TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2395	7408;7409;7410	chr2:178773985;178773984;178773983	chr2:179638712;179638711;179638710
N2AB	2395	7408;7409;7410	chr2:178773985;178773984;178773983	chr2:179638712;179638711;179638710
N2A	2395	7408;7409;7410	chr2:178773985;178773984;178773983	chr2:179638712;179638711;179638710
N2B	2349	7270;7271;7272	chr2:178773985;178773984;178773983	chr2:179638712;179638711;179638710
Novex-1	2349	7270;7271;7272	chr2:178773985;178773984;178773983	chr2:179638712;179638711;179638710
Novex-2	2349	7270;7271;7272	chr2:178773985;178773984;178773983	chr2:179638712;179638711;179638710
Novex-3	2395	7408;7409;7410	chr2:178773985;178773984;178773983	chr2:179638712;179638711;179638710

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-13
• Domain position: 40
• Structural Position: 58
• Q(SASA): 0.1991
• 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/A	None	None	0.517	N	0.505	0.353	0.568143352941	gnomAD-4.0.0	6.84081E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99311E-07	0	0
V/E	rs1193803834	None	0.983	D	0.659	0.633	0.85125097569	gnomAD-4.0.0	2.73632E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.7337E-04	0	3.47794E-05	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	0.5844	likely_pathogenic	0.6013	pathogenic	-1.99	Destabilizing	0.517	D	0.505	neutral	N	0.516057993	None	None	N
V/C	0.8419	likely_pathogenic	0.8482	pathogenic	-1.344	Destabilizing	0.996	D	0.638	neutral	None	None	None	None	N
V/D	0.9454	likely_pathogenic	0.9512	pathogenic	-2.574	Highly Destabilizing	0.987	D	0.725	prob.delet.	None	None	None	None	N
V/E	0.8675	likely_pathogenic	0.8764	pathogenic	-2.399	Highly Destabilizing	0.983	D	0.659	neutral	D	0.584107626	None	None	N
V/F	0.2978	likely_benign	0.2996	benign	-1.33	Destabilizing	0.923	D	0.637	neutral	None	None	None	None	N
V/G	0.7161	likely_pathogenic	0.7326	pathogenic	-2.464	Highly Destabilizing	0.949	D	0.681	prob.neutral	D	0.584107626	None	None	N
V/H	0.9399	likely_pathogenic	0.9446	pathogenic	-2.148	Highly Destabilizing	0.996	D	0.712	prob.delet.	None	None	None	None	N
V/I	0.0664	likely_benign	0.065	benign	-0.688	Destabilizing	0.005	N	0.162	neutral	None	None	None	None	N
V/K	0.9112	likely_pathogenic	0.917	pathogenic	-1.791	Destabilizing	0.961	D	0.651	neutral	None	None	None	None	N
V/L	0.1812	likely_benign	0.1777	benign	-0.688	Destabilizing	0.003	N	0.187	neutral	N	0.435617838	None	None	N
V/M	0.2041	likely_benign	0.2016	benign	-0.541	Destabilizing	0.901	D	0.597	neutral	N	0.516057993	None	None	N
V/N	0.8672	likely_pathogenic	0.8776	pathogenic	-1.963	Destabilizing	0.987	D	0.734	prob.delet.	None	None	None	None	N
V/P	0.9315	likely_pathogenic	0.9413	pathogenic	-1.095	Destabilizing	0.987	D	0.687	prob.neutral	None	None	None	None	N
V/Q	0.8775	likely_pathogenic	0.8834	pathogenic	-1.9	Destabilizing	0.987	D	0.695	prob.neutral	None	None	None	None	N
V/R	0.895	likely_pathogenic	0.8994	pathogenic	-1.5	Destabilizing	0.961	D	0.733	prob.delet.	None	None	None	None	N
V/S	0.7955	likely_pathogenic	0.8104	pathogenic	-2.499	Highly Destabilizing	0.961	D	0.622	neutral	None	None	None	None	N
V/T	0.6688	likely_pathogenic	0.6808	pathogenic	-2.189	Highly Destabilizing	0.775	D	0.513	neutral	None	None	None	None	N
V/W	0.9195	likely_pathogenic	0.9224	pathogenic	-1.786	Destabilizing	0.996	D	0.713	prob.delet.	None	None	None	None	N
V/Y	0.781	likely_pathogenic	0.7872	pathogenic	-1.399	Destabilizing	0.961	D	0.672	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.