TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1750	5473;5474;5475	chr2:178776616;178776615;178776614	chr2:179641343;179641342;179641341
N2AB	1750	5473;5474;5475	chr2:178776616;178776615;178776614	chr2:179641343;179641342;179641341
N2A	1750	5473;5474;5475	chr2:178776616;178776615;178776614	chr2:179641343;179641342;179641341
N2B	1704	5335;5336;5337	chr2:178776616;178776615;178776614	chr2:179641343;179641342;179641341
Novex-1	1704	5335;5336;5337	chr2:178776616;178776615;178776614	chr2:179641343;179641342;179641341
Novex-2	1704	5335;5336;5337	chr2:178776616;178776615;178776614	chr2:179641343;179641342;179641341
Novex-3	1750	5473;5474;5475	chr2:178776616;178776615;178776614	chr2:179641343;179641342;179641341

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-8
• Domain position: 48
• Structural Position: 115
• Q(SASA): 0.2656
• Predicted PPI site: I

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
R/S	rs924534786	None	1.0	D	0.751	0.526	0.604474940213	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
R/S	rs924534786	None	1.0	D	0.751	0.526	0.604474940213	gnomAD-4.0.0	6.5703E-06	None	None	None	None	I	None	2.41243E-05	0	None	0	0	None	0	0	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
R/A	0.9828	likely_pathogenic	0.9816	pathogenic	-1.365	Destabilizing	0.999	D	0.534	neutral	None	None	None	None	I
R/C	0.9308	likely_pathogenic	0.9284	pathogenic	-1.236	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
R/D	0.9841	likely_pathogenic	0.9837	pathogenic	-0.353	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
R/E	0.9479	likely_pathogenic	0.9481	pathogenic	-0.154	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	I
R/F	0.989	likely_pathogenic	0.9891	pathogenic	-0.817	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
R/G	0.9475	likely_pathogenic	0.9505	pathogenic	-1.722	Destabilizing	1.0	D	0.723	prob.delet.	D	0.683744564	None	None	I
R/H	0.6044	likely_pathogenic	0.6034	pathogenic	-1.775	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
R/I	0.9673	likely_pathogenic	0.9667	pathogenic	-0.361	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
R/K	0.6797	likely_pathogenic	0.7044	pathogenic	-0.865	Destabilizing	0.997	D	0.443	neutral	D	0.581133395	None	None	I
R/L	0.9364	likely_pathogenic	0.9349	pathogenic	-0.361	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
R/M	0.9833	likely_pathogenic	0.9838	pathogenic	-0.836	Destabilizing	1.0	D	0.736	prob.delet.	D	0.771986523	None	None	I
R/N	0.9692	likely_pathogenic	0.9657	pathogenic	-0.792	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
R/P	0.9867	likely_pathogenic	0.9884	pathogenic	-0.679	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
R/Q	0.6439	likely_pathogenic	0.6411	pathogenic	-0.768	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
R/S	0.9804	likely_pathogenic	0.9786	pathogenic	-1.649	Destabilizing	1.0	D	0.751	deleterious	D	0.708718949	None	None	I
R/T	0.972	likely_pathogenic	0.9684	pathogenic	-1.23	Destabilizing	1.0	D	0.754	deleterious	D	0.732777833	None	None	I
R/V	0.974	likely_pathogenic	0.9731	pathogenic	-0.679	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
R/W	0.9243	likely_pathogenic	0.9198	pathogenic	-0.381	Destabilizing	1.0	D	0.749	deleterious	D	0.805744296	None	None	I
R/Y	0.9621	likely_pathogenic	0.9605	pathogenic	-0.207	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I

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.