TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6952	21079;21080;21081	chr2:178724521;178724520;178724519	chr2:179589248;179589247;179589246
N2AB	6635	20128;20129;20130	chr2:178724521;178724520;178724519	chr2:179589248;179589247;179589246
N2A	5708	17347;17348;17349	chr2:178724521;178724520;178724519	chr2:179589248;179589247;179589246
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-54
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.5917
• 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
E/A	rs779587161	0.033	0.698	D	0.461	0.388	0.446111551642	gnomAD-2.1.1	4.15E-06	None	None	None	None	N	None	6.51E-05	0	None	0	0	None	0	None	0	0	0
E/K	None	None	0.822	N	0.471	0.356	0.41337360676	gnomAD-4.0.0	1.38516E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.81787E-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
E/A	0.3926	ambiguous	0.4076	ambiguous	-0.458	Destabilizing	0.698	D	0.461	neutral	D	0.531403319	None	None	N
E/C	0.962	likely_pathogenic	0.963	pathogenic	-0.222	Destabilizing	0.998	D	0.63	neutral	None	None	None	None	N
E/D	0.2424	likely_benign	0.2553	benign	-0.482	Destabilizing	0.006	N	0.129	neutral	D	0.524285345	None	None	N
E/F	0.9442	likely_pathogenic	0.9461	pathogenic	-0.152	Destabilizing	0.956	D	0.587	neutral	None	None	None	None	N
E/G	0.332	likely_benign	0.3325	benign	-0.695	Destabilizing	0.822	D	0.462	neutral	N	0.486542157	None	None	N
E/H	0.744	likely_pathogenic	0.7526	pathogenic	0.085	Stabilizing	0.998	D	0.409	neutral	None	None	None	None	N
E/I	0.7866	likely_pathogenic	0.8014	pathogenic	0.149	Stabilizing	0.787	D	0.53	neutral	None	None	None	None	N
E/K	0.3488	ambiguous	0.3363	benign	0.145	Stabilizing	0.822	D	0.471	neutral	N	0.506563589	None	None	N
E/L	0.764	likely_pathogenic	0.7766	pathogenic	0.149	Stabilizing	0.754	D	0.489	neutral	None	None	None	None	N
E/M	0.7999	likely_pathogenic	0.8071	pathogenic	0.198	Stabilizing	0.994	D	0.567	neutral	None	None	None	None	N
E/N	0.5685	likely_pathogenic	0.579	pathogenic	-0.288	Destabilizing	0.956	D	0.359	neutral	None	None	None	None	N
E/P	0.9776	likely_pathogenic	0.9722	pathogenic	-0.033	Destabilizing	0.993	D	0.46	neutral	None	None	None	None	N
E/Q	0.2334	likely_benign	0.231	benign	-0.223	Destabilizing	0.97	D	0.39	neutral	N	0.49469037	None	None	N
E/R	0.5141	ambiguous	0.5135	ambiguous	0.456	Stabilizing	0.978	D	0.408	neutral	None	None	None	None	N
E/S	0.4399	ambiguous	0.4462	ambiguous	-0.458	Destabilizing	0.86	D	0.429	neutral	None	None	None	None	N
E/T	0.5141	ambiguous	0.5354	ambiguous	-0.261	Destabilizing	0.86	D	0.423	neutral	None	None	None	None	N
E/V	0.5547	ambiguous	0.5744	pathogenic	-0.033	Destabilizing	0.032	N	0.31	neutral	N	0.50229392	None	None	N
E/W	0.9645	likely_pathogenic	0.9646	pathogenic	0.054	Stabilizing	0.998	D	0.674	neutral	None	None	None	None	N
E/Y	0.882	likely_pathogenic	0.8818	pathogenic	0.102	Stabilizing	0.978	D	0.558	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.