TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27091	81496;81497;81498	chr2:178564861;178564860;178564859	chr2:179429588;179429587;179429586
N2AB	25450	76573;76574;76575	chr2:178564861;178564860;178564859	chr2:179429588;179429587;179429586
N2A	24523	73792;73793;73794	chr2:178564861;178564860;178564859	chr2:179429588;179429587;179429586
N2B	18026	54301;54302;54303	chr2:178564861;178564860;178564859	chr2:179429588;179429587;179429586
Novex-1	18151	54676;54677;54678	chr2:178564861;178564860;178564859	chr2:179429588;179429587;179429586
Novex-2	18218	54877;54878;54879	chr2:178564861;178564860;178564859	chr2:179429588;179429587;179429586
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: Fn3-85
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1413
• 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	0.967	D	0.815	0.539	0.779090105017	gnomAD-4.0.0	1.59314E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86002E-06	0	0
V/G	None	None	0.967	D	0.821	0.481	0.843077508603	gnomAD-4.0.0	1.59314E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43612E-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	0.8813	likely_pathogenic	0.8494	pathogenic	-2.245	Highly Destabilizing	0.892	D	0.659	neutral	N	0.509658117	None	None	N
V/C	0.9363	likely_pathogenic	0.9291	pathogenic	-1.098	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
V/D	0.9986	likely_pathogenic	0.9983	pathogenic	-2.899	Highly Destabilizing	0.987	D	0.871	deleterious	None	None	None	None	N
V/E	0.9937	likely_pathogenic	0.9927	pathogenic	-2.602	Highly Destabilizing	0.967	D	0.815	deleterious	D	0.522028381	None	None	N
V/F	0.8275	likely_pathogenic	0.7872	pathogenic	-1.293	Destabilizing	0.987	D	0.711	prob.delet.	None	None	None	None	N
V/G	0.9454	likely_pathogenic	0.9339	pathogenic	-2.771	Highly Destabilizing	0.967	D	0.821	deleterious	D	0.522028381	None	None	N
V/H	0.9971	likely_pathogenic	0.9968	pathogenic	-2.657	Highly Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
V/I	0.0786	likely_benign	0.0771	benign	-0.683	Destabilizing	0.128	N	0.299	neutral	None	None	None	None	N
V/K	0.9944	likely_pathogenic	0.994	pathogenic	-1.658	Destabilizing	0.975	D	0.815	deleterious	None	None	None	None	N
V/L	0.3448	ambiguous	0.3005	benign	-0.683	Destabilizing	0.63	D	0.661	neutral	N	0.42863787	None	None	N
V/M	0.6603	likely_pathogenic	0.5963	pathogenic	-0.863	Destabilizing	0.983	D	0.643	neutral	N	0.488920516	None	None	N
V/N	0.9944	likely_pathogenic	0.9932	pathogenic	-2.399	Highly Destabilizing	0.987	D	0.873	deleterious	None	None	None	None	N
V/P	0.9894	likely_pathogenic	0.9882	pathogenic	-1.193	Destabilizing	0.073	N	0.723	prob.delet.	None	None	None	None	N
V/Q	0.9907	likely_pathogenic	0.9892	pathogenic	-1.992	Destabilizing	0.987	D	0.855	deleterious	None	None	None	None	N
V/R	0.9896	likely_pathogenic	0.989	pathogenic	-1.931	Destabilizing	0.987	D	0.881	deleterious	None	None	None	None	N
V/S	0.9768	likely_pathogenic	0.97	pathogenic	-2.69	Highly Destabilizing	0.975	D	0.785	deleterious	None	None	None	None	N
V/T	0.9317	likely_pathogenic	0.9148	pathogenic	-2.252	Highly Destabilizing	0.916	D	0.638	neutral	None	None	None	None	N
V/W	0.9973	likely_pathogenic	0.9963	pathogenic	-1.639	Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	N
V/Y	0.9869	likely_pathogenic	0.9838	pathogenic	-1.493	Destabilizing	0.996	D	0.706	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.