TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25054	75385;75386;75387	chr2:178570972;178570971;178570970	chr2:179435699;179435698;179435697
N2AB	23413	70462;70463;70464	chr2:178570972;178570971;178570970	chr2:179435699;179435698;179435697
N2A	22486	67681;67682;67683	chr2:178570972;178570971;178570970	chr2:179435699;179435698;179435697
N2B	15989	48190;48191;48192	chr2:178570972;178570971;178570970	chr2:179435699;179435698;179435697
Novex-1	16114	48565;48566;48567	chr2:178570972;178570971;178570970	chr2:179435699;179435698;179435697
Novex-2	16181	48766;48767;48768	chr2:178570972;178570971;178570970	chr2:179435699;179435698;179435697
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-70
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.6907
• 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
M/I	rs1410088991	0.263	0.007	N	0.164	0.117	0.377097596864	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-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
M/A	0.7839	likely_pathogenic	0.7676	pathogenic	-1.491	Destabilizing	0.543	D	0.425	neutral	None	None	None	None	I
M/C	0.8694	likely_pathogenic	0.8619	pathogenic	-1.072	Destabilizing	0.996	D	0.402	neutral	None	None	None	None	I
M/D	0.9726	likely_pathogenic	0.9703	pathogenic	-0.383	Destabilizing	0.984	D	0.417	neutral	None	None	None	None	I
M/E	0.7879	likely_pathogenic	0.7981	pathogenic	-0.369	Destabilizing	0.984	D	0.395	neutral	None	None	None	None	I
M/F	0.6232	likely_pathogenic	0.5987	pathogenic	-0.553	Destabilizing	0.742	D	0.404	neutral	None	None	None	None	I
M/G	0.8798	likely_pathogenic	0.8652	pathogenic	-1.781	Destabilizing	0.953	D	0.395	neutral	None	None	None	None	I
M/H	0.8077	likely_pathogenic	0.8026	pathogenic	-0.822	Destabilizing	0.996	D	0.416	neutral	None	None	None	None	I
M/I	0.5644	likely_pathogenic	0.5333	ambiguous	-0.759	Destabilizing	0.007	N	0.164	neutral	N	0.442833745	None	None	I
M/K	0.4858	ambiguous	0.4913	ambiguous	-0.437	Destabilizing	0.815	D	0.385	neutral	N	0.430635239	None	None	I
M/L	0.1665	likely_benign	0.1582	benign	-0.759	Destabilizing	0.028	N	0.229	neutral	N	0.484872368	None	None	I
M/N	0.7727	likely_pathogenic	0.766	pathogenic	-0.281	Destabilizing	0.984	D	0.42	neutral	None	None	None	None	I
M/P	0.9898	likely_pathogenic	0.9878	pathogenic	-0.976	Destabilizing	0.984	D	0.421	neutral	None	None	None	None	I
M/Q	0.4115	ambiguous	0.4158	ambiguous	-0.385	Destabilizing	0.984	D	0.425	neutral	None	None	None	None	I
M/R	0.5096	ambiguous	0.5119	ambiguous	0.083	Stabilizing	0.979	D	0.412	neutral	N	0.467518759	None	None	I
M/S	0.7512	likely_pathogenic	0.7429	pathogenic	-0.86	Destabilizing	0.854	D	0.384	neutral	None	None	None	None	I
M/T	0.5303	ambiguous	0.5268	ambiguous	-0.74	Destabilizing	0.684	D	0.372	neutral	N	0.459917996	None	None	I
M/V	0.1844	likely_benign	0.1716	benign	-0.976	Destabilizing	0.063	N	0.285	neutral	N	0.444025824	None	None	I
M/W	0.8722	likely_pathogenic	0.8648	pathogenic	-0.483	Destabilizing	0.996	D	0.422	neutral	None	None	None	None	I
M/Y	0.8131	likely_pathogenic	0.8048	pathogenic	-0.497	Destabilizing	0.953	D	0.408	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.