TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6030	18313;18314;18315	chr2:178730312;178730311;178730310	chr2:179595039;179595038;179595037
N2AB	5713	17362;17363;17364	chr2:178730312;178730311;178730310	chr2:179595039;179595038;179595037
N2A	4786	14581;14582;14583	chr2:178730312;178730311;178730310	chr2:179595039;179595038;179595037
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-44
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.434
• Predicted PPI site: N

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
Q/E	None	None	0.174	N	0.577	0.139	0.0846915920261	gnomAD-4.0.0	1.59729E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86743E-06	0	0
Q/R	rs1560784359	None	0.505	N	0.595	0.146	0.0762999501168	gnomAD-4.0.0	6.16735E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.20277E-06	0	1.65848E-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
Q/A	0.2173	likely_benign	0.2256	benign	-0.564	Destabilizing	0.575	D	0.592	neutral	None	None	None	None	N
Q/C	0.5487	ambiguous	0.5694	pathogenic	-0.062	Destabilizing	0.991	D	0.734	prob.delet.	None	None	None	None	N
Q/D	0.3954	ambiguous	0.4436	ambiguous	-0.597	Destabilizing	0.575	D	0.543	neutral	None	None	None	None	N
Q/E	0.0885	likely_benign	0.0949	benign	-0.517	Destabilizing	0.174	N	0.577	neutral	N	0.427539005	None	None	N
Q/F	0.4593	ambiguous	0.4977	ambiguous	-0.253	Destabilizing	0.826	D	0.734	prob.delet.	None	None	None	None	N
Q/G	0.321	likely_benign	0.3476	ambiguous	-0.909	Destabilizing	0.575	D	0.62	neutral	None	None	None	None	N
Q/H	0.1526	likely_benign	0.1603	benign	-0.797	Destabilizing	0.003	N	0.405	neutral	N	0.435851844	None	None	N
Q/I	0.2118	likely_benign	0.2261	benign	0.305	Stabilizing	0.906	D	0.733	prob.delet.	None	None	None	None	N
Q/K	0.0971	likely_benign	0.1047	benign	-0.443	Destabilizing	0.505	D	0.629	neutral	N	0.428077723	None	None	N
Q/L	0.0902	likely_benign	0.0964	benign	0.305	Stabilizing	0.505	D	0.645	neutral	N	0.426192211	None	None	N
Q/M	0.2772	likely_benign	0.2877	benign	0.682	Stabilizing	0.967	D	0.626	neutral	None	None	None	None	N
Q/N	0.2639	likely_benign	0.2961	benign	-0.941	Destabilizing	0.404	N	0.555	neutral	None	None	None	None	N
Q/P	0.2739	likely_benign	0.3674	ambiguous	0.047	Stabilizing	0.879	D	0.669	neutral	N	0.459780264	None	None	N
Q/R	0.0971	likely_benign	0.1007	benign	-0.362	Destabilizing	0.505	D	0.595	neutral	N	0.410838757	None	None	N
Q/S	0.2271	likely_benign	0.2513	benign	-0.999	Destabilizing	0.575	D	0.575	neutral	None	None	None	None	N
Q/T	0.1486	likely_benign	0.164	benign	-0.733	Destabilizing	0.733	D	0.609	neutral	None	None	None	None	N
Q/V	0.1525	likely_benign	0.1572	benign	0.047	Stabilizing	0.906	D	0.688	prob.neutral	None	None	None	None	N
Q/W	0.3584	ambiguous	0.3852	ambiguous	-0.141	Destabilizing	0.991	D	0.723	prob.delet.	None	None	None	None	N
Q/Y	0.3097	likely_benign	0.334	benign	0.068	Stabilizing	0.704	D	0.655	neutral	None	None	None	None	N

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.