TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13775	41548;41549;41550	chr2:178636404;178636403;178636402	chr2:179501131;179501130;179501129
N2AB	12134	36625;36626;36627	chr2:178636404;178636403;178636402	chr2:179501131;179501130;179501129
N2A	11207	33844;33845;33846	chr2:178636404;178636403;178636402	chr2:179501131;179501130;179501129
N2B	4710	14353;14354;14355	chr2:178636404;178636403;178636402	chr2:179501131;179501130;179501129
Novex-1	4835	14728;14729;14730	chr2:178636404;178636403;178636402	chr2:179501131;179501130;179501129
Novex-2	4902	14929;14930;14931	chr2:178636404;178636403;178636402	chr2:179501131;179501130;179501129
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-87
• Domain position: 92
• Structural Position: 176
• Q(SASA): 0.798
• 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
V/E	None	None	1.0	D	0.756	0.841	0.905287540064	gnomAD-4.0.0	1.61995E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.90757E-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
V/A	0.7955	likely_pathogenic	0.7964	pathogenic	-1.407	Destabilizing	0.999	D	0.727	prob.delet.	D	0.762547304	None	None	I
V/C	0.9741	likely_pathogenic	0.9712	pathogenic	-0.987	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
V/D	0.996	likely_pathogenic	0.9956	pathogenic	-1.202	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
V/E	0.9835	likely_pathogenic	0.9826	pathogenic	-1.068	Destabilizing	1.0	D	0.756	deleterious	D	0.761821382	None	None	I
V/F	0.8354	likely_pathogenic	0.8258	pathogenic	-0.723	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
V/G	0.9284	likely_pathogenic	0.9235	pathogenic	-1.854	Destabilizing	1.0	D	0.719	prob.delet.	D	0.761821382	None	None	I
V/H	0.9943	likely_pathogenic	0.9945	pathogenic	-1.397	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
V/I	0.1262	likely_benign	0.1362	benign	-0.225	Destabilizing	0.997	D	0.703	prob.neutral	D	0.580578592	None	None	I
V/K	0.973	likely_pathogenic	0.9764	pathogenic	-1.192	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
V/L	0.7316	likely_pathogenic	0.729	pathogenic	-0.225	Destabilizing	0.997	D	0.731	prob.delet.	D	0.634599555	None	None	I
V/M	0.727	likely_pathogenic	0.7295	pathogenic	-0.282	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
V/N	0.9853	likely_pathogenic	0.9844	pathogenic	-1.277	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
V/P	0.9837	likely_pathogenic	0.9788	pathogenic	-0.585	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
V/Q	0.978	likely_pathogenic	0.9767	pathogenic	-1.213	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
V/R	0.9569	likely_pathogenic	0.9598	pathogenic	-0.945	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
V/S	0.9459	likely_pathogenic	0.9406	pathogenic	-1.921	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
V/T	0.8005	likely_pathogenic	0.7995	pathogenic	-1.65	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	I
V/W	0.996	likely_pathogenic	0.9957	pathogenic	-1.087	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
V/Y	0.986	likely_pathogenic	0.9854	pathogenic	-0.692	Destabilizing	1.0	D	0.809	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.