TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7455	22588;22589;22590	chr2:178722424;178722423;178722422	chr2:179587151;179587150;179587149
N2AB	7138	21637;21638;21639	chr2:178722424;178722423;178722422	chr2:179587151;179587150;179587149
N2A	6211	18856;18857;18858	chr2:178722424;178722423;178722422	chr2:179587151;179587150;179587149
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-59
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.4616
• 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
D/E	rs756430663	-0.373	0.907	D	0.42	0.45	0.251639045875	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
D/E	rs756430663	-0.373	0.907	D	0.42	0.45	0.251639045875	gnomAD-4.0.0	1.36869E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73491E-04	0	0	1.65706E-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
D/A	0.5127	ambiguous	0.5609	ambiguous	-0.549	Destabilizing	0.998	D	0.624	neutral	D	0.577810953	None	None	N
D/C	0.9085	likely_pathogenic	0.9119	pathogenic	-0.095	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	N
D/E	0.3834	ambiguous	0.4307	ambiguous	-0.397	Destabilizing	0.907	D	0.42	neutral	D	0.542502284	None	None	N
D/F	0.9207	likely_pathogenic	0.9329	pathogenic	-0.317	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
D/G	0.2823	likely_benign	0.3144	benign	-0.791	Destabilizing	0.984	D	0.617	neutral	D	0.534760488	None	None	N
D/H	0.6384	likely_pathogenic	0.6965	pathogenic	-0.295	Destabilizing	1.0	D	0.654	neutral	D	0.605609991	None	None	N
D/I	0.9185	likely_pathogenic	0.9293	pathogenic	0.057	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
D/K	0.7578	likely_pathogenic	0.7933	pathogenic	0.152	Stabilizing	0.999	D	0.657	neutral	None	None	None	None	N
D/L	0.8486	likely_pathogenic	0.8688	pathogenic	0.057	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	N
D/M	0.9349	likely_pathogenic	0.9449	pathogenic	0.31	Stabilizing	1.0	D	0.646	neutral	None	None	None	None	N
D/N	0.1209	likely_benign	0.1438	benign	-0.263	Destabilizing	0.545	D	0.339	neutral	N	0.50497444	None	None	N
D/P	0.9792	likely_pathogenic	0.9857	pathogenic	-0.122	Destabilizing	0.994	D	0.674	neutral	None	None	None	None	N
D/Q	0.6898	likely_pathogenic	0.7467	pathogenic	-0.211	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
D/R	0.7471	likely_pathogenic	0.7892	pathogenic	0.326	Stabilizing	1.0	D	0.646	neutral	None	None	None	None	N
D/S	0.2675	likely_benign	0.3147	benign	-0.393	Destabilizing	0.991	D	0.59	neutral	None	None	None	None	N
D/T	0.7891	likely_pathogenic	0.8117	pathogenic	-0.196	Destabilizing	0.994	D	0.662	neutral	None	None	None	None	N
D/V	0.7844	likely_pathogenic	0.8034	pathogenic	-0.122	Destabilizing	0.999	D	0.669	neutral	D	0.582363165	None	None	N
D/W	0.9727	likely_pathogenic	0.9764	pathogenic	-0.096	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
D/Y	0.5497	ambiguous	0.6026	pathogenic	-0.058	Destabilizing	1.0	D	0.659	neutral	D	0.61254457	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.