TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19507	58744;58745;58746	chr2:178593781;178593780;178593779	chr2:179458508;179458507;179458506
N2AB	17866	53821;53822;53823	chr2:178593781;178593780;178593779	chr2:179458508;179458507;179458506
N2A	16939	51040;51041;51042	chr2:178593781;178593780;178593779	chr2:179458508;179458507;179458506
N2B	10442	31549;31550;31551	chr2:178593781;178593780;178593779	chr2:179458508;179458507;179458506
Novex-1	10567	31924;31925;31926	chr2:178593781;178593780;178593779	chr2:179458508;179458507;179458506
Novex-2	10634	32125;32126;32127	chr2:178593781;178593780;178593779	chr2:179458508;179458507;179458506
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-29
• Domain position: 29
• Structural Position: 30
• Q(SASA): 0.2378
• 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
D/V	rs1177368382	0.205	0.989	N	0.696	0.485	0.515882253919	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.93E-06	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
D/A	0.7854	likely_pathogenic	0.7989	pathogenic	-0.281	Destabilizing	0.978	D	0.599	neutral	N	0.492564139	None	None	I
D/C	0.9419	likely_pathogenic	0.949	pathogenic	0.212	Stabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	I
D/E	0.7761	likely_pathogenic	0.8064	pathogenic	-0.525	Destabilizing	0.928	D	0.407	neutral	N	0.489246003	None	None	I
D/F	0.9661	likely_pathogenic	0.9696	pathogenic	-0.541	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	I
D/G	0.7728	likely_pathogenic	0.7635	pathogenic	-0.506	Destabilizing	0.865	D	0.467	neutral	N	0.506922639	None	None	I
D/H	0.8309	likely_pathogenic	0.8627	pathogenic	-0.839	Destabilizing	0.994	D	0.677	prob.neutral	N	0.509124685	None	None	I
D/I	0.9053	likely_pathogenic	0.9321	pathogenic	0.269	Stabilizing	0.992	D	0.699	prob.neutral	None	None	None	None	I
D/K	0.8987	likely_pathogenic	0.9319	pathogenic	0.241	Stabilizing	0.968	D	0.563	neutral	None	None	None	None	I
D/L	0.9233	likely_pathogenic	0.9299	pathogenic	0.269	Stabilizing	0.992	D	0.677	prob.neutral	None	None	None	None	I
D/M	0.963	likely_pathogenic	0.9635	pathogenic	0.702	Stabilizing	0.999	D	0.676	prob.neutral	None	None	None	None	I
D/N	0.2498	likely_benign	0.2214	benign	-0.007	Destabilizing	0.039	N	0.204	neutral	N	0.472409196	None	None	I
D/P	0.974	likely_pathogenic	0.9768	pathogenic	0.109	Stabilizing	0.992	D	0.695	prob.neutral	None	None	None	None	I
D/Q	0.9081	likely_pathogenic	0.9294	pathogenic	0.026	Stabilizing	0.983	D	0.676	prob.neutral	None	None	None	None	I
D/R	0.9076	likely_pathogenic	0.9327	pathogenic	0.121	Stabilizing	0.983	D	0.695	prob.neutral	None	None	None	None	I
D/S	0.4538	ambiguous	0.4361	ambiguous	-0.131	Destabilizing	0.895	D	0.475	neutral	None	None	None	None	I
D/T	0.6446	likely_pathogenic	0.6116	pathogenic	0.05	Stabilizing	0.983	D	0.544	neutral	None	None	None	None	I
D/V	0.8229	likely_pathogenic	0.8554	pathogenic	0.109	Stabilizing	0.989	D	0.696	prob.neutral	N	0.505655191	None	None	I
D/W	0.9922	likely_pathogenic	0.9933	pathogenic	-0.524	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	I
D/Y	0.7643	likely_pathogenic	0.8086	pathogenic	-0.326	Destabilizing	0.999	D	0.683	prob.neutral	D	0.536383199	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.