TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21700	65323;65324;65325	chr2:178584453;178584452;178584451	chr2:179449180;179449179;179449178
N2AB	20059	60400;60401;60402	chr2:178584453;178584452;178584451	chr2:179449180;179449179;179449178
N2A	19132	57619;57620;57621	chr2:178584453;178584452;178584451	chr2:179449180;179449179;179449178
N2B	12635	38128;38129;38130	chr2:178584453;178584452;178584451	chr2:179449180;179449179;179449178
Novex-1	12760	38503;38504;38505	chr2:178584453;178584452;178584451	chr2:179449180;179449179;179449178
Novex-2	12827	38704;38705;38706	chr2:178584453;178584452;178584451	chr2:179449180;179449179;179449178
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: Fn3-45
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.2867
• 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	rs2048488125	None	1.0	N	0.673	0.561	0.611786747218	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/G	rs2048488125	None	1.0	N	0.673	0.561	0.611786747218	gnomAD-4.0.0	6.57678E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47093E-05	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	0.9212	likely_pathogenic	0.8944	pathogenic	-0.849	Destabilizing	0.999	D	0.631	neutral	N	0.48491759	None	None	N
E/C	0.9954	likely_pathogenic	0.9927	pathogenic	-0.47	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
E/D	0.656	likely_pathogenic	0.5871	pathogenic	-1.126	Destabilizing	0.999	D	0.433	neutral	N	0.508053951	None	None	N
E/F	0.9977	likely_pathogenic	0.9967	pathogenic	-0.055	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/G	0.9068	likely_pathogenic	0.8914	pathogenic	-1.252	Destabilizing	1.0	D	0.673	neutral	N	0.490539904	None	None	N
E/H	0.9903	likely_pathogenic	0.9846	pathogenic	-0.234	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
E/I	0.9897	likely_pathogenic	0.9835	pathogenic	0.266	Stabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/K	0.9638	likely_pathogenic	0.9503	pathogenic	-0.555	Destabilizing	0.999	D	0.555	neutral	N	0.487889323	None	None	N
E/L	0.9862	likely_pathogenic	0.9767	pathogenic	0.266	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/M	0.9858	likely_pathogenic	0.9787	pathogenic	0.71	Stabilizing	1.0	D	0.664	neutral	None	None	None	None	N
E/N	0.9644	likely_pathogenic	0.9533	pathogenic	-1.213	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
E/P	0.986	likely_pathogenic	0.9805	pathogenic	-0.084	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/Q	0.8455	likely_pathogenic	0.79	pathogenic	-1.032	Destabilizing	1.0	D	0.611	neutral	N	0.474584789	None	None	N
E/R	0.9733	likely_pathogenic	0.9606	pathogenic	-0.207	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
E/S	0.9558	likely_pathogenic	0.9438	pathogenic	-1.539	Destabilizing	0.999	D	0.606	neutral	None	None	None	None	N
E/T	0.982	likely_pathogenic	0.9766	pathogenic	-1.189	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/V	0.967	likely_pathogenic	0.951	pathogenic	-0.084	Destabilizing	1.0	D	0.761	deleterious	N	0.500250368	None	None	N
E/W	0.9988	likely_pathogenic	0.9981	pathogenic	0.266	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/Y	0.9943	likely_pathogenic	0.9921	pathogenic	0.23	Stabilizing	1.0	D	0.721	prob.delet.	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.