TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18304	55135;55136;55137	chr2:178602492;178602491;178602490	chr2:179467219;179467218;179467217
N2AB	16663	50212;50213;50214	chr2:178602492;178602491;178602490	chr2:179467219;179467218;179467217
N2A	15736	47431;47432;47433	chr2:178602492;178602491;178602490	chr2:179467219;179467218;179467217
N2B	9239	27940;27941;27942	chr2:178602492;178602491;178602490	chr2:179467219;179467218;179467217
Novex-1	9364	28315;28316;28317	chr2:178602492;178602491;178602490	chr2:179467219;179467218;179467217
Novex-2	9431	28516;28517;28518	chr2:178602492;178602491;178602490	chr2:179467219;179467218;179467217
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-21
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.2048
• 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/V	rs1011162214	None	0.002	N	0.218	0.112	0.355242300401	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs1011162214	None	0.002	N	0.218	0.112	0.355242300401	gnomAD-4.0.0	1.73747E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.37539E-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
I/A	0.9274	likely_pathogenic	0.9573	pathogenic	-2.331	Highly Destabilizing	0.547	D	0.633	neutral	None	None	None	None	N
I/C	0.9441	likely_pathogenic	0.9676	pathogenic	-1.404	Destabilizing	0.985	D	0.737	prob.delet.	None	None	None	None	N
I/D	0.9959	likely_pathogenic	0.9982	pathogenic	-2.128	Highly Destabilizing	0.945	D	0.807	deleterious	None	None	None	None	N
I/E	0.9811	likely_pathogenic	0.9912	pathogenic	-2.045	Highly Destabilizing	0.945	D	0.801	deleterious	None	None	None	None	N
I/F	0.7519	likely_pathogenic	0.8969	pathogenic	-1.544	Destabilizing	0.864	D	0.708	prob.delet.	N	0.515813864	None	None	N
I/G	0.9862	likely_pathogenic	0.993	pathogenic	-2.752	Highly Destabilizing	0.945	D	0.797	deleterious	None	None	None	None	N
I/H	0.9847	likely_pathogenic	0.9945	pathogenic	-1.972	Destabilizing	0.995	D	0.781	deleterious	None	None	None	None	N
I/K	0.9531	likely_pathogenic	0.9799	pathogenic	-1.752	Destabilizing	0.945	D	0.801	deleterious	None	None	None	None	N
I/L	0.2536	likely_benign	0.3332	benign	-1.181	Destabilizing	0.141	N	0.373	neutral	N	0.473502514	None	None	N
I/M	0.3914	ambiguous	0.5689	pathogenic	-0.851	Destabilizing	0.864	D	0.688	prob.neutral	D	0.524932124	None	None	N
I/N	0.9447	likely_pathogenic	0.9774	pathogenic	-1.69	Destabilizing	0.975	D	0.809	deleterious	D	0.537302388	None	None	N
I/P	0.9265	likely_pathogenic	0.9614	pathogenic	-1.539	Destabilizing	0.981	D	0.812	deleterious	None	None	None	None	N
I/Q	0.964	likely_pathogenic	0.9848	pathogenic	-1.792	Destabilizing	0.981	D	0.805	deleterious	None	None	None	None	N
I/R	0.9365	likely_pathogenic	0.972	pathogenic	-1.145	Destabilizing	0.945	D	0.809	deleterious	None	None	None	None	N
I/S	0.9501	likely_pathogenic	0.9779	pathogenic	-2.354	Highly Destabilizing	0.864	D	0.777	deleterious	D	0.525185614	None	None	N
I/T	0.8943	likely_pathogenic	0.9554	pathogenic	-2.149	Highly Destabilizing	0.645	D	0.732	prob.delet.	N	0.510208457	None	None	N
I/V	0.1062	likely_benign	0.0866	benign	-1.539	Destabilizing	0.002	N	0.218	neutral	N	0.492895285	None	None	N
I/W	0.9882	likely_pathogenic	0.9957	pathogenic	-1.739	Destabilizing	0.995	D	0.729	prob.delet.	None	None	None	None	N
I/Y	0.9607	likely_pathogenic	0.9859	pathogenic	-1.53	Destabilizing	0.945	D	0.768	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.