TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26748	80467;80468;80469	chr2:178565890;178565889;178565888	chr2:179430617;179430616;179430615
N2AB	25107	75544;75545;75546	chr2:178565890;178565889;178565888	chr2:179430617;179430616;179430615
N2A	24180	72763;72764;72765	chr2:178565890;178565889;178565888	chr2:179430617;179430616;179430615
N2B	17683	53272;53273;53274	chr2:178565890;178565889;178565888	chr2:179430617;179430616;179430615
Novex-1	17808	53647;53648;53649	chr2:178565890;178565889;178565888	chr2:179430617;179430616;179430615
Novex-2	17875	53848;53849;53850	chr2:178565890;178565889;178565888	chr2:179430617;179430616;179430615
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-82
• Domain position: 66
• Structural Position: 98
• Q(SASA): 0.4067
• 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
T/A	None	None	None	N	0.126	0.099	0.181679512989	gnomAD-4.0.0	1.59159E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-05	0
T/R	None	None	0.188	N	0.328	0.163	0.247322355667	gnomAD-4.0.0	1.59161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85915E-06	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
T/A	0.0671	likely_benign	0.0683	benign	-0.747	Destabilizing	None	N	0.126	neutral	N	0.476306892	None	None	N
T/C	0.2991	likely_benign	0.3114	benign	-0.408	Destabilizing	0.824	D	0.341	neutral	None	None	None	None	N
T/D	0.4227	ambiguous	0.392	ambiguous	0.224	Stabilizing	0.081	N	0.332	neutral	None	None	None	None	N
T/E	0.292	likely_benign	0.2722	benign	0.188	Stabilizing	0.149	N	0.27	neutral	None	None	None	None	N
T/F	0.1932	likely_benign	0.197	benign	-1.041	Destabilizing	0.38	N	0.361	neutral	None	None	None	None	N
T/G	0.1845	likely_benign	0.1867	benign	-0.942	Destabilizing	0.081	N	0.321	neutral	None	None	None	None	N
T/H	0.2532	likely_benign	0.2471	benign	-1.143	Destabilizing	0.824	D	0.343	neutral	None	None	None	None	N
T/I	0.0868	likely_benign	0.0938	benign	-0.334	Destabilizing	0.001	N	0.184	neutral	N	0.428515732	None	None	N
T/K	0.2406	likely_benign	0.2211	benign	-0.502	Destabilizing	0.002	N	0.184	neutral	N	0.41352485	None	None	N
T/L	0.06	likely_benign	0.067	benign	-0.334	Destabilizing	0.001	N	0.159	neutral	None	None	None	None	N
T/M	0.0676	likely_benign	0.0679	benign	-0.122	Destabilizing	0.38	N	0.342	neutral	None	None	None	None	N
T/N	0.1031	likely_benign	0.0998	benign	-0.343	Destabilizing	0.001	N	0.129	neutral	None	None	None	None	N
T/P	0.1656	likely_benign	0.1632	benign	-0.441	Destabilizing	0.484	N	0.349	neutral	N	0.509939463	None	None	N
T/Q	0.1979	likely_benign	0.1951	benign	-0.523	Destabilizing	0.38	N	0.348	neutral	None	None	None	None	N
T/R	0.225	likely_benign	0.2011	benign	-0.231	Destabilizing	0.188	N	0.328	neutral	N	0.470802285	None	None	N
T/S	0.0944	likely_benign	0.0972	benign	-0.648	Destabilizing	0.027	N	0.24	neutral	N	0.434286911	None	None	N
T/V	0.074	likely_benign	0.0825	benign	-0.441	Destabilizing	0.012	N	0.207	neutral	None	None	None	None	N
T/W	0.5446	ambiguous	0.5299	ambiguous	-0.972	Destabilizing	0.935	D	0.429	neutral	None	None	None	None	N
T/Y	0.2651	likely_benign	0.2674	benign	-0.728	Destabilizing	0.555	D	0.356	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.