TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9553	28882;28883;28884	chr2:178709662;178709661;178709660	chr2:179574389;179574388;179574387
N2AB	9236	27931;27932;27933	chr2:178709662;178709661;178709660	chr2:179574389;179574388;179574387
N2A	8309	25150;25151;25152	chr2:178709662;178709661;178709660	chr2:179574389;179574388;179574387
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: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-81
• Domain position: 61
• Structural Position: 140
• Q(SASA): 0.0971
• 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
V/I	rs763879363	None	None	None	0.256	0.064	0.202949470691	gnomAD-4.0.0	2.7367E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59778E-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	0.5485	ambiguous	0.5041	ambiguous	-1.941	Destabilizing	0.052	N	0.639	neutral	None	None	None	None	N
V/C	0.7984	likely_pathogenic	0.8031	pathogenic	-1.587	Destabilizing	0.935	D	0.817	deleterious	None	None	None	None	N
V/D	0.9035	likely_pathogenic	0.8807	pathogenic	-2.506	Highly Destabilizing	0.484	N	0.873	deleterious	None	None	None	None	N
V/E	0.8216	likely_pathogenic	0.7905	pathogenic	-2.424	Highly Destabilizing	0.555	D	0.841	deleterious	None	None	None	None	N
V/F	0.2675	likely_benign	0.2137	benign	-1.406	Destabilizing	0.317	N	0.772	deleterious	None	None	None	None	N
V/G	0.602	likely_pathogenic	0.5796	pathogenic	-2.353	Highly Destabilizing	0.484	N	0.826	deleterious	None	None	None	None	N
V/H	0.8629	likely_pathogenic	0.8355	pathogenic	-1.969	Destabilizing	0.935	D	0.881	deleterious	None	None	None	None	N
V/I	0.0766	likely_benign	0.0673	benign	-0.851	Destabilizing	None	N	0.256	neutral	None	None	None	None	N
V/K	0.8131	likely_pathogenic	0.7806	pathogenic	-1.62	Destabilizing	0.555	D	0.843	deleterious	None	None	None	None	N
V/L	0.2471	likely_benign	0.2059	benign	-0.851	Destabilizing	0.004	N	0.359	neutral	None	None	None	None	N
V/M	0.2281	likely_benign	0.196	benign	-0.737	Destabilizing	0.38	N	0.686	prob.neutral	None	None	None	None	N
V/N	0.7273	likely_pathogenic	0.6913	pathogenic	-1.658	Destabilizing	0.791	D	0.879	deleterious	None	None	None	None	N
V/P	0.9746	likely_pathogenic	0.9629	pathogenic	-1.184	Destabilizing	0.791	D	0.871	deleterious	None	None	None	None	N
V/Q	0.7745	likely_pathogenic	0.7485	pathogenic	-1.742	Destabilizing	0.791	D	0.875	deleterious	None	None	None	None	N
V/R	0.7618	likely_pathogenic	0.7291	pathogenic	-1.178	Destabilizing	0.555	D	0.881	deleterious	None	None	None	None	N
V/S	0.6688	likely_pathogenic	0.6371	pathogenic	-2.204	Highly Destabilizing	0.555	D	0.817	deleterious	None	None	None	None	N
V/T	0.6137	likely_pathogenic	0.5719	pathogenic	-2.005	Highly Destabilizing	0.149	N	0.642	neutral	None	None	None	None	N
V/W	0.9082	likely_pathogenic	0.8791	pathogenic	-1.768	Destabilizing	0.935	D	0.871	deleterious	None	None	None	None	N
V/Y	0.7199	likely_pathogenic	0.6764	pathogenic	-1.456	Destabilizing	0.555	D	0.804	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.