	prob.neutral	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.