TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28860	86803;86804;86805	chr2:178559554;178559553;178559552	chr2:179424281;179424280;179424279
N2AB	27219	81880;81881;81882	chr2:178559554;178559553;178559552	chr2:179424281;179424280;179424279
N2A	26292	79099;79100;79101	chr2:178559554;178559553;178559552	chr2:179424281;179424280;179424279
N2B	19795	59608;59609;59610	chr2:178559554;178559553;178559552	chr2:179424281;179424280;179424279
Novex-1	19920	59983;59984;59985	chr2:178559554;178559553;178559552	chr2:179424281;179424280;179424279
Novex-2	19987	60184;60185;60186	chr2:178559554;178559553;178559552	chr2:179424281;179424280;179424279
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: Fn3-98
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.5402
• 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/D	None	None	0.004	N	0.076	0.03	0.0884992946249	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	0	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	0.1358	likely_benign	0.1276	benign	-0.595	Destabilizing	0.201	N	0.348	neutral	N	0.452795314	None	None	N
E/C	0.7277	likely_pathogenic	0.7195	pathogenic	0.027	Stabilizing	0.992	D	0.29	neutral	None	None	None	None	N
E/D	0.07	likely_benign	0.0714	benign	-0.659	Destabilizing	0.004	N	0.076	neutral	N	0.393784296	None	None	N
E/F	0.6275	likely_pathogenic	0.5949	pathogenic	-0.651	Destabilizing	0.972	D	0.324	neutral	None	None	None	None	N
E/G	0.1234	likely_benign	0.114	benign	-0.834	Destabilizing	0.334	N	0.3	neutral	N	0.423627201	None	None	N
E/H	0.4158	ambiguous	0.3877	ambiguous	-0.847	Destabilizing	0.92	D	0.332	neutral	None	None	None	None	N
E/I	0.356	ambiguous	0.3309	benign	0.017	Stabilizing	0.85	D	0.373	neutral	None	None	None	None	N
E/K	0.2342	likely_benign	0.2027	benign	0.078	Stabilizing	0.334	N	0.316	neutral	N	0.446618703	None	None	N
E/L	0.3804	ambiguous	0.3558	ambiguous	0.017	Stabilizing	0.617	D	0.399	neutral	None	None	None	None	N
E/M	0.4032	ambiguous	0.3846	ambiguous	0.442	Stabilizing	0.992	D	0.285	neutral	None	None	None	None	N
E/N	0.1419	likely_benign	0.1389	benign	-0.179	Destabilizing	0.021	N	0.099	neutral	None	None	None	None	N
E/P	0.88	likely_pathogenic	0.8705	pathogenic	-0.166	Destabilizing	0.92	D	0.396	neutral	None	None	None	None	N
E/Q	0.1598	likely_benign	0.1467	benign	-0.159	Destabilizing	0.712	D	0.383	neutral	N	0.465993898	None	None	N
E/R	0.3665	ambiguous	0.3172	benign	0.104	Stabilizing	0.766	D	0.352	neutral	None	None	None	None	N
E/S	0.1344	likely_benign	0.1343	benign	-0.388	Destabilizing	0.026	N	0.063	neutral	None	None	None	None	N
E/T	0.1359	likely_benign	0.1338	benign	-0.194	Destabilizing	0.021	N	0.152	neutral	None	None	None	None	N
E/V	0.2165	likely_benign	0.2031	benign	-0.166	Destabilizing	0.549	D	0.399	neutral	N	0.492564424	None	None	N
E/W	0.8506	likely_pathogenic	0.8355	pathogenic	-0.542	Destabilizing	0.992	D	0.445	neutral	None	None	None	None	N
E/Y	0.46	ambiguous	0.4329	ambiguous	-0.414	Destabilizing	0.972	D	0.313	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.