TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19015	57268;57269;57270	chr2:178598574;178598573;178598572	chr2:179463301;179463300;179463299
N2AB	17374	52345;52346;52347	chr2:178598574;178598573;178598572	chr2:179463301;179463300;179463299
N2A	16447	49564;49565;49566	chr2:178598574;178598573;178598572	chr2:179463301;179463300;179463299
N2B	9950	30073;30074;30075	chr2:178598574;178598573;178598572	chr2:179463301;179463300;179463299
Novex-1	10075	30448;30449;30450	chr2:178598574;178598573;178598572	chr2:179463301;179463300;179463299
Novex-2	10142	30649;30650;30651	chr2:178598574;178598573;178598572	chr2:179463301;179463300;179463299
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: Fn3-26
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.3338
• 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/G	None	None	1.0	N	0.753	0.535	0.494568219684	gnomAD-4.0.0	1.60579E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.04229E-05

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	0.9029	likely_pathogenic	0.8843	pathogenic	-0.323	Destabilizing	1.0	D	0.769	deleterious	N	0.48384118	None	None	I
D/C	0.9816	likely_pathogenic	0.9749	pathogenic	0.15	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
D/E	0.8243	likely_pathogenic	0.8383	pathogenic	-0.564	Destabilizing	1.0	D	0.437	neutral	N	0.482168885	None	None	I
D/F	0.9847	likely_pathogenic	0.9793	pathogenic	-0.603	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
D/G	0.8663	likely_pathogenic	0.8093	pathogenic	-0.553	Destabilizing	1.0	D	0.753	deleterious	N	0.501326778	None	None	I
D/H	0.9566	likely_pathogenic	0.9309	pathogenic	-0.931	Destabilizing	1.0	D	0.699	prob.neutral	N	0.502705904	None	None	I
D/I	0.9684	likely_pathogenic	0.959	pathogenic	0.24	Stabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
D/K	0.9804	likely_pathogenic	0.972	pathogenic	0.152	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
D/L	0.963	likely_pathogenic	0.9583	pathogenic	0.24	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
D/M	0.9863	likely_pathogenic	0.982	pathogenic	0.686	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
D/N	0.4308	ambiguous	0.3841	ambiguous	-0.092	Destabilizing	1.0	D	0.736	prob.delet.	N	0.494490008	None	None	I
D/P	0.9803	likely_pathogenic	0.9809	pathogenic	0.076	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
D/Q	0.9736	likely_pathogenic	0.9619	pathogenic	-0.055	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
D/R	0.9818	likely_pathogenic	0.9699	pathogenic	0.021	Stabilizing	1.0	D	0.764	deleterious	None	None	None	None	I
D/S	0.7571	likely_pathogenic	0.7004	pathogenic	-0.226	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
D/T	0.8652	likely_pathogenic	0.805	pathogenic	-0.04	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
D/V	0.919	likely_pathogenic	0.8862	pathogenic	0.076	Stabilizing	1.0	D	0.767	deleterious	N	0.500059331	None	None	I
D/W	0.9954	likely_pathogenic	0.9923	pathogenic	-0.595	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
D/Y	0.8717	likely_pathogenic	0.822	pathogenic	-0.394	Destabilizing	1.0	D	0.708	prob.delet.	D	0.535560279	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.