TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23366	70321;70322;70323	chr2:178576036;178576035;178576034	chr2:179440763;179440762;179440761
N2AB	21725	65398;65399;65400	chr2:178576036;178576035;178576034	chr2:179440763;179440762;179440761
N2A	20798	62617;62618;62619	chr2:178576036;178576035;178576034	chr2:179440763;179440762;179440761
N2B	14301	43126;43127;43128	chr2:178576036;178576035;178576034	chr2:179440763;179440762;179440761
Novex-1	14426	43501;43502;43503	chr2:178576036;178576035;178576034	chr2:179440763;179440762;179440761
Novex-2	14493	43702;43703;43704	chr2:178576036;178576035;178576034	chr2:179440763;179440762;179440761
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-129
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.1509
• 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	rs372782502	-1.931	0.994	N	0.683	0.369	0.497679007273	gnomAD-2.1.1	3.01745E-04	None	None	None	None	N	None	0	0	None	0	0	None	2.4521E-03	None	0	0	0
V/A	rs372782502	-1.931	0.994	N	0.683	0.369	0.497679007273	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	1.65906E-03	0
V/A	rs372782502	-1.931	0.994	N	0.683	0.369	0.497679007273	1000 genomes	9.98403E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	5.1E-03	None
V/A	rs372782502	-1.931	0.994	N	0.683	0.369	0.497679007273	gnomAD-4.0.0	1.12193E-04	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.86715E-03	1.7609E-04
V/E	rs372782502	-2.582	0.999	N	0.841	0.682	0.785853343848	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	1.17924E-03	None	0	0	None	0	None	0	0	0
V/E	rs372782502	-2.582	0.999	N	0.841	0.682	0.785853343848	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
V/E	rs372782502	-2.582	0.999	N	0.841	0.682	0.785853343848	gnomAD-4.0.0	1.23979E-06	None	None	None	None	N	None	0	3.33511E-05	None	0	0	None	0	0	0	0	0
V/M	rs1238454141	-0.195	0.998	N	0.72	0.306	0.388334884743	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
V/M	rs1238454141	-0.195	0.998	N	0.72	0.306	0.388334884743	gnomAD-4.0.0	4.77649E-06	None	None	None	None	N	None	0	0	None	4.76917E-05	0	None	0	0	2.86007E-06	0	3.0248E-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
V/A	0.848	likely_pathogenic	0.8432	pathogenic	-1.873	Destabilizing	0.994	D	0.683	prob.neutral	N	0.466694826	None	None	N
V/C	0.9113	likely_pathogenic	0.9194	pathogenic	-1.254	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/D	0.9982	likely_pathogenic	0.9984	pathogenic	-2.601	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
V/E	0.9945	likely_pathogenic	0.9943	pathogenic	-2.365	Highly Destabilizing	0.999	D	0.841	deleterious	N	0.486891102	None	None	N
V/F	0.8193	likely_pathogenic	0.831	pathogenic	-1.137	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
V/G	0.9455	likely_pathogenic	0.9518	pathogenic	-2.393	Highly Destabilizing	0.999	D	0.856	deleterious	N	0.507197442	None	None	N
V/H	0.9956	likely_pathogenic	0.9959	pathogenic	-2.046	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/I	0.1143	likely_benign	0.1155	benign	-0.415	Destabilizing	0.611	D	0.335	neutral	None	None	None	None	N
V/K	0.9947	likely_pathogenic	0.9946	pathogenic	-1.672	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/L	0.6565	likely_pathogenic	0.6573	pathogenic	-0.415	Destabilizing	0.948	D	0.65	neutral	N	0.512525903	None	None	N
V/M	0.7459	likely_pathogenic	0.7447	pathogenic	-0.365	Destabilizing	0.998	D	0.72	prob.delet.	N	0.475281307	None	None	N
V/N	0.9907	likely_pathogenic	0.9918	pathogenic	-2.093	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
V/P	0.9944	likely_pathogenic	0.9953	pathogenic	-0.876	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/Q	0.9872	likely_pathogenic	0.9873	pathogenic	-1.921	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/R	0.9876	likely_pathogenic	0.988	pathogenic	-1.526	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/S	0.9331	likely_pathogenic	0.938	pathogenic	-2.646	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/T	0.8829	likely_pathogenic	0.8776	pathogenic	-2.263	Highly Destabilizing	0.996	D	0.738	prob.delet.	None	None	None	None	N
V/W	0.9967	likely_pathogenic	0.9973	pathogenic	-1.644	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
V/Y	0.9844	likely_pathogenic	0.9856	pathogenic	-1.204	Destabilizing	1.0	D	0.775	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.