TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24361	73306;73307;73308	chr2:178573051;178573050;178573049	chr2:179437778;179437777;179437776
N2AB	22720	68383;68384;68385	chr2:178573051;178573050;178573049	chr2:179437778;179437777;179437776
N2A	21793	65602;65603;65604	chr2:178573051;178573050;178573049	chr2:179437778;179437777;179437776
N2B	15296	46111;46112;46113	chr2:178573051;178573050;178573049	chr2:179437778;179437777;179437776
Novex-1	15421	46486;46487;46488	chr2:178573051;178573050;178573049	chr2:179437778;179437777;179437776
Novex-2	15488	46687;46688;46689	chr2:178573051;178573050;178573049	chr2:179437778;179437777;179437776
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: Fn3-65
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.0967
• 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/K	None	None	0.999	N	0.67	0.437	0.485493271093	gnomAD-4.0.0	6.84462E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99645E-07	0	0
E/Q	None	None	1.0	N	0.745	0.364	0.392855499163	gnomAD-4.0.0	6.84462E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65733E-05

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	0.4388	ambiguous	0.3697	ambiguous	-1.364	Destabilizing	0.999	D	0.687	prob.neutral	D	0.545395647	None	None	N
E/C	0.9521	likely_pathogenic	0.9457	pathogenic	-0.599	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/D	0.7464	likely_pathogenic	0.6853	pathogenic	-1.931	Destabilizing	0.999	D	0.645	neutral	N	0.493475965	None	None	N
E/F	0.9815	likely_pathogenic	0.9744	pathogenic	-1.146	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/G	0.6629	likely_pathogenic	0.5772	pathogenic	-1.693	Destabilizing	1.0	D	0.736	prob.delet.	D	0.529230403	None	None	N
E/H	0.9085	likely_pathogenic	0.8844	pathogenic	-0.969	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/I	0.9236	likely_pathogenic	0.8951	pathogenic	-0.412	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/K	0.7944	likely_pathogenic	0.7192	pathogenic	-1.334	Destabilizing	0.999	D	0.67	neutral	N	0.501994661	None	None	N
E/L	0.918	likely_pathogenic	0.8881	pathogenic	-0.412	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/M	0.8539	likely_pathogenic	0.8151	pathogenic	0.147	Stabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/N	0.891	likely_pathogenic	0.8575	pathogenic	-1.569	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/P	0.9987	likely_pathogenic	0.9981	pathogenic	-0.718	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/Q	0.3263	likely_benign	0.2791	benign	-1.275	Destabilizing	1.0	D	0.745	deleterious	N	0.518692232	None	None	N
E/R	0.873	likely_pathogenic	0.833	pathogenic	-1.264	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/S	0.6412	likely_pathogenic	0.5739	pathogenic	-2.059	Highly Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
E/T	0.8351	likely_pathogenic	0.7853	pathogenic	-1.732	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/V	0.8063	likely_pathogenic	0.7471	pathogenic	-0.718	Destabilizing	1.0	D	0.73	prob.delet.	N	0.512087199	None	None	N
E/W	0.9956	likely_pathogenic	0.9936	pathogenic	-1.347	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/Y	0.971	likely_pathogenic	0.9627	pathogenic	-1.021	Destabilizing	1.0	D	0.762	deleterious	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.