TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15974	48145;48146;48147	chr2:178616969;178616968;178616967	chr2:179481696;179481695;179481694
N2AB	14333	43222;43223;43224	chr2:178616969;178616968;178616967	chr2:179481696;179481695;179481694
N2A	13406	40441;40442;40443	chr2:178616969;178616968;178616967	chr2:179481696;179481695;179481694
N2B	6909	20950;20951;20952	chr2:178616969;178616968;178616967	chr2:179481696;179481695;179481694
Novex-1	7034	21325;21326;21327	chr2:178616969;178616968;178616967	chr2:179481696;179481695;179481694
Novex-2	7101	21526;21527;21528	chr2:178616969;178616968;178616967	chr2:179481696;179481695;179481694
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-109
• Domain position: 7
• Structural Position: 16
• Q(SASA): 0.4841
• Predicted PPI site: I

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	rs1346269011	-0.405	0.016	N	0.275	0.076	0.32471235697	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
V/I	rs1346269011	-0.405	0.016	N	0.275	0.076	0.32471235697	gnomAD-4.0.0	1.36925E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79988E-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	0.7053	likely_pathogenic	0.7156	pathogenic	-2.016	Highly Destabilizing	0.834	D	0.484	neutral	D	0.53897833	None	None	I
V/C	0.9149	likely_pathogenic	0.9128	pathogenic	-1.646	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	I
V/D	0.9555	likely_pathogenic	0.9542	pathogenic	-2.407	Highly Destabilizing	0.973	D	0.742	deleterious	D	0.614499048	None	None	I
V/E	0.918	likely_pathogenic	0.9134	pathogenic	-2.279	Highly Destabilizing	0.979	D	0.707	prob.neutral	None	None	None	None	I
V/F	0.7122	likely_pathogenic	0.7122	pathogenic	-1.303	Destabilizing	0.946	D	0.719	prob.delet.	D	0.571685124	None	None	I
V/G	0.7583	likely_pathogenic	0.7569	pathogenic	-2.462	Highly Destabilizing	0.973	D	0.743	deleterious	D	0.612585371	None	None	I
V/H	0.9794	likely_pathogenic	0.9773	pathogenic	-2.077	Highly Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	I
V/I	0.1736	likely_benign	0.1727	benign	-0.818	Destabilizing	0.016	N	0.275	neutral	N	0.46744077	None	None	I
V/K	0.9439	likely_pathogenic	0.9359	pathogenic	-1.694	Destabilizing	0.979	D	0.705	prob.neutral	None	None	None	None	I
V/L	0.8152	likely_pathogenic	0.8148	pathogenic	-0.818	Destabilizing	0.263	N	0.415	neutral	D	0.56666651	None	None	I
V/M	0.6819	likely_pathogenic	0.6664	pathogenic	-0.858	Destabilizing	0.959	D	0.671	neutral	None	None	None	None	I
V/N	0.9098	likely_pathogenic	0.9123	pathogenic	-1.79	Destabilizing	0.993	D	0.749	deleterious	None	None	None	None	I
V/P	0.9913	likely_pathogenic	0.9923	pathogenic	-1.188	Destabilizing	0.993	D	0.717	prob.delet.	None	None	None	None	I
V/Q	0.9303	likely_pathogenic	0.9275	pathogenic	-1.794	Destabilizing	0.993	D	0.722	prob.delet.	None	None	None	None	I
V/R	0.9196	likely_pathogenic	0.9191	pathogenic	-1.339	Destabilizing	0.979	D	0.747	deleterious	None	None	None	None	I
V/S	0.8576	likely_pathogenic	0.8655	pathogenic	-2.385	Highly Destabilizing	0.979	D	0.717	prob.delet.	None	None	None	None	I
V/T	0.7072	likely_pathogenic	0.681	pathogenic	-2.135	Highly Destabilizing	0.87	D	0.627	neutral	None	None	None	None	I
V/W	0.9933	likely_pathogenic	0.9929	pathogenic	-1.686	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	I
V/Y	0.9424	likely_pathogenic	0.939	pathogenic	-1.356	Destabilizing	0.979	D	0.721	prob.delet.	None	None	None	None	I

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.