TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28070	84433;84434;84435	chr2:178561924;178561923;178561922	chr2:179426651;179426650;179426649
N2AB	26429	79510;79511;79512	chr2:178561924;178561923;178561922	chr2:179426651;179426650;179426649
N2A	25502	76729;76730;76731	chr2:178561924;178561923;178561922	chr2:179426651;179426650;179426649
N2B	19005	57238;57239;57240	chr2:178561924;178561923;178561922	chr2:179426651;179426650;179426649
Novex-1	19130	57613;57614;57615	chr2:178561924;178561923;178561922	chr2:179426651;179426650;179426649
Novex-2	19197	57814;57815;57816	chr2:178561924;178561923;178561922	chr2:179426651;179426650;179426649
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-92
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.6219
• 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/N	None	None	0.999	N	0.639	0.37	0.344017737713	gnomAD-4.0.0	6.84334E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.9953E-07	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
D/A	0.4562	ambiguous	0.4295	ambiguous	-0.636	Destabilizing	0.999	D	0.699	prob.neutral	N	0.498982921	None	None	I
D/C	0.8263	likely_pathogenic	0.8289	pathogenic	-0.019	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
D/E	0.2363	likely_benign	0.2373	benign	-0.585	Destabilizing	0.767	D	0.287	neutral	N	0.494604651	None	None	I
D/F	0.8564	likely_pathogenic	0.8438	pathogenic	-0.745	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	I
D/G	0.3685	ambiguous	0.3446	ambiguous	-0.872	Destabilizing	0.998	D	0.673	neutral	N	0.483498785	None	None	I
D/H	0.5254	ambiguous	0.5345	ambiguous	-0.989	Destabilizing	1.0	D	0.641	neutral	N	0.484005764	None	None	I
D/I	0.7872	likely_pathogenic	0.7543	pathogenic	-0.044	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
D/K	0.7067	likely_pathogenic	0.6883	pathogenic	-0.02	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	I
D/L	0.7299	likely_pathogenic	0.7209	pathogenic	-0.044	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
D/M	0.8626	likely_pathogenic	0.8582	pathogenic	0.463	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
D/N	0.1372	likely_benign	0.137	benign	-0.301	Destabilizing	0.999	D	0.639	neutral	N	0.481480639	None	None	I
D/P	0.9593	likely_pathogenic	0.9477	pathogenic	-0.219	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
D/Q	0.564	ambiguous	0.5646	pathogenic	-0.275	Destabilizing	0.999	D	0.65	neutral	None	None	None	None	I
D/R	0.7261	likely_pathogenic	0.7076	pathogenic	-0.043	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	I
D/S	0.2107	likely_benign	0.2065	benign	-0.466	Destabilizing	0.997	D	0.605	neutral	None	None	None	None	I
D/T	0.395	ambiguous	0.3937	ambiguous	-0.274	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
D/V	0.6161	likely_pathogenic	0.5699	pathogenic	-0.219	Destabilizing	0.999	D	0.695	prob.neutral	N	0.499400994	None	None	I
D/W	0.9663	likely_pathogenic	0.9666	pathogenic	-0.631	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
D/Y	0.5159	ambiguous	0.4857	ambiguous	-0.517	Destabilizing	1.0	D	0.691	prob.neutral	N	0.515112166	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.