TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15041	45346;45347;45348	chr2:178621703;178621702;178621701	chr2:179486430;179486429;179486428
N2AB	13400	40423;40424;40425	chr2:178621703;178621702;178621701	chr2:179486430;179486429;179486428
N2A	12473	37642;37643;37644	chr2:178621703;178621702;178621701	chr2:179486430;179486429;179486428
N2B	5976	18151;18152;18153	chr2:178621703;178621702;178621701	chr2:179486430;179486429;179486428
Novex-1	6101	18526;18527;18528	chr2:178621703;178621702;178621701	chr2:179486430;179486429;179486428
Novex-2	6168	18727;18728;18729	chr2:178621703;178621702;178621701	chr2:179486430;179486429;179486428
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-102
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.8167
• 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/G	None	None	0.946	D	0.645	0.53	0.476676017676	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.1936	likely_benign	0.2524	benign	-0.59	Destabilizing	0.834	D	0.648	neutral	D	0.543296112	None	None	N
E/C	0.9194	likely_pathogenic	0.9602	pathogenic	-0.367	Destabilizing	0.998	D	0.742	deleterious	None	None	None	None	N
E/D	0.1392	likely_benign	0.2508	benign	-0.613	Destabilizing	0.016	N	0.271	neutral	D	0.595027038	None	None	N
E/F	0.8355	likely_pathogenic	0.9214	pathogenic	-0.263	Destabilizing	0.998	D	0.701	prob.neutral	None	None	None	None	N
E/G	0.2714	likely_benign	0.4177	ambiguous	-0.848	Destabilizing	0.946	D	0.645	neutral	D	0.631822754	None	None	N
E/H	0.5568	ambiguous	0.7434	pathogenic	-0.167	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
E/I	0.4649	ambiguous	0.572	pathogenic	0.079	Stabilizing	0.979	D	0.726	prob.delet.	None	None	None	None	N
E/K	0.2345	likely_benign	0.3568	ambiguous	-0.255	Destabilizing	0.834	D	0.615	neutral	N	0.510439237	None	None	N
E/L	0.5453	ambiguous	0.6836	pathogenic	0.079	Stabilizing	0.979	D	0.709	prob.delet.	None	None	None	None	N
E/M	0.5738	likely_pathogenic	0.6562	pathogenic	0.18	Stabilizing	0.998	D	0.686	prob.neutral	None	None	None	None	N
E/N	0.2959	likely_benign	0.4841	ambiguous	-0.56	Destabilizing	0.921	D	0.744	deleterious	None	None	None	None	N
E/P	0.7621	likely_pathogenic	0.9092	pathogenic	-0.123	Destabilizing	0.979	D	0.742	deleterious	None	None	None	None	N
E/Q	0.1957	likely_benign	0.2657	benign	-0.49	Destabilizing	0.946	D	0.699	prob.neutral	N	0.516250163	None	None	N
E/R	0.3572	ambiguous	0.5433	ambiguous	0.087	Stabilizing	0.959	D	0.763	deleterious	None	None	None	None	N
E/S	0.2144	likely_benign	0.3232	benign	-0.774	Destabilizing	0.769	D	0.636	neutral	None	None	None	None	N
E/T	0.232	likely_benign	0.2983	benign	-0.573	Destabilizing	0.959	D	0.716	prob.delet.	None	None	None	None	N
E/V	0.2715	likely_benign	0.3384	benign	-0.123	Destabilizing	0.973	D	0.694	prob.neutral	N	0.502467075	None	None	N
E/W	0.9403	likely_pathogenic	0.9782	pathogenic	-0.067	Destabilizing	0.998	D	0.749	deleterious	None	None	None	None	N
E/Y	0.7515	likely_pathogenic	0.8855	pathogenic	-0.036	Destabilizing	0.998	D	0.692	prob.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.