TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25111	75556;75557;75558	chr2:178570801;178570800;178570799	chr2:179435528;179435527;179435526
N2AB	23470	70633;70634;70635	chr2:178570801;178570800;178570799	chr2:179435528;179435527;179435526
N2A	22543	67852;67853;67854	chr2:178570801;178570800;178570799	chr2:179435528;179435527;179435526
N2B	16046	48361;48362;48363	chr2:178570801;178570800;178570799	chr2:179435528;179435527;179435526
Novex-1	16171	48736;48737;48738	chr2:178570801;178570800;178570799	chr2:179435528;179435527;179435526
Novex-2	16238	48937;48938;48939	chr2:178570801;178570800;178570799	chr2:179435528;179435527;179435526
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-134
• Domain position: 1
• Structural Position: 1
• Q(SASA): 1.2186
• 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
I/T	rs879132850	None	0.892	N	0.616	0.607	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/T	rs879132850	None	0.892	N	0.616	0.607	None	gnomAD-4.0.0	2.56315E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.78806E-06	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	0.8488	likely_pathogenic	0.8504	pathogenic	-1.802	Destabilizing	0.845	D	0.615	neutral	None	None	None	None	I
I/C	0.8632	likely_pathogenic	0.8657	pathogenic	-1.056	Destabilizing	0.999	D	0.675	neutral	None	None	None	None	I
I/D	0.9942	likely_pathogenic	0.9943	pathogenic	-1.341	Destabilizing	0.996	D	0.664	neutral	None	None	None	None	I
I/E	0.9881	likely_pathogenic	0.9884	pathogenic	-1.246	Destabilizing	0.987	D	0.665	neutral	None	None	None	None	I
I/F	0.3321	likely_benign	0.3322	benign	-1.066	Destabilizing	0.975	D	0.656	neutral	None	None	None	None	I
I/G	0.9697	likely_pathogenic	0.9686	pathogenic	-2.225	Highly Destabilizing	0.987	D	0.667	neutral	None	None	None	None	I
I/H	0.9728	likely_pathogenic	0.9742	pathogenic	-1.564	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	I
I/K	0.9746	likely_pathogenic	0.9769	pathogenic	-1.246	Destabilizing	0.983	D	0.661	neutral	N	0.520190816	None	None	I
I/L	0.1822	likely_benign	0.1774	benign	-0.663	Destabilizing	0.426	N	0.504	neutral	N	0.492661904	None	None	I
I/M	0.236	likely_benign	0.2255	benign	-0.553	Destabilizing	0.983	D	0.659	neutral	N	0.496806642	None	None	I
I/N	0.9358	likely_pathogenic	0.9366	pathogenic	-1.207	Destabilizing	0.996	D	0.685	prob.neutral	None	None	None	None	I
I/P	0.977	likely_pathogenic	0.9747	pathogenic	-1.014	Destabilizing	0.996	D	0.678	prob.neutral	None	None	None	None	I
I/Q	0.976	likely_pathogenic	0.9773	pathogenic	-1.24	Destabilizing	0.996	D	0.679	prob.neutral	None	None	None	None	I
I/R	0.9619	likely_pathogenic	0.9654	pathogenic	-0.845	Destabilizing	0.983	D	0.683	prob.neutral	N	0.520190816	None	None	I
I/S	0.9197	likely_pathogenic	0.916	pathogenic	-1.884	Destabilizing	0.987	D	0.614	neutral	None	None	None	None	I
I/T	0.8987	likely_pathogenic	0.8974	pathogenic	-1.659	Destabilizing	0.892	D	0.616	neutral	N	0.519430348	None	None	I
I/V	0.119	likely_benign	0.1151	benign	-1.014	Destabilizing	0.011	N	0.316	neutral	D	0.525922928	None	None	I
I/W	0.9591	likely_pathogenic	0.9571	pathogenic	-1.286	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	I
I/Y	0.8221	likely_pathogenic	0.83	pathogenic	-1.001	Destabilizing	0.987	D	0.636	neutral	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.