TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31262	94009;94010;94011	chr2:178547842;178547841;178547840	chr2:179412569;179412568;179412567
N2AB	29621	89086;89087;89088	chr2:178547842;178547841;178547840	chr2:179412569;179412568;179412567
N2A	28694	86305;86306;86307	chr2:178547842;178547841;178547840	chr2:179412569;179412568;179412567
N2B	22197	66814;66815;66816	chr2:178547842;178547841;178547840	chr2:179412569;179412568;179412567
Novex-1	22322	67189;67190;67191	chr2:178547842;178547841;178547840	chr2:179412569;179412568;179412567
Novex-2	22389	67390;67391;67392	chr2:178547842;178547841;178547840	chr2:179412569;179412568;179412567
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-151
• Domain position: 45
• Structural Position: 121
• Q(SASA): 0.1302
• 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/E	None	None	0.484	D	0.68	0.571	0.784914850903	gnomAD-4.0.0	3.18217E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71556E-06	0	0
V/G	None	None	0.317	N	0.696	0.525	0.767050086336	gnomAD-4.0.0	1.59108E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88253E-05	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
V/A	0.4661	ambiguous	0.4695	ambiguous	-1.876	Destabilizing	0.027	N	0.61	neutral	D	0.525498854	None	None	N
V/C	0.7057	likely_pathogenic	0.7219	pathogenic	-1.509	Destabilizing	0.935	D	0.643	neutral	None	None	None	None	N
V/D	0.8616	likely_pathogenic	0.8705	pathogenic	-2.025	Highly Destabilizing	0.555	D	0.727	prob.delet.	None	None	None	None	N
V/E	0.7306	likely_pathogenic	0.7434	pathogenic	-1.974	Destabilizing	0.484	N	0.68	prob.neutral	D	0.525312016	None	None	N
V/F	0.2128	likely_benign	0.2022	benign	-1.389	Destabilizing	0.001	N	0.467	neutral	None	None	None	None	N
V/G	0.509	ambiguous	0.538	ambiguous	-2.256	Highly Destabilizing	0.317	N	0.696	prob.neutral	N	0.513195242	None	None	N
V/H	0.794	likely_pathogenic	0.7979	pathogenic	-1.809	Destabilizing	0.935	D	0.689	prob.neutral	None	None	None	None	N
V/I	0.0761	likely_benign	0.0766	benign	-0.897	Destabilizing	0.002	N	0.345	neutral	None	None	None	None	N
V/K	0.718	likely_pathogenic	0.7254	pathogenic	-1.6	Destabilizing	0.38	N	0.665	neutral	None	None	None	None	N
V/L	0.1937	likely_benign	0.2128	benign	-0.897	Destabilizing	None	N	0.193	neutral	D	0.527170935	None	None	N
V/M	0.1454	likely_benign	0.1661	benign	-0.798	Destabilizing	0.004	N	0.416	neutral	N	0.490318047	None	None	N
V/N	0.6712	likely_pathogenic	0.6841	pathogenic	-1.516	Destabilizing	0.555	D	0.719	prob.delet.	None	None	None	None	N
V/P	0.9722	likely_pathogenic	0.9754	pathogenic	-1.191	Destabilizing	0.791	D	0.688	prob.neutral	None	None	None	None	N
V/Q	0.6223	likely_pathogenic	0.6443	pathogenic	-1.642	Destabilizing	0.38	N	0.675	prob.neutral	None	None	None	None	N
V/R	0.6538	likely_pathogenic	0.6506	pathogenic	-1.113	Destabilizing	0.38	N	0.73	prob.delet.	None	None	None	None	N
V/S	0.5575	ambiguous	0.5628	ambiguous	-2.087	Highly Destabilizing	0.38	N	0.672	neutral	None	None	None	None	N
V/T	0.3982	ambiguous	0.3904	ambiguous	-1.92	Destabilizing	0.149	N	0.643	neutral	None	None	None	None	N
V/W	0.8378	likely_pathogenic	0.8493	pathogenic	-1.639	Destabilizing	0.935	D	0.701	prob.neutral	None	None	None	None	N
V/Y	0.6076	likely_pathogenic	0.5992	pathogenic	-1.349	Destabilizing	0.235	N	0.688	prob.neutral	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.